A TEXT-BOOK OF 
HISTOLOGY A TEXT BOOK OF 
HISTOLOGY 
BY 
HARVEY ERNEST JORDAN, A.M., Ph.D. 
, T- -_ 
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 LONDON 
D. APPLETON AND COMPANY 
1 6 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 
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 end in view comparative anatomic and 
embryologic facts are frequently presented.* 
Since Embryology usually constitutes*!a*fefe]iarate .-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- PREFACE 
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' II. 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 
XL-The Skin 262 
XII.-The Respiratory System' . . 292 
XIII. -The Digestive System 320 
XIV. -The UrinaLy System 423 
XV.-The Reproductive System 455 
XVI.-The Ductless Glands : Endocrin Glands .... 548 
XVII.-The Nervous System 587 
XVIII-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 
8. -Spermatid of opossum in early stage of metamorphosis into a sper- 
mium ........... 8 
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 pyramidal 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 LIST OF ILLUSTRATIONS 
X 
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 crgastoplasmic 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 ILLUSTRATIONS 
XI 
FIGUBE 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 fundus 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 ILLUSTRATIONS 
FIGURE PAGE 
85. -Notochordal 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 
110. -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 nuciear 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 ILLUSTRATIONS 
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 . . . .Ill 
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 .... 124 
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 
FIGURE 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 transection of the sciatic nerve of a dog . . 134 
147. -A group of large medullated 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 
184. -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 . . 168 
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 173 
193. -Neurotendinous end organ or tendon spindle of Golgi . . .174 
194. -Nerve endings in cardiac muscle, from the heart of a cat . . 175 
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 artery 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 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. -'Vasoformative' 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 sinoventricular system (bundle of His) of 
the calf's heart ......... 200 
217. -Oxalated 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 red 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 ....... 228 
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 .......... 230 
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 .... 238 
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 .......... 249 
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 LIST OF ILLUSTRATIONS 
XVIII 
FIGURE PAGE 
265. -Three early stages in the histogenesis of the skin . . . 270 
266. -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 
XIX 
FIGURE PAGE 
298. -From the lung of a child . . . . . . . .315 
299. From the lung of a dog whose blood vessels had been injected with 
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 ......... 338 
319. -One lateral half of a coronal section of a dog's tongue . . . 339 
320. -Filiform papillae of the dog's tongue ...... 340 
321. -A filiform and a fungiform papilla, from an injected specimen of 
tongue of cat ......... 341 
322. -Circumvallate papillae of the human tongue .... 342 
323. -Two foliate papillae 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 Lieberkuhn) 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 Lieberkuhn) cut longitudinally . . . . . .378 
351. -Section of portion of large intestine of dog, showing the intestinal 
glands (crypts of Lieberkuhn) 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 ILLUSTRATIONS 
XXI 
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 retrolingual gland of the rat ... 388 
359. -Diagram of the arrangement of the cells in a mixed salivary 
gland . . . . . . . . . . . 389 
360. -Diagrams of parotid gland, submaxillary gland, sublingual gland, 
and pancreas ......... 389 
361. -From a section of the human parotid gland .... 390 
362. -From a section of the human submaxillary gland . . .391 
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 zymogen 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 uppei* 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 transection . . . .411 XXII 
LIST OF JLLUSTKAT1ONS 
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, 
hepatic artery, hepatic (bile) duct, lymphatic and non-medul- 
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 .... 432 
404. -From a longitudinal section of a convoluted tubule of the guinea- 
pig's kidney ......... 433 
405. -Cross section of a proximal convoluted tubule from the kidney of 
a mouse, showing basal filaments breaking up into granules cen- 
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 ....... 446 
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 
XXIII 
FIGURE . PAGE 
416. -Epithelial cells from the bladder of the rabbit .... 452 
417. -Transection of the female urethra ...... 453 
418. -Diagram of a male genitalia ....... 455 
419. -Diagram of female internal genitalia ...... 456 
420. -Diagrams illustrating the metamorphoses of the indifferent urogeni- 
tal system into the male and female systems .... 457 
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 . . . 464 
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 
426. -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 . . 483 
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. -A group of interstitial cells from the testis of a thirty-five year old negro 488 
434. -Interstitial cells from the human testis ..... 489 
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 . 495 
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 (Graafian) 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 glomcrulosa, 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 trabeculae, 
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 LIST OF ILLUSTRATIONS 
XXVI 
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 cerebellar 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 
XXVII 
FIGURE PAGE 
541. -Corneal 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 Muller, or sustentacular cell, from the dog's retina . 658 
559. -Transection through the fovea centralis retinae .... 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 ILLUSTRATIONS 
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 with 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- 
plete histologic description embraces, therefore, 
details of the relationships of the component cells 
of a tissue and of the protoplasmic structure, and 
nuclear characteristics of the types of cells in- 
volved. Histology includes further a knowledge of 
tissue origin and development, or histogenesis, and 
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 which con- 
siders the relationships between tissues in organs is sometimes spoken of 
as microscopic anatomy. 
Fig. 1-Various 
Spheroidal Cells „ 
1, ovum from ovary 
of a child; 2, sperm- 
atocyte; and 3, sperm- 
atid, from the testicle 
of a rabbit. Hema- 
tein and cosin. x 
750. 
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 were the recognition of 
the nucleus by Robert Brown in 1831, and of protoplasm by v. Mohl 
in 1846. 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, PROTOPLASM 
3 
carbon, oxygen, hydrogen, nitrogen, and small quantities of sulphur, 
phosphorus, calcium, sodium, chlorin, magnesium, potassium and iron. 
The principal compounds of protoplasm are proteins, which furnish 
the main source of energy expended in function; carbohydrates; fats; 
and water, which constitutes about three-quarters of its weight. It is 
believed by one school of biologists (mechanists) that if we had the 
Fig. 2.-Ameba Proteus in Motion 
c.v., contractile vacuole; f.v., 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 crystalloids. 
The physicochemical laws which govern the crystalloids and colloids 
underlie the properties of living matter. An organism is essentially 4 
INTRODUCTION-PROTOPLASM-CELL 
an aqueous solution, holding in suspension colloidal substances of great 
complexity. Crystalloids are 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 
hydrosol. It passes readily into a 
gel condition, thus becoming a hy- 
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 
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. 
TRICHOCYSTS 
S' CANALS 
MICRONUCLEUS 
MACRONUCLEUS 
GASTRIC VACUOLE- 
pER ISTOME - 
MOUTH ANO GULLET- 
CONTRACTILE VACUOLE. 
Fig. 3.-Paramecium caudatum. 
Note the peripheral cilia and the gran- 
ulo-alveolar character of the protoplasm. 
(From Calkins' "Biology," H. Holt 
& Co.) THE CELL 
5 
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 membrane. 
Fig. 4.-A Generalized Cell. 
a, exoplasm; b, endoplasm; c, spongioplasm; d, hyaloplasm; e, microsomes; f, 
chromidia; g, centrosome (centriole); h, centrosphere, surrounded by astrosphere; i, cell 
membrane;), 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 6 
INTRODUCTION-PROTOPLASM-CELL 
or granules (Fig. 5). The shape 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 
wall. Whether as a membrane it be complete or reticulated, whether of 
nuclear, cytoplasmic 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 nucleoplasm or karyoplasm ; 
that constituting the remainder of the cell, the 
cytoplasm. The nuclear constituents include a more 
fluid ground substance or nuclear sap (karyo- 
lymph: 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 oxychromatin (lan- 
tanin) and hasichrQmatin. Linin 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 chromatin 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 
7 
continue to live for a time, but it can neither grow nor undergo progres- 
sive differentiation. All changes in enucleated protoplasm are regressive, 
leading to death. The nucleus is also largely the reproductive center, as 
will be described below. The nucleolus plays the role, among other pos- 
sible functions, of a center of storage, perhaps also elaboration, of chro- 
matin. Nuclear protoplasm, more especially the chromatin, is relatively 
rich in phosphorus. 
Astral System.-Another organ of a typical cell is the aster, astral 
system or attraction sphere. Its substance is collectively known as archo- 
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- 
troplasm. The centrosome may 
divide into two, becoming a diplo- 
some, or in some instances it 
may become multiple, when it is 
known as a pluricorpuscular cen- 
trosome. Surrounding the cen- 
trosome is a clearer, minutely 
granular sphere, the centrosphere; 
radiating from this peripherally are delicate astral rays, collectively 
known as the astrosphere (Fig. 6). 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 kinoplasm. 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 exoplasm (ectoplasm), 
and the main central mass, the endoplasm. In certain highly differen- 
tiated cells the exoplasm is not discernible. Tn others, at certain stages 
in the development it contains the products of differentiations, 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 
(n) at the right. X 1000. 8 
INTRODUCTION-PROTOPLASM-CELL 
known as 'deuteroplasm (Studnicka). I he endoplasm is commonly 
described as consisting of a more fluid, finely granular ground substance, 
the hyaloplasm (paraplasm, interfilar mass, para- 
mitome, enchylema, cytolymph), containing a del- 
icate denser reticulum, or cytoreticulum, with 
polygonal or spheroidal meshes. The substance of 
the reticulum is called spongioplasm (mitome; 
-filar mass'). 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- 
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 (ch ondrio mites; 
chondrioconts; pseudochromosomes) (Figs. 9 
and 10). Both chromidia and trophospongium 
(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. 7.-P rim a r y 
Spermatocyte of 
a Turtle (Cistudo 
Carolina). 
Showing chromatic 
spherules ('chromidia') 
apparently in process 
of extrusion from the 
nucleus. X 1500. 
Fig. 8.-Spermatid of 
Opossum in Early 
Stage of Metamor- 
phosis into a Sper- 
mium. 
Showing granular 
mitochondria, m, in the 
cytoplasm, n, nucleus, 
s, archoplasmic sphere. 
X 2000. THE CELL 
9 
gium at least is a distinct structure, and chromidia more probably also, 
though by some regarded as the elements from which the filamentous 
mitochondria are formed. Mitochondria have been credited with most 
Fig. 9.-Cells from the Newly Hatched Rainbow Trout, Treated According 
to Meves' Technic for the Demonstration of Mitochondria (Plastosomes). 
a and b, 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 (Maximow), and in animal cells grown in 
artificial media they were observed by M. R. 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 
with metabolic activity. They have the chemical 
composition of a lipoid (probably a phosphatid) 
united to an albuminoid base. It has been sug- 
gested that they are a support to, and the region 
of, oxidation. Chambers suggests that they 'may 
be expressions of changes in the physical states of 
the cytoplasmic colloids.' 
Schreiner's findings in developing fat cells sug- 
gest a nutritive significance. 
Fig. 11. - Intra- 
cellular N E T- 
WORK, OR 'TROPH- 
OSPONGIUM,' WITH- 
IN a Purkinje 
CELL OF THE CERE- 
BELLUM OF Strix 
FLAMMEA. 
Golgi's stain. (After 
Golgi.) 
STRUCTURE OF PROTOPLASM 
Four main types of protoplasmic structure are generally recognized: 
(1) the homogeneous; (2) 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 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. 12.-Diagram Illustrating Theories of Protoplasmic Structure. 
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. 
Fig. 13.-Egg of the Blood Starfish in Later Growth Period. 
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, 
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 Lenhossek.) STRUCTURE OF PROTOPLASM 
13 
or distortion) of the spherical alveoli into polyhedral or irregular com- 
partments. Likewise the /i&nZZar or -filar types may be interpreted as 
similar more extensive modifications 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 Neurofibrils. 
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). 
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 
Fig. 18.-Devel- 
oping Fat Cells. 
The fat droplets, 
after extraction 
with alcohol and 
ether, appearing as 
vacuoles. Hematein 
and eosin. X 550. 14 
INTRODUCTION-PROTOPLASM-CELL 
(Amer. .Tour. 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 
'granules' of the nucleus Kite regards as optical phe- 
nomena, areas of greater concentration in the nuclear 
gel, not separated from, but grading into the sur- 
rounding diluter gel of the 'nuclear sap.' Spindle 
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.' 
Fig. 19.-Columnar 
Ciliated Epithe- 
lial Cells, Show- 
ing Canalicular 
Apparatus. 
After Holgrem. 
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; (4) 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 anil differentiation. Development also is VITAL PROPERTIES 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 generalized beginnings' (Conklin). 
(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 conductivity, and its expres- 
sion in many instances depends upon the property of contractility. 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 (Verworn). 
Fig. 20.-Successive Stages in the Movement of an Ameba. 
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. Response 
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 
tropisms respectively. Responses 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 contractility. 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 
(a) Ameboid motility 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 on 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. Flagellate 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. 
Usually in higher animals the number of flagella is limited to one to a 
cell. The best examples of flagella are furnished by spermatozoa (Fig. 23). 
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. 
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 CELLS 
17 
(c) Molecular motility is a dancing or oscillatory movement of the 
granules in living protoplasm. Such granules may be non-living matter, 
pigment, etc. This type of motion is also called brownian movement. 
It is probably purely a physical phenomenon. It may be simulated by 
mixing finely divided carmin with 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. 
(e) The reason for listing muscu- 
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 
process of contraction of specially dif- 
ferentiated muscle fibrils. It perhaps 
most closely resembles streaming motil- 
ity. It leads to least confusion, in view 
of our present lack of definite knowl- 
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., 
Fig. 23.-Ciliate and Flagellate 
Cells. 
A, ciliated cells isolated from the 
trachea of a cat; B, human sperma- 
tozoa-1, in surface view; 2, in 
profile. Examined fresh in normal 
saline solution. X 550. 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 two smaller 
cells reestablishes the original and more favorable nucleo-cytoplasmic 
dimensional relationship. 
(a) Amitosis.-In typical amitosis the nucleolus first becomes 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. 
each resulting nucleus enclosing one of the nucleoli. Nuclear division is 
followed by cytoplasmic division. A centrosonie is generally neither 
active nor even visible during this process. This typical condition is 
rarely realized. It was first described by Remak (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 
far behind nuclear division, or 
may even fail to appear, thus 
producing bi- 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 
Fig. 26.-Multinucleated Giant Cell, 
from the Yolk-Sac of a 10 mm. Pig 
Embryo. X 2000. 20 
INTRODUCTION-PROTOPLASM-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 
material. Wieman 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 by a considerable 
amount of undifferentiated cy- 
toplasm. that divide by mitosis. 
The factors underlying amito- 
sis most probably exert their 
final effect indirectly through 
initial influence upon the cen- 
trosome. The best experi- 
mental evidence in favor of 
this view is supplied by Nathansohn 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 
Fig. 27.-Spermatocyte of Pyeris cra- 
tegi, a Butterfly, Showing a Cilium 
Attached to the Centrosome. 
(After Meves.) Fig. 28.-Diagrams Illustrating Successive Stages of Mitosis. 
A-F, prophase; G, metaphase; H, anaphase; I-J, telophase, a, achromatic 
spindle; c, centrosome; ep, equatorial plate of chromosomes; if, interzonal fibers; 
n, nucleolus. (After Wilson.) 
21 22 
INTRODUCTION-PROTOPLASM-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 
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- 
vision. For con- 
venience of descrip- 
tion the process, 
which must of 
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. 29.-Cells from Epidermis of the Salamander. 
Three cells are in process of division by mitosis, a, 
prophase; b, anaphase. The second cell above b, whose 
cell body is in process of fission, presents a stage of the 
telophase. (After Wilson.) Fig. 30.-Successive Stages of Mitosis in the Root Tip of the Dogtooth Violet 
(Erythronium americanum). 
a, resting nucleus; b, close spireme; c, loose spireme; d, segmented spireme; e, late 
prophase;/ and g, metaphase; h and i, anaphase;./-?, telophase (showing mid-body or 
cell plate); m and n, daughter cells, n, with resting nuclei. X 1500. 
23 24 
INTRODUCTION-PROTOPLASM-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) Prophase.-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 PROPERTIES OF CELLS 
25 
are extremely difficult if not at present actually impossible. It may be 
noted in passing also, that the chromosomes are believed by many to be the 
bearers of the determiners of hereditary characters-a point to be further 
discussed below. 
(2) Metaphase.-This is a relatively brief stage in mitosis. It 
includes the period when the chromosomes are arranged upon the spindle 
in the equatorial plate. Seen in polar view this is called the monaster 
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 IT-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) Anaphase.-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 mantle fibers') presumably by process 
of contraction. The inner or 'interzonal fibers' constitute the central 
spindle. 
(4) Telophase.-Meanwhile a plate of granules (cell plate; mid- 
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 chromosomes 
and centrosomes (archoplasm material in plants) pass through the stages 
of the prophase, but in inverse order: segmented spireme, loose spireme, Fig. 31.-Successive Stages in the Maturation, Fertilization and Segmenta- 
tion of the Starfish (Asterias forbesii) Egg. 
a, first maturation spindle (m.sJ) and the spermatozoon (s); b, formation of the 
first polar body (p.b.l) and the residual substance of the nucleus (r.s.); c, second 
maturation spindle (m.s.£); d, female pronucleus ( ? ); e, union of male ( $ ) and female 
pronuclei (the male pronucleus is derived from the spermatozoon); f, first segmenta- 
tion spindle; g, two-cell stage of division, d and e are less highly magnified. 
26 HISTOGENESIS 
27 
close spireme, resting daughter nucleus with its daughter centrosome 
and ultimately a nucleolus (Figs. 30, k, 1, m, n). Where a cell plate 
appears, division is consummated without constriction. In certain 
pathological tissues, e.g., cancers, the cells divide in various 
atypical 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-or blastomeres 
(Fig. 31, f and g), 
and each of these 
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 histogenesis. The first 
outstanding stage in the differentiation is that when the three funda- 
Fig. 32.-Transverse Section of a Frog Embryo, 
Showing the Three Germ Layers. 
a, neural crest; b, neural groove; c, neural plate; d> 
coelom; e, ectoderm;/, mesoderm; g, entoderm; h, somite; 
i, notochord; j, parietal mesoderm; k, visceral meso- 
derm; I, yolk; central opening, the primitive intestine. 
(Drawing by G. A. Pagenstecker.) 28 
INTRODUCTION-PROTOPLASM-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 buccal 
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 perilymph 
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 CYTOMORPHOSIS 
29 
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. 
MESODERM 
ear (scalae tympani and 
vestibuli). 
ENTODERM 
Bartholin in the fe- 
male. 
Nuclei pulposi of 
vertebrae, 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 
Fig. 33.-Group of Epithelial Cells from the Malpighian Layer of 
the Skjn. 
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 syncytia (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 may distinguish 
Fig. 34.-A Villus of the Human 
Placenta, Showing a Periph- 
eral Syncytium of Irregular 
Thickness. 
The connective tissue inclosed 
by the syncytium contains three 
capillary vessels. Hematein and 
eosin. X 500, 
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; (d) nervous; and (e) vascular. 
Lymphoid tissue may be regarded as still another fundamental tissue; 
Fig. 36.-Various i or..\is 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 capillary contains 
one leukocyte, and its wall contains the 
nucleus of a flattened endothelial cell. 
Hematein and eosin. X 550. 
Fig. 38.-Goblet and Columnar Cells 
from the Large Intestine of the 
Cat. 
A, Goblet cells; B, isolated columnar 
cells. X 900. 
usually designated cubical or cuboidal (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. 4G). 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 sim- 
ple squamous epithelium, as the case may 
be. Moreover, an epithelium may consist 
of several or many layers, when it becomes 
a complex or stratified epithelium. The 
uppermost type of cells gives the name to 
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 
Fig. 39.-Columnar Epithe- 
lium from the Pyloric Re- 
gion of the Human Stomach. 
(Profile view.) 
Hematein and eosin. X 550. 34 
EPITHELIAL TISSUES 
secreting glands, such as the salivary glands, kidney, and liver. In many 
epithelia, however, secretion is a subsidiary function, protection being 
the primary purpose. 
In all epithelia a cement substance is present between the cells. 
This 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 
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: 
Fig. 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. 
The columnar epithelium is seen in 
profile at a; at b, the free ends of the 
cells are seen. Hematein. X 550. 
CLASSIFICATION OF EPITHELIA 
I. SIMPLE (NON-STRATIFIED) 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) mesenchymal epithelium; synovial membranes, 
bursas, and tendon sheaths, lining of the anterior EPITHELIAL TISSUES 
35 
1. Squamous, 
composed of 
flattened, 
scale-like 
cells. 
chamber of the eye, and of the perilymph spaces 
of the internal ear. 
(b) Lining the alveoli of the lungs, some tubules of 
the kidney, the middle ear, and the membranous 
labyrinth of the internal ear. 
(c) As the superficial cells of stratified epithelium 
(vide 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. 
(A) Plain 
(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.) 
(B) Modified 
(1) Ciliated 
2. Columnar. 
(2) Pyramidal 
or 'glandular' 
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. 
(3) Goblet* 
* Cells whose protoplasm has been converted into mueinogen. They may 
be considered unicellular, mucus-secreting glands. 36 
EPITHELIAL TISSUES 
(a) Eye-the rod and cone cells 
of the retina. 
(h) Ear-in the cristae and mac- 
ulae of the labyrinth and in Cor- 
ti's organ. 
(c) Nose-in the olfactory mucous 
membrane (true neuron). 
(d) Tongue-in the taste buds. 
(4) Neuro-epi- 
thelium. 
2. Columnar. 
II. COMPLEX (STRATIFIED) EPITHELIA-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, polyhe- 
dral', the deep- 
est, columnar 
in shape. 
1. Squamous. 
Superficial cells, 
columnar; 
deeper cells, 
polyhedral or 
spindle-shaped. 
(a) Non-ciliated 
(rare) 
(b) Ciliated. 
(a) Part of vas deferens. 
(b) Respiratory tract; nasal mu- 
cous membrane and passages 
connected therewith, tear-ducts, 
auditory tube, etc., larynx, 
trachea, and bronchi. 
Genital tract; epididymis and vas 
deferens. 
2. Columnar 
(Pseudo- 
stratified 
columnar). 
Superficial cells 
only somewhat 
flattened; next 
deeper layer, 
pear-shaped; 
deepest layers, 
polyhedral. 
Found only in the urinary system 
-viz., pelvis of the kidney, ure- 
ter, bladder, and first portion of 
the urethra. 
3. Transitional. NON-STRATIFIED EPITHELIA 
37 
I. NON-STRATIFIED EPITHELIA 
1. Simple Squamous Epithelium 
(Pavement Epithelium) 
This variety of epithelium comprehends two main groups: (1) the 
endotlielia, lining the vascular system, and (2) the mesothelia of the 
serous membranes lining the large internal closed cavities-pleurae, peri- 
cardium and peritoneum. This distinction is 
somewhat arbitrary but 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, bursas, joint or synovial cavities, cham- 
bers of the eye, and the scalae 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 
on epithelioid characters and arranging themselves 
in the form of a membrane. In their method of 
derivation these cells resemble more closely the 
earliest endothelial 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- 
Fig. 41.-Semidiagram- 
matic Illustration 
of Endothelium Lin- 
ing a Large Ar- 
tery. 38 
EPITHELIAL TISSUES 
neous 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 (IF. 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. NON-STRATIFIED EPITHELIA 
39 
2. Simple Columnar Epithelium 
(a) Plain 
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 
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. 43). The phe- 
nomenon of polarity 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 distal, end 
of the cell, dependent in a final an- 
alysis in larger measure upon dis- 
tance from source of the nutritive 
and oxygenative stream in the blood. 
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, rodlets and 
fibrils 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 
in the columnar cells of the intes- 
tine. In the secreting cells of the 
Fig. 43.-Cuboidal Epithelium from the 
Rete Testis of the Rabbit. 
a, epithelium; b, connective tissue. Hema- 
tein and eosin. X 550. 
Fig. 44.-Tip of a Villus 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. 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 crusta. 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 fiagellum (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 
free extremities of columnar cells 
(Figs. 45, 51 and 52). In some of the 
lower animals, as for example in the 
mouth of the frog, cilia are found also 
upon polyhedral and pear-shaped cells. 
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 
Fig. 45.-Columnar Ciliated Epi- 
thelium from the Epididymis 
of a Rabbit. 
a, epithelium; b, connective tissue; 
c, cilia. A leukocyte is seen between 
the bases of the columnar cells. 
Hematein and eosin. X 550. NON-STEATIFIED EPITHELIA 
41 
structurally expressed in segregation of the presecretion bodies (gran- 
ules, rods, threads) in the basal 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. 46). 
The cells of glandular epithelium usually lack cuticular borders. Pyram- 
idal or glandular epithelium is found in tubules 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 
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 hnucinogen,' 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 
Fig. 46.-A Group of Cells from 
a Transection of an Acinus of 
the Human Pancreas; Glandu- 
lar Epithelium. 
Hematein and eosin. X 550. 42 
EPITHELIAL TISSUES 
the basement membrane. The further history of these cell remnants is 
somewhat doubtful. They are possibly resorbed 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 fine 
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) Neuro-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. Neuro-epithe- 
li um 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; b, connective tissue. Hematein and eosin. X 410 
slant. 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 of 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. New 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 areolas 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 prominent 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 eleidin and keratohydlin-substances chemi- 
cally intermediate between the unaltered and keratized protoplasm. 
As stated, the formation of keratin within these cells is more active 
in those membranes which are comparatively dry from exposure to the 
air. Consequently, it is most active in the epidermis of the skin. If 
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; b, 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, even 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 (keratization) factors. 
2. PSEUDO-STRATIFIED COLUMNAR 
Epithelium 
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. 51. P s e u d o - stratified 
Columnar Ciliated Epithe- 
lium from a Bronchial Tube 
of Man. 
a, a goblet cell; b, 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 
Fig. 52. - Diagram 
Showing the Man- 
ner in Which All 
the Epithelial 
Cells of Pseudo- 
stratified Ciliated 
Epithelium Reach 
the Basement Mem- 
brane. 
Letters as in the pre- 
ceding figure. STRATIFIED EPITHELIUM 
47 
the cytoplasmic portion of the columnar cells with their ciliated bor- 
ders. 
This type 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 basement 
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. Transitional 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 usually 
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 cells which lie in the midregion of the epithelial layer 
possess a peculiar flask or pear shape, with well-rounded bodies and a 
FlG' 53--Transitional Epithelium from a Tran- 
section of the Ureter of an Infant. 
a, epithelium; 6, connective tissue. Hematein 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 somewhat 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 
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 
Fig. 55.-Embryonal Connective 
Tissue, Early Stage. 
Highly magnified. (After Mall.) 
Fig. 56.-Embryonal Connective Tis- 
sue at a Later Stage than Is Rep- 
resented in Fig. 55. (After Mall.) 
varieties: white or collagenous fibers, elastic fibers, and reticulum. 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 fibroblasts, not only 
increase in number by cell division but also secrete an intercellular 
ground substance of semifluid consistence. The fibroblasts fuse with each 
49 50 
CONNECTIVE TISSUE-CARTILAGE-BONE 
other and finally form a syncytial tissue, the mesenchyma, 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 
fibrils soon make their appearance, according to Meves, by processes 
of fusion and chemical alteration of mitochondria (chondrioconta). 
This process continues, now ground substance and fibers being con- 
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; KI, 
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 (ZXFall), 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 
onic connective tissue is found 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. 
Connective Tissue Cells 
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. 58. - Plasma 
Cells of Connec- 
tive Tissue from 
the Human Breast. 
Hematein and eosin. 
X 750. 
Fig. 59.-Spindle-shaped 
Connective Tissue 
Cells from the Stroma 
of the Human Ovary. 
Hematein and eosin. 
X 550. 52 
CONNECTIVE TISSUE-CARTILAGE-BONE 
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 basophil granule cells, 
or mast cells (Mastzellen of the German authors). 
The granules of other granulocytes are readily stained 
with acid dyes, such as eosin (eosinophil, acidophil 
or oxyphil 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 differentiate 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 
Fig. 60.-Pigmented 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. 
Fig. 61.-Granule 
Cells from the 
Fibrous Con- 
nective Tissue 
of the Human 
Mammary Gland. 
A, a basophile 
cell; B, an eosino- 
phile cell. Hema- 
tein and eosin. X 
750. CONNECTIVE TISSUE 
53 
Testing-wandering' cells, or 'clasmatocytes,' are perhaps to be regarded 
as varieties of basophilic granulocytes characterized principally by the 
presence of irregular protoplasmic processes. According to Kite (Jour. 
Infec. Dis., 15, 2, 1914) the 'clasmatocytes' described for the frog by 
Ranvier in 1891 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 fibers 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 fibro-elastic or areolar; (5) 
dense fibrous; (6) dense elastic; (7) cartilage; (8) bone. 
Embryonal Connective Tissue.-Embryonal connective tissue (Figs. 
55 and 56) occurs not only in fetal 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 identi- 54 
CONNECTIVE TISSUE-CARTILAGE-BONE 
cal with mesenchyma; from the viewpoint of progressive differentiation 
it properly heads the list 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 num- 
Fig. 62.-Gelatinous Connective Tissue from the Umbilical Cord of a New- 
born Infant. 
Safranin and water blue. X 410. 
ber in the vitreous, but more abundant in the umbilical cord. In the 
vitreous humor also, there are very few fibers; those which are present 
are very tine 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 mucus is mucin, a glycoproteid. The 
most typical mucous substance is the secretory content of goblet cells. 
The mucus of embryonic and gelatinous connective tissue is closely CONNECTIVE TISSUE 
55 
similar. Less closely similar 'mucous' substances of the more compact 
connective tissues are properly designated, mucoids. 
Reticular Tissue (Reticulum).-Reticular tissue occurs as the 
stroma of adenoid tissue in the lymphatic glands and other lymphoid or- 
gans, and according to Mall (Johns Hopkins Hosp. Rep., 1896), is found 
also in the membrana propria of the secreting tubules of the stomach, 
intestine, kidney, testis, and thyroid, and in the marrow of bone 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 tissue 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 be readily dem- 
onstrated in these bundles only 
after the action of alkalies, diges- 
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, 
large 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; 
they also stain less readily than white fibers and yield reticulin, 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- 
differentiated 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 mesenchyme (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 tissue- 
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 (lb. G. Mac- 
Callum, Arch. f. Anat., 1902; also 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 one another to form an open net- 
work. Each bundle consists of a number of very fine fibers whose CONNECTIVE TISSUE 
57 
course is characteristically wavy or undulating. Though the individual 
fibers rarely branch, the fiber bundles frequently anastomose with one an- 
other. The white fibers are readily stained with most 'acid' dyes, and 
possess a special affinity for acid fuchsin. 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 tliis 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 
Fig. 66. - Portion of 
Tendon from a Cow. 
conn. t. 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.) 
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. 
structure. V\ hether the fibers are deposited as such or arise by coales- 
cence of more fundamental granular elements 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 to, 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 
Tendon fibre- 
Nucleus of a 
tendon cell,- 
surface view 
Ridges on cell 
due to pressure' 
Tendon cells seen. 
from edge 
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 fibers 
outlined by finer processes of the wings. 
The individual fibers are not shown. Gold 
chlorid. X 1000. 
Fig. 68.-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. 64-67). These should be studied 
in dissociated tendinous tissue. It also forms the ligaments, the fasciae, 
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-CARTILAGE-BONE 
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 chordae 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 be 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 p ) 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 
61 
with the elastic fibers of the other 
types of connective tissue. 
The elastic fibers are bound to- 
gether by delicate sheaths of very fine 
collagenous fibers, and are united into 
bundles by coarser bands of fibrous 
tissue. Elastic tissue is found in the 
ligamenta flava, the stylohyoid liga- 
ment and in the ligamentum nuchse 
('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 yellow 
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 (J. S. 
Schaeffer, 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, panni cuius adiposus, 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. 71.-Transection of a Fascic- 
ulus OF THE LlGAMENTUM NuCHjE 
of the Ox, Showing the Very 
Large Elastic Fibers Embedded 
in a Very Delicate Network of 
Collagenous Fibers. 
Picro-fuchsin. X 550. 
Fig. 72.-Portion of Ligamentum 
Nucile of Ox. 
conn. t. c., connective tissue cells. 
(From Dahlgren and Kepner.) 62 
CONNECTIVE TISS UE-CART IL AGE-BONE 
supported by fibrous bands 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 
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; f. 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 
fat globules black; Sudan III, which gives a 
red reaction; and scharlack R (fettponceau), 
which also stains fat'red. For the successful 
application of these stains it is required that 
the tissue has not been previously subjected 
to 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. Rec., 
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 1000. 
Fig. 75.-Fat Cells from a Teased Prep- 
aration of Adipose Tissue of Man. 
X no. 64 
CONNECTIVE TISSUE-CARTILAGE-BONE 
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 
cells 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 
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. 76.-Adipose Tissue. 
The fat cells have been blackened by osmium 
tetroxid. X HO. 
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. Fig. 78.-Reticulum from the Mucosa of the Fundus Region of 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 Niall.) 
Fat 
Lymph sinus 
Cortical 
substance 
Capsule 
r 
Medullary cords 
Follicles 
Hilus with vessels 
entering 
I JTrabeculse 
Medullary substance 
Fig. 79.-Section through a Small Lymph Node of a Dog. X 20. 
(From Szymonowicz-MacCallum, "Histology and Microscopic Anatomy.") 
65 66 
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- 
ferent organs and even in different 
portions of the same organ. The 
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; 
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) 
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. 
X 475. 
* Mali'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 Tissues 
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 
ends 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 fibro-elastic tissue. This membrane is the 
perichondrium. The inner portion of this membrane is richly supplied 
with small cells, and it is from this cell layer, the chondrogene tic layer, 
that the cartilage is presumably developed. 
The cartilage blastema is essentially mesenchyma. The chondro- 
genetic cells of this precartilage 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 matrix. The cells, which in the 
perichondrium 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 with the 
perichondrium 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 a 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. 70 
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 intervertebral 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 
as occurs in the tendons of muscles. At 
the attached margins of the cartilaginous 
plates its tissue is continued by imper- 
ceptible gradations into the surrounding 
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 entodermal 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 
Fig. 84.-Fibrocartilage, Show- 
ing a Group of Oval Car- 
tilage Cells. 
From the semilunar cartilage of 
the knee of man. Hematein and 
eosin. X 550. 72 
CONNECTIVE TISSUE-CARTILAGE-BONE 
syncytial network with a mucin-like substance in its vacuoles; and finally 
it becomes cellular and closely resembles cartilage.*' 
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. 
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.) 
Fig. 85.-Notochordal Tissue 
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 lacunce; 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 dense 
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 
spongy or cancellous bone, while the more superficial lamellae contain 
compact bone. 
In the long bones a similar condi- 
tion exists in the epiphyses, which 
consist of a wall 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 epiphyseal lines between the epiphysis and 
the diaphysis. This plate, which extends through the entire axis of the 
Fig. 86.-Transection through the 
Compact Bony Wall of a Human 
Metacarpal Bone. 
a, outer circumferential lamella;; 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 
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 
fibro-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 internum, endosteum, or 
membrana medullaris. 
Compact Bone.-Compact bone, such as that composing the shafts 
of the long bones, consists of concentric lamelice of calcified fibrous tissue 
which constitute the Haversian systems, together with groups of parallel 
laminae, which are interposed between adjacent Haversian systems and 
are known as the interstitial or ground lamelice. Many of the interstitial 
lamellae are the remains of Harversian systems which have been partially 
Fig. 87.-Longitudinal Section of 
Ground Bone from the Shaft of 
the Human Femur. 
a, Haversian canals; b, lacunae; c, 
canaliculi. X 100. (After Kolliker.) BONE 
75 
absorbed during the development of the bone. In a section through 
the shaft of a long bone the Haversian systems are found in the middle of 
the wall, while superficial to them and just within the periosteum are a 
number of lamellae 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 lamellae. 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- 
teal lamellae. In their finer structure 
the circumferential lamellae are exactly 
similar to the cylindrical bony lamellae of 
the Haversian systems. 
Haversian 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 
lamellae. 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 80 per cent.) 
and carbonates of calcium. From 
four to twenty such calcareous lam- 
ellae 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 lamellae are many small ovoid spaces which 
are partially filled by small flattened cells, the bone cells; these spaces 
are known as the lacunae. From each lacuna minute canals, the canaliculi, 
Fig. 88.-Isolated Bone Cell, 
Shrunk Away from Wall 
of Lacuna at I. 
(Schafer, after Joseph.) 
Fig. 89.-An Haversian System, 
Including the Central Canal, 
Several Lamellae, Lacunae and 
Canaliculi. 76 
CONNECTIVE TISSUE-CARTILAGE-BONE 
radiate in all directions, thns 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. 
Interstitial 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 lamellae 
of the Haversian systems. Coursing through the interstitial and circum- 
ferential lamellae are Volkmann's canals, which are similar in origin, con- 
tents, and function to the Haversian canals but which are not surrounded 
by concentric lamellae. Volkmann's canals frequently arise as branches of 
the Haversian canals which wander out, as it were, into the interstitial 
lamellae. 
Circumferential Lamellae.-The circumferential lamellae do not 
differ in structure from the other osseous lamellae. They possess the 
same arrangement of laminated calcareous connective tissue, with lacunae, 
canaliculi, and bone cells, as in the concentric and interstitial lamellae. 
Even more than elsewhere, however, the outer circumferential lamella1 are 
firmly bound together by collagenous and elastic fibers which pass from 
Fig. 90.-Transverse Section of 
Haversian Canal, with Contents. 
ti, arteriole; v, venule; I, lymphatic; 
n, non-medullated nerve fibers; c, 
bone cell. (After Schafer.) BONE 
77 
the periosteum into and through the superficial lamellae; these are known 
as the perforating fibers of Sharpey. Similar fibers connect together the 
concentric and interstitial lamellae. 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. 
Red Marrow.-Red 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 in 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 the 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 
enchondral 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, tympanies, 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- 
branous ossification. 
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 the 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- 
Fig. 91.-The Primary Changes in Intracartilaginous Bone Formation 
A, metatarsus; 7? 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 areola:. 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 of 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 Sabotta's "Histology.") 
81 82 
CONNECTIVE TISSUE-CARTILAGE-BONE 
Primordial Mar- 
row Cavities.-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, 
and 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 and bur- 
rows its way into the 
enlarged cartilage 
lacunae whose cells are now replaced by primary osteogenic marrow. The 
destruction of cartilage is initiated and maintained by agency of the 
osteogenic tissue, presumably through specific cells, the so-called chon- 
Fig. 93.-Reconstruction of Cartilage into Bone 
car. c., cartilage cells in successive stages of degenera- 
tion; ost, osteoblasts; gi. c., giant cells (osteoclasts); b, 
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., Ketterer, 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 lacunae 
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 Newly 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 lacunce of Howship. 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. 
Perichondrial 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 
perichondrial {periosteal} 
ossification proceeds in a 
manner similar to that by 
which bone is formed in 
membrane which is not 
closely applied to cartilage. 
Perichondrial bone for- 
mation is essentially of the 
intramembranous type. In 
essence there is no valid dis- 
tinction between endochon- 
dral, perichondrial a n d 
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 perichondrial 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 perichondrial 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 lamelice. The Haversian canals 
are actually continuations of the marrow cavity, and the larger are even 
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 lamellse 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 endochondral 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 
synchondrosis 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. 
Intramembranous 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 (Sharpey), 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 trabeculae, which arise 
in the manner described for the initial spicules and then unite into a BONE 
87 
bony sponge-like structure enclosing vascular meseiichyma, the primary 
marrow. The spicules of the cancellous 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 double layer of osteoblasts, which contribute 
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. 88 
CONNECTIVE TISSUE-CARTILAGE-BONE 
In the flat bones of the skull, the central cancellous bone is designated 
diploe, the peripheral compact bone, tables. Membrane bones lack Haver- 
sian systems. 
The conditions which determine that certain bones may arise directly 
in mesenchyma 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) diarthroses 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 invertebral disks of the vertebral column). 
In relation with diarthroses are in several instances (mandibular, 
lower radio-ulnar, costosternal, sternoclavicular, 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 
89 
of the fibrous type. These cartilages serve to deepen the sockets in which 
the upper ends of the femur and humerus 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 fibro-elastic continuous with the periosteum and 
an inner cellular layer, the synovial 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 
94 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 
MUSCULAR 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 
differentiation. 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 mesoderm. 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- 
cosae 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. 92 
MUSCULAR TISSUE 
The early myoblast, of short spindle shape with central oval nucleus, 
contains a granular cytoplasm, limited by 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 
spongioplasm 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 (Internal. 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 myofibrils 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- 
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- 
ble-an obviously important condition. 
The oval or rod-shaped nucleus retains its cen- 
tral location, and is surrounded by a mass of gran- 
ular, relatively undifferentiated sarcoplasm, con- 
taining mitochondria, lipoid, and glycogen gran- 
ules. It changes its shape with the phase and 
degree of contraction, occasionally even assuming a short, spiral form. 
It has been shown (McGill, 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 up 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. 
Fig. 100.-Smooth 
Muscle Cells 
from the Wall of 
the Human Intes- 
tine. 
Transection. Hema- 
tein and eosin. X 750. 94 
MUSCULAR 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. 
(2) In the respiratory system: trachea and bronchial tubes. 
(3) In the genito-urinary system: ureter, bladder, urethra, penis, 
prostate, vagina, uterus, oviduct, and ovary. 
(4) In the vascular system: 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 
mesothelium, which soon becomes 
modified into a loose-meshed syncy- 
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 myofibrillas subse- 
quently acquire a cross striation. Adult muscle consists of stouter mus- 
cle fibers or trabecuhe joined into an intricate close meshwork, by means 
of less robust branches. The nuclei retain their axial position in the 
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 syncytium 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. HISTOGENESIS AND STRUCTURE 
95 
fibers and are surrounded by an oval area of undifferentiated granular 
sarcoplasm. The cardiac fibers and their branches contain peripheral 
myofibrils, 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 undiffer- 
entiated sarcoplasm swelling to an oval, more expansive mass where the 
Fig. 103.-Cardiac 
Muscle of Guinea 
Pig, Showing Sev- 
eral Branches, 
Cross Striations 
(Ground M e m- 
branes) and a Num- 
ber of Intercalated 
Disks. 
Zimmermann's tech- 
nic. X 1000. 
Fig. 102.-A Group of Myo- 
blasts from 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. 
nuclei are located; this core is surrounded bjr 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 fibrillae-a correspondence which indicates a definite func- 
tional stimulus to a structural modification (Fig. 103). The sarcoplasm 
contains mitochondria (Fig. 102), lipoid, albuminoid (interstitial gran- 96 
MUSCULAR TISSUE 
ules of Kblliker), 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 {Bullard, Amer. Jour. Anat., 14, 1, 1912). 
This fatty content can be demonstrated by the several microchemical 
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 myofibrillae, 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 
97 
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 
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- 
cle, as seen under ordinary 
low magnification, its band- 
ed appearance in uncontracted 
fibers. The term telophragma 
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 inokommaia (Heidenhain, Fig. 110). In macerating fluids 
Fig. 106.-The Central Portion of the 
Preceding Figure, More Highly Mag- 
nified. 
a, intercalated disk; en, endothelial nuclei 
of a capillary; IVuc, nucleus of muscle syn- 
cytium. Hematein and eosin. X 500. 
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 STRUCTURE 
99 
fractures occur at the Z lines. These membranes extend completely across 
the fiber, through the axial strand of sarcoplasm-a significant fact con- 
troverting the cellular idea of cardiac muscle originally advanced by 
Apathy. The interstitial granules of Kblliker (sarcosomes of Retzius) 
scattered throughout the Q and J disks in 
striped muscle, both cardiac and skeletal, 
are designated the Q and J granules re- 
spectively (Holmgren). 
Intercalated Disks.-A unique char- 
acteristic of cardiac muscle pertains to the 
presence of the intercalated disks, func- 
tional lines/ or bands of Eberth. These 
are barely visible in ordinary histologic 
preparations, but can be rendered conspic- 
uous by the special technics of Heidenhain 
and of Zimmermann. In gross appear- 
ance they are of several sorts: straight 
bands, step-like forms, and serrated forms. 
The bands (disks) may extend completely 
across a fiber, or only the width of a single 
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 a 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 
Fig. 108.-Developing Muscle 
Fibers from the Heart of a 
Human Fetus at Seven 
Months. 
Fibrillae are well developed at 
the periphery; the undifferenti- 
ated cytoplasm in the center 
presents a clear appearance and 
in some cases is partially occu- 
pied by the nucleus. Hematein 
and eosin. X 750. 100 
MUSCULAR TISSUE 
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- 
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. HISTOGENESIS AND STRUCTURE 
101 
ger-Seidel}; this interpretation has recently been again supported by 
Zimmermann. 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 
• Telophragma 
_ J-granule 
- Q-granule 
- Mesophragma 
-Q-granule 
_ J-granule 
_ J-granule 
Transverse 
'fiber net- 
work 
Transverse 
• fiber net- 
work 
Sarcomere 
or 
Inokomma 
Sarcomere 
or 
Inokomma 
Fig. 111. - Six- 
lobed Nucleus 
from the Heart 
Muscle of Lim- 
ulus, Showing 
the Continuity 
of the Nuclear 
Wall with the 
Telophragmata . 
X 1300. 
Fig. 110. - Diagram of a 
Striped Muscle Fiber, Ac- 
cording to Heidenhain. 
The transverse fiber network 
may be a trophospongium. 
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 irreversible contraction bands rests largely upon the similarity be- 
tween the simplest types and the 'contraction bands' of 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 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 
undemonstrable by the method employed; also that 
while nerves might be unnecessary for maintaining 
rhythmic contraction during embryonic life, they 
nevertheless became necessary in fetal and adult life. 
The discovery of the atrioventricular bundle of 
IIis (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. (It 
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 
Purjinke 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 are the fibers of the myocardium proper. They would 
Fig. 112.-Seven 
Nuclei, the 
Product of 
Amitotic Divi- 
sion, Lying in 
an Undifferen- 
tiated Mass of 
Sarcoplasm, 
from the Heart 
of Limulus. 
The telophrag- 
mata are seen span- 
ning the space be- 
tween the nuclear 
membrane and the 
next adjacent myo- 
fibril. X 700. HISTOGENESIS AND STRUCTURE 
103 
seem to 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 3V2 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 said to be 15 minutes. 
Fig. 113. Longi- 
TUDINAL SECTION 
Trabecula 
OP Limulus 
(King Crab) 
Heart Muscle, 
Showing an In- 
Disk Separat- 
ing a Contract- 
ed from an Un- 
contracted 
Portion. 
Nitric acid-alco- 
(Zim- 
mermann s tech- 
njc) 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 neurogenic. 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; b, 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 sarcomeres 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 Bollet (N line; nebenscheibe) bisects the HISTOGENESIS AND STRUCTURE 
105 
portion of the J disk between the Z line and the succeeding Q disk. 
It is interpreted more or less tentatively by 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 disk 
of Engelmann (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 the posi- 
tion of the nucleus. In skeletal mus- 
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. 
Fig. 115.-Successive Stages of 
Skeletal Muscle Histogenesis 
in Mammals. 
a, myoblast with fine cytoplasmic 
granules (myochondria), from a 13 
mm. sheep embryo; b, 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.) 
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 
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 
myoblasts. 
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) : 
Q, 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., 86, 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 sarcoplasm contains filar and 
granular mitochondria. Both the perinuclear 
and interfibrillar sarcoplasm contain also fat 
granules and globules (liposomes), interstitial 
granules of Kolliker and glycogen. 
Heidenhain (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 mesodermic segments or primitive somites, 
called the myotomes. The myoblasts pass through 
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; m, 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.) 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, Krause's 
membrane or Dobie's 
line, in the middle of 
the light disk. Hema- 
tein. X 1200. (After 
Bohm and von David- 
off.) 
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. Tn the tongue a small number of 
branched fibers have been described. 
Striped muscle fibers differ in the relative amounts of myofibrillar and 
sarcoplasmic content. When the myofibrillae 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 centrally located. 
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 undifferenti- 
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. 
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 fine of Hensen in the dark disk are 
well shown. Very highly magnified. 
(After Schafer.) 
Most mammalian muscles contain both types of fibers, but with the 
'light' greatly in excess. When a muscle consists chiefly of Tight' fibers 
it is a 'white' muscle; when the 'dark' fibers are abundant it may be 110 
MUSCULAR 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 
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, 
isotropic disk; M, mem- 
brane of Heidenhain 
(mesophr agma); Z, 
membrane of Krause (telo- 
phragma) ; H, median disk 
of Hensen; N, accessory 
disk of Merkel; E, terminal 
disk of Engelmann. X 
1000. 
ZJQJZJOJZJQJZ 
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 fibrillae 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 
is suddenly raised by 
passage of ann electric 
current, namely, a swell- 
ing and consequent 
shortening of the fiber 
(Engelmann). 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- 
en and thicken in con- 
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 
Sarcolemma 
Doyere's hillock 
Nerve 
fibre 
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.") 112 
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, fibro-elastic mem- 
brane, the epimysium (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- 
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- 
mysium. 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, Kollikers 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. 
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. 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 fibrils 
to the limits of visibility. 
Heart muscle can be similarly, but less precisely divided, the endo- 
cardium and epicardium corresponding to the epimysium. Fasciculi and 
perimysium are not so readily distinguished, but the endomysium is re- 
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. Tn 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 
MUSCULAR TISSUE 
have a central nucleus and peripheral fibrillae; 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 
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.) 
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, af. (After Boeke, 
Anat. Anz., 44, 15, 1913.) 
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 
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 by 
the anastomosing 
processes of the ten- 
don cells (cells of 
Ranvier). The cell 
bodies lie between 
these primary bun- 
dles; they are connected to each other by their processes, forming an 
'endothelial' 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 elas- 
tic tissue. Each cell contains 
a spherical or oval deeply 
staining nucleus; the nuclei 
Fig. 130.-Portion of a Transection of a Large 
Tendon. 
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.) 
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 Ran- 
vier. Both come from mesenchyme cells, but the fibroblasts entirely 
disappear, while the cells of Ranvier 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. Schultze, 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. Tn neither type 
does he recognize a direct continuity between muscle and tendon fibrils. 
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 fibrillae from a 
large fibroblastic cell 
situated among the 
tendon fibrillae. (Af- 
ter Baldwin.) X1000. 118 
MUSCULAR TISSUE 
In the first type the sarcolenima presents pointed ends, to which the ten- 
don fibrils are attached; in the second, the sarcolenima 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 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 n, nucleus of the neurolemma of 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.) 
Fig. 133.-Diagram of a Neuron. 
120 THE NERVE 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 neuroglia, is also found. This is de- 
scribed below. 
THE NERVE CELL 
(Cyton, 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 /z 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 excentrically 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). 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, chromophilic 
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 cyto chromatin. 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 pyknomorphous, 
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). Cowdry 
(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. Fig. 139.-Three Types of Nerve Cells Supplying Respectively Cardiac (1), Smooth (2) and (3) Striated 
Muscle. 
The cells supplying heart muscle are histologically intermediate between those supplying smooth and those 
supplying striated muscle; 1, cells from nucleus cardiacus nervi vagi of lemur; 2, cells from vagus sympathetic nucleus 
of lemur; 3, cells from hypoglossus nucleus of lemur. X 580. (After Malone; Amer. Jour. Anat., 15, 1, 1913.) 
126 THE NERVE CELL 
127 
directly connected by fibrillae, which pass from the 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 j nice 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; b, 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 intracellular 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 dendron; 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 dendrons. 
Dendrons {Dendrites, Protoplas- 
mic Processes').-The dendrons of a 
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 dendronic 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 synapsis. 
Dendrons are cellulipetal processes, transmitting impulses to the cyton. 
The Axon (Neuraxis, Neuraxon, Neurite, Axis Cylinder Process).-- 
Fig. 141.-A Neuron (Giant Pyrami- 
dal Cell, or Cell of Betz) from 
the Cerebral Cortex of Man, 
Showing the Neurofibrils. 
Bielschowsky technic. X 500. 
Fig. 142. - Intra- 
cellular Net- 
work (Tropho- 
spongium) 
within a Pur- 
kinje Cell of 
the Cerebellum 
of Strix flam- 
mea. 
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 axon hillock or implantation cone, which, 
like the process itself, is devoid of chromophilic granules. It consists of 
Fig. 143.-Golgi Cell, Type I. 
c, collaterals; n, axon. Golgi's stain. (After Kolliker.) 
a bundle of delicate neurofibrils (axon fibrils) embedded in axoplasm. 
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 
NERVOUS 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 with 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 axon 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 
NERVOUS 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: 
A. Medulla ted nerve fibers 
P1. With a neurolemnia 
I 2. Without a neurolemma. 
B. Non-medullated nerve 
fibers. 
\3. With a neurolemnia 
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 neurofibrillar 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 
The axis cylinders, the enveloping myelin sheaths, and the nodes of Ranvier are 
clearly shown. Intra-vitam methylene blue stain. (Barker, after von Kolliker.) 
Fig. 145.-Isolated Nerve Fibers from a Frog. 
which are not supplied with a medullary sheath. In mammals, however, 
the fibrillae 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 fibrilla? to be the conducting element of the nerve fiber. Others, 
however, lay greater stress upon the intervening clear portion, the 134 
NERVOUS TISSUES 
neuroplasm of Schiefferdecker or axoplasm, as containing the active 
conducting substance of the fiber. 
According to Verworn, Lenhossek and R. Goldschmidt, these elemen- 
tary fibrillae (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 
eff6ct of stimulation favors 
the view that the neuro- 
plasm is the essential con- 
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 K iihne. 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. 
The Medullary Sheath (IJ7u7e 
Substance of Schwann, Myelin 
Sheath}. - The medullary sheath 
forms a cylindrical investment for the 
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. 146.-A Small Portion of a Transection 
of the Sciatic Nerve of a Dog. 
Nerve fibers are seen in transection; their 
myelin sheaths are black, their neuraxes un- 
stained. Osmium tetroxid. Photo. X 700. 
Fig. 147.-A Group of Large Med- 
ullated Fibers from a Nerve in 
the Peritracheal 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 
latter is ruptured the myelin exudes 
in the form of 'myelin drops.' The 
myelin 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 amounts 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 Ranvier. 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 incisures of Schmidt 
{Schmidt-Lantermann 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 
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 fines; n, nodes of Ran- 
vier. Osmium tetroxid. A and B, 
X 670; C, X 900. 136 
NERVOUS TISSUES 
osmic 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 Ranvier, 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 -f-like appear- 
ances are seen at each node. By 
prolonged maceration in weak 
solutions of silver nitrate the so- 
lution penetrates still farther 
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 Sheath 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 Ranvier 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. This 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; 
Fig. 149.-Cross and Longitudinal Sec- 
tions of the Same Funiculus (TV) 
of Non-medullated Nerve Fibers 
(Turned Up at the Left), Showing 
the Perineurium (F) 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. 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 neurolemma. 
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 Ranvier. 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. 
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 (Sympar 
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; 
Fig. 150.-Cross-section of the Trunk of the 
Human Vagus Nerve, Some Distance Below 
the Nodose Ganglion, Showing Medullated 
and Non-medullated Fibers. 
Pyridin-silver. X 680. (After Ranson.) 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-medu Hated fibers are very abundant. 
In the vagus of the dog, for 
example, the non - 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 cytodistal end prior to the 
termination of the axon in its 
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. 
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.) 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 
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 Wallerian 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 
Fig. 153.-Transection of the Spinal Cord of an Embryo Chick. 
c. rad. ant., axons to the ventral roots; c. rad. post., axons to the dorsal roots; 
col, collateral from an axon back to the gray matter; gg, dorsal root ganglion; rac. ant., 
Ventral root; rac. 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 
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 -fillers. 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 
choroideae. 
The ependyma consists of 
long nucleated columnar cells 
whose free ends, in fetal and 
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 astrocytes, when stained by the Golgi method, apparently con- 
sist of a small cell body and an innumerable number of long slender 
Fig. 154.-Transection of the Spinal Cord 
of a Child, Fifth Lumbar Segment. 
The central H-shaped gray substance con- 
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. 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. 
(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 NEUROGLIA 
143 
processes. Two varieties of these cells are recognized: the spider 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 
Fig. 157.-Neuroglia from the Spinal Cord of a Fetal Pig. 
The portion above shows the result of the Golgi stain; below, that of a hematein and Congo red stain, a, 
inner layer of neuroglia, adjoining the central canal; b, boundary between the nucleated and mantle layers 
of neuroglia; cs, connective tissue; ep, ependyma; m, mantle layer; mn, middle or nucleated layer of neu- 
roglia; mv, ventral raphe; p, pia mater; r, radial filaments of the neuroglia. X 320. (After Hardesty.) 
astrocytes, whose processes are shorter and somewhat thicker but de- 
cidedly more varicose than those of the long-rayed type. 
Recent 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- 
work 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.-Neuroglia 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, 
Fig. 161.-Neuroglia Cells and Fibers from the Spinal Cord of an Elephant. 
The letters indicate various types of neuroglia cells. I, 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 epineurium, 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 framework, 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 
fibers of the medullated 
type do not generally 
branch except in those 
portions which are naked 
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- 
Fig. 162.-Transection of the Sciatic Nerve 
of a Dog. 
The fat cells and the myelin sheaths of the nerve 
fibers have been blackened by osmium tetroxid. a, 
fat cells; b, b', blood vessels, that at b' lies within a 
funiculus; c, epineurium; d, perineurium; e, coarser 
bands of the endoneurium. Osmium tetroxid. Photo. 
X 30. 148 
NERVOUS TISSUES 
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 
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, a, 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, f, 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 Lenhossek.) 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, after van Gehuch- 
ten.) 
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 
NERVOUS TISSUES 
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, Ranvier, 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 
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 
branches penetrate the capsule to form 
a pericellular arborization about the 
nerve cell itself. The cells of this lat- 
ter type suggest association neurons 
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.) 
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 also enter 
the spinal ganglia and form pericellular arborizations about the cells 
of the second type. Dogiel 
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 Ranson (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 Ranson 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 Ranson 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 
to arise in sympathetic gang- 
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 
Fig. 168.-Schematic Representation of the 
Relations of 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 
type of ganglion cells. (After Dogiel.) 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 
(Ranson, Jour. Comp. Neur., 24, 6, 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 fenestrations 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 
NERVOUS 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, perhaps 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 prevertebral autonomic ganglia are bi-nucleate (Car- 
penter and Conel, 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 156 
NERVOUS TISSUES 
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 neurolemma 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 larvae 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 neuro- 
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 
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- 
boid movements. 
(Harrison.) 
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. Recently 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 
('bandfasern' 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 neurolemma cells. 
Mitochondria of granular and rod forms are abundant in the neuro- 
blasts. Meves, 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 untenability 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 cells 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. CHAPTER VI 
PERIPHERAL 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 NERVE TERMINATIONS: END ORGANS 
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 
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 
papillae. 
Taste buds are ovoid, ellipsoidal, or spheroidal masses which occupy 
almost the entire depth of the epithelial layer. Their broad base rests 
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.) 
Fig. 174.-Tactile Cells in the Epithelium 
of the Groin of a Guinea-pig. 
et, tactile cell; c, epithelial cell; m, tactile men- 
iscus, at the end of a nerve fibril; n, nerve fiber. 
Chlorid of gold. Highly magnified. (After 
Ranvier.) NERVE ENDINGS IN EPITHELIUM 
161 
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 
papillae 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 sur- 
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 
Epithelium 
of mouth. 
~ Nerve 
fibrils. 
' Hair-like 
process. 
Pore. 
Cone. 
Supporting cell. 
'Neuro-epit helial 
cell. 
Rod cell. 
'Nerve fibrils. 
Fig. 175.-Schematic Representation of a Taste 
Bud. 
(After Hermann, from Bohm and von Davidoff.) 162 
PERIPHERAL 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 
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.) 
Fig. 176.-Taste Bud from the Human Tongue 
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. NERVE ENDINGS IN CONNECTIVE TISSUE 
163 
The Fibers.-The nerve fibrils of the taste 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 
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 
PERIPHERAL 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 of 
Meissner. 
b, epithelioid cells; c, nerve endings; 
e, connective tissue capsule. (Maxi- 
mow, after Van de Velde.) 
Fig. 179.-Tactile Corpuscle of 
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 papillae 
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 NERVE ENDINGS IN CONNECTIVE TISSUE 
165 
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. Ruffini 
(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- 
ally at its end. . Now and then a single branching nerve fiber is dis- 
tributed to several of these end organs. 
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.) 166 
PERIPHERAL NERVE TERMINATIONS: END ORGANS 
3. End Bulbs (Krause).-These structures (bulbous corpuscles), 
together with those which follow, form the true so-called encapsulated 
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 
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 
either 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 the cerium of the skin. Similar, though more highly developed, 
end bulbs form the so-called genital 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 tire eat 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 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.) 
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 of 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 
PERIPHERAL 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 
Fig. 190.-Motor Nerve Endings in Striated Muscle. 
A, 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, a, 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 
PERIPHERAL 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 (Neuromus- 
cular Spindles, Neuromuscular 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 neuromuscular 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, 
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 
axial sheath of connective tissue which is united to the capsule by bands 
of fine fibrous tissue which span the broad periaxial 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 
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. NERVE ENDINGS IN MUSCLE AND TENDON 
173 
connected with the tendon, or they may join other muscle fiber 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. Ruffini 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 fibers 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 
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, Huber and 
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- 
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. 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.) 
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 VASCULAR 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 endothelium. 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 witli 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 1111- 
176 AKTEKiES 
177 
named arteries 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 pavementepithelium. 
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. Tn the largest arteries it increases in amount also 
with age, becoming especially well developed in the aorta. Tn 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 internal 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. Tn 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, 3, 
tunica adventitia. Weigert's elastic 
tissue stain and picro-fuchsin. Photo. 
X 64. 
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 
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 intima. 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 
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 
-Elastica interna 
layer 
-Elastic J.bers 
Media 
f Bundles of mooth 
" (muscle cells 
.Elastica externa 
Adventitia 
■ Vas vasis 
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-sized 
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 intima 
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 adventitia 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 the 
Celiac Axis of Man. 
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 VASCULAR SYSTEM 
The tunica medig, 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 
Fig. 201.-A Group of Small Blood-vessels. 
A, small artery 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 ARTERIES 
183 
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 muscle 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. 202.-Semi-dia- 
GRAMMATIC ILLUS- 
TRATION of Small 
Branch of Pulmo- 
nary Artery of 
Ox. 
(After Piana.) X70. 
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 VASCULAR SYSTEM 
Comparison of Large and Small Arteries.-The larger arteries are 
typically elastic, the smaller typically muscular. In 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. Fig. 204.-The Capillary Network Connecting an Arteriole and Venule 
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 I' 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 endothelial cells. Highly 
magnified. (After Ranvier.) 
185 186 
THE BLOOD VASCULAR 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 
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 
Fig. 206.-Two Sinusoidal Vessels from 
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. 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 endo- 
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, coccygeal 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 mirabilia 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 
delicate connective tissue membrane. In the 
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. 
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.-Tn 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. 
Fig. 208.-Transection of an Arteriole and Venule. 
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 large 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. 189 
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 
dense white fibers, among which is a network of fine elastic fibers. Occa- 
a, tunica intima; b, 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. 
Fig. 209.-Transection of the Wall of the Human Vena Cava. 
sional small bundles of longitudinal smooth muscle fibers occur in the 
adventitia of the largest veins. Tn 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 
venae 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 cavae, 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 venules 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 venae 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. Hence, of any two vessels in close proximity to 
each other, 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 VASCULAR 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 
infrequency that valves are not often met with in those transections of 
the smaller veins which are seen in nearly all microscopical preparations. 
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 endo- 
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 
(angioblast 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 
193 
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 mesenchyma 
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, 
Huntington, 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-endothelial layers of muscular and 
connective tissue elements from the surrounding mesenchyme, and their 
association into the several tunics of the various subdivisions of these 
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 be summarized 
in the following schemes. 
Media (elastic tissue). 
Media (smooth muscle). 
Adventitia. 
Large Artery (typically elas- 
tic) 
Comprises about one-half of 
the entire wall. 
Small relative amount-com- 
prises about one-third of 
wall. 
Relatively very thin. 
Small Artery (typically mus- 
cular) 
Much diminished. 
Large relative amount-com- 
prises about three-fourths 
of wall. 
Somewhat thicker (ratio re- 
mains constant for smaller 
vessels). 
Large Vein 
Small amount. 
Large relative amount. 
Large amount. 
Small Vein 
Scanty. 
Small amount. 
Large relative amount. 
Lumen. 
Wall. 
Media 
(elastic 
TISSUE AND 
SMOOTH 
muscle). 
Thickest 
Layer. 
Internal 
Elastic 
Membrane. 
Alternating 
Layers of 
Elastic 
and Muscular 
Tissue. 
Valves. 
Medium-sized 
' Artery ... 
Smaller. 
o 
z 
Thicker, 
more rigid. 
Large amount. 
Media. 
Very conspicu- 
ous, discernible 
even in smaller 
arteries. 
In small 
arteries. 
Absent. 
Vein 
Larger. 
Thinner, less 
rigid. 
Deficient 
(collagenous 
fibers in excess 
of all other 
tissue). 
Adventitia. 
Present only 
in larger 
veins. 
In largest 
veins. 
Present in 
some veins. HEART 
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 fibro-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 196 
THE BLOOD VASCULAR SYSTEM 
small openings 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 trabecula? 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- 
dothelium of this membrane is 
continuous with that of those 
blood-vessels which open from 
the cavities of the heart. Its 
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 fibro-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 
Fig. 212.-The Parietal Layer of the 
Pericardium of a Child. 
a, mesothelium; b, connective tissue. 
Hematein and eosin. Photo. X 500. 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, where 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 aortas. 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 elastic fibers, 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 chordae 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 tendines 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. 
Columns Carns.-The columns earns 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 earns. HEART 
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 be attached only at their two ends, the mid- 
portion being free; (3) they may be attached to the myocardium at one 
end only, the other end projecting into the ventricular cavity as a papil- 
lary muscle, from whose apex chordie tendinese pass to the auriculoven- 
Main Bundle of His 
Pulmonary Veins 
■Sup. Cava 
Aorta 
.Pulmonary Artery 
( Muscular Fibers Streaming to 
( the Reticulum 
Right Auricle 
Pars Mem. Septi 
5 Bifurcation of Main Bundle into 
( Right and Left Sept. Branches 
Right Septal Branch 
Moderator Band 
Fossa Ovalis 
Inf. Cava- 
Coronary Sinus 
Reticulum 
Artery to Bundle 
Tricuspid Valve 
Right Ventricle 
Chordae Tendinece 
Papillary Muscle 
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 tendinese, 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. 
Columnae carnae which span the ventricular cavity constitute moderator 
hands. One such band 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 was 
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 nieshwork 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 atrioventricular 
groove (sinus region; hence, sinoventricular conducting system, Retzer, 
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- 
branacea 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. Rec., 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 (1906) 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 fibers. 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 venae 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. 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, 1914) 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 blood-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 be 
traced to the smallest blood-vessels, and even in the capillaries terminal 
fibrillae 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 clot 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 {erythrocytes} 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 p in musk ox; 
9.4 p in elephant; dog, 7.5 p ) are all of circular outline, except those 
of the camelidaa (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 hypotonic; 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 
hlood shadows; and 
final bursting, leav- 
ing a debris called 
hemokonia. 
The number of 
red corpuscles in 
the blood is subject 
to constant varia- 
tion 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; b, higher focus; 
D, two polymorphonuclear 
leukocytes; E, large mono- 
nuclear leukocyte. X 750. 
Fig. 220. - Showing the 
Action of Water upon 
the Red Blood Cor- 
puscle. 
a, the corpuscle in pro- 
file; b-e, various stages in 
the transformation which 
leaves only a 'shadow' e; 
diagrammatic. (After 
Schafer.) 207 
THE WHITE BLOOD CELLS 
concentration of the blood and an apparent increase in the number 
of its corpuscles. The number of red blood corpuscles in the female 
Fig. 222.-Three Nu- 
cleated Red Blood 
Cells (Erythro- 
cytes) from THE 
Marrow of a Hu- 
man Rib. 
Eosin - methylene 
blue. Nocht method. 
X 1200. 
Fig. 221.-Five Nucleated Red Cells 
(Erythrocytes) from the Blood of 
a Frog. 
Eosin-methylene blue. Hasting's 
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 mononuclear leukocytes and (3) granular leukocytes 
-granulocytes. 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 
blood 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 lop.) 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 
1, red blood corpuscles in rouleau formation; 2, 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. 
Fig. 223.-A Group of Cells from Normal Human Blood. 
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 leukocyte 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 giant cells. These are of two sorts, depending upon 
whether the nucleus is single or multiple, the megakaryocyte and the 
polykaryocyte. 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 io 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 
supposed to be the essential elements, probably 
liberating 'thrombin', in clotting, hence their 
synonym, thrombocyte. This term, however, is ill- 
chosen, for these elements contain no nucleus. 
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. Wright'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) 
eosinophils (oxyphils') and (3) basophils, 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 p. to 10 p in diameter. They are predominantly phagocytic. 
They constitute in normal adult life about 70 per cent, of the total white- 
cell blood content. 
Fig. 224.-A Group 
of Blood Plate- 
lets, from the Hu- 
man Blood. 
Very highly magni- 
fied. (After Eisen.) 210 
BLOOD 
The eosinophils contain larger spheroidal cytoplasmic 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 fuchsin, 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.; ( 8) 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. 
3. Neutral-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). 
HEMOGLOBIN 
Hemoglobin is a very 
complex chemical compound 
of iron with a globulin; it 
gives the characteristic color- .. t .. ... ., 
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 
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. 
In the course of half an hour the cells develop 
retractile undulatory processes, a, hyaline-sur- 
face phase; x, hyaline layer; b and c, ciliated 
phase; d, flagellated phase. Leukocytes of all 
classes of vertebrates undergo similar changes. 
(After Kite, Jour. Infectious Dis., 15, 2, 
1914.) 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 hematin, 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. Hemin 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 are 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; f, 
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 hemosiderin, an iron-containing 
hemoglobin derivative, in the form of light-brown granules, frequently 
found in phagocytic leukocytes as 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 application 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 hematoidin, 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. HEMAPOIESIS 
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- 
city of germ layers. Such 
position is hardly tenable in 
view of the fact that origin- 
ally there is only one gerrq 
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 
Fig. 229.-Wall of Yolk-sac of a 13 mm. 
Human Embryo (Fig. 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. 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 
Fig. 230.-Large Blood Island from (Fig. 210), a 13 mm. Human Embryo. 
a1 and a2, mesenchymal cells; a1 is differentiating into an endothelial cell; a3, endo- 
thelial cells becoming separated from wall to form hemoblasts ('lymphocytes'); 
bl and b2, hemoblasts (mesameboids); c, megaloblasts; dl and d2, 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., Minot,-and still in accord with the monophyletic 
teaching-regards the later embryonic, 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 
differs 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) megaloblast; 
(2) normoblast; (3) erythroblast and (4) erythroplastid ('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 normoblast 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 (karyorfhexis) 
in the cat; Emmel (Amer. Jour. Anat., 16, 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- 
blast; 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 Erythro- 
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. Pig 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.) primitive 
erythroblast 
ca. 11m 
T 
primitive 
erythrocyte 
I 
i 
this line 
dies out in 
early embry- 
onic stages. 
It is charac- 
terized by 
relatively 
greater size 
of cells. 
(Primary wandering cell, Saxer; lymphocyte, Maximow; hemagonium, Mollier; mesameboid cell, Minot; hemoblast) 
(giant cell; 14 to 20m; basophilic cytoplasm) pro- 
duces blood-plates by segmentation of pseudopods. 
I 
definitive erythroblast 
7.5m 
(extrudes nucleus to form) 
megaloblast-ca. 8m 
(little hemoglobin, 
amblychromatic) 
(ichthyoid stage, Minot) 
i 
normoblast 
(much hemoglobin, 
trachychromatic) 
(sauroid stage, Minot) 
I 
definitive erythrocyte, or 
erythroplastid. 
large mononuclear 
and transitional 
types) 
megakaryocyte 
megaloblast 
Y 
normoblast 
I 
erythroplastid 
i 
leukocyte 
PRIMITIVE BLOOD CELL 
{primitive') lymphocyte (basophilic cytoplasm, ca. 9.5 m) 
erythro- 
blasts 
lymphocyte 
lymphocyte 
lymphoblast 
★lymphocyte 
(divides into) 
MZ 
small lymphocyte 
(grows to) 
large lymphocyte 
lymphocyte 
{granuloblast; in red bone marrow, 
premyelocyte, or myeloblast') 
/ I \ 
basophil 
leukocyte, 
or 
mast leukocyte 
*Elsewhere 'lymphocyte' is used in 
the sense of a primitive or mesa- 
meboid blood-cell, according to 
Maximow's terminology. 
lymphocyte {leukoblast) 
lymphocyte 
. A 
neutrophil 
leukocyte 
eosinophil 
leukocyte 
219 220 
BLOOD 
BONE-MARROW 
The red variety of bone-marrow, found in the flat bones generally 
and in the epiphyses 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- 
Fig. 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; f, 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 hematoidin it is apparently appropriated in the manufacture 
of the bile pigment, bilirubin. 
The generic name for the specific hemogenic cells of marrow is 
myelocyte. 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-cells both white (eosinophil, neu- 
trophil, and basophil polymorphonuclear leukocytes, and lymphocytes) 
and red (erythroplastids). Potential osteoblasts and osteoclasts are BONE-MARROW 
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 {Premyelocyte ; Ilemoblast, Mesameboid Cell; Prim- 
itive Blood Cell; 'Lymphocyte'}.-This is the parent blood-cell of bone- 
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, polynuclear 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 tabulated 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 tabulated 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 disintegra- BONE-MARROW 
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., trichiniasis; 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 (Mast 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 polykaryocyte 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- 224 
BLOOD 
ber 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 transudates 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 bursae. 
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 lymphatic corpuscles. 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- 
clavian 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. Recent 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 tissue 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 all tissues where blood capil- 
laries are found. They are most abundant in the perivascular connective 
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 SYSTEM 
continuous with the lymphatic capillaries, but the more recent observa- 
tions, represented by those of MacCallum (Johns Hop. Hosp. 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 toward 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 smaller lymphatic vessels. 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 membrane. 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 perivascular 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. Rec., 6, 6, THE DEVELOPMENT OF LYMPH VESSELS 
231 
1912, and others) interpret these sacs as the products of fusions of still 
more primitive discrete lymphatic anlages which arose as mesenchymal 
spaces; and their connection with the subclavian, sciatic and renal veins 
as secondary unions. Sabin 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- 
intimal 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 mesothelial lining and a support- 
ing membrane of areolar connective tissue which is richly supplied with 
capillary blood-vessels and lym- 
phatics. The mesothelium 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 cavity and 
the surface of the organ which it envelops, or it may be attached by a 
loose layer of submesothelial 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 
233 
are clothed by a single layer of pavement cells which is said to be in- 
complete in places. Its mesothelium (mesenchymal 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 bur see 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 lobule 
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 tine 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 mononuclear 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- 
vertebral 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 fibro-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 
An afferent lymph vessel, pursuing its course within the 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 lymph sinus, 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 
portion, the cortex, 
f o r 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 trabeculae 
which extend inward 
from the fibrous cap- 
sule, and along which 
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 
Fx«. 242.-Diagrammatic Illustration of a Lymph 
Node. THE LYMPH NODES 
237 
ramifications of these medullary trabeculae are continuous with those 
of the cortex. 
The denser portions of lymphoid tissue are light in the figure, a, medullary cord 
of dense lymphoid tissue; b, 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; V, blood-vessel. Magnified 
several diameters. (After Ranvier.) 
Fig. 243.-Transection of a Cervical Lymph Node of a Dog. 
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 whieh 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. Reticulum 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., 1900) 
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; II, fol- 
licular artery; I, arterial capil- 
laries in a follicle; J, vein from 
capsule; K, cord; L, trabecula; 
V, 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 polymorphonuclear 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 
(Calvert, 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 trabeculae in their course toward the 
medulla, where they enter the medullary trabeculae, are augmented by 
venous radicals from the capillary plexuses of this portion of the gland, 
and thence follow the trabeculae to the hilum, where they unite to form 
the efferent vein. 
Certain of the arteries also pass from the medulla through the inter- 
nodular trabeculae 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. Mie. 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 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 hlood 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 'splenolymph glands' and the 'marrowlymph glands.' 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 trabeculae 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 (intermodular 
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 endothelium. 
The function of lymph nodes is 1he production of lymphocytes, which 
become phagocytic leukocytes. Besides having a leukopoietic 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 endothelial 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 {Palatine Tonsils; Amygdalae}.-The tonsils 
consist of a mass of lymphoid tissue 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 connective 
tissue. 
The epithelial coat here and there penetrates the substance of the 
organ 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- 
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; f, 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.' Tf 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 circumvallate 
papillae 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 commoidy 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 albuginea, 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 trabeculae project from the capsule into the paren- 
chyma of the organ. These trabeculae are of similar structure to the 
capsule. The supporting tissue of the parenchyma is a delicate reticu- 246 
THE LYMPHATIC SYSTEM 
lum. This is continuous with the fibro-elastic terminal processes of the 
fibromuscular trabeculae. 
The primary trabeculae divide the parenchyma imperfectly into 
roughly pyramidal compartments about one millimeter in diameter, with 
three trabeculae 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 trabeculae. 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 trabeculae 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 
excentri 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 intralobular 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 Ruysch. On these appear an ellipsoidal 
condensation of reticular tissue forming the so-called splenic ellipsoids. 
These arterioles (six to ten microns in diameter) are known as sheathed 
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 ampullev 
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- 
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 trabeculae, 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 trabeculae 
(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 which, in the out- 
lying connective tissue, form by their union the splenic vein. 
Fig. 252.-The Origin of a Vein in the 
Splenic Pulp. 
a, venous endothelium; b, leukocytes; c, 
red blood corpuscles (appearing rather too 
dark in the reproduction); d, a mesh of the 
splenic pulp. Highly magnified. (After 
Bannwarth.) THE SPLEEN 
249 
Differentiation of Spleen from Lymph Node-The spleen in sec- 
tion can be readily differentiated from a lymph node: it lacks a definite 
subdivision into cortex and medulla characteristic of the lymph node, its 
pulp contains a preponderating number of red blood corpuscles, and its 
capsule is relatively very robust and contains a greater amount of smooth 
muscle. The spleen may be thought of as a congested lymph node, con- 
sisting wholly of medulla, throughout which are scattered lymph nodules, 
the splenic nodules. It might quite properly be described as a huge hemo- 
lymph node. 
Splenic Cells.-Besides erythroplastids and occasional erythrocytes, 
the pulp contains also the 
several varieties of leuko- 
cytes : lymphocytes, granu- 
locytes, a few megakaryo- 
cytes, and blood-platelets. 
The leukocytes of the spleen 
are largely of the large 
mononuclear type. These 
are notably phagocytic, fre- 
quently containing erythro- 
plastids, fragments of cells, 
pigment and other granular 
debris. They are in a sense 
specific for the spleen, hence 
called splenic cells. Mega- 
karyocytes are abundant in 
the fetal spleen during its 
period of erythropoietic 
function, but rare in the 
adult spleen. 
Lymph Supply. - The 
lymph supply of the spleen 
is relatively scanty. The capsular is independent of the parenchymal 
system, which latter consists chiefly of perivascular lymph spaces and 
vessels draining toward the hilum. 
Nerve Supply.-The innervation includes both medullated and non- 
medullated fibers. The latter predominate, and are distributed to the 
smooth muscle of the capsule, trabeculae, and blood-vessels. 
Functions.-The spleen functions as a leukopoietic organ and as a 
blood filter. This is indicated both by the direct evidence of lymphocyte 
pIG 253.-Types of Cells from a Smear Prep- 
aration of the Pulp of the Human Spleen. 
a, lymphocytes; b, polymorphonuclear neutro- 
Phil leukocytes whose granules are not stained 
by the method used; c, large mononuclear leuko- 
cyte; d, eosinophil cells; e, basophil cell; f, red 
blood corpuscles. Hematein and eosin. X 1200. 250 
THE LYMPHATIC SYSTEM 
proliferation and the ingestion of erythroplastid debris by the splenic 
and endothelial cells, and by the fact that the proportion of lymphocytes 
to erythroplastids in the splenic vein is very much greater than in the 
splenic artery. After severe hemorrhage or certain anemias the spleen 
may resume its fetal erythropoietic function. Numerous small super- 
numerary spleens, of varying size but usually about the size of a pea, 
are frequently found in the vicinity of the spleen. 
Besides the production of lymphocytes and the destruction of senile 
red corpuscles, the normal adult spleen has been credited also with an eryth- 
ropoietic role, and with a function concerned with the metabolism of iron. 
That the spleen does not, however, have any specific function absolutely 
essential to life is proved by the fact that it may be removed without 
serious consequence. Obviously its function may be taken over by some 
other organs. Such compensatory role is usually attributed to the hemo- 
lymph nodes and the red marrow. However, splenectomy in dogs is not 
followed by increase in the number or size of the hemolymph nodes, nor by 
a production of accessory spleens (Meyer, Jour. Exp. Zool., 16, 2, 1914). 
Removal of the spleen in dogs seems to exert a stimulating effect upon the 
formation of red cells in bone-marrow (Krumbhaar and Musser, Jour. Exp. 
Med., 20, 2, 1914). Pearse and Pepper (Jour. Exp. Med., 20, 1, 1914) found 
that splenectomy caused a transformation of yellow into red marrow. The 
result is interpreted as showing that in the absence of the spleen the mar- 
row may take on the function of storing and elaborating the iron of the 
blood pigment for future utilization by new red cells. The experiments 
of Austin and Pearse (Jour. Exp. Med., 20, 2, 1914) on the contrary lead 
them to conclude that the spleen does not exert a constant and important 
function on iron metabolism. The complete function of the spleen appar- 
ently remains largely unknown. Like the thymus it is sometimes classified 
among the organs of internal secretion. 
Development.-The anlage of the spleen appears at the beginning of 
the second month as a condensation and swelling in the mesenchyma on 
the left border of the dorsal mesogastrium. The overlying mesothelium 
proliferates extensively and its cells invade the mesenchyma obliterating 
the line of demarcation. The early histogenesis is obscure. The mesen- 
chyma is potentially capable of producing all the definitive elements of the 
spleen: connective tissue capsule and framework, and The 
mesothelium, genetically closely related to mesenchyma, probably aids in 
the general process. Probably also the bulk of the later lymphocytes invade 
the spleen from without. CHAPTER X 
MUCOUS MEMBRANES-GLANDS 
The histologic structures which are necessary for the formation of 
a secretion include an epithelial surface, and a tunica propria of con- 
nective tissue which supports the requisite blood and lymphatic vessels 
and the controlling nerve supply. These structures may either form 
smooth membranous surfaces or apparent epithelial invaginations. The 
former are found on the surface of the mucous membranes, the latter 
are the secreting glands. 
MUCOUS MEMBRANES 
The mucous membranes may be said to include all those secreting 
surfaces which are directly or indirectly connected with the surface of 
the body, hence their epithelial clothing is continuous with that of the 
skin. The mucous membranes form the lining coat of the respiratory 
and alimentary systems, together with the ducts of their secreting glands; 
in the nose this membrane is continuous through the tear ducts with 
the conjunctiva of the eye and through the auditory (Eustachian) tubes 
with the lining membrane of the middle ear. The broad expanse thus 
formed is known as the gastropneumonic mucous membrane. A second 
membranous sheet, the genito-urinary mucous membrane, clothes the 
organs of the genital and urinary systems; it thus forms the lining mem- 
brane of the vagina, uterus, and Fallopian tubes, of the urethra, bladder, 
ureters and pelvis of the kidney, of the ducts and tubules of the prostate 
gland, the testis, and the smaller secreting glands which are connected 
with the genital system. 
A mucous membrane consists of a superficial layer of epithelium 
of varying type, which rests upon a 'basement membrane (membrana 
propria) and is in turn supported by an investment of connective tissue, 
the tunica propria, or corium. The tunica propria is richly supplied 
with small blood-vessels and lymphatics; its nerve fibrils are not only 
distributed to the walls of the blood-vessels but in many cases send ter- 
251 252 
MUCOUS MEMBRANES-GLANDS 
minal filaments which enter the epithelial layer and terminate in 
contact with the secreting cells. The mucous membranes are mostly 
contained within hollow organs which are subject to alternate col- 
lapse and distention; hence the membranes are frequently much folded. 
The deeper portion of the mucous membrane usually contains a more 
or less well-defined layer of smooth muscle fibers, the muscularis mU- 
COSa. 
The mucous membranes, as their name indicates, are nearly all moist- 
ened by a mucus-containing secre- 
tion. The relative amount of mu- 
cus which its secretion contains, 
and consequently the viscidity of 
the secretion, bears a close physio- 
logic relation to the intensity of 
the mechanical irritation to which 
the membrane is subjected. Thus 
the mucus-secreting goblet cells 
of the gastropneumonic membrane 
are here and there reenforced by 
numerous mucus-secreting glands 
of considerable size; these are es- 
pecially abundant in the oral cav- 
ity, pharynx, and esophagus, and 
in the nose, trachea, and bronchi; 
in the urinary system even the 
goblet cells are absent. 
The basement membranes, upon 
which the epithelium of the mu- 
cous membranes and the secreting 
glands is supported, are connective 
tissue structures. They are some- 
times formed by interlacing bun- 
dles of delicate collagenous fibers intermingled with numerous elastic 
fibers. Frequently, however, they consist of reticular tissue. Basement 
membranes of this nature have been demonstrated by Mall and his pupils 
in the mucous membranes and glandular tubules of the stomach, intes- 
tine, liver, salivary glands, kidney, testis, and thyroid. Occasionally 
basement membranes are homogeneous or hyaline in structure and pre- 
sent a more or less clear or glassy appearance. 
Fig. 254.-Diagram of a Mucous Mem- 
brane Having Simple Tubular 
Glands. 
a, artery; b-b, basement membrane; v, 
connective tissue; d, duct of the gland, 
lined by cuboidal cells; E, epithelium of 
the free surface with clear, columnar 
cells; G, lumen of the fundus of the gland, 
lined by granular, serous secreting, col- 
umnar cells surrounded by secretory 
capillaries; V, veins. The arteries are 
striped, the capillaries and veins, black. 
Nerves are not represented. GLANDS 
253 
GLANDS 
The secreting glands may be quite properly considered as invagina- 
tions of the epithelial surfaces of the mucous membranes. They appear 
as such in the embryo. Their earliest anlage is formed by a solid or 
funnel-shaped process of epithelium, in which a distinct lumen soon 
appears, and which grows into the surrounding mesoblast, carrying with 
it its embryonal tunica propria. 
Classification of Glands 
The form of the glandular invaginations is subject to great variation. 
They may be straight and simple, more or less branched and compound, 
convoluted or coiled, or the tubules may terminate in minute ampullary 
T, simple tubular (intestinal glands); Ts, slightly coiled tubular (intestinal glands 
and small sweat glands); Tss, more extensively coiled tubular (larger sweat glands); 
Tr, branched tubular (gastric glands); compound tubular (kidney, lacrimal glands); 
Ts, simple alveolar or saccular (small sebaceous glands); Ar, branched alveolar (larger 
sebaceous glands, tarsal glands of eyelid); Ac, compound tubulo-alveolar or racemose 
(A) (salivary glands); compound saccular (B) (mammary gland). In major part after 
Prevant, Brown and Maillard. 
Fig. 255.-Diagrams of the Principal Types of Glands 
enlargements, the acini or alveoli. The invaginations may also be dis- 
tinctly tubular and of approximately equal diameter throughout, or 
they may form pouch-like saccules. According to the form of the organ, 
it is thus possible to distinguish the following 254 
MUCOUS MEMBRANES-GLANDS 
HISTOLOGIC TYPES OF GLANDS: 
1. Simple. 
2. Convoluted. 
3. Branched. 
4. Compound. 
5. Compound tubulo-acinar (alveolar) ; racemose. 
I. Tubular 
II. Saccular 
(alveolar) 
1. Simple. 
2. Branched. 
3. Compound. 
III. Ductless 
glands; endocrine glands, 
Glands of the tubidar and saccular types contain an actively secreting 
portion or fundus and a duct. Such externally secreting glands are also 
known as 'exocrine' glands. In the ductless ('endocrine') glands the 
duct is absent. The duct, though its epithelium may take some part 
in the formation of the glandular secretion, primarily serves to convey 
the secretion of the fundus to the free surface of the mucous membrane. 
The epithelium of the duct, as a rule, more or less closely resembles 
that of the mucous membrane upon whose surface it opens. The epi- 
thelium of the fundus, on the other hand, usually differs from that of 
the duct and varies according to the nature of its secretion. In many of 
the glands the epithelium is typically mucus secreting; others produce 
a clearer, watery, and less viscid serous secretion. Hence it is possible 
to distinguish the following 
PHYSIOLOGIC TYPES OF GLANDS: 
I. Serous glands. 
II. Mucous glands. 
III. Glands which are both mucous and serous (mixed glands). 
IV. Glands which are neither mucous nor serous. 
This physiologic classification is not in any way the equivalent of 
the histologic gland types mentioned above. Thus both serous and 
mucous glands, in different locations, form almost every variety of 
tubular gland. 
Description of Physiologic Types 
The glands of the fourth type are too varied in their structure 
to be considered collectively to advantage. The reader is referred to GLANDS 
255 
the several chapters in which they are described in detail. This type 
includes the testis, the prostate, the ceruminous glands, many of the 
ductless glands, and also some authors describe the ovary and the lungs 
as comforming to the glandular type of structure. 
The mixed glands include some tubules which are characteristically 
mucous, while others are typical serous secreting. Occasionally both 
types of secreting cells are contained within the same tubule. 
Mucus-secreting cells possess the general characteristics which 
have been previously recited 
under the head of goblet cells 
(Chapter II). When void of 
secretion the cytoplasm of 
mucous cells is granular, 
their nucleus centrally situ- 
ated, and their shape more or 
less columnar. The pre-secre- 
tion accumulates in the cen- 
tral portion of the cell and 
occupies an area, adjacent to 
the glandular lumen, which 
steadily increases in size until 
the greater part of the cyto- 
plasm has been replaced; the 
nucleus is pushed to the distal 
or attached end of the cell; 
and the whole cell often be- 
comes swollen and distended to more than double its original size. Finally 
the cell membrane ruptures and the mucus pours out upon the free sur- 
face of the membrane. 
At the base of the mucus-secreting cells, and between them and 
their basement membrane, are groups of epithelial cells having a finely 
granular cytoplasm, which form crescentic cell masses, the demilunes 
of Heidenhain (crescents of Gianuzzi). In the tubules of some glands 
these demilunes are extremely minute, in others they occupy a con- 
siderable portion of the epithelial coat and encroach upon the glandular 
lumen. Their significance is not definitely understood. They have 
been considered as representing either secreting cells which are in a 
state of rest following the discharge of their secretion, or as primordial 
cells which by reproduction give origin to true mucus-secreting cells. 
It is quite possible that both of these functions are assumed by the several 
Fig. 256.-Transection of Three Secreting 
Tubules of the Submaxillary Gland of 
Man. 
A, a serous tubule; B, a mucous tubule; C, 
a mucous tubule with a demilune, d. Hematein 
and eosin. X 665. 256 
MUCOUS MEMBRANES-GLANDS 
cells which compose the demilunes. Many of these cells contain an 
independent, intracellular, secretory, canalicular system, which indi- 
cates a specific and independent functional role. 
Mucus, the product of the mucus-secreting cells, possesses peculiar 
properties. In the fresh condition it has a clear, glairy appearance and 
a pearly white color. Acted upon by alcohol or acids it gives a heavy 
precipitate of stringy white flocculi. Within the tissues these delicate 
flocculi stain slightly with basic dyes and readily with the muchematin 
and mucicarmin of Mayer. The very clear glairy appearance of the 
fluid and the slightly basophil properties of the precipitated flocculi are 
so characteristic that when typical mucus-containing cells are once care- 
fully observed they can be thereafter readily distinguished from other 
types of epithelium. 
Serum-secreting cells differ greatly in appearance with the vary- 
ing character of their secretions, yet they present certain general char- 
acteristics. These cells are unquestionably capable of alternate phases 
of secretory activity and comparative rest. At the end of a period of 
activity they appear shrunken and small, and the lumen of their tubule 
is consequently increased in size. Their nucleus is centrally located, 
and their cytoplasm is relatively devoid of secretion and frequently 
presents a faintly rodded or striated appearance. 
During rest secretion accumulates within the cell, and the cytoplasm 
consequently becomes either clearer or more granular, according as the 
nature of the secretion is watery, or is granular and zymotic in char- 
acter; thus the secreting cells of the sweat glands become clearer as 
their secretion accumulates, whereas those of the pancreas become more 
granular. 
As a rule the pre-secretion accumulates at the central end of the cell, 
the nucleus is thus crowded toward the basement membrane and is sur- 
rounded by the least altered cytoplasm. The whole cell becomes swollen 
and distended by the accumulated secretion and the tubular lumen is 
consequently diminished in size or even occluded. 
Finally the period of secretory activity arrives, and the secretion 
is poured into the glandular lumen; the cells become shrunken and the 
lumen of the tubule correspondingly dilated. The cytoplasm returns 
to its former condition; if the secretion is of a granular character the 
cell becomes clearer, but if watery the cytoplasm acquires a finely granu- 
lar appearance. The nucleus resumes its former central location and 
the cell enters upon a second period of constructive and accumulative 
activity. GLANDS 
257 
Many of the serum-secreting cells contain minute intracellular canals 
which connect with a network of intercellular passages about the cell. 
The intercellular canaliculi may, on the one hand, open into the glandu- 
lar lumen, or they may communicate with the tissue spaces of the tunica 
propria. This system of intracellular and intercellular canaliculi may 
thus serve either as a system of nutrient channels or as a network of 
secretory capillaries by which the secretion is conveyed from the interior 
of the secreting cells to the lumen of the gland or even to the duct 
system. Nutrient and secretory canaliculi of this nature have been 
demonstrated in the secreting cells of the liver, cardiac glands of the 
stomach, salivary glands, pancreas, adrenal, and epididymis, but they 
are not by any means confined to the actively secreting cells, for they 
have been found in the. cells of bladder epithelium (Holmgren) and 
are highly developed in the nerve cells (Holmgren, Golgi, et al.). 
Description of Histologic Types 
Simple Tubular Glands.-Simple tubular glands occur in the mu- 
cous membrane of the small and large intestine as the crypts of Lieber- 
kuhn or intestinal glands. In shape these glands resemble a test-tube. 
They form straight tubules which open on the free surface of the mem- 
brane, are of approximately equal caliber throughout, and at their deeper 
end terminate in a blind extremity. The tubules are lined with epi- 
thelium and are embedded in a thin vascular tunica propria. Their 
epithelium includes the usual columnar and goblet cell types, the latter 
being more abundant near the mouth of the gland. Near the blind 
extremity are certain granular cells, the granules of some of which are 
slightly basophilic: other cells possess coarse granules which are highly 
acidophil, as demonstrated by Kultschitsky (Arch. f. mik. Anat., 1897) 
in the intestinal glands of the dog, an observation which is easily cor- 
roborated for the simple tubular glands in the small intestine of man. 
Convoluted Tubular Glands.-Convoluted tubular glands occur as 
the sweat glands of the skin, the ceruminous glands of the ear, and the 
glands of Moll in the eyelids. The above are typical simple coiled 
glands. Certain other glands, which are less typically coiled but are 
more or less convoluted near their blind extremities and are frequently 
branched, are also to be included under this type. Such glands are the 
pyloric glands of the stomach, and the small mucous glands of the 
oral and nasal cavities, pharynx, larynx, trachea, bronchi, and esophagus. 
Some of these glands, and especially those of the pyloric end of the 258 
MUCOUS MEMBRANES-GLANDS 
stomach, present terminal acinar dilatations, hence they also resemble 
to some extent a small tubulo-acinar type of gland. 
The typical coil glands consist of a duct whose epithelium resembles 
an attenuated layer of the stratified epithelium upon which they open, 
and a fundus or secreting portion which is lined by columnar epithelium 
of the glandular type. They also possess a connective tissue basement 
membrane and a vascular tunica propria. 
Branched Tubular Glands.-Branched tubular glands include the 
cardiac and pyloric glands of the stomach and the glands of the uterine 
mucous membrane. These glands possess a 
duct whose epithelium corresponds in type 
with that of the surface upon which they 
open. Several secreting tubules open into 
this duct by means of a short constricted por- 
tion, the neck. The fundus or secreting 
portion, after a typically spiral course, ends 
with a blind extremity which is often curved 
or hooked. This portion of the gland is 
clothed with columnar or glandular epi- 
thelium and invested with a thin basement 
membrane and tunica propria. 
Compound Tubular Glands.-Com- 
pound tubular glands include the kidney, 
testis, lacrimal gland, and liver. The finer 
structure of the glands of this type is so pe- 
culiar that the reader must be referred to 
the several chapters in which they are more 
fully described. 
Compound Tubulo-alveolar Glands (Tubulo-acinar or Racemose 
Glands').-This is the most widely distributed of all the types of se- 
creting glands. It includes the parotid, the submaxillary, the larger 
mucous and serous glands of the oral cavity, and of the nose, pharynx, 
trachea, bronchi, and esophagus, the duodenal (Brunner's) glands, the 
pancreas, bulbo-urethral (Cowper's) glands, urethral (Littre's) glands, 
and the large mucous glands of the cervix uteri. 
The form of these glands may be likened to a much branched tree, 
whose stem as the main excretory duct opens upon the free surface of 
a mucous membrane, and the branches and twigs as the larger and 
smaller interlobular ducts reach out in all directions to finally end in 
minute alveolar dilatations, the secreting acini. 
Fig. 257.-Model of a Re- 
construction of the Lac- 
rimal Gland of Man. 
The tubular duct divides 
into the terminal secreting 
tubules, forming a compound 
tubular gland. X 170. (After 
Maziarski.) GLANDS 
259 
Except for the ducts of certain mucous glands whose epithelial coat 
resembles that of the mucous membrane to which they are attached, the 
ducts of this type of secreting gland are 
lined by columnar cells whose cytoplasm fre- 
quently presents a rodded appearance at the 
deeper end of the cell. The acini contain 
typical serous or mucous, secreting epithe- 
lium. Occasionally the secreting cells are 
also found for some distance beyond the 
acinus in the lining membrane of the small- 
est ducts. 
The tubules and acini of these glands are 
invested with a 
basement mem- 
brane and a 
delicate tunica 
propria. The 
acini are united 
by the connec- 
tive tissue into 
small groups 
which inclose a 
central duct of 
the smallest type, the intercalary (or inter- 
mediate) duct. These acinar groups are 
again united into the lobules of the gland 
by fine bands of connective tissue, and 
broader bands of loose connective tissue ce- 
ment the many lobules into one glandular 
mass. The intercalary ducts by union within 
the lobule form numerous small intralobular 
ducts which approach the periphery of the 
lobule and at its margin open into the inter- 
lobular ducts; the latter are found in the 
broader septa of connective tissue between 
the lobules. The interlobular ducts by union 
with one another result in progressively 
larger branches which finally form the 
main excretory duct of the gland. 
Simple Saccular Glands.-Simple saccular glands occur as the 
Fig. 258.-Reconstruction of 
a Mucous Gland from the 
Respiratory Region of the 
Nasal Mucosa of a Child. 
The duct passes directly into 
the secreting alveoli. A typical 
small tubulo-alveolar gland. X 
200. (After Maziarski.) 
Fig. 259.-Reconstruction 
of an Intralobular Duct 
Dividing into Its Ter- 
minal Intercalary Ducts 
and Acini. 
The terminal divisions of a 
large compound tubulo-aci- 
nar gland. The model was 
made from serial sections of 
the human pancreas. X 344. 
(After Maziarski.) 260 
MUCOUS MEMBRANES-GLANDS 
smallest sebaceous glands of the skin. These are small glandular pouches 
with a short duct, a constricted neck, and a dilated fundus which, in- 
stead of having a single coat of epithelium as in most of the tubular 
glands, is more or less completely filled with a mass of epithelial cells. 
The cells as they approach the duct of the gland show progressive stages 
of degeneration and disintegration which culminate in the formation 
of a thick, viscid, fatty secretion. Since these cells form their secretion 
by disintegration they are obviously capable of passing through the 
various stages of secretory activity but once, and hence they must be 
renewed by the repeated mitotic cell division which occurs at the periph- 
ery of the saccule. 
The epithelium of the secreting saccule rests upon a distinct base- 
ment membrane and is invested with a very vascular tunica propria. 
Branched Saccular Glands.-Branched saccular glands include the 
larger of the sebaceous glands of the skin, in which several saccules 
pour their secretion into a common duct, and the tarsal (Meibomian) 
glands of the eyelids in which a considerable number of saccules open 
into an axial canal by which the secretion is conveyed to the terminal 
duct. The structure of each glandular saccule of this type is identical 
with that of a simple saccular gland. 
Compound Saccular Glands.-This type includes only the mam- 
mary gland. It consists of a system of tubular ducts which possess 
ampullary dilatations and many branches. Its ducts terminate in small 
saccular alveoli which have a thin epithelial lining. During the period 
of their inactivity the lining epithelial cells are much flattened and 
the acini appear shrunken. The epithelium of the lactating gland, on 
the other hand, is cuboidal or columnar, the height being more or less 
dependent upon the accumulation of secretion within the cell. 
The secretion is formed in the same manner as in the tubular glands 
with an additional process of fatty infiltration by which fat droplets 
are formed within the cytoplasm. These droplets collect in the central 
portion of the cell and are finally discharged into the lumen of the acinus 
with apparent rupture of the cell membrane and the escape of a portion 
of its superficial cytoplasm. The epithelium is thus capable of repeated 
secretion. 
The mammary glands may be considered as offering an inter- 
mediate type between the branched saccular and the tubulo-acinar 
types. 
Ductless Glands (Endocrine Glands).-Under the head of glands 
it is necessary to consider certain structures which apparently contain GLANDS 
261 
secreting epithelium and which present a more or less distinct tubular 
arrangement. These bodies are the adrenals, thyroids, parathyroids, 
carotid glands, coccygeal gland, paraganglia, hypophysis cerebri, and 
epiphysis cerebri (pineal gland). These are also known as organs of 
internal secretion. 
While these glands do not possess an excretory duct, nevertheless 
some of them certainly, and the others probably, form certain products 
which find their way into the blood or lymph as so-called 'internal se- 
cretions/ The epithelium of the glands may form either alveoli, tubules, 
or solid cell columns, which are supported by very delicate connective 
tissue tunics. Many blood-vessels, often of the thin walled sinusoidal 
type, are found within these tunics and are thus brought into intimate 
relation with the epithelial parenchyma. In some instances lymphatics 
are distributed in a similar manner within the gland. 
The property of internal secretion is not peculiar to the ductless 
glands. It has long been ascribed to the liver cells in connection with 
their influence upon nitrogenous and carbohydrate metabolism, and, in 
fact, many secreting glands, even though not of vital importance, are 
nevertheless found to influence the economy in certain ways which can 
not be accounted for by the properties of their external secretions. 
Finally, it must be emphatically stated that the types of secreting 
glands, as above described, are not bound by hard and fast lines, but 
many forms will be found which might well be placed under either 
of two or more types. Hence any classification of secreting glands be- 
comes more or less arbitrary; nevertheless such a classification is of 
extreme importance as serving to establish in the mind of the student 
certain typical pictures with which individual glands may be compared, 
and important structural details will thus be noticed which might other- 
wise escape observation. CHAPTER XI 
THE SKIN 
The skin, or integument, consists of an outermost ectodermal layer 
of stratified squamous epithelium, the epidermis (cuticle), and a sub- 
jacent mesodermal layer of dense connective tissue, the corium or derma 
(derma vera, cutis vera), homologous with the tunica propria of the 
mucous membranes. The corium contains the nerves and the nerve end 
organs of special sense, and rests upon a subcutaneous layer of areolar 
and adipose connective tissue which, blending with fascia or periosteum, 
unites the skin to the underlying muscles and bones. 
The skin serves a composite function: protection, regulation of body 
temperature, tactile sensation, and excretion. Its excretory role is in 
fact accessory to the kidney. 
The skin is typically a stratified organ, and for convenience of 
description may be divided into the following layers: 
1. Scaly layer. 
2. Flattened cell layer. 
3. Eleidin-containing layer; 
stratum lucidum 
Horny layer; 
stratum corneum. 
I. Epidermis. 
4. Granular layer; stratum' 
granulosum. 
5. Prickle cell layer. 
6. Cylindrical cell layer. 
SKIN. 
Germinal, l\Tal- 
pighian or mu- 
cous layer. 
II. Derma. 
1. Papillary layer. 
2. Beticular layer. 
TIT. Subcutaneous tissue. 
THE EPIDERMIS 
The epidermis (cuticle) or scarf skin serves for the protection of 
the more sensitive corium or True skin.' It is formed by a dense layer 
of stratified epithelium and varies in thickness in different portions 
262 THE EPIDERMIS 
263 
of the body, being thickest upon those surfaces which are exposed to the 
greatest mechanical violence, e.g., the palms of the hands and soles of 
the feet; and thinnest in the least exposed portions, e.g., inner sides 
of the arms and the back. 
The layer of stratified squamous epithelium composing the epidermis 
differs from that of the mucous mem- 
branes in that its superficial cells con- 
tain an abundance of keratin, a peculiar 
horny material. The production of 
keratin in the cells of stratified epi- 
thelium appears to be more or less de- 
pendent upon the desiccation which oc- 
curs in those cells which form the com- 
paratively dry cutaneous surface. The 
cornification can scarcely be demon- 
strated in the stratified squamous epi- 
thelium of the moistened mucous mem- 
brane of the mouth, esophagus, etc.; it 
is present though not pronounced in 
the partially moistened margins of the 
eyelids, lips, labia minora, glans penis, 
etc. In the epidermis, however, corni- 
fication is pronounced and characteris- 
tic in all portions of the body. 
The thickness of the cornified lay- 
ers appears to be in proportion to, 
if not entirely dependent upon, the 
amount of mechanical violence to which 
the cutaneous surface is subjected. Ac- 
cordingly the increased thickness of 
the epidermis covering the palms and 
soles is found to be due almost entirely 
to an increase in the superficial horny 
portion of the epidermis, the germinal 
layers being no more pronounced than in other portions of the body. 
The epidermal tissue is divisible into a superficial horny portion 
consisting of flattened, desiccated, cornified cells-the stratum corneum 
or horny layer-and a deeper protoplasmic, so-called 'mucous' portion, 
which consists of polyhedral and cylindrical cells-stratum germinati- 
vum, or mucosum, rete mucosum, rete Malpighii. 
Fig. 260.-Epidermis of the Foot. 
a, flattened cells; b, stratum luci- 
dum; c, granular layer; d, germinal 
layer; e, cylindrical cell layer; f, 
derma. Picrocarmin. Moderately 
magnified. (After Ranvier.) 264 
THE SKIN 
Cylindrical Cell Layer (Stratum Cylindricum).-The deepest cells 
of the stratum mucosum are elongated in a direction nearly perpendicu- 
Fig. 261.-Section of Thin Skin from Abdomen of Negro, Showing the Distri- 
bution of the Pigment Granules in Dermal and Epidermal Cells. X 750. 
lar to the basement membrane upon which they rest; they are thus 
irregularly cylindrical in shape. It is these cells which in the pig- 
mented portions of 
the body, i.e., areo- 
ke of the nipples, 
scrotum, circu- 
manal region, etc., 
and in the skin of 
brunettes and the 
colored races con- 
tain the pigment 
which gives rise to 
the darkened color 
of the skin. 
In the skin of 
the negro, the pig- 
ment (melanic) 
granules, while 
most abundant in the basal cylindrical cells, are nevertheless present, but 
in progressively smaller number, in all of the outer cell layers. In the 
Fig. 262.-Section of Thin Skin from Abdomen of 
Light Brown Mulatto. X 750. THE EPIDERMIS 
265 
various shades of mulatto skin, there is a close correspondence between 
the degree of color and the number of pigmented layers of epidermal 
cells. Certain connective tissue cells of the corium of pigmented skins 
also contain abundant melanin granules; in the darker skins such cells 
are numerous. However, the dermal pigmented cells are not correctly 
regarded as the sources of supply of melanic granules for the epidermal 
cells, as has been maintained. The latter can produce their own 
granules; both dermal and epidermal pigmented cells owe their condi- 
tion to the same underlying cause (Jordan; Amer. Nat., vol. 45, 1911). 
The pigment granules are said to arise as a differentially staining nuclear 
substance ('pyrenoid substance') which passes through the nuclear mem- 
brane into the cytoplasm, where it gradually acquires the character of 
pigment granules (Meirowsky: "On the Origin of the Melanotic Pig- 
ment in the Skin and the Eye," Leipzig, 1908). The nuclear origin of 
the pre-pigment granules is, however, disputed by some. The more re- 
cent investigations indicate that the physiology of melanic pigment for- 
mation involves the interaction of a nuclear oxidase (tyrosinase) with 
an extranuclear, perhaps cytoplasmic, chromogen (tyrosin). 
The processes of mitotic cell division are very active in these 
columnar cells, and they, with the adjacent portion of the prickle cell 
layer, form the stratum germinativum of Flemming, in which the re- 
generation of the epidermis occurs. The cylindrical cells are firmly 
united to the basement membrane by delicate cytoplasmic fibrils, the 
intercellular bridges. Their nuclei are ovoid in shape, and vesicular in 
appearance. 
Prickle Cell Layer (Stratum Spinosum).-Superficial to the cylin- 
drical cells is a stratum of polyhedral epithelium which extends inward 
between the adjacent papillae of the corium (interpapillary region of 
the epidermis), and is therefore thick in these portions, but is rela- 
tively much thinner over the apices of the dermal papillae (suprapa- 
pillary portion of the epidermis). 
The polyhedral cells of this layer contain a soft granular cytoplasm 
and a very chromatic, though vesicular, spheroidal nucleus. They are 
separated from one another by narrow intercellular spaces which are 
bridged across by innumerable delicate cytoplasmic fibrils. These fibrils 
connect adjacent cells and are frequently continued without interruption 
through one, two, or even three or four neighboring cells. Their course 
is characteristically curved, the convexity being directed toward the 
nucleus. Those portions of the numerous cytoplasmic fibrillae which 
span the intercellular spaces form the so-called intercellular bridges. 266 
THE SKIN 
It is because of the resulting spinous appearance that the polyhedral 
cells have been termed prickle cells (Schultze). 
In the thinner portions of the epidermis the prickle cells are imme- 
diately covered by several layers of hard flattened cells whose nuclei 
have partially or wholly disappeared, and whose cytoplasm has been 
changed into a horny, keratin-containing mass. The flattening and 
desiccation of these cells becomes more pronounced as they approach 
the surface. In the 
thin portions of the 
epidermis the change 
from the prickle cell 
layer to the horny lay- 
er is abrupt. 
In the thicker por- 
tions of the epidermis, 
as in the palms of the 
hands, the change is 
more gradual, and re- 
sults in the appearance 
of two additional cell 
layers, in the cytoplasm 
of whose cells are in- 
termediate products of 
chemical metamorpho- 
sis, keratohyalin and 
elei din, which may be 
considered as the prede- 
cessors of the keratin 
or pareleidin which is 
peculiar to the cells of 
the horny portion. 
Granular Layer 
(S tr a turn Granule- 
sum).-In the thicker 
parts of the cuticle the 
most superficial prickle 
cells become slightly 
flattened, and coarse granules appear within their cytoplasm. These 
cells form the granular layer (stratum granulosum), a double cell layer 
which occupies the superficial portion of the rete mucosum. 
Fig. 263.-Skin from Sole of Human Foot, Show- 
ing Spiral Ducts of Two Sweat Glands Opening 
THROUGH THE EPIDERMIS. 
The stratum germinativum is represented by the 
dark, wavy line; below this is the stratum papillare of 
the derma, above the stratum lucidum. THE EPIDERMIS 
267 
The cells of the granular layer are flattened and angular. They 
possess an indistinct, apparently degenerating nucleus, and their cyto- 
plasm contains large plate-like granules of keratoliyalin (eleidin of 
Ranvier), which are strongly basophil and stain readily with most 
nuclear dyes. 
Eleidin-containing Layer (Stratum Lucidum).-The granule cells 
are abruptly transformed into the shiny cells of the stratum lucidum, 
which is the deepest layer of the horny portion of the epidermis. The 
cells of this layer possess an indistinct nucleus, are irregularly flattened 
and angular in shape, are more or less fused together at their adjacent 
margins, and contain a smooth, highly refractive, glassy cytoplasm which 
reacts feebly to most 
staining reagents, but is 
deeply colored by safranin. 
The stratum lucidum 
is so named because of its 
highly refractive appear- 
ance; it is usually about 
two cells thick. Its cyto- 
plasm contains eleidin, a 
substance which is prob- 
ably intermediate in chem- 
ical composition between 
the keratohyalin of the 
stratum granulosum and 
the keratoid pareleidin of 
the horny cells. 
Flattened Cell Layer 
and Scaly Layer (Stra- 
tum Corneum and Stra- 
tum Disjunctum of Ran- 
vier).-Above the stratum 
lucidum the horny layer 
consists of flattened corni- 
fied cells which are closely 
packed and somewhat fused and blended with each other at their faintly 
serrated margins. Intercellular bridges and spaces have almost entirely 
disappeared. The nuclei of the cells are no longer demonstrable, and 
their cytoplasm has been changed into a dry, shiny, highly refractive 
mass of 'keratin3 (pareleidin) which responds but slightly to ordinary 
Fig. 264.-Transection of the Epidermis of the 
Foot. 
a, superficial scaly layer; b, layer of flattened 
cells, the inner and outer portions of which have 
been characteristically blackened by osmium tet- 
roxid; c, stratum lucidum; d, granular layer; e, 
prickle cells; f, cylindrical cells; g, papillary layer 
of the derma. Osmium tetroxid, carmin. Moder- 
ately magnified. (After Ranvier.) 268 
THE SKIN 
stains. Its superficial layers stain deeply in osmic acid, indicating a 
considerable fatty alteration. If, however, these cells are acted upon 
by solutions of strong alkalies, soda, potassa, etc., the outlines of the 
degenerated nuclei reappear. As the cells are pushed nearer the free 
surface, by the process of cell division in the deeper layers and the 
coincident desquamation of cells from the free surface, they become 
more and more flattened and desiccated and more completely and firmly 
fused together until at the surface they form the partially detached 
cell masses or scales-scaly layer, stratum squamosum-which are 
eventually removed by continued desquamation. 
It is the thicker portions of the epidermis only, which possess all the 
characteristic layers above described. In other portions of the body 
the horny layer is much thinner (Fig. 262). In these thinner parts 
the cuticle of the epidermis consists of a prominent rete mucosum which 
is covered by a relatively very thin layer of horny cells. The stratum 
granulosum, in such portions, is not usually demonstrable, the stra- 
tum lucidum is absent or indistinct, and the entire horny layer consists 
only of flattened cornified cells, the more superficial of which form 
a very thin scaly layer. 
THE DERMA 
The derma or corium (derma vera, cutis vera) forms a connective 
tissue bed or matrix upon which the epidermis lies. It is divisible into 
two strata, a deeper reticular layer in which coarse fiber bundles inter- 
lace to form a loose connective tissue network, and a superficial papil- 
lary layer in which the finer bundles of connective tissue form a more 
closely meshed network. 
The Papillary Layer {Stratum Papillare).-The surface of the 
papillary layer presents numerous conical elevations, the papillae of 
the corium, which project into corresponding cup-shaped cavities in the 
under surface of the epidermis. Many of the connective tissue papillse 
contain tactile end-organs (touch corpuscles of Meissner), and terminal 
filaments of the nerve fibers. They may therefore be regarded as the 
special organ of tactile sensation. Other papillae contain no touch cor- 
puscles but are richly supplied with capillary blood-vessels. Two types 
are thus distinguished, the tactile papillae and the vascular papillae. 
Papillae are most abundant in the palms of the hands and the soles of 
the feet, where they are mostly arranged in rows which are responsible 
for the fine lines and ridges visible to the naked eye. In other portions SUBCUTANEOUS TISSUE 
269 
of the body they are less numerous and are often less regularly disposed. 
The papillary layer consists entirely of white fibrous and elastic con- 
nective tissues which form a supporting membrane for the finer branches 
of the cutaneous blood-vessels and nerves. The elastic tissue supplies 
a rich network of fine fibrils to all portions of the papillary layer, and 
just beneath the epidermis it forms a delicate elastic membrane whose 
fibers intermingle with the hyaline cuticular deposit of the columnar 
epidermal cells to form a firm resistant basement membrane. Many 
of the elastic fibers of the papillae, especially the more superficial ones, 
pursue a peculiar archiform course from the base to the apex of the 
conical papillae. In this way they surround and inclose the centrally 
situated capillaries and the tactile corpuscles of the papillae. 
The Reticular Layer (Stratum Beticular}.-The deeper portion of 
the corium consists of interlacing bundles of connective tissue fibers 
which form a dense meshwork. These bundles are much coarser than 
those of the papillary layer with which they are imperceptibly blended. 
The reticular layer contains the larger blood-vessels of the corium, many 
small nerve trunks, the ducts and parts of the secreting portions of the 
sweat glands, the more superficial sebaceous glands, and many of the 
smaller hair follicles. Lamellar corpuscles and nerve end-organs of 
Ruffini are also found in this layer. 
The skin of the face contains many striated muscle fibers which are 
derived from the insertions of the mimetic muscles. The corium of the 
scrotum (where it forms the tunica dartos), of the penis, perineum, 
and areola of the nipple contain much smooth muscle, intermingled 
with which is a considerable amount of elastic tissue. 
SUBCUTANEOUS TISSUE 
The subcutaneous tissue (tela subcutanea, subcutis) consists of bands 
and septa of fibrous connective tissue which extend from the deeper 
margin of the derma to the underlying fasciae of the muscles, the peri- 
osteum of the bones, etc. The direction of these fibrous bundles is very 
variable. The more nearly parallel to the cutaneous surface the fiber 
bundles are, and the looser the meshes which they form, the greater is 
the mobility of the skin. 
The meshes of the subcutaneous network are occupied by lobules 
of adipose tissue. When abundant the subcutis is termed panniculus 
adiposus. The subcutaneous tissue contains the main nerve trunks and 270 
THE SKIN 
larger blood-vessels of the skin, the larger sudoriparous and sebaceous 
glands, and the coarser hair follicles. It also, together with the deeper 
part of the derma, contains the nerve end-organs of Pacini, Ruffini, and 
the Golgi-Mazzoni corpuscles (see Chapter VI). 
Small bundles of smooth muscle fibers which form the arrectores 
pilorum muscles take origin from the deeper surface of the corium and 
are inserted into that portion of the hair follicle which is embedded in 
the subcutaneous tissue. These fusiform or columnar muscle bundles 
are found in connection with all the hairs, but in the scalp they are 
most highly developed and lie most deeply in the subcutaneous tissue. 
At the level of the vascular 
plexuses between the corium 
and the tela subcutanea, Hagg- 
quist (Anat. Anz., 45, 2, 1913) 
has described a thick bundle 
of smooth muscle not previous- 
ly recognized. It lies directly 
beneath a cold spot, and is not 
found in skin lacking cold 
spots. The muscle is believed 
to contract reflexly when a cold 
object is placed on the skin and 
constrict the local blood supply. 
DEVELOPMENT AND 
GROWTH OF THE SKIN 
The skin may be said to 
arise with the first differen- 
tiation of the embryo into 
its three germ layers. The 
ectoblast, which is at first a 
single cell layer, becomes a 
double layer by the end of the 
first month. It continues to 
increase in thickness until by 
the end of the second month 
it can be differentiated into 
two layers, a superficial periderm (epitrichium), and a deeper germinal 
layer. 
Fig. 265.-Three Early Stages in the 
Histogenesis of the Skin. 
A, single-layered epidermis from dorsal 
body wall of a 5 mm. human embryo; B, two- 
layered epidermis, from dorsal body wall of 
13 mm. human embryo; C, multiple-layered 
epidermis from nose of 21 mm. pig embryo. 
Per, periderm (epitrichium); Ppi, epidermis; 
Mes, mesenchyma differentiating into the 
derma. X 750. CUTANEOUS APPENDAGES 
271 
The periderm forms a layer of peculiar dome-shaped cells with flat- 
tened margins and a vesicular center. It continues to form the super- 
ficial layer of the epidermis until about the sixth month, when it is 
lost by desquamation. The germinal layer consists of a deep stratum of 
cylindrical cells and one or two superficial strata of spheroidal vesicular 
cells. The latter are known as the stratum intermedium. By the fifth 
or sixth month cell differentiation has advanced in the intermediate 
portion until cornification can be distinguished in its superficial cells. 
Further development is analogous to the growth of the mature epi- 
dermis; new cells are rapidly formed in the deeper portion, stratum 
germinativum, and are steadily pushed toward the surface, their migra- 
tion being either accompanied by slight, or later by more pronounced 
cornification, which in the latter case gives rise to the stratum granulo- 
sum, stratum lucidum, and horny layer, but in the former produces 
only relatively slight flattening of the superficial cells without the ap- 
pearance of keratin or the disappearance of the nucleus. 
The derma arises superficial layers of the mesoblast as 
ordinary connective tissue, in which the appendages of the skin make 
their appearance as ingrowths from the epidermis. Certain mesenchymal 
cells form the smooth muscle fibers of the arrectores pilorum muscles 
and of the derma of those locations where muscle is present in the mature 
skin. Other mesenchymal cells produce the fat lobules of the subcu- 
taneous tissue. Papillae appear during the fourth or fifth month but 
do not attain their completed development until much later. 
CUTANEOUS APPENDAGES 
The cutaneous appendages include the sudoriparous glands, the nails, 
the hairs, and the sebaceous glands. 
Sudoriparous Glands 
(Glandules Sudoriparcs, Sweat Glands') 
The sudoriparous glands occur in all portions of the skin, hut more 
abundantly in certain locations, e.g., palms of the hands and soles of 
the feet,-where their number has been estimated at between two and 
three thousand to the square inch-axillae, groin, and circumanal re- 
gion. Over the back, where they are least numerous, their number is 
said to be less than five hundred to the square inch. They are long, 
coiled or convoluted, tubular glands whose secreting portions lie in the 272 
THE SKIN 
subcutaneous tissue and in the deeper part of the corium; their ducts 
extend through the corium to the under surface of the epidermis where 
the lining epithelium of the duct becomes continuous with the cells of 
the interpapillary portion of the stratum germinativum. In its further 
course through the epidermis the duct of the gland forms only a 
Fig. 266.-From a Section of the Abdominal Integument of an Infant. 
Beneath a, and a', sweat glands are seen; the secreting portion of a' is detached 
from its duct; b, b, epidermis; c, c, derma; d, d, panniculus adiposus. Hematein and 
eosin. Photo. X 65. 
tortuous spiral cleft or passage whose wall is formed only by the con- 
centrically placed cells of the various epidermal layers through which 
it passes. The glands of the axilla and circumanal region are branched. 
The secreting or coiled portion of the gland (fundus) consists of a 
secretory epithelium resting upon a delicate hyaline membrana propria 
in whose outer portion are concentrically disposed connective tissue 
fibers. The inner portion of this membrane contains many longitudinal CUTANEOUS APPENDAGES 
273 
fusiform fibers whose nature is somewhat doubtful, though they have 
been most frequently considered to be smooth muscle fibers. These 
fibers are frequently branched, their processes often extending between 
the cells of the secreting epithelium nearly to the lumen of the gland. 
The secreting epithelium of the fundus consists of tall columnar 
cells which possess a large spheroidal chromatic nucleus and a finely 
granular cytoplasm. The basal portion of their cytoplasm is often 
slightly rodded and the cells are so closely pressed together that it is 
frequently impossible to distinguish their outlines. The secreting cells 
are disposed in a single layer and, except after active secretion, are so 
Fig. 267.-Several Coils of a Sudoriparous Gland of the Human Finger. 
a, secreting portions, their lumen containing traces of secretion; b, ducts; m, muscle 
cells. Hematein and picrofuchsin. X 550. 
tall as to leave only a very narrow, central, glandular lumen. During 
secretory activity the cells become shrunken and their cytoplasm more 
granular. After a period of rest the cytoplasm again becomes clear 
and vesicular in appearance and the cells are much distended. The 
secretion reaches the lumen through intra- and intercellular canaliculi. 
The ducts are lined by a double, occasionally triple, layer of some- 
what flattened epithelial cells, which rest upon a delicate membrana 
propria continuous with that of the secreting portion. The gross di- 
ameter of the duct is much less than that of the secreting portion of 
the gland, yet the lumen of the duct may be larger. That portion 
of the duct which is lined by the thin stratified epithelial layer pursues 
a spiral course through the subcutaneous tissue and the derma. Tt finally 274 
THE SKIN 
reaches the epidermis, which it enters in the interval between the dermal 
papillae (interpapillary portion of the epidermis). Its lining epithelium 
is continuous with that of the stratum germinativum, and in its course 
through the epidermis the wall of the duct consists solely of the sur- 
rounding epidermal cells. The stratum granulosum and adjacent portion 
of the horny layer in the immediate neighborhood of the duct is in- 
vaginated into the stratum mucosum, which is thus considerably thinned 
by the passage of the duct. 
The sweat glands are abundantly supplied with capillary blood- 
vessels and small non-medullated nerves, which form plexuses about 
the walls of the coiled portion of the gland, and from which terminal 
fibrils penetrate the basement membrane and end in contact with the 
secreting cells. 
Development.-The sudoriparous glands first appear in the embryo 
during the fifth month as solid columnar ingrowths from the stratum 
germinativum of the epidermis. These processes grow inward through 
the primitive corium to its junction with the looser subcutaneous tissue. 
Here the cell columns become thickened and convoluted, and at about 
the same period their lumen appears. The glandular lumen is not at 
first connected with the free surface, but as the cells of the germinal 
layers of the epidermis gradually replace those which are more super- 
ficial the epidermal portion of the duct is formed. At about the seventh 
month the lumen of the duct opens upon the epidermal surface. 
The membrana propria of the fundus and dermal portion of the 
duct is derived from the surrounding connective tissue elements of the 
mesenchyma. 
The Nails 
The nails are produced by a peculiar modification of the epidermis 
by which the stratum liicidum becomes greatly thickened (Bowen, 1899) 
while the horny layer (eponychium of the embryonic nail) is at the same 
time wanting. The nail is divisible into the nail body and nail root; 
the former comprising the exposed, the latter the hidden portion of 
the organ. The root of the nail is overhung by a fold of the skin, the 
thickened horny layer at the margin of which forms an adherent border, 
the eponychium of the adult nail. 
The nail groove or sulcus is included between the overhanging skin 
and the root of the nail. It is deep at its proximal end but is shallow 
at the lateral margins of the nail. The distal or free border of the nail 
projects over the skin at the tip of the finger and the thickening of CUTANEOUS APPENDAGES 
275 
the horny layer of the subjacent epidermis forms the so-called hypony- 
chium. 
Finer Structure.-The nail consists of two layers, the superficial 
stratum lucidum and the deeper germinal layer. These are continuous 
at the border of the nail with the corresponding layers of the epidermis 
which lines the nail groove. At the distal border, however, the nail 
268.-Terminal Phalanx of Finger of Human Fetus. 
Showing N, nail; F, nail fold; H, hyponychium; E, eponychium; developing 
sudoriparous glands, and developing bone. 
proper or thickened stratum lucidum ends in a free margin. The finer 
structure of these two layers does not essentially differ from that of 
the corresponding layers of the epidermis. 
The stratum lucidum in the body of the nail is very thick and its 
cells are so completely blended with each other through the excessive 
eleidin production that it is impossible to distinguish their outlines. 
By maceration in alkaline solutions, however, the outlines of both cells 
and nuclei may be caused to reappear. In the nail root the stratum 
lucidum increases rapidly in thickness as it grows distalward; in the 
body of the nail this layer is not very materially thickened as it ap- 
proaches the distal or free margin. 
The stratum germinativum is of nearly equal thickness in all por- 
tions of the nail body. In the nail root it is somewhat thicker and 276 
THE SKIN 
forms the nail matrix of Ranvier. In this portion also is a distinct 
stratum granulosum, a layer which is absent or rudimentary beneath 
the body of the nail. It is the presence within this layer of numerous 
keratohyalin granules which renders the root of the nail opaque and 
thus forms the dull white lunula which contrasts with the transparent, 
eleidin-containing, stratum 
lucidum, which latter layer 
alone covers the germinal 
layer of the nail body (Unna). 
The Nail Bed.-The nail 
rests upon a very vascular co- 
rium or nail bed (matrix of 
authors) which is continuous 
with the corium or derma of 
the skin. The nail bed is some- 
times regarded as active in nail 
formation, but this process is 
now generally believed to be 
limited to the matrix of the 
root. The nail bed at the 
margins of the nail is provided 
with papillae as in other por- 
tions of the skin, but beneath 
the body of the nail its surface 
is raised into longitudinal 
ridges which possess only very 
minute secondary papillae. 
Nail Growth.-The growth 
of the nail occurs in the matrix 
of the nail root. The cells of 
the stratum germinativum of this portion, having been once formed by 
active mitosis push obliquely forward and outward toward the nail body. 
It is thus that the more advanced are constantly carried onward toward 
the free border. The growth of the nail occurs at the rate of about one 
thirty-second of an inch per week (Schafer). 
Development.-In the fetus the nail appears as a direct formation 
of the epidermis, which is very early evidenced by a thickening of 
the stratum lucidum in the nail area. The nail is therefore at first 
covered by the superficial peridermal cells of the cuticle. The nail groove 
is rapidly formed by an invasion of the mesoblast by the epidermal 
Fig. 269.-Transection through the Mar- 
gin of a Finger Nail. 
On the left is the skin, on the right the nail. 
a, a', horny layer; b, b', germinal layer; c, c', 
corium; d, margin of the nail; s, nail sulcus. 
Moderately magnified. (After von Brunn.) THE HAIR 
277 
cells which become piled up at the margin of 
the groove to form an excessive horny layer, 
the definitive representative of the embryonic 
eponychium. At the distal extremity of the 
nail the superficial cells are also accumulated 
into a considerable mass which forms a promi- 
nent hyponychium. Further growth of the nail 
pushes its distal margin forward over the 
hyponychium so that the border becomes free 
shortly prior to birth. The peridermal cells are 
then shed and the nail body filially presents, at 
about the time of birth, its naked stratum lu- 
cidum. 
THE HAIR 
Development.-The structure of the hair 
will be most readily appreciated if preceded by 
a brief introductory sketch of its development. 
The Hair Germ.-The hairs arise at any 
time after the third month of fetal life, their 
earliest anlage appearing as a slightly increased 
proliferation of the cells of the germinal layer 
of the epidermis. The further multiplication 
of the cylindrical cells produces a solid colum- 
nar ingrowth of the epidermis which pene- 
trates into, and sometimes through, the primi- 
tive derma. The spheroidal cells of the inter- 
mediate layer of the epidermis increase in size, 
assume a vesicular character, and finally by 
fatty degeneration form the epidermal hair 
canal through which the future hair reaches the 
surface. 
The Hair Column.-The columnar epi- 
dermal ingrowths, hair columns or hair pegs, 
come into early relation with the anlage of the 
hair papilla which is formed by a proliferation 
of the mesenchymal cells at the tip of the hair 
column. Further development of the papilla 
Fig. 270.-Longitudinal 
Vertical Section of 
the Young Nail and 
Nail-bed of an In- 
fant. 
n. r., nail root or lunula; 
n., nail; n. b., nail bed; 
e., eponychium; h., hy- 
ponychium. (From Dahl- 
gren and Kepner.) a, papilla; b, arrector pili; c, the line is directed toward the primordial shaft; 
d, cells which form the hair canal; e, sebaceous gland; f, hair germ in epidermis; 
g, hair shaft; h, Henle's layer; i, Huxley's layer; k, cuticle of the root sheath; I, 
inner root sheath; m, outer root sheath in tangential section; n, outer root sheath 
in longitudinal section; o, dermal root sheath; P, epithelial bed,. X 460. (After 
Stohr.) 
Fig. 271.-Five Stages in the Development of a Human Hair. 
278 THE HAIR 
279 
produces an indentation of the advancing hair column and gives rise to 
a true dermal papilla of considerable size. 
The Hair Bulb.-Coincident with the formation of the papilla 
there is an increased proliferation of the cells of the hair column by 
which it is surrounded, and which therefore represents the future hair 
bulb. Two other swellings appear in the hair column; one, the more 
superficial, forming the anlage of the sebaceous gland, and the other, 
the deeper, forming the so-called epithelial bed or matrix of the hair 
which stands in close relation with the growth and future regeneration 
of the hair. This second swelling is sometimes interpreted as simply 
offering a point of attachment for the arrector pili muscle. 
The development of the hair papilla produces a slight evagination 
of the epithelium of the hair bulb, which is just sufficient to redirect 
the growth of central cells of the hair column toward the cutaneous 
surface. It is thus that the younger cells which arise by mitosis in 
the germinal layers of the hair bulb are pushed outward along the axis 
of the hair column where they form the shaft of the future hair. The 
growth of the hair from the germinal cells of the hair bulb is accom- 
panied by beginning cornification of the newly formed cells of the primi- 
tive hair shaft and of the intermediate cells of the hair column. The 
growth of the shaft is, however, preceded by enlargement, vesiculation, 
and fatty degeneration of the central cells of the hair column, thus 
producing a central canal through which the hair may grow, and which 
later becomes continuous with the hair canal of the epidermis. 
The Hair Follicle.-At this stage the hair column has become 
differentiated into a peripheral follicle, the primitive root sheath, and 
a central hair. Continued multiplication of the cells in the germinal 
layer of the bulb pushes the advancing tip of the hair nearer and nearer 
the surface until it forces its way into the epidermal hair canal. Finally 
the thin cuticular covering is ruptured and the eruption of the hair 
shaft occurs. 
Further differentiation of the cells of the epidermal root sheath and 
the formation of a mesenchymal or dermal sheath of connective tissue 
completes the development of the hair follicle. This process is fre- 
quently repeated and results in the formation of new hairs not only 
during fetal life, but also, in constantly decreasing numbers, through- 
out childhood and adult life. 
The Mature Hair.-Its development teaches that the hair follicle, 
being formed as it were by an invagination of the epidermis, contains 
a dermal and an epidermal sheath and that the outer portion of the 280 
THE SKIN 
latter, being identical with the deeper portion of the epidermis, must 
possess a close structural resemblance to the rete mucosum, while its 
inner portion, like the horny layer of the skin, is more or less cornified. 
There is thus an outer and an inner epidermal root sheath corre- 
Fig. 272.-From a Section of the Skin of an Infant's Arm, Showing Small 
Immature Hair Follicles in Transection. 
a-a, epidermis; b-b, derma; c-c, subcutaneous connective tissue; d-d, muscle. 
Hematein and eosin. Photo. X 95. 
spending respectively to the mucous and horny layers of the epidermis; 
the cornified portion, inner root sheath, becomes progressively thinner 
toward the hair bulb. The hair, on the other band, represents an ex- 
cessively developed horny layer whose rete mucosum is found in the 
germinal layer of the hair bulb. 
The mature hair is divisible into a hair shaft or free portion, and a 
hair root or concealed portion. The latter is inclosed within an epi- THE HAIR 
281 
dermal and a dermal root sheath which together form the hair follicle. 
The Hair Shaft.-Sections of the hair shaft present a thin cuticle 
which Consists of delicate horny scales whose free edges are imbricated 
upward, viz., toward the tip of the hair. Within the cuticle the hair 
may consist solely of a hair cortex formed by flattened and very much 
elongated horny epithelial cells, which frequently retain the remnant 
of a nucleus, and whose keratized cytoplasm is often much pigmented; 
or the axis of the coarser hair may contain enlarged angular cells in 
which eleidin granules and much pigment are found. In the latter case 
the hair is said to possess a medulla. The medulla is seldom if ever 
present throughout the entire length of the hair. When present it 
sometimes contains numerous air bubbles which, together with the 
paucity of pigment, produce the lighter shades of hair peculiar to certain 
individuals. 
In the light of its development it is obvious that the several layers 
of the hair shaft are comparable to the homologous layers of the horny 
epidermis, the cuticle, cortex, and medulla of the hair being respectively 
homologous with the scaly layer, the flattened cell layer, and the eleidin- 
containing layer or stratum lucidum of the epidermis. 
The Hair Root.-The root of the hair, except for the fact that it 
is immediately invested with a hair follicle, does not in any way differ 
in structure from the hair shaft. It possesses the same three layers, the 
medulla, however, being very irregularly developed. 
The imbricated cells of its cuticle interdigitate with the similar 
cells of the cuticle of the inner root sheath in the deeper half of the 
follicle; in its superficial half, viz., above the opening of the sebaceous 
gland, a narrow space intervenes between the cuticle of the hair and that 
of the root sheath. 
The axis of the hair root is always inclined at an angle to the epi- 
dermis; it therefore makes with the epidermis an obtuse angle on one 
side and an acute angle on the other. The arrector pili muscle is always 
found on the side of the obtuse angle; it therefore, by drawing the hair 
follicle and its inclosed hair root nearer the perpendicular, causes the 
erection of the hair. The sebaceous gland is included in the angle be- 
tween the arrector muscle and the hair follicle. Contraction of the 
muscle may aid also in the expulsion of the sebum. Extreme contraction 
of the arrectores pilorum muscles may result from fright, causing the 
hair to 'stand on end'; in a similar manner cold air may effect, through 
the pilomotor fibers, the erector muscles of the small hairs distributed 
over the body and cause the so-called 'goose-flesh.' Ap, arrector pili muscle; c, corium; ep, epidermis; fp, epidermal root sheath; 
Gap, muscular aponeurosis; gls, sudoriparous gland; glse, sebaceous gland; KH, 
so-called 'club-hairs' in various stages of molting and regeneration; pp, papilla of 
the hair; Rc, fibrous band in the subcutaneous tissue; Rp, hair root; Sp, hair shaft; 
ts, subcutaneous adipose tissue. Hematoxylin and eosin. X 15. (After Sobotta.) 
Fig. 273.-From a Section of the Human Scalp. 
282 THE HAIR 
283 
The Epidermal Root Sheath.-The epidermal root sheath con- 
sists of an inner and an outer portion, each of which at about the mid- 
level is divisible into three layers corresponding to the three similar 
layers of the horny and the mucous portions of the epidermis. In those 
portions of the follicle and in those individual hairs in which the process 
of cornification is less advanced these subdivisions cannot all be demon- 
strated, and it is only in the most highly developed hairs that they 
are typically found. This is in accordance with the structure of the 
epidermis, in which the subdivisions of its horny and mucous portions 
are typically found only in the more highly developed portions, e.g., the 
palms and soles. 
Inner Root Sheath.-The cuticle of the inner root sheath consists of 
thin horny epithelial scales which are imbricated downward, viz., toward 
the hair bulb, and which interdigitate, in the deeper portion of the fol- 
licle, with the similar scales of the hair cuticle. The direction of the 
imbrication explains the removal of the epidermal root sheath when the 
hair is artificially extracted. 
The mid-layer of the inner root sheath, layer of Huxley, one or two 
cells thick, consists of horny cells which are somewhat flattened, and in 
which the semblance of a nucleus is sometimes present. It corresponds 
to the flattened cell layer of the epidermis. 
The outer layer of the inner root sheath, layer of Henle, is frequently 
wanting or imperceptibly blended with the preceding layer. Its cells 
are clear and highly refractive and their nuclei can but rarely be demon- 
strated in the usual microscopical preparations. The layer is seldom 
more than one cell deep. It is homologous with the stratum lucidum of 
the epidermis. 
Outer Root Sheath.-The outer root sheath is continuous with the 
stratum mucosum of the epidermis and therefore contains similar cell 
types. The granular layer, as in the epidermis, is frequently absent or 
rudimentary, but can be readily demonstrated in hematein-stained sec- 
tions of the more highly developed hair follicles. It rests upon a layer, 
several cells deep, of spheroidal prickle cells. The outermost layer of 
the outer root sheath is formed by a basal layer of cylindrical cells. 
It grows progressively thinner toward the hair bulb, where its cells 
become mingled with the germinal cells of the hair matrix. 
Dermal Root Sheath.-The dermal root sheath presents three 
layers, an innermost basement membrane or glassy layer, a layer of 
circular connective tissue fibers and a similar layer of longitudinal 
fibers. These layers are obviously homologous with the basement mem- 284 
THE SKIN 
brane, the papillary layer, and the reticular layer of the derma, respec 
tively. The dermal root sheath is, however, devoid of papillae. 
Fig. 274.-Transection of a Hair Near the Middle of the Root Sheath. 
a, dermal root sheath; b, outer margin of the epidermal root sheath-the light 
space is the glassy membrane, the polyhedral cells form the outer root sheath; c, 
Henle's layer of the inner root sheath; d, Huxley's layer; e, cuticle of the root sheath; 
f, cuticle of the hair; g, cortex of the hair shaft. Highly magnified. (After Kolliker.) 
The glassy membrane is a peculiarly thick homogeneous membrane 
which is chiefly mcsoblastic in origin, but whose innermost portion is 
formed as an exoplasmic product of the adjacent epithelium. This THE HAIR 
285 
membrane is highly refractive and contains very few connective tissue 
cells or fibers. 
The circular fibers of the dermal root sheath contain interlacing, 
bundles of connective tissue fibers, which are mostly disposed in a ring- 
like manner. Elastic fibers are absent. Within this layer is a dense 
anastomosing plexus of capillary blood-vessels, together with a rich 
subepithelial plexus of non-medullated nerve fibers. 
The longitudinal fibers of the connective tissue root sheath also form 
interlacing fiber bundles, most of which are somewhat obliquely disposed. 
The bundles are coarser than those of the preceding layer and contain 
a few elastic fibers. This portion of the root sheath contains many small 
blood-vessels and nerves which supply the plexuses of the circular layer. 
The hair follicle in transverse section varies in different races from 
circular to elliptical form. Tn the Chinese race the diameter of the fol- 
licle and the hair is 100 X 77 to 85, in the European 100 X 62 to 72, 
and in the Negro 100 X 40 to 60. The more elliptical the form of the 
follicle the greater the curl of the hair. 
Atypical Portions of the Hair Follicle.-As already indicated, 
the hair follicle presents some structural differences at various levels. 
The typical arrangement is found only in the mid-portion of the fol- 
licle. 
In its superficial portion the hair lies free in the follicular lumen, 
the interval between it and the inner root sheath being only partially 
occupied by the fatty secretion of the sebaceous gland which enters the 
lumen of the follicle at the deeper portion of its middle segment. At 
this level also, the root sheaths of the hair offer a gradual transition 
from their typical structure to that of the dermal and epidermal layers 
with which they are continuous. 
The hair bulb likewise differs prominently from the typical struc- 
ture of the hair root. In this portion the germinal layers are very 
highly developed at the expense of the horny layers. It is, therefore, 
in this portion that growth is most active. The cells of this region are 
often deeply pigmented. The increased size of the germinal layer, more- 
over, produces a distinct bulging of the follicle, which incloses the hair 
papilla and results in the peculiar bulbous shape of the extremity of the 
hair follicle. 
The Hair Papilla.-The structure of the hair papilla is identical 
with that of the vascular papillae of the derma except that it is con- 
structed upon a much larger scale. It consists of a conical or club- 
shaped elevation of connective tissue which indents the extremity of 286 
THE SKIN 
the hair bulb, It contains an abundant plexus of capillary blood-vessels 
and a rich supply of non-medullated nerves. It also contains an undue 
proportion of connective tissue cells. 
Regeneration of the Hair.-Hairs are being continuously shed 
and regenerated, the average life of a hair of the scalp being stated as 
sixteen hundred days (Stbhr). The shedding of a hair is first heralded 
by an atrophy of its papilla and a cornification of its bulb. Growth 
ceases, and the hair, firmly adherent to its root sheath, is gradually 
carried, by the continued growth of the latter, nearer and nearer the 
surface of the skin. 
Its excursion leaves behind a narrowed cell column which still unites 
the hair with its former papilla. 
From this rudiment a new hair germ may form (Unna), a new papilla 
develop, and the resulting hair grow toward the surface in the path of 
the molting hair, its eruption being preceded by the falling of its pred- 
ecessor. The formation of the new hair germ very probably occurs at a 
point nearly corresponding with the insertion of the arrector pili muscle, 
where there is a swelling of the root sheath which has been already men- 
tioned as the matrix of the hair follicle. This matrix appears very 
early in the development of the hair, but remains quiescent until regen- 
eration becomes necessary, when the cells are said to proliferate and 
grow downward filling the space between the atrophic hair and the new 
bulb. 
In infancy and youth shed hairs are also compensated for by new 
formation from hair germs appearing at the germinal border of the epi- 
dermis, the process proceeding in the manner already described for the 
development of the hair. 
The Sebaceous Glands 
These are compound saccular glands which may be subdivided into 
two classes, (1) those whose ducts open into the hair follicles, and (2) 
those whose ducts open upon the free surface of the epidermis. The 
former are by far the more numerous; the latter occur in the skin of 
the face, red margins of the lips, labia minora, glans penis and prepuce, 
and the tarsal glands of the eyelids. With the above exceptions the dis- 
tribution of the sebaceous glands is coextensive with that of the hairs. 
They are therefore absent from the palms of the hands and soles of 
the feet. 
A sebaceous gland consists of a dilated saccular fundus, a constricted Fig. 275.-Regeneration of a Hair. 
Only the follicles and the inclosed portion of the hair shafts are represented. The 
various stages are numbered in order. (After Unna.) 
287 288 
THE SKIN 
neck, and a short and narrow duct. Occasional glands are formed by a 
single saccule, but more frequently they are compound, the several sac- 
cules opening by a single short duct which is lined by flattened cells. 
In the tarsal glands the secreting saccules are connected with the long 
Fig. 276.-Sebaceous Glands in the Scalp of a Child. 
a, hair follicle; b, sebaceous gland; c, hair follicles in oblique section; d, horny 
layer of the epidermis; e, germinal layer; f, derma; g, blood-vessel. Hematein and 
eosin. Photo. X 83. 
excretory duct by means of a short intercalary duct. The fatty secretion 
of the sebaceous glands, sebum, is formed by the direct disintegration 
of the protoplasm of the glandular epithelium. 
The saccules of the sebaceous glands are invested by a thin connective 
tissue tunic and a delicate basement membrane. They are embedded in 
the subcutaneous fat or in the deeper part of the corium near the 
hair follicle. The glands are so disposed as to be included within a THE HAIR 
289 
triangular space beneath the cerium, which is bounded by the arrector 
pili muscle and the hair follicle. The saccules are lined by several 
layers of polygonal epithelial cells the outermost of which are cuboidal 
and rest upon the basement membrane. 
In the peripheral layers the lining epithelial cells multiply so actively 
that the daughter-cells are pushed inward until they fill the entire sac- 
cule. During this excursion they are progressively farther and farther 
removed from their source of 
nutrition, and as they approach 
the outlet or duct of the sac- 
cule, a process of fatty degen- 
eration appears within the cell, 
Fig. 278.-Cells from the 
Central Portion of the 
Preceding Figure, Show- 
ing Two Successive Stages 
in Sebum Formation by 
Processes of Fatty Meta- 
morphoses of the Cyto- 
plasm. 
Note the shrunken character 
of the nuclei of the upper more 
degenerate cells. The cyto- 
plasm is filled with fat spher- 
ules. X 550. 
Fig. 277.-Section of a Sebaceous Gland 
from the Human Scalp, through Point 
of Opening into a Hair Follicle 
(Obliquely Cut). 
Between the basement membrane of the 
sebaceous alveolus and the hair follicle, the 
cells exhibit successively later stages of fatty 
degeneration ending in the formation of 
sebum. X 160. 
by which its protoplasm becomes changed into a granulofatty mass. 
The accumulated product of this degeneration and final disintegration 
of the epithelial cells forms the secretion of the gland. Continued cell 
multiplication at the periphery maintains the integrity of the organ. 290 
THE SKIN 
Sebaceous glands of the scalp may become cystic through occlusion of 
the duct and form wens. 
Development.-The sebaceous glands are developed as minute epithe- 
lial buds from the sides of the hair columns or from the deeper surface 
of the epidermis. These buds soon assume the characteristic flask shape 
and later become hollowed out by fatty metamorphosis of their central 
cells. By this process also their lumen is eventually made continuous 
with that of the follicle. Secondary saccules of the sebaceous glands are 
developed in a similar manner by outgrowing germs which appear near 
the constricted neck portion of the primary saccule. 
BLOOD SUPPLY OF THE SKIN 
The larger arteries supplying the skin lie in the subcutaneous tissue. 
From these vessels branches pass toward the surface, giving off lateral 
twigs to the rich capillary plexuses in the subcutaneous connective and 
Fig. 279.-Reconstruction of the Cutaneous Blood-vessels. 
a, epidermis; b, derma; c, subcutaneous tissue; d, deep, and e, superficial arterial 
plexus; f-d, successive venous plexuses. X (After Spalteholz.) 
adipose tissues and about the sweat glands, hair follicles, and sebaceous 
glands. These arteries continue their course to the deeper part of the 
corium, where they form an anastomosing cutaneous plexus of small NERVE SUPPLY 
291 
vessels. Branches from this plexus pass to the papillary layer-, where they 
form a second (subpapillary) plexus from which terminal arteries are 
distributed to the capillaries of the papillae. 
The distribution of the veins is similar to that of the arteries. The 
primary plexus is found in the papillary layer; occasionally a second 
plexus immediately underlies the first, and from these, venules pass to 
the deeper part of the corium, whence after free anastomosis they pro- 
ceed to the subcutaneous tissue, collecting on the way the venules return- 
ing from the hair follicles and secreting glands, and from the subcuta- 
neous connective tissue. The very rich capillary network in the papilla 
of the hair bulb is worthy of special mention. 
The lymphatic vessels of the skin begin as a terminal lymphatic 
plexus in the corium, which collects the lymph from the tissue spaces 
of both derma and epidermis. The vessels of this plexus communicate 
with a subcutaneous lymphatic plexus of larger vessels which follow the 
course of the blood-vessels on their way to reach the neighboring groups 
of superficial lymph glands. 
NERVE SUPPLY 
The skin is abundantly supplied with large nerve trunks, both sympa- 
thetic and cerebrospinal (sensory), which find their way along the sub- 
cutaneous fat and send branches directly to the larger blood-vessels, 
the hair follicles, the sebaceous and sudoriparous glands, to the cor- 
puscles of Pacini, Ruffini, and Golgi-Mazzoni, and to the end bulbs of 
Krause, which lie in the connective tissue. 
In the cutis vera the nerve trunks form a plexus of delicate fiber 
bundles in the reticular layer, with a secondary, more closely meshed 
plexus of finer nerve bundles in the papillary layer. From these 
plexuses fibrils are distributed to the smaller blood-vessels and to the 
papillae, where many end in tactile corpuscles. Other fibrils penetrate 
the epidermis, terminating as naked fibrils or on tactile cells. 
In the region of the hair follicle small branches form a network 
of fibrils in the dermal root sheath. Branches (pilomotor nerves) are 
also distributed to the arrectores pilorum muscles. 
In the sudoriparous glands the nerves form a fine plexus about the 
membrana propria (epilamellar plexus), from which naked axis cylin- 
ders penetrate the basement membrane and terminate between the 
secreting cells. CHAPTER XII 
THE RESPIRATORY SYSTEM 
The respiratory system may be said to comprise a true respiratory 
organ, the pulmonary alveoli, in which the interchange of gases between 
the air and the blood occurs, and a system of duct-like passages leading 
Olfactory nerve 
Superior turbinate bone 
Sup. meatus 
/ .St 
Frontal sinus . 
Nasal sinus. 
Mid. turbinate , 
Mid. meatus-. 
Inf. 
/Sphenoidal sinus 
* Nasal nerve 
•Auditory tube opening 
. Inf. meatus-* 
Hard palate. 
Tongue. 
Lower jau, 
-Anterior pillar 
-Tonsil 
-Uvula 
'Post, pillar of fauces 
-■-Pharynx 
-Epiglottis 
Ventricle 
- Vocal cords 
- Esophagus 
Hypoglossal nerve - 
Larynx, 
Thyroid cart.- 
Cricoid 
Trachea- 
Fig. 280.-Photograph of Azoux Model, Showing Nostril, Pharynx, Larynx 
and Related Structures. 
292 THE NASAL CAVITY 
293 
thereto, which, beginning with the nasal cavity, successively includes 
the nasopharynx, larynx, trachea, and bronchi of gradually diminishing 
caliber, and which finally ends in the terminal bronchioles leading to the 
air sacs and pulmonary alveoli. 
The arrangement of these several portions of the respiratory system 
has been frequently compared to the structure of the tubulo-acinar 
glands. From this point of view the larynx and trachea form the duct 
stem of the gland, the bronchi form the branching interlobar and inter- 
lobular ducts, and the terminal bronchioles (intercalary ducts) end in 
the numerous acinar air saccules of the lung. 
Development.-The original anlage of the respiratory system, begin- 
ning with the larynx, is a short linear ventromedial evagination from 
the cephalic end of the primitive esophagus. This tracheal groove be- 
comes separated, distally, thus forming a tube, which grows backward, 
meanwhile dividing distally into the bronchi which undergo further 
division to form the successively finer branches of the pulmonary system. 
The respiratory epithelium is thus of entodermal origin, and becomes 
enveloped in connective tissue of mesodermal origin. 
THE NASAL CAVITY 
This cavity is bounded by a cartilaginous and bony wall and is lined 
by a mucous membrane which, according to the nature of its epithelium, 
may be divided into three portions: (1) the vestibule, (2) the respira- 
tory portion, and (3) the olfactory portion. 
Its external and internal openings are the nares and choance respect- 
ively. Communicating with the nasal chambers are the sphenoidal, maxil- 
lary, frontal, and palatal accessory sinuses, and the ethmoidal air cells. 
Their lining membrane is continuous with, and histologically essentially 
like, though thinner than, that of the respiratory portion of the nostril. 
The Vestibule 
The vestibule of the nose corresponds very closely to the cartilaginous 
portion of the nasal wall. Its mucous membrane is continuous anteriorly 
with the skin and posteriorly with the mucous membrane of the res- 
piratory portion. The vestibule is lined by stratified squamous epithe- 
lium, which offers a gradual transition from the moist respiratory epithe- 
lium to the dense horny epidermis of the skin. Near its external ori- 294 
THE RESPIRATORY SYSTEM 
fice are numerous coarse stiff hairs, vibrissa?, connected with which are 
many sebaceous glands. The vibrissae have no associated arrectores 
pilorum muscles. Some of the glands also open directly upon the 
surface of the mucous membrane. 
The fibrous tunica propria of the vestibule is continuous with the 
corium of the skin, and in it are embedded the deeper portions of the 
vibrissae and the secreting portions of the sebaceous glands. By its 
deeper surface the tunica propria is closely attached to the perichon- 
drium of those plates of hyaline cartilage which form the septum and 
alae of the nose. 
The Respiratory Portion 
The respiratory portion of the nasal mucous membrane (Schneider- 
ian membrane) clothes the middle and inferior meati of the nose. It 
is continuous anteriorly with the mucous membrane of the vestibule, 
Fig. 281.-From a Section of the Mucous Membrane of the Respiratory 
Region of the Human Nose. 
a-a, ciliated epithelium; b, b, mixed mucoserous glands; c, blood vessel. Hema- 
tein and Congo red. Photo. X 185. THE NASAL CAVITY 
295 
above with the olfactory mucous membrane, and posteriorly with that 
of the nasopharynx. The respiratory region is lined by columnar ciliated 
epithelium of the pseudo-stratified type, which also contains many 
mucus-secreting, goblet-cells. 
The epithelium rests upon a distinct basement membrane which 
reacts to the specific stains for elastic tissue. The tunica propria 
consists of a very vascular connective tissue; it varies much in thickness 
in different portions. It is thinnest in the accessory sinuses and is thick- 
est where it covers the turbinal bones and the adjacent portions of the 
nasal septum. The tunica propria is richly supplied with both mucous 
and serous glands. The smaller ones, in the thinner portions of the mu- 
cous membrane, are somewhat convoluted; the larger and more numer- 
ous are tubulo-acinar glands. Many of the latter are mixed glands con- 
taining both mucous and serous acini. They produce an abundant secre- 
tion. 
The Schneiderian membrane is in all portions extremely vascular, 
many of its vessels having very thin walls. The thicker portions bver the 
turbinals and the septum are typically erectile. The dense connective 
tissue of these portions is permeated with broad venous channels which 
are surrounded by bands of smooth muscle. Other muscular bundles 
are longitudinally distributed. The small arteries are contained within 
the fibromuscular stroma. 
The subepithelial portion of the tunica propria contains fine inter- 
lacing bundles of connective tissue and many capillary blood-vessels. 
Here and there it is also infiltrated with lymphocytes and occasional 
very minute solitary nodules are found. The lymphatics of the Schnei- 
derian membrane lead posteriorly to the lymph nodules of the naso- 
pharynx. 
The Organ of Jacobson 
Associated with the respiratory portion is the rudimentary vomero- 
nasal organ (of Jacobson). In the embryo of one month it appears as 
a tubular extension, one on either side, into the corium of the median 
septum, opening anteriorly. In transverse section it has a semicircular 
outline, with its convexity mesial. In lower forms, e.g., Amphibia, it 
persists in the adult as a functionally important organ concerned 
with smell. It is innervated by fibers from the olfactory nerves, vomero- 
nasal nerves, and by the nervus termi nails, which is present also in man 
(Johnston, Anat. Rec., 8, 4, 1914). In the cat the tall columnar ciliated 
epithelium (pseudo-stratified) includes true sensory cells, similar to the 296 
THE RESPIRATORY SYSTEM 
olfactory cells. The nervus terminalis contains some medullated fibers, 
and may contain both afferent and efferent components (Johnston). In 
the rabbit it innervates in addition to Jacobson's organ, also a wide 
area of the nasal septum (Huber and Guild). 
The Olfactory Portion 
The olfactory portion of the nasal mucous membrane, the olfactory 
organ, lines the superior meatus, a portion of the superior turbinate 
bone and a corresponding portion of the median septum, and its 
irregular border here and there invades the upper portion of the middle 
meatus. It consists of a fibrous tunica propria and a clothing of 
a, epithelium; b, basement membrane; c, corium; d, cuticle; e, sustentacular cell 
layer; f, olfactory cell layer; g, basal cells; h, blood-vessel; i, a tubule of Bowman's 
glands; k, bone. Hematein and picrofuchsin. Photo. X 270. 
Fig. 282.-The Olfactory Mucosa of a Cat. 
nemo-epithelium. The tunica propria contains elastic as well as col- 
lagenous fibers, and many small tubulo-acinar serous glands, the olfac- 
tory glands of Bowman. Beneath the epithelium is an indistinct base- 
ment membrane. THE NASAL CAVITY 
297 
The neuro-epithelium contains three intermingled cell types, the 
sustentacular, olfactory, and basal cells. 
The sustentacular cells are columnar ciliated epithelial cells 
which possess a distinct cuticular margin. Their nuclei are ovoid, and, 
since they lie at the same level, they form a continuous superficial zone 
of oval nuclei. The deep ends of the cells are often branched; they 
interlace with one another and with the processes of the olfactory and 
a, duct of gland; b, basal cells; c, cuticular border with olfactory cilia; k, nuclei 
of the sustentacular cells; k', nuclei of the olfactory cells; r, layer of olfactory cells; 
s, corium, containing connective tissue cells and nerve fibers; st, sustentacular 
cells. X 465. (After Kolliker.) 
Fig. 283.-The Olfactory Mucous Membrane. 
basal cells. The cytoplasm of the sustentacular cells is finely granular 
and contains a yellow pigment. 
The olfactory cells occupy a unique position among neuro-epithe- 
lial cells in that they are true nerve or ganglion cells. They possess a 
small cytoplasmic body and two processes, a distal and a central. Their 
nuclei are spherical and are disposed in several rows beneath the nuclear 
zone of the sustentacular cells; thus they form a broad zone of spherical 
nuclei. The distal process of the olfactory cell projects as a slender 
filament whose free end, carrying several fine cilia, reaches the surface of 298 
THE RESPIRATORY SYSTEM 
the membrane through a pore-like opening in the cuticular membrane 
which is formed by the cuticle of adjacent sustentacular cells. The 
central process of the olfactory cell penetrates to the tunica propria and 
becomes a non-medullated nerve fiber of one of the many rami of the 
olfactory nerve; it passes to the olfactory bulb, where its terminal arbori- 
zation with the dendrites of the mitral cells forms the olfactory glom- 
eruli. 
The basal cells are flattened cells which form the deepest nuclear 
zone of the olfactory neuro-epithelial layers. Their cytoplasm is finely 
granular and their nu- 
clei are ovoid or flat- 
tened. Frequently they 
send a short process be- 
tween the branched ends 
of the sustentacular cells. 
Many small nerve 
trunks occur in the 
tunica propria. The 
great majority of these 
are non-medullated and 
are formed by the cen- 
tral processes of the ol- 
factory cells, which proc- 
esses are true axons. 
Several of the smaller 
superficial fiber bundles 
unite in the deeper part 
of the tunica propria to 
form one of the small 
olfactory nerves. Taken 
together, about twenty in number, these form two olfactory ('first' cere- 
bral) nerves, unique among cerebrospinal nerves in being collectively 
non-medullated. A few medullated fibers, derived from the trigeminus, 
are also found in the tunica propria; they distribute their terminal vaso- 
motor branches to the blood-vessels, and, by fine sensory filaments which 
end between the epithelial cells, supply the neuro-epithelial layer. The 
trigeminus fibers supply a similar innervation to the respiratory mucosa. 
The blood vessels of the olfactory mucous membrane are abundant. 
Their capillary plexuses form several layers in the tunica propria, and 
their veins mostly empty, through the ethmoidal veins, into the superior 
Fig. 284.-Vertical Section of the Olfactory 
Mucosa of a Kitten. 
a, deep, and b, superficial border of the epithe- 
lium; c, olfactory cells; d, sustentacular cells; g, ol- 
factory nerve fibers in the corium of the mucosa. 
Golgi stain. X 325. (After Kblliker.) THE NASOPHARYNX 
299 
longitudinal sinus-a most significant fact. On the other hand the 
veins of the respiratory region return their blood to the internal maxil- 
lary vein, while some of those of the vestibule anastomose with the radi- 
cals of the facial vein which supply the adjacent skin. 
Fig. 285.-Diagram of the Relations of the Neurons of the Olfactory Nerve 
and Olfactory Bulb. 
olf. c., olfactory nerve cells, located in the olfactory region of the nasal mucosa, 
whose axons enter the olfactory nerve, olf. n., and terminate in relation with the 
dendrites of the mitral cells, me., in the olfactory glomeruli, gl. The axons of the 
mitral cells, a., enter the olfactory tract, where they make a sharp bend and pass 
toward the cerebrum giving off frequent collaterals. At n' a nerve fiber appears 
to end by a free ramification among the mitral cells of the olfactory bulb. (After 
Schafer.) 
The lymphatics of the olfactory can be readily injected from the 
sub-dural spaces of the meninges. They form a network in the con- 
nective tissue of the tunica propria. 
THE NASOPHARYNX 
This cavity, like that of the nose, is limited by a bony wall. Its 
mucous membrane is continuous anteriorly with that of the respiratory 
portion of the nose, and posteriorly with that of the oropharynx. The 300 
THE RESPIRATORY SYSTEM 
structure of its mucous membrane resembles that of the Schneiderian 
membrane, but its dorsal wall, in addition to the ciliated epithelium, the 
thin-walled blood-vessels, and the numerous secreting glands, contains 
many small nodules of lymphoid tissue. These nodules form a consider- 
able mass, the pharyngeal tonsil. 
The ciliated epithelium of the nasopharynx is also continuous with 
the lining epithelium of the auditory (Eustachian) tube. The tunica 
propria is firmly adherent to the bony wall of the dorsal surface, but is 
more loosely attached laterally and ventrally to the pharyngeal and 
palatine muscles. 
THE LARYNX 
The wall of the larynx is formed by several large plates of hyaline 
cartilage-thyroid, cricoid, and arytenoid cartilages-which are firmly 
united by ligamentous bands of fibrous tissue; the cartilaginous wall in- 
closes a mucous membrane of considerable thickness. 
The larger cartilages are of the hyaline variety and are prone to 
ossify in adult life. The tips of the arytenoids, the cornicula of San- 
torini, the cuneiform cartilages of Wrisberg, and the epiglottis are of 
the elastic variety of cartilage, and, though frequently much infiltrated 
with fat, are not, like the hyaline cartilages, subject to ossification. The 
median portion of the thyroid cartilage is also generally elastic in char- 
acter; this portion does not generally ossify in women. In the lateral 
hyothyroid ligaments are the minute triticeous cartilages, generally 
hyaline but occasionally fibrous in character. 
The intrinsic muscles of the larynx, taking origin from these car- 
tilages, pursue their course beneath the mucous membrane. 
The upper portion of the larynx, including the greater part of the 
epiglottis, as far as the false vocal cords is lined by stratified squamous 
epithelium which is continuous with that of the pharynx. 
The epithelium of the vocal cords and that covering the anterior 
surface of the arytenoids is also of the stratified squamous variety. 
The remaining portions of the larynx, including the base of the epiglottis 
on its laryngeal surface, the ventricle, and the entire portion below the 
level of the true vocal cords, are lined by columnar ciliated epithelium 
of the pseudo-stratified type. The ciliary motion is directed toward the 
pharynx. The epithelium rests upon a basement membrane which is 
less highly developed than in other portions of the respiratory tract. 
The tunica propria consists of fibro-elastic connective tissue in which THE LARYNX 
301 
are many small tubulo-acinar mucous glands. These are most abun- 
dant in the region of the ventricle and the false vocal cords. In this 
region also there is much diffuse lymphoid tissue, and the lateral and 
dorsal wall contains several solitary nodules which are so constant in 
their appearance as to warrant designating them 'laryngeal tonsil' 
(Frankel). Occasionally, however, 
lymph nodules are not present in the 
mucous membrane of the human 
larynx. The deeper portion of the 
tunica propria in certain parts, e.g., in 
the false vocal cords, contains a few 
striped muscle fibers in addition to those 
of the named muscles of the larynx. The 
false vocal cords and the aryteno-epi- 
glottic folds contain loose fibrous tissue 
and frequently much fat. 
The true vocal cords are formed by 
dense bands of elastic and a few col- 
lagenous fibers which are covered by a 
mucosa clothed with stratified squamous 
epithelium. Their free margin is sharp- 
ly defined; at their attached margin, 
however, they blend indistinctly with 
the tunica propria. The free margin of 
the vocal cords has no connective tissue 
papillae on the surface of the tunica 
propria, but toward the trachea super- 
ficial papillae of connective tissue pro- 
ject into the deeper surface of the 
stratified epithelium. 
The mucous membrane of the larynx 
is freely supplied with blood-vessels 
and lymphatics. The latter terminate in the deep cervical lymph 
nodes. The nerve fibers form an abundant plexus in the laryngeal 
mucosa, from which motor fibers are distributed to the muscles and 
sensory fibers to the epithelium. The latter end in fine fibrils between the 
cells of the lining epithelium. In the stratified squamous epithelium, 
especially that of the epiglottis, small taste buds are also found; none, 
however, occur on the vocal cords. 
Fig. 286.-A Vertical Section 
THROUGH THE LATERAL WALL 
of the Human Larynx. 
a, cartilage; b, laryngeal mucosa, 
clothed with ciliated epithelium; 
c, transection of the vocal cord, in 
this region the mucosa is clothed 
with stratified epithelium; d, ducts 
of mucous glands; e, lymphoid 
nodule; f, muscle; g, mucous 
glands; h, submucosa; i, blood- 
vessel; V, ventricle of the larynx. 
Hematein and eosin. Photo. X 8. 302 
THE RESPIRATORY SYSTEM 
THE TRACHEA 
The trachea proper extends from the lower border of the cricoid car- 
tilage to the point where it bifurcates into the two primary bronchi, a 
distance of about four and one-half inches. The wall of the trachea 
somewhat resembles that of the larynx. It consists of three layers: 
1. The mucous membrane, or mucosa. 
2. The submucosa. 
3. The fibrocartilaginous coat, or adventitia. 
The mucous membrane presents slight longitudinal folds, and is 
lined by columnar ciliated epithelium, like that of the larynx, which 
Fig. 287.-Transection of the Wall of a Child's Trachea. 
I, mucosa; 77, submucosa; III, cartilage; IV, outer fibrous coat; a, columnar 
ciliated epithelium; b, tunica propria; c, layer of elastic fibers; d, mucous glands; 
e, perichondrium. Hematein and eosin. Photo. X 90. 
rests upon a delicate basement membrane. The tunica propria includes 
a thin inner layer of connective tissue which is richly supplied with 
small blood-vessels and infiltrated by many lymphocytes, and an outer THE TRACHEA 
303 
layer of elastic tissue most of whose fibers are longitudinally disposed. 
The elastic layer begins in the region of the vocal cords in the larynx 
and is continuous below with the similar layer of the bronchial mucous 
membrane. Elastic fibers are more numerous in the trachea of the lower 
mammals than in that of man. A muscularis mucosa, a characteristic 
structure of the mucosa of the digestive tube, 
is lacking in the trachea. The elastic mem- 
brane occupies the position held by the mus- 
cularis mucosa in other organs. 
The submucosa consists of loose areolar 
tissue which contains many small tubulo-acinar 
mucous glands. The ducts of these glands 
penetrate the mucosa and open upon the free 
surface of the trachea. They supply an abun- 
dant mucous secretion. This coat also contains 
the larger blood-vessels and nerves which are 
destined for the supply of the mucosa. 
The fibrocartilaginous coat is formed by 
the C-shaped Ting cartilages' of the trachea 
(from sixteen to twenty in number) which are 
firmly united to one another by ligamentous 
membranes of fibrous tissue continuous with 
the perichondrium of adjacent cartilage plates. 
The cartilages are of the hyaline variety and 
are subject to more or less ossification as age 
advances. They rarely overlap each other, so 
that but a single plate of cartilage forms the 
wall at any given point. Their borders are 
irregular, and horizontal sections near the 
upper or lower margin of the cartilage frequently pass through several 
projections, which, unless properly interpreted, would lead one to infer 
that the cartilaginous plate was interrupted. 
The interval between the ends of the C-shaped cartilage plates is 
occupied by a membrane of smooth muscle whose transverse fibers unite 
the adjacent ends of the cartilages. The muscle fibers are inserted into 
the perichondrium of the cartilages. Many of the fibers are obliquely, 
and a few of the outermost are longitudinally, disposed. This muscular 
portion of the tracheal wall forms the so-called track ealis muscle. The 
mucous membrane and submucosa of this portion of the trachea are un- 
usually thick and their mucous glands are exceptionally large. The 
Fig. 288.-Mucus-Se- 
creting, TUBULO - AL- 
VEOLAR Gland of the 
Human Tracheal Mu- 
cosa. 
The terminal dark areas 
are demilunes. Recon- 
struction. X 200. (After 
Maziarski.) 304 
THE RESPIRATORY SYSTEM 
loose fibrous tissue which invests the outer surface of the cartilaginous 
coat contains many small sympathetic nerve trunks and ganglia. 
THE LUNG 
At the root of the lung the trachea divides into a primary bronchus 
for each lung. By repeated subdivisions-the earliest branches being 
given off at acute angles, the later ones at more obtuse angles-the 
smaller and smaller bronchi finally end in minute terminal bronchioles 
which lead through the alveolar ducts to the pulmonary air sacs and 
alveoli. One may thus distinguish between primary, secondary, and 
tertiary bronchi, and bronchioles. The mode of division for the main 
series of bronchi is monopodial, of the smaller bronchi a mixed dichot- 
omy and monopody (Miller, Jour. Morph., 24, 4, 1913). 
Bronchi 
The wall of the primary bronchi is similar in structure to that of 
the trachea, but in bronchial tubes which are two or three divisions 
removed (secondary and tertiary bronchi) from the primary bronchi 
the plates of cartilage are no longer C-shaped, and a complete muscularis 
mucosae, within the cartilages, forms the outermost boundary of the 
mucous membrane. In such tubes-typical bronchi-the wall, as in the 
trachea, comprises: 
1. A mucosa. 
2. A submucosa. 
3. A fibrocartilaginous coat. 
The mucosa, a continuation of that of the trachea, is lined by 
tall, columnar, pseudo-stratified, ciliated epithelium which rests upon a 
distinct elastic basement membrane. The epithelium is thrown into 
wavy longitudinal folds. The tunica propria is extremely vascular; it 
possesses an abundant supply of thin-walled veins of small caliber, to- 
gether with many lymph vessels. Its connective tissue forms a delicate 
fibrous reticulum in the meshes of which are many lymphocytes. The 
outer portion of the tunica propria contains bundles of fine longitudinal 
elastic fibers, which form a complete layer about the tube. This elastic 
layer is thickest opposite the ridges and thinnest opposite the troughs of 
the epithelial waves. 
The outer boundary of the mucous membrane contains a well- THE LUNG 
305 
Fig. 289.-A Bronchus from the Human Lung. 
a, lining epithelium; b, duct of a mucous gland; c, muscularis mucosae; d, accu- 
mulated mucus, etc., bathing the surface of the epithelium; e, mucous glands; f, 
hyaline cartilage; g, outer fibrous coat; h, pulmonary alveoli. Hematein and eosin. 
Photo. X 34. 
developed muscularis mucosce composed of interlacing bundles of circular 
smooth muscle fibers. This layer forms a complete muscular coat which 306 
THE RESPIRATORY SYSTEM 
is here and there pierced by the ducts of mucous glands whose secreting 
portions lie in the submucosa. 
The submucosa, by its broad-meshed areolar tissue, loosely unites 
the mucous membrane to the cartilage plates. This coat contains the 
larger blood-vessels, nerves, and lymphatics which are distributed to the 
mucosa. It also contains the secreting portions of many tubulo-acinar 
mucous glands, which occur in groups that in the larger bronchi almost 
completely surround the tube. The number and size of these glands is 
in direct proportion to the size of the bronchus. The efferent ducts of 
the mucous glands penetrate the muscularis mucosae and open upon the 
free surface in the interval between adjacent folds of the epithelial lining. 
In the tunica propria the ducts possess ampullary dilatations which are 
lined by ciliated cells and contain portions of the mucous secretion. 
The fibrocartilaginous coat is formed by a dense fibrous membrane 
in which the cartilages are embedded. The plates of hyaline cartilage 
vary much in number and size, being more or less highly developed in 
proportion to the size of the bronchial tube. They possess at all times 
a somewhat crescentic shape. In the larger bronchi three or four car- 
tilage plates with overlapping edges encircle the entire tube. In the 
lower mammals, e.g., the pig, these overlapping cartilages are so highly 
developed that the plates often lie three or four deep; in man they are 
rarely more than one or two deep. As the bronchi diminish in size by 
division, the cartilage plates are no longer of sufficient size to completely 
encircle the wall but leave broad intervals in which this coat is only 
represented by fibrous tissue. In tubes of a diameter of 0.8 to 1 milli- 
meter, bronchioles, the cartilages entirely disappear, and in these or some- 
what smaller bronchioles the mucous glands are, likewise, no longer 
found. According to Cutore (Anat. Anz., 47, 13, 1914), the cartilage 
plates of the intrapulmonary bronchi contain elastic fibers, and are in 
fact true elastic cartilages. 
The outer surface of the cartilages is invested with a clothing of 
loose fibrous tissue of varying thickness-sometimes known as the outer 
fibrous coat-in which the branches of the pulmonary artery and veins 
and also many nerve trunks and ganglia are found. In the larger bronchi 
the two vessels, pulmonary artery and. pulmonary vein, are found on 
opposite sides of the tube; in the bronchioles only one vessel, the artery, 
is in relation with the tube, the vein pursuing an independent course 
within the pulmonary tissue. 
Near the root of the lung many small lymph nodes are found in the 
outer fibrous coat. In the smaller bronchi these are represented by THE LUNG 
307 
solitary nodules which, it is important to note, are always found in 
the fibrous connective tissue which forms the outer portion of the 
bronchial wall. The bronchial lymph nodes and nodules are deeply 
pigmented, the volume of the pigment being dependent upon the age 
and occupation of the individual. It is apparently derived by absorption 
from the surface of the bronchi and is therefore absent in infancy, defi- 
cient in youth, abundant in adult life, and especially abundant in those 
individuals whose occupations have necessitated the inhalation of a dusty 
atmosphere. 
The Bronchioles 
The bronchioles possess neither cartilage, mucous glands, nor 
lymph nodules. Their epithelium, though still ciliated, is low-short 
columnar, or, in the smaller bronchioles, cuboidal. The tunica propria 
contains many lym- 
phocytes and the 
elastic tissue forms 
an almost complete 
layer of longitudi- 
nal elastic fibers. 
The muscularis 
mucosae is relatively 
more highly devel- 
oped than in the 
larger bronchi; it 
completely encircles 
the wall and is in- 
vested with an ad- 
ventitious layer of 
fibrous tissue which 
contains the small 
arteries, nerves, 
lymphatics, a capil- 
lary plexus with 
elongated meshes, 
and occasional ven- 
ules. 
The fibrous coat 
of the bronchiole here and there blends with the fibrous bands of inter- 
lobular tissue and is in contact with the adjacent pulmonary alveoli. 
Fig. 290.-Diagram of Primary Lobule of Lung 
(Lung Unit). 
b.r., respiratory (terminal) bronchiole; d. al., alveolar 
duct; a, atria; s. al., alveolar or air sac; a.p., pulmonary 
alveoli; art., pulmonary artery; v., pulmonary vein. (After 
Miller.) 308 
THE RESPIRATORY SYSTEM 
Each bronchiole enters the apex of a pulmonary lobule (secondary) and 
divides into terminal so-called respiratory bronchioles (terminal bron- 
chioles). 
Fig. 291.-From a Section of a Child's Lung. 
B, bronchiole in transection, with its adjacent pulmonary artery, A; TB, bron- 
chiole, ending in a terminal bronchiole, from which are derived the alveolar duct, I, 
the atrium, A, and the pulmonary alveoli, PA. In the center of the figure a pul- 
monary alveolus, PA, is seen in transection; many similar ones are shown. Hema- 
tein and eosin. Photo. X 45. 
The respiratory bronchiole bears alveoli which become more numer- 
ous toward its distal end. It thus contains a variable epithelial lining 
consisting proximally of a low columnar, sometimes ciliated, epithelium, 
with distally a more flattened non-ciliated type, and in the alveoli a 
typical greatly flattened respiratory epithelium including non-nucleated THE LUNG 
309 
plates. It has a diameter of 0.5 millimeter or less. The epithelium 
rests upon a thin fibromuscular coat, the continuation of the mucous 
membrane of the bronchioles. The muscle still forms an almost com- 
plete though very thin investment of circular fibers; the muscle fibers, 
a, a small tertiary bronchus; b, bronchioles; c, bronchioles ending in terminal 
bronchioles, alveolar ducts, etc.; d, terminal bronchioles in transection, they have 
a more regular contour and thicker wall than the alveoli; e, pulmonary arteries; 
f, a bronchial artery; g, a bronchial vein; h, interlobular fibrous septum. Hematein 
and eosin. Photo. X 62. 
Fig. 292.-From a Section of a Child's Lung. 
however, are not continued into the wall of the pulmonary air sacs. The 
elastic fibers, derived from the elastic layer of the bronchioles, pass over 
to the alveolar walls in which they form a delicate network. 
The respiratory bronchioles are short branching tubules leading to 310 
THE RESPIRATORY SYSTEM 
broader spaces, the alveolar ducts (infundibula of Schultze), which are 
surrounded by air saccules with pulmonary alveoli. According to Miller 
the alveolar ducts bear numerous alveoli, and are lined with flattened 
respiratory epithelium, and contain scattered bundles of smooth muscle 
which end in a delicate sphincter where the duct passes into the non- 
Fig. 293.-From a Section of a Child's Lung. 
A, atrium; B, bronchioles ending in terminal respiratory bronchioles, TB; PA, 
pulmonary artery; PV, pulmonary vein. Hematein and eosin. Photo. X 50. 
muscular atria, from three to six for each alveolar duct. Each atrium, 
of more or less circular outline, opens into a variable number (two to 
five) of irregular and variable alveolar saccules (air sacs). Each sac- 
cule bears on its periphery numerous pulmonary alveoli. The epithelium 
of the entire bronchial tree, including the nucleated respiratory cells, con- 
tains abundant mitochondria (Meves and Tsukaguchi, Anat. Anz., 46, 
1, 1914). THE LUNG 
311 
The Pulmonary Alveoli 
The pulmonary alveoli are minute air cells, open toward the alveolar 
ducts, whose extremely thin wall consists of a capillary network, a deli- 
Fig. 294.-Diagram of the Three Pulmonary Lobules Connected with a 
Terminal Bronchiole (TB). 
The middle lobule is stippled. BR, bronchiole; .RB, respiratory bronchiole of 
the first order; TB, respiratory bronchiole of the second order (terminal bronchiole); 
/, II, III, alveolar ducts; 1, 2, and 3 a, b, c and d, atria; As, alveolar sacs with 
pulmonary alveoli or air cells. (Adapted from Miller, Join-. Morph., 20, 4, 1913.) 
cate fibro-elastic reticulum, and a lining epithelium. The alveoli are 
so densely clustered about the alveolar duct that the capillary plexus, in 
the form of a reticulated membrane of wide capillary vessels, is exposed 
to the air of two adjacent alveoli, being separated therefrom only by its 
own endothelium and the epithelial lining of the alveolus. 312 
THE RESPIRATORY SYSTEM 
The lining epithelium of the alveoli, continuous through the alveolar 
ducts with that of the respiratory bronchioles, consists of flattened cells 
and broad protoplasmic non-nucleated plates. These cells are narrower 
and thicker (cubi- 
cal) in the prenatal 
lung and when the 
lung is collapsed, 
broader and thin- 
ner when it is fully 
expanded. The 
completely expand- 
ed alveolus in full 
respiration is two 
to three times the 
size of the collapsed 
or retracted alveo- 
lus of full expira- 
tion (Kblliker). 
The elastic fibers of 
the alveolar wall 
form a delicate net 
among the capillaries; in the meshes of this net a few white fibers are 
found. The normal respiratory epithelium does not become phagocytic 
(Miller, 1911). 
An alveolar duct with its atria, alveolar saccules, blood-vessels, lymph- 
vessels and veins forms a natural unit of structure, the primary pul- 
monary lobule. 
Pores leading from one alveolus to another have been described, but 
Miller denies their presence in the lung of the cat (Jour. Morph., 24, 4, 
1913). 
Fig. 295.-Two Alveoli of a Child's Lung. 
In A, the wall is cut across and viewed in profile; B, a 
tangential section showing the cup-shaped bottom of 
the alveolus and the pulmonary epithelium in surface 
view; c, a pulmonary venule. Hematein and eosin. X 
425. 
The Pleura 
The pleura is a serous membrane whose visceral layer (pleura pul- 
monalis) envelops the lung, and whose parietal layer (pleura costalis, 
diaphragmatis et mediastinalis) lines the thoracic cavity. 
The surface of the pleura is clothed with a layer of mesothelium 
which rests upon a 'subserous' layer of connective tissue. The mesothe- 
lium contains frequent 'stomata' which in the costal pleura are only 
present over the intercostal spaces. THE LUNG 
313 
These pleural pores have been the subject of considerable discussion. 
They have been regarded by some as giving direct vent to lymphatics; 
but Walters (Anat. 
Hefte, Bd. 46, 1913) has 
quite conclusively shown 
that they are artifacts, an 
interpretation maintained 
also by Miller. 
The connective tissue 
contains an abundant 
network of elastic fibers. 
It is loosely attached to 
the chest wall but is more 
firmly united to the pul- 
monary tissue. Normally 
the pleura contains no 
lymph nodes (Miller). 
The pleura contains 
many small blood-vessels 
and an abundant plexus 
of blood and lymphatic 
capillaries. Its innerva- 
tion includes both sym- 
pathetic and cerebral (vagus) fibers. Both are apparently non-medul- 
lated. The sympathetic nerve fibers are supplied to the walls of the 
blood vessels; they are vasomotor in function. The vagus fibers are sen- 
sory in nature, and terminate in lamellar corpuscles, and as fine free 
sensory fibers. 
Fig. 296.-Transection of the Pleura of an 
Infant. 
a-a, layer of mesothelium; b, submesothelial con- 
nective tissue; c, pulmonary alveoli; d, a small blood- 
vessel. Hematein and eosin. Photo. X 470. 
Fig. 297.-From a Section of the Pleura of Man. 
The elastic tissue appears black, a-a, mesothelial surface; b-b, submesothelial 
connective tissue. Weigert's elastic tissue stain, hematein and picrofuchsin. X 110. 314 
THE RESPIRATORY SYSTEM 
The Lobule of the Lung 
If carefully examined, the surface of the pulmonary pleura presents 
minute polygonal areas (10 to 25 mm. in diameter), the bases of the 
anatomical (or secondary) lobules, whose borders mark the attachment 
of fine bands of interlobular connective tissue, outlined by pigmented 
lines. In microscopical preparations still finer bands may be found, 
which traverse the pulmonary tissue in the direction of the root of the1 
lung, and which partially outline minute conical areas, the true pul- 
monary (or primary) lobules, or lung units, whose bases are directed 
toward the pleura, and their apices toward the root of the lung. In many 
of the lower mammals, e.g., ox, these lobules are more distinctly outlined 
by interlobular connective tissue than is the case in man. 
At the apex of the secondary lobule a small bronchiole (intralobular 
bronchiole) enters' and divides into its respiratory bronchioles (from 30 
to 100). This secondary pulmonary lobule consists of a collection of 
the smaller units or primary pulmonary lobules above described. At 
the same point a terminal branch of the pulmonary artery enters with 
the bronchiole and supplies the anastomosing capillary plexus in the 
alveolar walls. Branches of the bronchial artery do not supply any of 
the primary intralobular structures, and the pulmonary veins which 
return the blood from the alveolar capillaries arise at the periphery of 
the primary lobule and immediately enter the interlobular connective 
tissue. 
The interlobular connective tissue contains the smaller branches of 
the pulmonary veins, the lymphatics returning from the pleura, and 
the non-medullated nerve trunks which are destined for the supply of 
the pleura and the intralobular pulmonary tissue. 
Blood Supply of the Lungs 
The blood supply of the lungs is derived from two distinct sources, 
the pulmonary arteries and the bronchial arteries. The former is des- 
tined chiefly for aeration in the capillaries of the alveolar walls, the 
latter for the nutrition of the bronchial walls. 
The pulmonary artery enters at the hilum in company with the 
vein and the bronchus. It follows the bronchus throughout its course 
and gives an arterial branch to each of its subdivisions. The large ar- 
teries nearly equal in size the bronchus in relation to which they lie, 
but the smaller branches are not more than one-fourth to one-fifth the THE LUNG 
315 
diameter of their bronchus. Throughout their course the branches of 
the pulmonary arteries lie on the wall of the bronchi, viz., in the outer 
fibrous coat or attached thereto by a broad band of fibrous tissue. More- 
Fig. 298.-From the Lung of a Child. 
At a, the origin of a pulmonary venule in the wall of a lobule is shown; at b, the 
pulmonary venule is just coming into relation with the bronchiole. Hematein, 
Weigert's elastic stain, and picrofuchsin. Photo. X 105. 
over each bronchus is accompanied by only one branch of the pulmonary 
artery and receives no capillaries from it. 
At the apex of the secondary pulmonary lobule the pulmonary artery 
enters with the bronchiole; it resolves into smaller arterioles correspond- 
ing in number approximately to the number of respiratory bronchioles, 
each of which again breaks into several small twigs-one for each atrium, 
according to Miller-which supply the capillary networks in the walls of 
the alveolar ducts and alveoli. The pulmonary capillaries form an ex- 316 
THE RESPIRATORY SYSTEM 
ceedingly dense net of anastomosing vessels in the walls of the alveoli, 
the meshes of the capillary net being frequently, in the deeper portions 
of the lung, of less diameter than the vessel itself. At the periphery of 
the lobule the capillaries converge to form several venules which unite 
to form larger veins in the interlobular tissue. These veins pursue an 
Fig. 299.-From the Lung of a Dog Whose Blood-vessels Had Been Injected 
with a Gelatinous Mass, and Appear Black. 
The outlines of the pulmonary alveoli and atria are well shown. Many of the 
alveoli have been cut tangentially and present a surface view of the capillary net- 
work; in others the alveolar wall is cut across and is seen in profile. X 125. 
independent course and are always found at a considerable distance from 
the bronchioles and lobular branches of the pulmonary artery. (See 
Fig. 290.) 
The smaller branches of the pulmonary artery near the surface of 
the lung give arterial twigs to the adjacent portions of the pleura. 
From the capillaries of the pleura minute venules enter the interlobular 
tissue and join the interlobular veins. THE LUNG 
317 
The interlobular veins {pulmonary veins) follow the fibrous septa 
toward the hilum. They soon come into relation with the bronchi and 
are then found on that side of the bronchus opposite the pulmonary 
artery. The vein, like the artery, lies outside of the bronchial wall in 
the adjacent fibrous tissue. It is, as a rule, only those bronchi whose 
wall contains cartilage plates which are in relation with both pulmonary 
artery and vein; the smaller bronchioles are usually accompanied by the 
artery only. Those veins which accompany the bronchi receive smaller 
branches from the bron- 
chial wall and by union 
with their fellows form 
larger and larger vessels 
which finally make their 
exit as the pulmonary 
veins and pass to the left 
auricle of the heart. 
The bronchial 
arteries also follow the 
bronchial tubes in all 
their ramifications. The 
larger branches are found 
in the outer fibrous coat 
near the cartilages, the 
smaller ones lie in the 
submucous and mucous 
coats. In contradistinc- 
tion to the pulmonary 
vessels the bronchial ar- 
teries are found in the 
wall of the bronchi, not 
outside of the bronchial wall. They supply capillaries to all of the tis- 
sues of the bronchi. The bronchial capillaries reunite to form small 
venules whose course differs with the size of the tube. In the terminal 
bronchioles these venules pass directly to the interlobular veins, and, 
according to Miller, the pulmonary veins receive a similar acquisition 
at each division of the bronchi. In the larger bronchi, however, the 
venules unite within the bronchial wall to form the radicals of the bron- 
chial vein which, lying in the fibrous tissue of the bronchial walls, re- 
trace the course of the bronchi to the hilum, where they make their exit 
as the bronchial veins and join the azygos veins. Thus, only the walls 
Fig. 300.-From the Central Portion of the 
Preceding Figure. 
a, two pulmonary alveoli in transection; b, tan- 
gential section showing the bottom of an alveolus; 
c, a minute pulmonary venule. Photo. X 500. 318 
THE RESPIRATORY SYSTEM 
of the larger bronchial tubes are supplied with bronchial blood, and, 
according to Schaffer, a few branches at the root of the lung are also 
distributed to the adjacent pleura. Many of the bronchioles, the res- 
piratory bronchioles, and also the alveolar ducts, pulmonary alveoli, and 
the pleura all receive their nutrition from the pulmonary arteries. 
Finally it may be said that there are no anastomoses between the pul- 
monary arteries and veins except among the capillaries of the alveolar 
walls. 
Lymphatics 
The pulmonary lymphatics form a plexus in the walls of the bronchi 
and bronchioles, penetrating to the mucous membrane. Branches from 
this plexus frequently anastomose with perivascular lymphatic vessels 
about the branches of the pulmonary artery and veins. A close network 
of lymphatic vessels is also found in the pleura, its efferent vessels passing 
into the interlobular tissue to join those vessels which accompany the 
veins. The pulmonary lymphatics are supplied with frequent valves and 
numerous anastomoses. 
The lymphatic vessels of the bronchi are connected with larger lym- 
phatic vessels of the outer fibrous coat and with the lymph nodules in 
the walls of the larger tubes. Many of the larger vessels in the outer 
fibrous coat of the bronchi, and also those which accompany the pul- 
monary artery, enter those lymph nodes which are in relation with the 
bronchial walls at the root of the lungs. The pleural lymphatic plexus 
and the vessels accompanying the pulmonary veins, after pursuing much 
of their course through the interlobular connective tissue in company 
with the pulmonary veins, also open into the bronchial lymph nodes. 
Much pigment is conveyed through these vessels and is deposited in (a) 
the interlobular connective tissue, (&) the fibrous tissue about the pul- 
monary arteries, and most abundantly in (c) the bronchial lymph 
nodules and nodes. 
Lymphoid tissue forms an important constituent of the lungs serv- 
ing as filters in the lymph circulation and as centers to which the 
phagocytes carry their collected material. It occurs as nodes, nodules, 
or as smaller masses of more diffuse lymphoid tissue; it may be peri- 
bronchial, periarterial, perivenous or subpleural in position. Lymph 
nodes are associated with the larger divisions of the bronchi and located 
at the points of branching. The smaller masses are found in greatest 
numbers at the periphery of the primary and secondary lobules (Miller, 
Anat. Rec., 5, 3, 1911), THE LUNG 
319 
Nerve Supply 
The nerves of the lungs are derived from the anterior and posterior 
pulmonary plexuses of the sympathetic system. They are distributed 
to the walls of the blood-vessels, where they form a delicate plexus with 
terminal fibrils among the smooth muscle fibers, and to the walls of the 
bronchial tubes. Small nerve trunks, with which many minute ganglia 
are connected, occur in large numbers in the outer fibrous coat of the 
bronchi. 
From these nerve trunks and ganglia fibrils are distributed to the 
bronchial mucous membrane, in which they supply the muscularis 
mucosse, and form a terminal plexus beneath the epithelial coat. These 
fibers have been traced to the respiratory bronchioles, where they are 
said to form a delicate plexus within the lobule in the interalveolar walls 
(Wolff, Arch. f. Anat., 1902). Sensory fibrils are supplied by the vagus 
nerve. The vagus contributes to the bronchi and their subdivisions also 
motor fibers, for the most part probably indirectly through the sym- 
pathetic ganglia. CHAPTER XIII 
THE DIGESTIVE SYSTEM 
The digestive system includes the cavities of the mouth, pharynx, 
esophagus, stomach, and intestines, together with the accessory glands- 
the salivary glands, pancreas, and liver. Associated with the mouth 
and cooperating in the function of the essential organs of digestion are 
also the teeth and the tongue. 
THE MOUTH 
The walls of the oral cavity comprise a mucous membrane, a sub- 
mucous layer of connective tissue, and a muscular or bony paries. 
The mucous membrane (mucosa) is clothed with a layer of strati- 
fied squamous epithelium which presents, at the margin of the lips, 
a gradual transition to the epidermis of the skin, and at the fauces is 
continuous with the lining epithelium of the faucial isthmus and the 
pharynx. 
The tunica propria (corium, stratum proprium) upon which the 
epithelium rests, consists of dense areolar tissue, the superficial portion 
of which specially abounds in elastic fibers. This portion of the corium 
consists of rather delicate connective tissue bundles which at frequent 
intervals are prolonged into the epithelial coat in the form of minute 
conical papillae, similar to those of the skin, whose height varies with 
the location. The tallest papillae are found on the gums and at the 
margins of the lips, the lowest on the inner surface of the cheeks and 
the soft palate. 
The papillary layer of the corium contains a plexus of capillary blood- 
vessels which is connected with a network of small arteries and veins in 
the deeper part of the tunica propria. 
The submucosa consists of looser connective tissue which blends 
insensibly with that of the mucosa, and unites the mucous membrane 
to the subjacent muscles and bones forming the wall of the oral cavity. 
In most portions the buccal mucous membrane is but loosely connected 
320 THE MOUTH 
321 
with the underlying parts, but in the hard palate and the gums this 
union is very firm. 
Lymphoid tissue occurs in considerable abundance in the oral mu- 
cous membrane. Areas 
of diffuse lymphoid 
tissue are of frequent 
occurrence and small 
lymph nodules are oc- 
casionally found. The 
lymphatic vessels form 
a plexus in the tunica 
propria, which empties 
into larger vessels in 
the submucosa. 
Secreting glands 
occur in considerable 
abundance in all por- 
tions of the buccal 
mucous membrane ex- 
cept that covering the 
gums. The glands are 
of the tubulo-acinar 
type and produce 
either a pure mucous 
secretion or, in the 
case of the larger ones, 
a mixed mucous and 
serous secretion. The 
ducts of the glands are 
lined by columnar 
cells which, near the 
mouth of the duct, of- 
fer a gradual transi- 
tion to the stratified squamous epithelium of the mucosa. The glandular 
epithelial cells of the secreting portions become swollen and clear after a 
period of rest, but are shrunken and present a faint cytoplasmic reticu- 
lum after activity. The different glands of the same region, and even 
different cells in the same gland, often exhibit various stages of secretory 
activity. The fundus of the secreting glands frequently extends into the 
loose connective tissue of the submucosa. At the margin of the lips and 
Fig. 301.-From a Section through the Lip of 
an Infant. 
a, cutaneous surface; b, epithelium of the oral mu- 
cosa; c, layer of striated muscle; d, layer of mucous 
glands. Hematein and eosin. Photo. X 10 322 
THE DIGESTIVE SYSTEM 
more rarely in the neighboring portions of the buccal mucous membrane 
are small sebaceous glands which open directly upon the free surface. 
The oral glands will be further described below under salivary glands. 
Fig. 302.-Axial Section of a Human Molar Tooth. 
C, cementum; D, dentin; P, pulp cavity; S, enamel. X 8. (After Sobotta.) THE TEETH 
323 
THE TEETH 
Structure 
Each tooth rests in a bony socket in the alveolar process of the maxil- 
lary bone, and is also held in place by the periosteum of the alveolar 
sac and the adjacent portion of the gum. The tooth is divisible into a 
free portion or crown, and a concealed portion or root which usually 
consists of from one to three fangs. The slightly constricted border 
between the root and the 
crown, which is surrounded by 
the soft tissues of the gum, is 
known as the neck of the tooth. 
The tooth consists of a su- 
perficial calcareous portion and 
a central medulla, the dental 
or pulp cavity, which occupies 
the axis of the tooth and which 
contains a peculiar embryonal 
type of connective tissue, very 
similar to reticular tissue, the 
dental pulp. At the tip of 
each fang is an opening, the 
foramen apicis dentis, leading 
to a narrow canal which pene- 
trates the wall of the tooth and 
permits the entrance of the 
nerves and blood-vessels which 
supply the pulp. 
The calcareous wall of the 
tooth is formed by three dis- 
tinct tissues: (1) dentin or 
ivory; (2) enamel; (3) cementum. The dentin incloses the entire pulp 
cavity and is in turn covered by the enamel and cementum, the enamel 
forming the superficial layer of the crown, the cementum that of the 
root of the tooth. 
The Dental Pulp.-The dental pulp is an embryonal type of con- 
nective tissue which is rich in branching stellate cells and poor in 
fibers. It contains no elastic fibrils, and the delicate collagenous fibers 
Enamel 
Contour lines of Retzius 
i Prism s'ripes of 
[ Schreger 
( Contour lines of 
( Owen 
Dentinal tubules 
Granular layer of 
Tomes 
f Incremental lines of 
I Schreger 
Cementum 
Root canal 
Fig. 303.-Diagram of an Axial Ground 
Section of Tooth, Showing the Sev- 
eral Stripes of the Dentin and the 
Enamel. 324 
THE DIGESTIVE SYSTEM 
instead of forming bundles are arranged in an interlacing network, the 
fine fibrils of which are in intimate relation with the connective tissue 
cells. It according- 
ly closely resembles 
reticular connective 
tissue. The stellate 
connective tissue 
cells are scattered 
throughout the en- 
tire pulp, but at the 
periphery of the 
cavity are closely 
crowded and are 
much enlarged. 
These peripheral 
cells form a layer 
o f odontoblasts 
which is in contact 
with the dentin. 
The odonto- 
blasts are cylindri- 
cal branched con- 
nective tissue cells 
whose long axis 
(about 40 /x) is 
perpendicular t o 
the surface of the 
adjacent dentin. 
From their apex a 
delicate process is 
sent into the den- 
tinal canals, in 
w h i c h they fre- 
quently extend all 
the way through 
the dentin. Lat- 
eral processes from 
the cell bodies of the odontoblasts interlace with each other and firmly 
unite the cells into a membranous layer. Other processes are given off 
from the base of these cells and intermingle with the fibers of the pulp, 
Fig. 304.-From a Longitudinal Section of the Neck 
of a Child's Tooth and the Adjacent Alveolus. 
a, enamel; b, cementum; c, dentin; d, bone; e, peri- 
osteum;/, corium; g, lymphoid tissue; h, stratified epithe- 
lium of the gum; i, circular dental ligament; k, epithelial 
remnants; I, blood-vessels. X 25. (After Kolliker.) THE TEETH 
325 
so that if this tissue is forcibly separated from the dentin the odonto- 
blasts remain adherent to the connective tissue of the pulp. The nuclei 
of the odontoblasts are found near their inner or basal extremity. Their 
cytoplasm is of considerable extent as compared with that of the other 
connective tissue cells of the pulp. 
The dental pulp is richly supplied with blood-vessels, derived from 
a nutrient artery which enters through the root canal, its several 
branches forming a network of minute arterioles and capillary vessels 
in the center of the pulp cavity, and a peripheral close-meshed capil- 
Fig. 305.-From a Section of a Human Tooth Which Had Been Ground to 
Extreme Thinness. 
a, dentin; 6, granular layer of Tomes; c, enamel. Photo. X 150. 
lary network which is in close relation with the layer of odontoblasts. 
Numerous delicate lymphatic vessels, uniting to leave the root as one 
or several large vessels, have also recently been demonstrated in the tissue 
of the dental pulp (Schweitzer). 
A rich nerve supply is derived from fine branches which also enter 
by the root canal. Most of the nerve fibers lose their myelin sheaths 
soon after they enter the pulp. They form a primary plexus in the 
connective tissue from which fine fibers pass to the periphery and 
form a marginal plexus beneath the odontoblasts. From here delicate 
terminal sensory fibrils ramify over the odontoblasts and pass in great 
abundance into the dentinal tubules, usually two to each tubule (Mum- 
mery, Proc. R. Soc., Series B, 85, 1912). This peripheral distribution 
of nerve fibrils explains the extreme sensitiveness of the dentin. Sympa- 
thetic fibers supply the muscle cells of the pulp arterioles. 
Dentin.-The dentin surrounds the entire pulp cavity except at 
the opening of the root canal. It is a fine calcareous substance which 
resembles bone in that it consists of a collagenous fibrous matrix and 
is infiltrated with lime salts. The matrix is a fine fibrous network of 326 
THE DIGESTIVE SYSTEM 
dense connective tissue, the majority of whose fibers are disposed in a 
longitudinal direction. The meshes of the matrix are almost completely 
filled by a deposit of calcareous salts 
which gives the dentin its bony consis- 
tence. Dentin consists of about 28 per 
cent, organic and 72 per cent, earthy 
matter. The latter includes calcium 
phosphate, about 67 per cent.; calcium 
carbonate, about 3 per cent.; and mag- 
nesium phosphate, with a trace of cal- 
cium fluorid. 
Here and there, especially toward its 
peripheral border and near the apex of 
the tooth, the dentinal matrix fails to 
become calcified. Such uncalcified areas, 
inter globular spaces, are encroached upon 
by the rounded or globular margins of 
the adjacent calcified matrix which 
forms the so-called dentinal globules. 
The dentin is everywhere permeated 
by a system of canaliculi, the dentinal 
tubules or canals, which extend in a ra- 
dial manner from the pulp cavity out- 
ward to the cementum and enamel 
Their course is characteristically curved, 
resembling the letter s. The cavity of 
the dentinal tubules is partially occupied 
by the dentinal processes (fibers) of the 
odontoblasts, an arrangement which may 
be compared to that existing between the 
processes of the bone cells and the canal- 
iculi of bone. At their inner extremity 
the dentinal tubules are 2 to 4 p. in di- 
ameter, but they taper very gradually, 
especially in the outer portion of their course, where they finally reach a 
diameter of no more than 0.5 to Ip. 
The dentinal tubules may divide dichotomously in the inner third of 
their course; beyond this point they give off very fine lateral twigs, 
which at first leave the parent tubule nearly at right angles, but later 
are slightly inclined outward. At their distal end most of the dentinal 
Fig. 306.-Section of Fang 
Parallel to the Dentinal 
Tubules, Human Canine. 
(Waldeyer). 
1, cementum, with large 
lacunae, canaliculi and indica- 
tions of lamellae; 2, granular 
layer of Tomes with large in- 
ter globular spaces; 3, dentinal 
tubules. X 300. (From Quain's 
"Anatomy.") THE TEETH 
327 
tubules divide into a group of terminal branches, some of the arboriza- 
tions being very extensive, others consisting of but two or three sub- 
divisions. The coarser branches are frequently looped, the distal end of 
the loop often anastomosing with adjacent tubules. In their course 
through the dentin those canaliculi which enter the larger interglobular 
spaces are continued through these spaces without interruption. 
The walls of the dentinal tubules are 
formed by extremely dense calcareous den- 
tinal sheaths (of Neumann) which are very 
resistant to the action of acids. The curva- 
tures in the course of the dentinal tubules 
are of two types; the longer primary curves 
and the shorter spiral secondary curves. 
They occur with extreme regularity and as 
a result give rise to certain parallel lines 
in the substance of the dentin which follow 
the contour of the dentinal surface. These 
are known as the incremental lines of 
Schreger. 
A second system of dentinal striae, vis- 
ible in ground sections of tooth under low 
magnification, are the contour lines of 
Owen {arched incremental lines of Salter). 
They run nearly parallel to the lines of 
Schreger in the crown and toward the tip 
of the root, but elsewhere cut these lines at 
wide angles (Fig. 303). They represent 
lines of defective calcification between suc- 
cessively deposited layers of dentin. 
The superficial portion of the dentin is formed by the granular layer 
of Tomes, in which there are no dentinal tubules, but instead there are 
in this layer numerous small interglobular spaces from which minute 
canaliculi radiate in various directions. Many of these canaliculi are 
on the one hand with the dentinal tubules, and on the 
other with the canaliculi and bony lacunae of the cementum. The 
canaliculi of the granular layer are readily distinguished from the ad- 
jacent dentinal tubules by the extreme irregularity of their course, which 
contrasts sharply with the straight or regularly curved course of the 
dentinal tubules. 
The granular layer is relatively thick in the root of the tooth, but 
Fig. 307.-Dentin from a 
Ground Section of a Hu- 
man Molar, Showing the 
Dentinal Tubules Cut 
Across. 
The tubules appear as dark 
round or oval areas in the den- 
tinal matrix. Each tubule is 
surrounded by a narrow lighter 
halo, corresponding to the 
sheath of the tubule, perhaps 
an optical effect. X 750. 328 
THE DIGESTIVE SYSTEM 
becomes much thinner toward the neck. Beneath the enamel it becomes 
so thin that toward the apex of the tooth it is scarcely demonstrable. At 
this point also, occasional dentinal tubules are continued for a short 
distance into the enamel, though this condition is more characteristically 
developed in some of the lower mammals (e.g., Bodentia) than in man. 
Enamel.-The enamel, which covers the exposed crown of the tooth, 
is the hardest tissue of the body. About 90 per cent, of its earthy matter 
is calcium phosphate; about 4 per cent, is calcium carbonate; less than 
5 per cent, of its substance consists of organic matter. 
It contains a slightly larger trace of calcium fluorid 
than dentin. 
Its unit of structure is a calcareous cylinder, the 
enamel prism. These prisms or 'fibers' radiate out- 
ward from the dentin and are disposed after the 
manner of a mosaic. They are firmly united to each 
other by a very thin layer of calcified interprismatic 
cement substance. They represent calcified colum- 
nar ectodermal cells. 
In transverse section the enamel prisms have a 
polygonal, frequently quite regular hexagonal, out- 
line. In certain bundles, especially toward the periphery, the prisms have 
the shape in transverse outline of stout crescents. In longitudinal view 
the prisms present a slightly beaded appearance, the constricted portions 
being darker and delicately cross-striped. This peculiar structure and 
optical condition results from the manner of the formation of the prisms 
by the deposition of successive globules of preenamel substance, subse- 
quently becoming calcified to form definitive enamel. The enamel cement 
exhibits a reciprocal beading. Since the external surface of the enamel is 
greater than the internal, and since the enamel prisms are of approx- 
imately uniform diameter throughout, additional shorter prisms, pointed 
at their inner end, are interpolated toward the surface. The striped and 
beaded character of the enamel prisms is especially conspicuous in the 
teeth of rodents. 
The enamel prisms are grouped into bundles within which the con- 
stituent prisms are parallel. The course of the prism bundles, however, 
is variable, so that, though following a more or less radial course through 
the enamel, the prism bundles frequently cross one another at acute 
angles. In axial longitudinal sections of ground tooth this crossed ar- 
rangement of the prism bundles produces the appearance of radially 
disposed alternating dark and light bands. This banding is seen under 
Fig. 308.-Enamel 
Prisms in Tran- 
section. 
From the tooth 
of a calf. X 350. 
(After Kolliker.) THE TEETH 
329 
low magnification, and is especially conspicuous in reflected light; it is 
due to the difference with which the groups of transverse and longitudi- 
nally cut enamel prisms reflect the rays of light. The dark bands are 
known as the radial lines, or the prism stripes of Schreger. 
Ground sections of dried tooth show also brownish lines in the enamel 
having an arrangement approximately parallel with 
the surface of the tooth: These contour lines of 
Retzius are explained by von Ebner as the result of 
air-filled fissures in the dried enamel. They are also 
said to be the result of the wavy direction of the 
enamel prisms. They are most probably caused by 
imperfect calcification, marking growth stages in the 
development of the enamel. 
Cementum.-The dental cement, or crusta pe- 
trosa, is a thin layer of bony tissue which invests the 
root of the tooth. It forms a very thin layer at the 
neck of the tooth, but gradually increases in thick- 
ness as it approaches the tip of the fang. 
The cementum consists of parallel layers of bony 
lamellae between which many lacunae with their bone 
corpuscles are included. Bone canaliculi radiate 
from the lacunae and frequently open into the inter- 
globular spaces of the granular layer. There are no 
Haversian systems in the cementum, but the thicker 
portions are frequently penetrated by vascular canals 
which, like Volkmann's canals, are not accompanied 
by concentric lamellae. The cementum is firmly 
united to the granular layer of the dentin, the matrix 
of the two tissues being continuous. 
The cementum is invested with a periosteal coat, 
the periodontium, pericementum, alveolar periosteum, 
or root (peridental) membrane, of dense fibrous tissue which, at the neck 
of the tooth, unites with the dense connective tissue of the gum to form 
an annular thickening of very dense fibrous tissue which encircles the 
tooth and is known as the circular dental ligament. The root membrane 
contains no elastic fibers, but sends considerable numbers of slender 
white fibrous bands (Sharpey's fibers) into the cementum. These bands 
effect a firm anchorage of the tooth to the alveolar wall. They are anal- 
ogous to the perforating fibers of Sharpey which bind the periosteum to 
the osseous lamellae. 
Fig. 309.-A Group 
of Enamel 
Prisms Cut Lon- 
GITUDINALLY 
from the Inci- 
sor Tooth of 
the Rat, Show- 
ing Their Ir- 
REGULARLY 
Beaded Charac- 
ter AND THE 
Cross Stria- 
tions. 
Shorter and slen- 
derer prisms are 
interpolated periph- 
erally. X 375. 330 
THE DIGESTIVE SYSTEM 
Fig. 310.-From a Section of a Human Tooth Which Had Been Ground to 
Extreme Thinness. 
a, dentin; b, granular layer of Tomes; c, cementum. Photo. X 140. 
Development of the Teeth 
The teeth arise in part from the ectodermal epithelium of the oral 
cavity and in part from the mesenchyma of the alveolar processes. In 
the seventh week of fetal life there appears upon the surface of the 
maxillary ridges a thickening of the epithelium which grows into the 
subjacent mesenchyma in the form of a longitudinal plate or shelf, 
the labiodental strand, whose position is indicated superficially by a 
dental groove which indents the epithelial surface of the primitive gum. 
The labiodental strand divides at its deeper border into a nearly vertical 
continuation, the labial lamina, which subsequently becomes hollow to 
form the labiogingival groove; and a horizontal inwardly directed shelf, 
the dental lamina, which forms the earliest anlage of the enamel, the 
enamel organ. 
At the beginning of the third month the dental shelf shows upon 
its deep margin a series of shallow inverted cups, one for each of the 
temporary teeth, produced by an up-pushing of a corresponding series 
of cone-shaped areas of condensing mesenchyma at the site of each 
tooth germ. Each mesenchymal thickening forms the anlage of a dental 
papilla. That portion of the dental shelf which spreads out laterally 
to cover the dental papilla of each tooth forms its enamel germ, from 
which the dental enamel is eventually produced. Further development 
of the enamel germ and dental papilla causes the former to surround the 
papilla like a cap. Figures 311 and 312 show four stages in the early 
development of a tooth. THE TEETH 
331 
During the third month of fetal life the anlages of all primitive 
(deciduous, milk, or temporary) teeth are formed in the above manner. 
At about the same time, also, a lateral growth from the lingual side of 
the thin portion of the dental shelf which still connects the enamel 
germs with the oral epi- 
thelium, forms the anlages 
of twenty of the permanent 
teeth. The twelve addi- 
tional permanent molars 
arise at a later period and 
in a similar manner by a 
dorsal extension of the 
dental lamina which grows 
backward through the con- 
nective tissue of the alveo- . 
lar process as a solid cell 
column from which the en- 
amel germs are formed 
and into which the dental 
papillae grow. 
Further development 
of the dental anlage in- 
cludes the differentiation 
of the enamel germ on the 
one hand and of the dental 
papilla on the other. From 
the former the enamel and 
the cuticular epithelial 
membrane arise; the latter 
produces the dental pulp 
and the dentin. 
The Enamel Germ. 
-The enamel germ or 
enamel organ soon differentiates into three layers: (1) an inner enamel 
epithelium which forms the enamel prisms; (2) an outer enamel epithe- 
lium which lines the dental sac; and (3) an intervening enamel pulp. 
The Inner Enamel Epithelium.-The innermost cells of the 
enamel organ, viz., those which rest directly upon the dental papilla, 
soon become elongated and attain a cylindrical form. The nucleus 
moves toward the distal pole, and the original basal end becomes modi- 
Fig. 311.-Developing Tooth from a Human 
Embryo 17 mm. Long. 
LF, dental groove; M, oral cavity; OK, meso- 
blast of upper jaw; UK, anlage of lower jaw; OL, 
epithelium of the primitive upper lip, and UL, 
of the lower lip; ZL, dental lamina (labiodental 
strand). X 120. (After C. Rose.) Fig. 312.-Dental Anlages from a Human Fetus 40 mm. Long. 
Letters as in the preceding figure. LFL, labial lamina, or anlage of the groove 
between the lip and the mandibular process; Pp, dental papilla; Z, outline of the 
margin of the tongue; ZL, dental lamina. X 60. (After C. Rose.) 
Fig. 313.-Two Stages in the Early Development of the Teeth, from a 25 mm 
Pig Embryo. 
In B is seen the developing bone and striped muscle of the lower jaw. In both 
stages the dental papilla and the three layers of the enamel organ are clearly shown. 
332 THE TEETH 
333 
fled to take on the characteristics of the distal end of a columnar cell. 
A cuticular border appears upon the inner (originally basal) extremities, 
and as the calcareous substance of the enamel begins to be deposited fine 
processes are seen extending inward from the extremities of the enamel 
cells, Tomes' processes. It is around these processes that the permanent 
Fig. 314.-Developing Tooth from a Human Fetus 30 cm. Long. 
D, dentin; K, bone of the jaw; RM, germinal layer of the oral mucosa; 8, enamel 
organ; SK2, enamel anlage of the permanent tooth; VB, epithelial bridge still uniting 
the anlages of the temporary and permanent teeth; ZL, disintegrating dental lamina; 
SP, enamel pulp. X 30. (After C. Rose.) 
enamel is deposited first in the form of globules, which become calcified 
and meanwhile fuse to form the enamel prisms. 
The deposit of lime salts by the cylindrical cells of the inner enamel 
layer, ameloblasts (adamantoblasts), occurs earliest at the apex of the 
dental germ. Thus, it is the enamel of the face of the tooth crown which 
is first formed, and this is therefore its thickest portion. The enamel 
on the sides of the tooth crown appears later and hence it gradually 334 
THE DIGESTIVE SYSTEM 
tapers in thickness as it approaches the neck of the tooth, in which latter 
place the last formed enamel is found. 
Fig. 315.-A Developing Tooth from an Infant's Jaw. 
a, papilla; b, crown; c, outer enamel epithelium. Hematein and eosin. Photo. X 65. 
The nucleated bases (originally apices) of the cylindrical cells of the 
inner enamel epithelium are also marked by a sharp cuticular margin 
and rest upon the adjacent cells of the enamel pulp, the innermost cells THE TEETH 
335 
of which retain a characteristic epithelial appearance. The thin layer 
formed by the uncalcified bases of the adamantoblasts, which still cover 
the free surface of the enamel at the eruption of the tooth, remains as 
the highly cornified dental cuticular membrane (of Nasmyth). This is 
soon lost over the crown by 
reason of mechanical wear. 
The Outer Enamel Epi- 
thelium.-T h e outermost 
cells of the enamel germ are 
immediately in contact with 
the mesenchyma of the prim- 
itive jaw. This connective tis- 
sue forms, toward the end of 
the third month, a vascular in- 
vesting sheath or dental sac, 
which incloses the entire den- 
tal germ and finally, by grad- 
ually encroaching upon the 
narrow neck which still con- 
nects the enamel germ with the 
dental lamina, severs the con- 
nection of these organs so that 
the primitive tooth lies free 
within the dental sac. The 
outer enamel epithelium, which 
lines all portions of the dental 
sac except at the base of the 
dental papilla, forms several 
layers of flattened epithelial 
cells. Remnants of this cell 
layer frequently persist, in re- 
lation to the inner margin of the bony alveolus whose wall is produced 
by intramembranous ossification in the connective tissue surrounding the 
embryonic dental sac. 
The Enamel Pulp.-This structure is produced by a remarkable 
differentiation which occurs within the mid-portion of the enamel organ. 
The epithelial cells of this region, which at first appear to form a 
delicate syncytium, become separated by wider and wider intercellular 
spaces, and are thus drawn out into stellate forms with long anastomosing 
processes. The resulting cells closely resemble in form the connective 
Fig. 316.-A Portion of Fig. 315, Near the 
Apex of the Developing Tooth. 
a, enamel epithelium; 5, ameloblasts; c, 
enamel; d, dentin; e, odontoblasts; f, border 
of the dental pulp. Between the formed 
enamel and the ameloblasts Tomes' processes 
can be seen. Hematein and eosin. X 550. 336 
THE DIGESTIVE SYSTEM 
tissue cells of embryonal or gelatinous connective tissue. They are, how- 
ever, inclosed on all sides by the epithelial cells of the inner and outer 
enamel epithelium and, like other epithelial tissues, are never penetrated 
by blood-vessels. 
The enamel pulp appears to serve a purely mechanical function, it 
being a soft tissue through which the grow- 
ing tooth readily pushes its way to the sur- 
face. 
The Dental Papilla.-The dental pa- 
pilla is a mesenchymal structure which is in- 
vested by and grows into the enamel organ. 
Coincident with the appearance of the amelo- 
blasts in the enamel organ, the superficial 
cells of the dental papilla become enlarged, 
elongated, and so arranged as to form a con- 
tinuous layer of odontoblasts on the surface 
of the papilla. These cells apparently secrete 
a thin homogeneous layer, membrana pre- 
formativa (Raschkow), which serves as a 
basement membrane upon which the amelo- 
blasts deposit the enamel prisms; it also 
forms the anlage of the granular layer of 
Tomes. 
The odontoblasts now form the dentin 
in a manner entirely analogous to the de- 
posit of bone by the osteoblasts, processes of 
the odontoblasts being included within the 
deposit of dentin to form the dentinal -fibers. 
Irregular spaces, occurring in the dentin and granular layer, in which, 
no calcification occurs produce the interglobular spaces. 
The central mass of the dental papilla develops the reticular tissue 
of the dental pulp. The blood-vessels and nerves enter the pulp through 
the base of the papilla, which thus becomes the anlage of the root canal. 
The cementum is formed by intramembranous ossification occurring 
in that portion of the dental sac which invests the base of the dental 
papilla and the primitive root of the tooth. 
The process of cementogenesis is essentially similar to that of peri- 
chondrial ossification. The vascular mesenchyma of the dental sac 
breaks through the epithelial sheath (the root extension of the enamel 
organ), and through the agency of modified mesenchymal cells similar 
Fig. 317.-Odontoblasts 
and Dentin of the 
. Tooth of a New-born 
Cat. 
o,odontoblasts; Tp, Tomes' 
processes, prolongations of 
the odontoblasts; de, den- 
tinal canal in the dentin (d). 
X 500. (After Prenant, 
Bouin and Maillard.) THE TONGUE 
337 
to the osteoblasts, the cementoblasts, deposits cementuni upon the dentin 
of the root. The first deposit is made in the neck region, and the 
deposition progresses from thence to the apex of the root, where the 
thickest layer is subsequently found. Cementoblasts become enclosed 
in lacunae of the cementum and persist as cementum cells. The periph- 
eral layer of the root portion of the sac differentiates into a dense fibro- 
elastic lamina which serves both as a pericementum to the tooth, and as 
periosteum to the bone of the jaw. The pericementum includes besides 
cementoblasts also odontoclasts which become active as tooth destroyers 
at about the age of five years. They absorb the roots of the deciduous 
teeth, and thus open the way for the eruption of the permanent teeth. 
THE TONGUE 
The tongue consists essentially of a mass of voluntary muscle in- 
vested by a continuation of the mucous membrane of the mouth and 
pharynx. The fibers of this striated muscle are separated into two lateral 
halves by a median septum of dense connective tissue which extends 
from the base to the tip of the organ, and is known as the Ungual 
septum. 
The Muscle Fibers.-The muscle fibers include two groups: (1) 
the intrinsic, those of the lingualis or tongue muscle proper; (2) the 
extrinsic, those entering from without and serving to attach the tongue: 
the genioglossus, the hyoglossus, the styloglossus, the palatoglossus, and 
the chondroglossus. The fibers are disposed in three planes and are so 
arranged that the bundles cross one another at right angles. They thus 
form: (1) sagittal or vertical fiber bundles which are slightly inclined 
outward from the septum linguae and are derived from the lingualis 
muscle, supplemented in the inferior median portion by fibers from 
the genioglossus and the hyoglossus; (2) longitudinal fibers peripherally 
distributed and running from the base to the apex of the tongue, de- 
rived chiefly from the lingualis but supplemented on the under surface 
by the styloglossus, and chondroglossus; (3) transverse or horizontal 
fibers extending laterally from the septum linguae, which are also de- 
rived from the lingualis muscle, and include a few fibers from the 
palatoglossus. 
The interlacing bundles of muscle fibers are embedded in loose 
areolar and adipose tissue. The muscle fibers are inserted into the 
corium of the lingual mucous membrane, their sarcolemma being firmly 338 
THE DIGESTIVE SYSTEM 
adherent to the connective tissue of the mucosa, which invests the 
rounded blunt extremity of the muscle cell. Many of these muscle 
fibers are branched. 
The Mucous Membrane.-The mucous membrane of the tongue 
Fig. 318.-View of Dorsum of Tongue, Showing the Various Parillas, the 
Tonsils and the Fauces. 
1, circumvallate papillae; 2, foramen cecum; 3, fungiform papillae; 4, filiform 
papillae; 5, transverse and oblique rugae; 6, mucous glands; 7, tonsils; 8, tip* of 
epiglottis; 9, median glosso-epiglottidean fold; f, foliate papillae; L, lenticular papil- 
lae. (After Sappey.) 
consists of a thick corium, and an epithelial covering. The deeper 
part of the corium, consisting of loose areolar tissue, is intimately 
connected with the muscle. The superficial portion of the corium, 
containing denser areolar tissue, carries upon its surface dorsally con- 
nective tissue papillae of unusually large size which project into the THE TONGUE 
339 
epithelial coat. The surface of the larger of these papillae is not smooth, 
but is covered with small secondary papilla. 
The dorsal surface of the tongue presents a sharp structural differ- 
ence between its anterior and posterior portions. The papillae are 
limited to the anterior portion, which includes about two-thirds of 
the entire surface; this is known as the papillary area. The posterior 
Fig. 319.-One Lateral Half of a Coronal Section of a Dog's Tongue. 
The dorsal surface presents numerousTarge filiform papillae, a, lingual papillae; 
b, corium; c, the fibromuscular substance of the tongue. Hematein and eosin. 
Photo. X 6. 
one-third lacks papillae, and is of lymphoid character, hence known as 
the lymphoid area (lingual tonsil). These two areas represent the 
originally separate anlages from which the definitive tongue develops: 
the anterior unpaired tuberculum impar, and the posterior paired radix 
lingua. The line of fusion is indicated in the fetus and infant by a 
shallow V-shaped groove, the sulcus terminalis. This subsequently 
disappears, and the boundary then remains marked by the position of the 
circumvallate papillae. 
Epithelium.-The epithelium of the tongue is of the stratified 340 
THE DIGESTIVE SYSTEM 
squamous variety. Upon the under surface and margins of the organ 
its surface is smooth, but on the dorsum of the tongue the stratified 
epithelium forms tall projections, which correspond with the papillae 
of the corium, and which constitute the so-called lingual papillce. These 
papillae are of three varieties: (1) conical or filiform; (2) fungiform; 
and (3) circumvallate. 
The Conical or Filiform Papillae.-These papillae consist of flattened 
Fig. 320.-Filiform Papillae of the Dog's Tongue. 
a, papillae; b, corium; c, insertion of the muscular fibers into the border of the corium, 
Hematein and eosin. Photo. X 60. 
and elongated epithelial cells which are often so arranged as to produce 
a slender conical projection or epithelial tuft of variable height, which 
covers the apex of each connective tissue papilla. This type is the 
most abundant of the three varieties of lingual papillae. They are 
found upon all portions of the dorsum of the tongue. They range in 
height from 0.5 to 2.5 millimeters. 
The Fungiform Papillce.-The fungiform papillae are formed by a 
large connective tissue papilla or core which projects above the general 
level of the epithelial surface and is covered by a smooth layer of strati- 
fied squamous epithelium in which occasional taste buds are found. This THE TONGUE 
341 
variety, though much less abundant than the former, is still very 
numerous and may be found upon any or all portions of the dorsum 
of the tongue, where they are irregularly scattered among the filiform 
papillae. The fungiform variety are most abundant near the margin 
of the tongue on its dorsal surface. Their maximum height is about 
1.5 millimeters. 
The Circumvallate Papilla.-The circumvallate papillae form a 
group of from eight to twelve 
elevations which are situated 
at the base of the tongue, and 
are arranged in the form of a 
V, the apex being directed 
toward the larynx. These 
papillae are much broader (2 
to 3 millimeters) than either 
of the former varieties. They 
extend slightly above the gen- 
eral level of the epithelial sur- 
face, are of an inverted coni- 
cal shape, and are covered by 
a smooth layer of stratified 
squamous epithelium. Their 
base is surrounded by a deep 
circular excavation, lined by 
an invagination of the layer 
of stratified epithelium, 
which thus forms a deep 
trench about the base of the 
papilla. 
The epithelium which 
covers the sides of the cir- 
cumvallate papillae, as well as that forming the lateral wall of the trench 
contains large numbers of taste buds (see Chap. VI). The large cen- 
tral connective tissue papilla carries upon its surface many small sec- 
ondary papillae of the corium, which project into the epithelial coat of the 
circumvallate papilla upon its free surface, but are not found upon its 
lateral margins. 
On the lateral margins of the tongue, just in front of the anterior 
pillars of the fauces, occur a variable number of transverse parallel 
folds or leaves, the foliate papilla. These are only slightly developed 
Fig. 321.-A Filiform and a Fungiform 
Papilla, from an Injected Specimen of 
Tongue of Cat. 342 
THE DIGESTIVE SYSTEM 
in man, but are well developed in the rabbit and certain other rodents. 
They contain numerous taste buds. In the lymphoid area also, at the 
anterior lateral margins, are a group of low irregularly disposed mucous 
folds, the so-called lenticular papillce. 
A, axial section; B, section through the side of a papilla. The serous glands of von 
Ebner occupy the lower portion of the figure. Hematein and eosin. Photo. X 40. 
Fig. 322.-Circumvallate Papilla of the Human Tongue. 
Mucous and serous glands occur in the deeper portion of the 
corium of the tongue and among its muscle bundles; they open upon 
its epithelial surface between the papillae. These glands are most 
abundant at the base of the organ but are also found along its margins 
as far forward as the tip, where a pair of small tubulo-acinar sero- 
mucous glands lie on either side of the median septum and open upon 
the ventral surface of the tongue. These are the anterior lingual THE TONGUE 
343 
glands of Nuhn. The serous glands of von Ebner are confined to the 
region of the circumvallate papillae at the base of the tongue. They 
pour their secretion into the trench which surrounds the base of the 
papilla or into the crypts of the lingual tonsil. Other lingual glands, 
of the small tubulo-acinar mucous type, occur at various portions of 
the dorsal surface of the tongue, being especially abundant in the 
lymphoid area. 
The Lingual Tonsil.-The lingual tonsil (Fig. 249) is a con- 
siderable collection of lym- 
phoid nodules which is 
found at the base of the 
tongue in and about the 
median line. These nod- 
ules are grouped about a 
large funnel-shaped crypt, 
the foramen cecum, which 
opens at the apex of the V 
formed by the group of 
circumvallate papillae and 
which in the embryo forms 
the lingual extremity of 
the so-called duct of the 
thyroid gland {thyroglos- 
sal duct}. Several smaller 
crypts are also included in the region of the lingual tonsil. 
The lymphoid nodules are embedded in the mucosa or corium of the 
tongue and are surrounded by mucous glands, many of whose ducts 
penetrate between the nodules to open into the branching crypts. 
Lymphocytes, apparently derived from the nodules, infiltrate the sur- 
rounding connective tissue and epithelium and find their way into the 
lumen of the tonsillar crypts. 
The Blood-vessels of the Tongue.-The blood-vessels of the tongue 
are supplied by large arteries (branches of the lingual artery) which, 
with the corresponding veins, are embedded in the muscular portion of 
the organ and supply capillary vessels to this tissue. From these ar- 
teries, also, small arterial branches enter the deeper portion of the 
corium and form a capillary plexus which supplies the connective tissue 
and whose terminal ramifications extend to the very apex of the con- 
nective tissue papillae. The blood is returned by veins which pursue 
a similar course. 
Fig. 323.-Two Foliate Papillae from a Rab- 
bit's Tongue, Showing Numerous Taste Buds 
Along Their Lateral Margins. 344 
THE DIGESTIVE SYSTEM 
The Lymphatics.-The lymphatics form a superficial set of small 
vessels and tissue spaces beneath the epithelial layer, which are espe- 
cially abundant in the region of the lingual tonsil at the base of the 
tongue. The lymphatic vessels of this superficial plexus frequently 
encircle the lymphoid nodules. A deeper plexus of lymphatics in the 
loose connective tissue of the submucosa receives the lymph from the 
superficial plexus and conveys it by efferent lymphatic vessels to the 
deep cervical lymphatic glands. 
The Nerve Supply.-The nerve supply of the tongue comprises 
cerebral, both sensory and motor fibers, and sympathetic fibers. The 
sympathetic elements supply the glands and blood-vessels; small ganglia 
occur along their course. The motor fibers supplying the striped muscle 
are derived from the hypoglossal nerve. These end in motor end- 
plates. The sensory fibers arise from the lingual branch of the tri- 
geminal and the glossopharyngeal nerves. These mediate both general 
sensibility and the sensation of taste. The fibers which receive the 
stimuli of general sensibility end as naked varicose fibrils in the con- 
nective tissue of the body of the tongue, and in the submucosa of 
the papillse. They are accompanied by small ganglia. Certain fibers 
also end in muscle spindles. The fibers of special gustatory sensation 
are also distributed to the papillae; the chorda tympani (branch of 
the facial) component of the lingual branch of the trigeminal supplying 
the anterior two-thirds, the glossopharyngeal the posterior one-third of 
the tongue. At the base of the tongue small nerve bundles of taste 
fibers are distributed to the circumvallate papillae, and form a subepi- 
thelial plexus from which fibrils are distributed: (1) to the interior 
of the taste buds where they end in relation with the gustatory cells, 
intragemmal fibers; (2) to the surface of the taste buds, perigemmal 
fibers; and (3) to the intervening portions of the epithelial layer, where 
they end between the epithelial cells as in other parts of the tongue, 
intergemmal fibers (Fig. 175, page 161). The taste buds of the soft 
palate are innervated through the palatine nerves (great superficial 
petrosal component) of the trigeminal. 
THE ALIMENTARY CANAL 
General Characteristics of the Walls 
It is convenient to consider collectively under this head the pharynx, 
esophagus, stomach, and the small and large intestines. This tract THE ALIMENTARY CANAL 
345 
forms a continuous tube whose wall has, throughout its entire extent, 
many common characteristics. Thus the wall in all portions consists of 
Parotid gland 
- Sublingual gland 
■ Submaxillary gland 
-Thyroid 
* Parathyroids 
Thymus 
Esophagus 
.<< Diaphragm 
- Duodenum 
- Appendices epiploicce 
-Jejunum 
-Longt. muscle band 
-Ileum 
■ Haustra 
Cecum- 
Vermiform appendix- 
Fig. 324.-Diagram of the Alimentary Canal of Man. 
Is, small intestine; Ca, Ct, and Cd, ascending, transverse and descending portions 
of the colon; Ph, pharynx; Vic, ileocolic valve. (Adapted from Wiedersheim.) 
four coats which are respectively known, from within outward, as the 
mucous, submucous, muscular, and fibroserous. The three outermost 
coats are of very similar structure in all portions of the tract. 
The Fibroserous Coat.-In the abdominal cavity the outermost 346 
THE DIGESTIVE SYSTEM 
coat is derived from the peritoneum, by which the stomach and intestines 
are invested. In the upper portion of the tract, pharynx and esophagus, 
the serous coat is replaced by a layer of areolar connective tissue which 
usually contains much fat. In the abdomen the homologous subserous 
connective tissue is covered by a layer of mesothelium. The connective 
tissue of the outer fibroserous coat contains the larger blood and lym- 
phatic vessels whose branches are distributed to the three inner coats. 
The Muscular Coat.-The muscular coat, situated next within the 
fibroserous, is divisible into two layers, an outer longitudinal the direc- 
tion of whose fibers is parallel 
to the long axis of the canal, 
and an inner transverse layer 
whose fibers are circularly dis- 
posed. The two layers are 
united by a thin septum of 
areolar connective tissue which 
serves for the support of the 
larger blood-vessels and lym- 
phatics, whose capillaries are 
distributed to the muscular 
coat. This septum also con- 
tains a coarse-meshed nerve 
plexus, consisting of small an- 
astomosing nerve trunks which 
are composed in large part of 
non-medullated fibers, at whose intersections are numerous small sym- 
pathetic ganglia, the myenteric (Auerbach's) plexus and ganglion. 
Below the level of the junction of the middle and lower third of the 
esophagus, and including the musculature of the stomach and intestines, 
the muscle is entirely of the non-striated or smooth variety. In the 
pharynx and upper third of the esophagus, the striated or voluntary 
type of muscle is exclusively found. In the mid-portion of the esophagus 
both striated and non-striated muscle occur in varying proportions, oc- 
casional striated fibers being found even in the lower third of the 
organ. 
The Submucous Coat.-The submucous coat consists of loose 
areolar tissue, and serves for the support of the larger blood and 
lymphatic vessels which supply this coat and the mucosa. A second 
plexus of nerve fibers, similar in structure to the intramuscular plexus, 
is found in the deeper layers of the submucosa, and is known as the 
Fig. 325.-Surface View of Auerbach's 
Intramuscular Nerve Plexus, from the 
Esophagus of a Cat. 
Methylene blue. X 40 to 50. (After DeWitt.) THE ALIMENTARY CANAL 
347 
submucous (Meissner s) plexus. Its nerve trunks and ganglia are some- 
what smaller than those of the myenteric plexus. The submucous 
plexus supplies the muscular and glandular tissues of the mucous mem- 
brane. 
The Mucous Membrane.-The mucous coat or mucosa of the 
gastro-intestinal canal contains four typical structures, (1) an internal 
lining epithelium; (2) the muscularis mucosae which forms the outer- 
most layer; between these is (3) a tunica propria or corium of diffuse 
lymphoid or areolar tissue, which serves chiefly for the support of (4) 
the secreting glands. 
The muscularis mucosce usually consists of a double layer of smooth 
muscle, the outer being longitudinally, the inner circularly disposed. 
This layer is most highly developed in the esophagus. 
The tunica propria consists of delicate fibro-elastic and reticular 
tissue whose volume is in inverse proportion to that of the secreting 
glands. It is most abundant in the esophagus. In the stomach and 
intestines it is considerably infiltrated by lymphocytes and often con- 
tains diffuse lymphoid tissue. Small lymph nodules are also found 
in the deeper part of this membrane; they progressively increase in 
size toward the lower portion of the tract, where they form the solitary 
nodules of the intestine. 
The nature of the lining epithelium and the type of glands differs 
in each succeeding portion of the canal, and must, therefore, together 
with the other peculiarities of the several subdivisions of the tract, 
be separately considered. 
The Pharynx 
The pharynx may be subdivided;, upon histological as well as physio- 
logical grounds, into (1) an upper respiratory portion, or nasopharynx, 
and (2) a lower portion, oropharynx and laryngopharynx; only the 
latter of these properly belongs to the alimentary tract. The soft palate 
and uvula form a thin partition between the naso- and oropharynx. The 
nasopharynx has already been described as a part of the respiratory 
system (see Chapter XII). 
The mucous .membrane of the lower portion of the pharynx is lined 
by stratified squamous epithelium which rests upon a thick corium of 
areolar tissue. The tunica propria is well supplied with thin-walled 
blood-vessels and lymphatics, and contains many mucus-secreting glands 
of the tubulo-acinar type whose secreting portions lie deeply embedded 
in the connective tissue of the muscular coat. 348 
THE DIGESTIVE SYSTEM 
There is no muscularis mucosae in the mucous membrane of the 
pharynx; its place is taken by a layer of connective tissue which is 
exceedingly rich in longitudinal elastic fibers. This layer lies imme- 
diately upon the muscular coat, into which processes of fibro-elastic tissue 
extend between the muscular bundles; hence this fibro-elastic layer also 
serves as a submucosa. 
The superficial layer of the corium contains diffuse collections of 
lymphoid tissue and occasional small lymph nodules. 
The muscular coat of the pharynx is formed by its constrictor 
muscles. Their striated fibers mostly pursue an oblique course. Where 
these muscles are not immediately attached to the periosteum of the 
vertebrae, the pharynx is invested with an outer coat of areolar con- 
nective tissue by which, it is loosely united to adjacent organs. 
Esophagus 
The esophagus or gullet is a short tube about 25 centimeters (10 
inches) in length, connecting the pharynx with the cardia of the 
stomach. Its wall contains the usual four coats: (1) the outer fibrous; 
(2) muscular; (3) submucous; and (4) mucous. 
The Outer Fibrous Coat.-The outer fibrous coat envelops the 
wall of the esophagus and unites it to the adjacent organs. It consists 
of loose fibrous tissue, and contains the blood and lymphatic vessels 
and nerve trunks which supply the three inner coats. It is not in- 
vested by a serous layer. 
The Muscular Coat.-The muscular coat contains an outer longi- 
tudinal and an inner circular layer of muscle fibers, which are sep- 
arated by a narrow septum of loose fibrous tissue. In the upper third 
of the esophagus the muscle is of the striated variety, in the middle 
third it is mixed, in the lower third it is generally smooth. The distri- 
bution of the muscle in the lower third is subject to great individual 
variation, and occasionally striated fibers are often found all the way 
down to the diaphragmatic opening. 
The fibrous septum between the muscular layers contains the larger 
blood-vessels and the myenteric nerve plexus. 
The Submucous Coat.-The submucous coat forms a layer of 
areolar connective tissue which firmly unites the muscular and the 
mucous coats. It contains those blood and lymphatic vessels, together 
with the submucous nerve plexus, whose branches supply the mucous 
membrane. It also contains a considerable number of tubulo-acinar THE ALIMENTARY CANAL 
349 
mucous glands whose ducts enter the mucous membrane and open upon 
the free epithelial surface. The secreting acini of these glands are 
short branching tubules with ampullary dilatations; they possess a 
characteristic, tortuous form. Their columnar secreting cells have a 
strong affinity for muchematein and other mucous stains. This basophil 
Fig. 326.-Photomicrograph of a Transverse Section through Upper Third 
of Cat's Esophagus. 
m, mucosa, consisting of a stratified squamous epithelium, a membrana propria, 
a tunica propria, and a muscularis mucosae (m-m.); sm., submucosa; me., muscular 
tunic, containing at this level an inner longitudinal layer of striped muscle fibers; 
f, fibrous tunic. 
reaction, together with the situation of their isolated groups of secreting 
acini in the sub mucosa, sharply distinguishes the esophageal mucous 
glands from the glands of the stomach and intestine, except those of the 
duodenum. 
The number of the esophageal glands in man is extremely variable. 
This numerical variability is associated with frequent cyst formation, 
stasis of secretion, and atrophy of the glandular elements; conditions 
indicating small functional significance. In certain mammals, e.g., 
rodents, ox, horse, sheep, cat, and bat, glands are entirely lacking; 350 
THE DIGESTIVE SYSTEM 
in others, e.g., opossum, dog, pig, they are very abundant. Except 
in man, the mucous alveoli contain demilunes. Esophageal glands 
are the exception rather than the rule' in mammals. The fact that they 
are absent in all vegetable feeders but present in mixed feeders indicates 
that they have a chemical rather than a mechanical function (Goetsch, 
Amer. Jour. Anat., 10, 1, 1910). 
The Mucous Coat (Mucosa).-The mucous coat of the esophagus 
consists of a tunica propria or corium of areolar tissue which rests 
upon a well-developed muscularis mucosae and is covered on its free 
surface by stratified squamous epithelium. 
The muscularis mucosae contains considerable bundles of smooth 
Fig. 327.-Photomicrograph of a Longitudinal Section through the Lower 
Third of the Human Esophagus, Showing a Group of Esophageal Glands. 
muscle whose general direction is a longitudinal one in its outer, and 
circular in its inner portion. This layer forms the outermost stratum 
of the mucous coat, and is penetrated by the ducts of the deep mucous 
glands whose secreting acini lie in the submucosa. 
The inner portion of the tunica propria carries on its surface many 
tall connective tissue papilla? which project well into the epithelial coat 
and which closely resemble the vascular papillae of the skin. 
The mid-portion of the corium is penetrated by the excretory ducts 
of the mucous glands. These are at first lined by low columnar cells 
which, as they approach the epithelial surface are changed into several 
layers of flattened cells, which thus form a thin stratified lining, con- 
tinuous with the superficial stratified squamous epithelium of the 
esophageal mucosa. Many of these ducts possess small cystic dilata- THE ALIMENTARY CANAL 
351 
tions which are found in the connective tissue of the corium or occa- 
sionally in the submucosa. 
Superficial Glands.-At about the level of the cricoid cartilage 
the esophageal mucous membrane presents two lozenge-shaped depres- 
sions, one on either side, whose diameter varies from 1 centimeter down 
to microscopical size. These areas mark the site of the superficial 
glands of the esophagus (Hewlett) or upper cardiac glands (Schafer). 
These are short 
branched tubular 
glands which closely 
resemble those of the 
cardiac region of the 
stomach. They are 
confined to the mu- 
cous membrane; 
their tubules, in 
marked contrast to 
those of the deep 
mucous glands of the 
esophagus, never 
penetrating the mus- 
cularis m u c o s se , 
which, however, is 
considerably thinned 
beneath the superfi- 
cial glands. These 
glands secrete a mu- 
cinous fluid, but 
their cells are not so 
strongly basophilic as 
those of true mucous glands such as the deep glands of the esophagus. 
The ducts of the superficial glands, as well as their secreting portions, 
and also the lining epithelium of the esophagus upon they open, 
are clothed with columnar epithelial cells. Many of the secreting tubules 
contain parietal cells similar to those of the fundus glands of the stomach. 
Both ducts and secreting tubules contain small, cystic dilatations. 
At the lower end of the esophagus a similar group of superficial 
glands, the longer cardiac glands of the esophagus, frequently mark the 
beginning transition to the structure of the cardiac portion of the 
stomach, with whose, glands they are continuous. 
Fig. 328.-From a Section of the Superficial Glands 
of the Human Esophagus. 
a, esophageal epithelium; b, superficial glands; c, mu- 
cous glands; d, tunica propria; e, muscularis mucosae. 
Hematoxylin and eosin. Photo. X 17. (After Hew- 
lett.) 352 
THE DIGESTIVE SYSTEM 
The lining epithelium of the esophagus is of the stratified squamous 
variety. Its attached surface is indented by the papillte of the corium; 
its free surface is smooth. In the collapsed state of the organ its mu- 
cous membrane is thrown into longitudinal folds or rugae and its lumen 
is largely obliterated. The small isolated areas of columnar or ciliated 
epithelium, which occur in occasional individuals on the surface of the 
esophageal mucosa, especially in its upper third, are to be regarded 
as examples of irregular development, involving a persistence of the 
ciliated areas occurring, according to Johnson (Amer. Jour. An&t., 10, 
4, 1910), in embryos ranging from 55 millimeters to birth. 
The Stomach 
The Serous Coat (Tunica serosa).-The serous coat of the stomach 
is derived from the peritoneum. It is formed by a thin layer of sub- 
Mucus 
■Longitudinal 
section of glands 
Tunica propria 
.Glands cut 
obliquely 
Muscularis mucosae 
Submucosa 
Inner muscle layer 
..Blood-vessel 
Outer muscle layer 
■Serosa 
Fig. 329.-Section through the Stomach Wall of Man (Pyloric Region). X 14 
(Szymonowicz-MacCalluni, "Histology and Microscopic Anatomy.") THE ALIMENTARY CANAL 
353 
serous connective tissue which is covered by mesothelium. The serous 
coat supports the larger blood and lymphatic vessels and nerve trunks 
which supply the organ. 
The Muscular Coat.-The muscular coat of the stomach consists in 
general of two layers of smooth muscle fibers-a thin outer longitudinal, 
and a much thicker inner circular and oblique layer. The regular cir- 
cular arrangement of these fibers is much distorted by the peculiar 
dilatation and partial rotation to which the stomach is subjected in the 
course of its development, and as a result of this change obliquely placed 
fibers form a considerable portion of the muscular coat. 
The oblique fibers are most numerous toward the cardiac end of the 
stomach, where they form a third muscular layer, the innermost portion 
of the muscular coat. The longitudinal fibers are most abundant toward 
the cardiac and pyloric orifices and along the lesser curvature; in the 
fundus and mid-region of the stomach they form only a very thin layer. 
The circular fibers form the thickest of the three muscular layers and 
are nearly equally distributed in all portions, except that at the cardiac 
and pyloric orifices they become much thickened to form the sphincter 
muscles. The pyloric sphincter is especially well developed. 
The layers of the muscular coat of the stomach are united by thin 
septa of connective tissue; that between the longitudinal and circular 
layers contains the myenteric nerve plexus and the larger blood-vessels 
which supply this coat. 
The Submucosa.-The submucosa consists of loose areolar tissue 
which supports the blood-vessels, lymphatics, and the submucous nerve 
plexus, all of which distribute their branches to the mucous membrane. 
In no portion of the stomach does this coat contain glands. 
The Mucous Coat.-The muscularis mucosae forms a thin but com- 
plete layer from one end of the stomach to the other, and marks the 
outer boundary of the mucous membrane. It usually consists of two 
thin layers, an inner circular and an outer longitudinal. Here and 
there muscle fibers extend from the muscularis mucosae into the corium 
between the gastric glands. 
The surface of the mucosa is clothed with tall columnar epithelium, 
and the whole membrane is thrown into wavy folds, an arrangement 
which is permitted by the very loose meshes of the submucous areolar 
coat. The corium of the mucosa is closely packed with tubular secreting 
glands, which open on the surface by wide-mouthed, crypt-like ducts 
or foveolae, and are embedded in a fine fibroreticular tissue containing 
many lymphocytes. 354 
THE DIGESTIVE SYSTEM 
The character of the gastric glands differs somewhat in various 
portions of the stomach. The three varieties, according to their dis- 
tribution, are known 
as the fundus glands, 
the pyloric glands, and 
the cardiac glands. 
The Fundus 
Glands {Peptic 
Glands').-These are 
somewhat branched 
tubular glands which 
possess short ducts, 
the crypts or foveola, 
and relatively long se- 
creting portions, sev- 
eral of which open, by 
means of short con- 
stricted portions, the 
necks of the glands, 
into the bottom of 
each crypt. 
The excretory 
ducts or crypts are 
lined with tall colum- 
nar cells which possess 
a remarkably clear cy- 
toplasm distally, and 
whose nuclei lie at the 
proximal or attached 
ends of the cells. This 
epithelium rests upon 
a distinct basement 
membrane of reticular 
tissue (Mall) ; it is 
also continued over that portion of the corium which occupies the inter- 
vals between adjacent ducts, where it forms the true lining epithelium of 
the stomach. Its cells secrete a clear muco-albuminous fluid. 
Between the distal ends of the cells terminal bars occur; they possess 
also indistinct cuticular borders. 
The secreting portion, or fundus, of the gland is five to eight times 
de d 
Fig. 330.-The Mucosa of the Fundus Region of 
the Dog's Stomach. 
a, gastric crypts; 6, neck region, and c, fundus por- 
tions of the gastric glands, the parietal cells being 
much more abundant in the former; d, muscularis mu- 
cosae; e, submucosa. Hematein and eosin. Photo. 
X 80. THE ALIMENTARY CANAL 
355 
as long as the duct or foveola, a fact which sharply differentiates the 
fundic from the pyloric glands of the stomach. The lumen of the se- 
creting portion is so narrow as to be 
scarcely perceptible except by the use 
of special stains (precipitation tech- 
nics) or high magnification. 
The fundus of the gland is lined 
by two distinct cell types, the chief 
and the parietal cells. The chief cells 
are relatively more abundant at the 
deeper portion of the fundus, where 
they form a complete lining for the 
tubule. In this portion the parietal 
cells are crowded away from the lu- 
men and consequently produce a 
bulging of the basement membrane. 
Toward the neck of the tubule the 
parietal cells are more abundant and 
draw progressively nearer and nearer 
the lumen until, in the neck of the 
gland, they possess a considerable free 
surface which encroaches upon the 
glandular lumen. 
The Chief Cells (Central, Peptic, 
or Adelomorphous Cells}.-The chief 
cells possess a cuboidal or pyramidal 
shape and a granular cytoplasm. The 
spheroidal nucleus is situated in the 
proximal or attached end, while the 
distal end of the cell is its most gran- 
ular portion. The breadth of the 
granular zone is dependent upon the 
state of secretory activity, the coarse 
zymogen granules accumulating dur- 
ing periods of rest and disappearing 
by secretion during activity. Thus 
the granular distal zone increases in 
breadth during rest and decreases during activity. The whole cell also, be- 
comes shrunken after prolonged secretion, but during rest it becomes so 
swollen that with its neighbors it nearly occludes the lumen of the tubule. 
Fig. 331.-Longitudinal Section 
of the Fundus Glands of Man. 
b, parietal cells; g, fundus of the 
gland; h, chief cells; k, body, and I, 
neck of the gland; m, muscularis 
mucosae; Mg, gastric crypts. X 85. 
(After Kolliker.) 356 
THE DIGESTIVE SYSTEM 
The coarse zymogen granules within the cell appear to be suspended 
within the meshes of a finely granular cytoplasmic reticulum. At the 
base or proximal end of the cell coarse elongated granules or filaments 
of prozymogen (ergastoplasm of Cade) may be demonstrated by the 
stronger basic or nuclear dyes, e.g., iron hematein, toluidin blue. These 
peculiar prozymogen granules are so disposed, parallel to the axis of 
the cell, as to give this portion of the cytoplasm a somewhat striated 
or rodded appearance when carefully examined after suitable staining. 
The chief cells are believed 
to elaborate the pepsin 
(pepsinogen) of the gas- 
tric juice. 
The Parietal Cells 
(Oxyntic or Delomorphous 
Cells').-The parietal cells 
are large ovoid or pyra- 
midal bodies which are 
frequently binucleated, 
and whose cytoplasm pos- 
sesses a strong affinity for 
acid dyes (eosin, Congo 
red, etc.). Their spherical 
nuclei contain much 
chromatin and are cen- 
trally situated; their cyto- 
plasm is homogeneous or 
finely granular. 
The shape of the oxyntic cells varies with their location. At the 
fundus of the gland where they are separated from the lumen by the 
chief cells they are ovoid or occasionally triangular in transection, the 
broad base of their triangular section being applied to the basement 
membrane, the wide-angled tip wedged between the bases of the adjacent 
chief cells. In the mid-portion of the secreting tubule the parietal 
cells approach nearer the lumen, and being inserted between the chief 
cells, they acquire an increased height and a pyramidal form. At the 
neck of the gland, where they present to the glandular lumen a broad 
surface, the parietal cells acquire a cuboidal shape. As the gland opens 
into its foveola the parietal cells, except for an occasional dislodged or 
misplaced individual, abruptly cease. 
In those portions of the tubule where the parietal cells are more or 
Fig. 332.-Transections of Three Glands of 
the Fundus Region of the Human Stomach. 
The section is taken from the portion of the 
glands near the muscularis mucosae. The parietal 
cells are red; the central cells, black. Hematein 
and eosin. X 800. THE ALIMENTARY CANAL 
357 
less removed from the lumen they possess an extensive system of peri- 
cellular secretory canals which invest the cell in a basket-like manner 
and convey its secretion to the glandular lumen, where it mixes with the 
secretion of the chief cells. The parietal cells 
also possess a system of intracellular canaliculi. 
The parietal cells are commonly believed 
to secrete the HC1 of the gastric juice. But 
Harvey and Bensley (Biol. Bull., 23, 4, 1912) 
claim to have shown 
that free HC1 is not 
present in these cells; 
their content is said to 
be chemically neutral 
or alkaline, and to con- 
sist largely of chlorids. 
The results of experi- 
ments with rabbits and 
various other verte- 
brates indicate that 
chlorin is secreted by 
the parietal cells in the 
form of a chlorid of an 
organic base, and that 
the HC1 is only set free 
after the secretion is 
poured out of the gland 
into the foveola. Ham- 
mett (Anat. Rec., 9, 1, 
1915), however, presents 
further evidence tend- 
ing to show the pres- 
ence of acid in the pari- 
etal cells. 
Pyloric Glands.- 
These are branched con- 
voluted tubular glands with relatively long crypt-like ducts, into the 
bottom of which several secreting tubules open. According to Piersol, 
they occupy the pyloric fifth of the stomach. 
The typical convolution is found only in the fundus of the gland, 
the course of the ducts being nearly straight. The branching, on the 
Fig. 334.-Portion of 
Gastric Gland 
from the Fundus 
Region of the 
Stomach. 
L, lumen, ending in 
intracellular secretory 
canaliculi in the parie- 
tal cells (P.c.); C.c., 
chief cells. Prepared 
by the Golgi chromate 
of silver impregnation 
method; highly magni- 
fied. (After Zimmer- 
mann.) 
Fig. 333. - A Pyloric 
Gland, from Section 
of the Dog's Stomach. 
(Ebstein.) 
m, mouth; n, neck; tr, a 
deep portion of a tubule 
cut transversely. (From 
"Quaih's Anatomy.") 358 
THE DIGESTIVE SYSTEM 
other hand, is chiefly confined to the ducts, which occupy the superficial 
two-thirds to three-fourths of the entire depth of the mucous membrane. 
In the pyloric mucosa, therefore, three zones may be distinguished: a 
superficial, middle, and deep. 
The superficial zone is narrow and contains the wide-mouthed crypts 
or foveolae which are lined by tall columnar 
cells similar to those of the fundus crypts. 
The middle zone contains the narrowed 
portion of the ducts and is the broadest of 
the three zones. Several of the narrow ducts 
open into each foveola and further branch- 
ing of the secreting tubules occurs to a lim- 
ited extent. The epithelium of the ducts is 
of the low columnar variety, whose deeply 
stained basal nuclei are spheroidal or ovoid, 
and are progressively flattened as the se- 
creting portion is approached. The super- 
ficial cytoplasm of these cells stains readily 
with muchematein and often has a coarsely 
granular or reticular appearance. 
The deepest zone contains the convoluted 
secreting portions and is sharply marked off 
from the adjacent ducts, since in a transec- 
tion of the stomach wall its tubules, owing 
to their convolution, are nearly all cut 
across, while the ducts are in longitudinal 
section; the clear tall columnar epithelium 
and broad lumen of the fundus also, contrast 
strongly with the low finely granular epithelium and narrow lumen 
of the duct. It is this narrow zone of peculiar convoluted tubules, 
lying just within the muscularis mucosae, by which the pyloric mucous 
membrane is most readily distinguished from all other regions of the 
alimentary canal. 
The tall columnar cells of the fundus possess a remarkably clear 
cytoplasm which reacts distinctly, though feebly, to the specific stains 
for mucus. The nuclei are flattened against the base of the cell and 
thus contrast sharply with the spheroidal nuclei of the ducts and crypts. 
During secretion the cells become shunken and their nuclei approach 
the center of the cell and become more nearly ovoid or spheroidal in 
shape. 
Fig. 335.-Secretory Cap- 
illaries of the Fundus 
Glands of the Dog's 
Stomach. 
Golgi stain. (After Muller, 
from Oppel.) THE ALIMENTARY CANAL 
359 
There is no sharp line of demarcation between the fundus and pyloric 
regions, the glands offering a gradual transition from the one type to 
the other. Thus, in the human stomach, there is a broad transition 
Fig. 336.-The Mucosa of the Pyloric Region of the Human Stomach. 
a, b, and c, respectively the crypt, neck, and fundus zones of the glands; d, muscu- 
laris mucosae; e, submucosa. Hematein and eosin. Photo. X 151. 
zone which contains both fundus and pyloric glands. Indeed, in many 
individuals, parietal cells may be distributed throughout almost the 
entire gastric mucosa. 360 
THE DIGESTIVE SYSTEM 
The Cardiac Glands.-A narrow region, about 5 millimeters in 
width, at the cardiac orifice of the human stomach contains glands 
whose form corresponds with that of the fundus glands, though they 
are slightly more branched and are rather more tortuous, but which 
are lined by relatively clear columnar epithelium. Only occasionally 
are the chief and the parietal cells, which are characteristic of the fundus 
glands, interspersed among the clear secreting cells of these tubules. 
The cardiac glands, therefore, appear to offer a transition from the 
esophageal to the more numerous fundus glands of the stomach. In 
certain mammals, e.g., the pig and the Marsupialia, the cardiac glands 
occupy a much larger area. 
The Corium.-The corium of the mucosa consists of a delicate 
fibroreticular connective tissue which supports the blood and lymphatic 
vessels and is more or less infiltrated with lymphocytes. Hence in many 
portions it possesses the character of diffuse lymphoid tissue, though this 
tissue is characteristic of the interglandular rather than the interfoveolar 
portion of the tunica propria. In the latter situation, in sharp contrast 
to the intestinal villi with which the student may confound this region, 
the corium is decidedly fibrous and contains relatively few lymph 
corpuscles. 
In the deeper part of the mucosa occasional small lymph nodules, 
homologues of the solitary follicles of the intestine, are seen. These 
nodules glands') lie just within the muscularis mucosae 
and do not, as a rule, penetrate into the submucosa. In the cardiac 
region they may lie very near the free surface .of the mucosa. 
Blood Supply.-The large blood-vessels, derived from the branches 
of the celiac axis, enter through the subserous connective tissue of the 
omentum and form arches at the greater and lesser curvatures of the 
stomach. 
From these arches, arteries lying in the subserous connective tissue 
are distributed to the ventral and dorsal surfaces of the gastric wall. 
These vessels supply branches which penetrate the muscular coat, giving 
off, on the way, arterioles to the intramuscular septum, and secondarily 
to the intramuscular capillary plexus, and spread out in the areolar 
tissue of the submucosa in which they form an extensive arterial plexus. 
Branches from this submucous plexus enter the mucous membrane and 
form a dense capillary plexus whose elongated meshes inclose the se- 
creting glands. 
Near the surface of the mucosa these vessels enter a plexus of small 
venules which, by union, form larger branches and convey the blood THE ALIMENTARY CANAL 
361 
outward to a venous plexus at the outer border of the mucosa, whence 
it returns to the larger veins of the submucosa. These veins, after 
Fig. 337.-Blood-vessels and Lymphatics of Stomach. (F. Mall.) 
M, mucosa; Mi, muscularis mucosae; S, submucosa; I and 0, circular and longi- 
tudinal muscles; A, blood-vessels, Ar., artery, V, vein; B, microscopic anatomy; 
C, lymphatics. (From Szymonowicz-MacCallum, "Histology and Microscopic 
Anatomy.") 
receiving venules from the muscular coat, pass outward to the subserous 
connective tissue in company with the entering arteries and finally 
reach the gastric, splenic, and portal veins. 362 
THE DIGESTIVE SYSTEM 
The Lymphatics.-The lymphatics arise hy vascular loops or dilated 
extremities between the secreting glands of the mucosa. At the outer 
border of the mucous membrane they form a delicate anastomosing 
plexus from which branches penetrate the muscularis mucosae and 
enter a broad submucous plexus whose efferent vessels pierce the mus- 
cular coat on their way to lymph 
nodes which are situated in the 
folds of the omentum at either 
curvature of the stomach. 
The Nerves.-The nerves of 
the stomach are derived from sym- 
pathetic trunks, the splanchnic 
nerves, and from the vagi. The 
vagi are believed to be chiefly ex- 
citatory, the splanchnics inhibitory 
in function. The nerves enter 
with the blood-vessels and pierce 
the muscular coat. They connect 
with two plexuses of anastomosing 
nerve trunks: the myenteric 
Auerbach's), in the intramuscular 
fibrous septum, which contains 
ganglionic enlargements at many 
of its intersections and distributes 
its fibrils to the smooth muscle; 
the submucous (Meissner's), lying 
in the deeper part of the submucosa, 
which also contains small ganglia 
at the intersections of its anastomosing branches. This latter plexus is 
much finer and contains smaller neurons than that of the muscular coat. 
Pericellular capsules are apparently lacking in these plexuses (Muller, 
Kuntz). The submucous plexus distributes its fibrils to the mucosa, 
where they terminate in and about the walls of the blood and lymphatic 
vessels, and to the epithelium of the secreting glands, where they end 
as varicose fibrils upon the cells. Kuntz (Jour. Comp. Neur., 23, 3, 
1913) suggests that the ganglia of the myenteric and submucous plexus 
include both motor and sensory neurons, and that the fibers which 
terminate on cells of the digestive epithelium are the dendrons of sen- 
sory cells. • 
Fig. 338.-Termination of Sympa- 
thetic Nerve Fibers. 
A, on smooth muscle cell; B, on cells 
of the digestive epithelium, ileum of cat; 
C, on cells of the digestive epithelium, 
stomach of cat; Z), on parietal cell, stom- 
ach of cat. (Kuntz, Jour. Comp. Neur., 
23, 3, 1913.) THE ALIMENTARY CANAL 
363 
Fig. 339.-Schematic Diagram Illustrating Probable Relationship of Sym- 
pathetic Neurons in Myenteric and Submucous Plexuses. 
Motor neurons, stippled; sensory neurons, solid. 1, tunica propria; 2, muscularis 
mucosae; 3, submucosa; 4, muscularis; M, myenteric plexus; S, submucous plexus; 
a, axons; d, dendrons. (Kuntz, Jour. Comp. Neur., 23, 3, 1913.) 
Small Intestine 
The small intestine constitutes the longest portion of the digestive 
tube. It connects the pylorus with the colon. It measures about 7% 
meters (24 feet) in length. It may be divided into three segments: (1) 
the duodenum, about 11 inches in length; (2) the jejunum, including 
the upper two-fifth, about 9 feet, and (3) the ileum, including the 
lower three-fifth, about 14 feet, of the remainder. The duodenum 
lacks a mesentery, it is only partially enveloped by a serosa, and it has 
the greater diameter, about 47 millimeters (2 inches). Below the 
duodenum the caliber of the small intestine gradually decreases until 364 
THE DIGESTIVE SYSTEM 
a diameter of 27 millimeters (a little over 1 inch) is attained, at the 
end of the ileum. The three portions differ also in the shape and 
number of villi, and in other histologic details which will be described 
below. The inner surface is modeled by a succession of tall circular 
folds, the valvules conni- 
ventes or plicae circulates, 
involving the submucous 
layer. These plicae be- 
come less closely-spaced 
throughout the lower 
portion of the ileum and 
generally disappear 
toward its end. They 
serve to increase the ab- 
sorbent surface of the 
intestinal mucosa, and 
unlike the villi, which 
are scattered over their 
surface, they are not sub- 
ject to variations depen- 
dent upon altering de- 
grees of distention. 
The structure of the 
serous coat of the small 
intestine is identical with 
that of the stomach. The 
muscular coat consists of 
an inner and an outer 
layer of unstriped muscle 
fibers which are sep- 
arated by a thin connec- 
tive tissue septum. The inner circular layer is much thicker than the 
outer longitudinal. 
The regular disposition of the muscle fibers as an outer longitudinal 
and an inner circular layer serves as a guide to the recognition of the 
direction in which a given microscopical section has been cut. In transec- 
tions of the intestine the muscle fibers of the outer layer of the mus- 
cular coat are transversely cut; in longitudinal sections of the organ 
the same fibers are seen in longitudinal section. 
The Submucosa.-The submucosa of areolar connective tissue is 
Fig. 340.-Section through the Commencement 
of the Duodenum at the Pylorus. (Klein.) 
v, villi; &, apex of a lymphoid nodule; c, crypts of 
Lieberkuhn; m, muscularis mucosae; s, secreting 
tubes of Brunner's glands; d, ducts of pyloric glands 
of stomach; g, tubes of these glands cut across in 
mucous membrane; t, deep-lying tubes situated in 
submucous tissue, and corresponding with Brun- 
ner's glands of the intestine. (From Quain's "Anat- 
omy.") THE ALIMENTARY CANAL 
365 
identical with that of the stomach except in the duodenum where it 
is penetrated by the branched tubulo-acinar mucous duodenal (Brun- 
Villus- 
Gland of Lieberkiihn- 
ifuscularis mucosae 
Bud of Brunner's 
gland "1 
Brunner's gland- 
Blood-vessel- 
Circular muscle layer 
Ganglion cells of, 
Auerbach' s plexus 
Longitudinal muscle 
layer' 
Fig. 341.-From a Longitudinal Section through the Duodenum oe a Cat. 
X 34. 
(From Szymonowicz-MacCallum, "Histology and Microscopic Anatomy.") 
nep's) glands. The muscularis mucosae forms a complete muscular 
layer and, except in the duodenum, is not penetrated by the glands. 366 
THE DIGESTIVE SYSTEM 
The Mucous Membrane.-The mucous membrane of the small in- 
testine is divisible into an inner and an outer zone. In the inner zone 
the corium forms finger-like projections, the intestinal villi, which are 
covered with tall columnar epithelium containing many mucus-secreting 
goblet cells. The villi are characteristic of the small intestine, in which 
alone they occur. They serve to increase the area of the lining epi- 
thelium of the intestine, whose chief function is that of absorption. 
The outer zone of the mucous membrane includes all that portion 
between the muscularis mucosae and the bases of the intestinal villi. It 
is almost completely occupied by the simple tubular intestinal glands 
(or crypts of Lieberkuhn). 
The Corium.-The corium of the small intestine, in which the 
intestinal glands are embedded, and which forms the substance of the 
intestinal villi, consists of a fibroreticular stroma which is so infiltrated 
with lymphocytes as to form a diffuse lymphoid tissue. In many parts 
of the mucosa the lymphoid tissue forms isolated nodules, the solitary 
nodules, or aggregations of such nodules, which are known as the agmi- 
nate nodules or Peyer s patches. Solitary nodules occur throughout 
both the large and the small intestine. Peyer's patches are found only 
in the small intestine and are most numerous in the upper portion of the 
ileum. 
Structure of the Solitary Nodules.-The structure of the solitary 
nodules does not differ from that of other lymph nodules. They vary 
much in size, most of them being of sufficient diameter to occupy 
the entire thickness of the mucous membrane. They push aside the 
adjacent intestinal glands by which they are encircled, and few or no 
villi project from their free surface. The adjacent villi are so inclined 
that their free ends often hide all but the projecting apex of the ovoid 
solitary nodule. 
The largest of the solitary nodules not only produce a distinct ele- 
vation of the surface of the mucous membrane but may even break 
through the muscularis mucosae and project into the connective tissue 
of the submucosa. The solitary nodules, like other lymph nodules, 
usually contain a germinal center. 
Agminate Nodules {Aggregate Nodules; Peyer's Patches}.-Agmin- 
ate nodules are formed by accumulations of lymph nodules, usually 
occurring in that portion of the intestinal mucosa which is farthest 
removed from the attachment of the mesentery. They frequently 
form oval areas of macroscopic size. They usually number about thirty, 
though there may be fewer, and frequently many more. The number THE ALIMENTARY CANAL 
367 
of their constituent nodules is variable, frequently they contain as many 
as fifteen or twenty. Each of these nodules is usually invested by a thin 
fibrous capsule, though frequently they are confluent with one another. 
Fig. 342.-The Central Portion of a Peyer's Patch in the Ileum of a Dog's 
Intestine. 
a, villi; b, glands; c, lymph nodules, an agminated follicle; d, connective tissue of 
the submucosa; e, a portion of the muscular coat. Hematein and eosin. Photo. 
X 35. 
The long axes of the ovoid nodules exceed the average thickness of 
the mucous membrane so that the patch forms a superficial elevation of 
the mucosa and its deeper surface penetrates the muscularis mucosae 
and enters the submucous coat. Hence occasional fragments of the mus- 
cularis mucosae often occur between the bases of the constituent nodules. 368 
THE DIGESTIVE SYSTEM 
Villi are found upon the free surface of the agminate nodules only 
in the intervals between the constituent units. The largest of the 
nodules lie near the center of the patch, the smallest are found at its 
periphery. The agminate nodules become the chief seats of infection in 
typhoid fever. 
Above the level of the ileum the largest collections of lymphoid 
tissue in the intestinal mucosa occur in the upper part of the duo- 
denum, where there are extensive infiltrations of dense lymphoid tissue, 
many of which contain typical nodules with germinal centers. These 
masses of lymphoid 
tissue are pene- 
trated by the ducts 
of the duodenal 
glands, whose se- 
creting portions 
form a bed upon 
which the lymphoid 
tissue rests. The 
duodenal patches 
differ slightly from 
those in the ileum 
Jn that they form a 
more confluent mass with relatively fewer nodules, possess a more diffuse 
character, are more deeply situated, and are therefore covered by the 
corium of the mucosa which contains both intestinal glands and villi. 
The Intestinal Villi.-The intestinal villi are long finger- 
like projections (from 0.5 to 1 millimeter in length) which vary 
much in form in different mammals and in different portions of the 
canal in the same individual. They are perhaps most highly developed 
in the dog, where they form long projections with expanded or clubbed 
extremities and a constricted base or neck. 
In man the villi are of a more conical shape, the base being, as a 
rule, slightly broader than the free extremity. In the duodenum of 
man they possess a foliate shape, in the jejunum they are conical or 
somewhat clavate, in the ileum they are generally filiform. The villi 
are most abundant in the duodenum and the jejunum (24 to 40 per 
square millimeter) and less numerous in the ileum (15 to 30 per square 
millimeter) (Piersol). According to Johnson (Amer. Jour. Anat., 14, 
2, 1913) they are more or less variable structures, their shape and 
height changing with the degree of distention of the tube. 
*- Villus 
- Lacteal 
-Goblet cell 
Intestinal gland 
-Muscularis mucosa 
Fig. 343.-Diagram of Small Intestine, Showing the 
Topographical Relationship of the Intestinal 
Glands (Crypts of Lieberkuhn) to the Villi. THE ALIMENTARY CANAL 
369 
The villus is formed by a projection of the corium which is cov- 
ered by the lining epithelium of the intestine. The axis of the villus 
contains a large lymphatic capillary or lacteal, which begins in the 
inner third and proceeds outward through the corium to enter a lym- 
phatic plexus lying just within the muscularis mucosse. An occasional 
villus may contain several lacteals. In the base or outer portion of 
the villus the lacteal is surrounded by small groups of smooth muscle 
fibers which are disposed in an axial 
direction, and which are ontogenet- 
ically derived from' the muscularis mu- 
cosae. Many of these fibers turn out- 
ward and are attached to the basement 
membrane beneath the epithelium at 
the sides and tip of the villus. By 
their rhythmic contraction the muscle 
fibers of the villus aid in expelling the 
contents of the lacteal. 
The body of the villus consists of 
diffuse lymphoid tissue having a reticu- 
lar stroma in which the lacteal, the 
muscle fibers, and the blood-vessels are 
embedded. 
Each villus is supplied with one or 
more arterioles which enter at the base 
and pass to the inner third, where they 
form an abundant capillary plexus 
about the blind extremity of the lacteal and in the apex of the villus. 
Minute venules collect the blood from this plexus, and following the 
course of the lacteal, make their exit from the base of the villus to join 
the venous plexus in the deeper part of the mucosa (Fig. 347). 
The Lining Epithelium.-The lining epithelium of the intestine, 
which also clothes the villi, rests upon a distinct reticular basement 
membrane and consists of columnar and goblet cells. The large num- 
ber and peculiar appearance of the goblet cells is highly characteristic 
of this tissue. 
The columnar cells are peculiar in that they possess a characteristic 
striated cuticular border when examined under moderately high magni- 
fication. They possess a finely reticulated cytoplasm and an ovoid 
nucleus which is situated at the proximal end or base of the cell. Fre- 
quently the cytoplasm contains droplets of fat which are in process 
Fig. 344.-Longitudinal Section 
of Villus. 
G, goblet cell; L, lacteal; s, stri- 
ated border of columnar cell. 370 
THE DIGESTIVE SYSTEM 
of absorption. Occasional leukocytes find their way into the epithelial 
coat, whence they may penetrate the intercellular substance and enter 
the intestinal canal. 
The Intestinal Glands {Glands of Lieberkuhn; Mucous Crypts'). 
-The intestinal glands occur throughout the entire extent of the small 
and large intestines, including the appendix. They are simple tubules 
Fig. 345.-Several Villi from the Small Intestine of the Dog, in Longitu- 
dinal Section. 
a, villi; b, crypts of Lieberkuhn. Hematein and eosin. Photo. X 185 
which extend the whole depth of the mucous membrane and in the 
small intestine open upon the free surface between the bases of the 
villi. Hence the lining epithelium of the glands becomes continuous 
with that which clothes the villi. The glands are imbedded in the 
diffuse lymphoid tissue of the corium; they rarely branch. They con- 
sist of a lining epithelium and a basement membrane. 
The epithelium of the glands contains three types of cells: (1) 
columnar cells; (2) goblet cells; and (3) the granule cells of Paneth. 
The columnar and goblet cells resemble those which clothe the villi. 
The columnar cells which line the neck of the glands, however, possess THE ALIMENTARY CANAL 
371 
only a very indistinct cuticular border and such border is entirely 
lacking in the fundus cells of the glands. The epithelium of the glands 
appears to take no part in the process of absorption and therefore con- 
tains no fat globules. It secretes a mucous fluid. 
At the neck of the gland the epithelium frequently contains mitotic 
figures which have been demonstrated in man (Schaffer, 1897) as well 
as in the lower mammals (Bizzozero, 1887). Little or no mitosis has 
been demonstrated in the fundus of the gland or upon the free surface 
of the villi. On these facts the so-called wander theory of Bizzozero 
is founded. According to this theory there exist in the neck of the 
glands certain indifferent cells which are capable of reproduction by 
mitosis and whose daughter-cells move toward the free surface, being 
at the same time differentiated into either the goblet or the columnar 
cells of the villi. 
Bizzozero originally considered that the granule cells of Paneth at 
the fundus of the glands were intermediate phases in the formation 
of goblet cells, but as there is little or no mitosis in the region where 
these peculiar cells occur and as the granule cells are never displaced 
toward the surface, it seems more probable that, as also in the gastric 
glands, the indifferent genetic cells of the neck of the tubule develop 
on the one hand the superficial goblet and columnar cells which clothe 
the villi, and on the other hand, the true secreting cells in the fundus 
of the intestinal glands. 
The granule cells of Paneth (Arch. f. mikr. Anat., 1888) are con- 
fined to the extreme tip or blind extremity of the fundus of the glands. 
They are pyramidal or low columnar cells whose spheroidal nuclei are 
situated close to the basement membrane. Their cytoplasm presents 
a delicate reticulum which is filled with coarse granules which in some 
cells are of a basophil nature (Klein, Amer. Jour. Anat., 1902). In 
others they contain still coarser granules which are strongly eosinophil. 
The exact function of these peculiar cells is unknown, but that they are 
true secreting cells seems highly probable. 
Still other types of granular cells of unknown significance have 
recently been described by Kull (Arch. mikr. Anat., 81, 3, 1913) in the 
fundus of the intestinal glands, and among the epithelial cells clothing 
the villi: (1) 'acidophil cells,' with the basal oxyphilic granules finer 
than those of the Paneth cells; and (2) 'chromaffin cells' with yellowish 
basal granules, coarser than those of the acidophil cells and finer than 
those of the cells of Paneth. These three types of cells are present in 
man and certain vertebrates; they are said to have no genetic relation- 372 
THE DIGESTIVE SYSTEM 
ship. The 'chromaffin cells' of the intestinal epithelium were first 
recognized by Schmidt, who designated them as 'yellow cells' (Arch, 
mikr. Anat., Bd. 66, 1905). Ciacco (Arch. Anat. e Embri., 6, 3, 1907) 
reports similar cells also in the duodenal (Brunner's) glands. Champy 
(Compt. rend. Soc. Biol., T. 66, 1909) 
has described also mitochondria in the 
cells of the intestinal glands. 
The intestinal glands are confined to 
the narrow deeper zone of the intestinal 
mucous membrane. Their lumen, after 
fixation, contains only the coarsely reticu- 
lar mucous secretion. 
The student should be warned to dis- 
tinguish carefully between the transverse 
sections of the tubular glands which are 
confined to the deep zone of the mucous 
membrane and the similar sections of the 
villi which are only found in the super- 
ficial zone and whose epithelial coat, in- 
stead of inclosing a mere reticular mass 
of mucous secretion invests an organized 
body of diffuse lymphoid tissue. 
The Duodenal (Brunner's) Glands. 
-The duodenal glands of Brunner are 
tubulo-acinar glands which furnish a 
muco-albuminous secretion. They appear 
to represent the continuation into the in- 
testine of the pyloric glands of the stom- 
ach, and they occur in decreasing propor- 
tion throughout the entire length of the 
duodenum; around the duodenal papillae, 
however, they become locally more numer- 
ous. They are sharply distinguished from the pyloric glands by their 
larger size. Moreover, the secreting portion of the duodenal glands is 
only found in the submucosa and the deeper part of the mucous mem- 
brane, where the secreting acini form very numerous groups, the tu- 
bules of each of which are connected with the terminal subdivision of a 
duct. 
The ducts of the duodenal glands open on the free surface between 
the villi by means of crypt-like tubules which are lined by tall columnar 
Fig. 346. - Reconstruction 
Model of a Brunner's 
Gland, from the Human 
Duodenum. 
Three partially blended ducts 
pass into the submucosa and end 
in expanded alveoli. X 344. 
(After Maziarski.) THE ALIMENTARY CANAL 
373 
epithelium and can only with 
difficulty be distinguished from 
the adjacent intestinal glands. 
In the deeper part of the mu- 
cous membrane the ducts 
branch and pursue a somewhat 
tortuous course to the fundus 
of the gland, where the ter- 
minal acini of each subdivision 
of a duct are invested with a 
distinct fibrous capsule. 
The secreting epithelium 
of the duodenal glands consists 
of tall columnar cells which 
surround a wide lumen. When 
loaded with secretion the cells 
are swollen and clear, but be- 
come shrunken and granular 
after a period of activity. 
Their cytoplasm reacts to the 
specific stains for mucin only 
when these are applied for a 
considerable time in concen- 
trated solution (Bensley). The 
spheroidal nucleus is situated 
at the proximal or basal end, 
and as the cell fills with secre- 
tion the nucleus becomes pro- 
gressively flattened. 
Blood Supply.-The blood 
supply of the small intestine 
resembles that of the stomach. 
The branches of the mesenteric 
arteries pass around the intes- 
tinal wall in the subserous con- 
nective tissue. From this point 
they penetrate the muscular 
coat to form intramuscular and 
submucous plexuses. From 
the latter a few branches sup- 
Fig. 347.-The Blood-vessels of the 
Small Intestine of a Dog, Drawn after 
an Injected Preparation. 
The arteries are striped, the veins black, 
the capillaries open. A, villi; B, glands; C, 
muscularis mucosa;; D, submucosa; E, cir- 
cular, and F, longitudinal layer of the mus- 
cular coat; a, venule beginning from the cap- 
illaries of the villus, and at b,- from those 
among the glands; c, artery to the villus; d, 
venules in the deeper part of the mucosa; e, 
main arterial trunk to several adjacent villi; 
/, arterial branch to the glandular region. 
Highly magnified. (After Mall, from Oppel.) 374 
THE DIGESTIVE SYSTEM 
ply the adjacent portion of the inner layer of the muscular coat, but most 
of them pass to the mucous membrane, in which a plexus lies just within 
the muscularis mucosae and distributes its branches to the capillaries 
about the intestinal glands and to the intestinal villi. 
The artery of the villus enters at its base, and distributing capillaries 
along its course, forms in the distal part of the villus an abundant 
capillary network from which efferent venules return by a similar course. 
The artery, however, is found near the axis, the venules near the per- 
iphery of the villus. 
Branches from the submucous and mucous arterial plexuses also 
supply capillaries to the duodenal glands in the duodenum as well as to 
the solitary and agminated lymph nodules. About each of the lymph 
nodules they form circular anastomoses, from which radial capillaries 
are distributed within the nodule. 
The veins pursue a course exactly similar to that of the arteries. On 
their way to the mesenteric vessels they form mucous, submucous, intra- 
muscular, and subserous plexuses, and drain into the portal system. 
The portal vein and its main tributaries lack valves. Valves are present 
only in the smaller tributaries, beginning in the tunica muscularis 
throughout the digestive tube and prevailing generally in the mesenteric 
veins. 
Lymphatics.-The lymphatics or lacteals of the small intestine be- 
gin in the distal part of the villi as lymphatic capillaries, each having, 
as a rule, a pouched, blind extremity. During the digestion of fats 
they become distended with a whitish fatty lymph called chyle. At their 
origin the lacteals are frequently branched, or they may even form 
a scanty anastomosis. They finally unite to form a central lacteal in 
the axis of the villus, which empties into a rich plexus about the intes- 
tinal glands, or like the efferent vessels of this plexus, they may pass 
directly to the larger lymphatic vessels of the submucosa. 
From the submucous plexus numerous efferent lymphatic vessels 
penetrate the muscular coat, receiving the lymph from the vessels of 
the intramuscular septum. They empty into the larger lacteal vessels 
of the mesentery which are intimately connected with numerous mesen- 
teric lymph nodes. In the mucosa and submucosa the lacteals form 
sinuses which surround the bases of the solitary and agminated nodules. 
Thus, much of the chyle is permitted to come into relation with the 
parenchyma of these organs before leaving the intestinal mucosa. 
Nerve Supply.-The nerve supply of the intestine is exactly similar 
to that of the stomach. The non-medullated fibers form an intra- THE ALIMENTARY CANAL 
375 
muscular myenteric ganglionic plexus (Auerbach's) for the supply of 
the muscular coat, and a submucous plexus (Meissner's) which sup- 
plies branches to the blood-vessels and to the glands of the mucosa. 
The finer branches in the mucous membrane penetrate to the villi, form- 
ing a delicate plexus of naked fibrils about its blood-vessels and lacteals, 
and upon its epithelium. 
Intestinal Absorption.-The absorption of fat consists essentially 
of three phases: (1) its absorption into the intestinal epithelium; (2) 
Fig. 348.-Intestinal Mucosa of a Frog During the Absorption of Fat. 
a, epithelium; b, tunica propria; c, an ameboid leukocyte. Osmium tetroxid. 
Highly magnified. (After Schafer.) 
its secretion into the lymphoid tissue of the villus; and (3) its entrance 
into the lacteal vessels. In an animal killed during the absorption of 
fat, the intestinal villi, after fixation by solutions of osmium tetroxid, 
contain fat in (a) the epithelium, (b) the lymphoid tissue, and (c) the 
central lacteal. 
In the epithelium, fat is contained in the form of fine droplets 
which are most numerous in the distal or free ends of the cells. They 
are also found in the intercellular spaces. During absorption the epi- 
thelial cells of the villi become much swollen and elongated. As the 
process subsides they return to their former size, and become relatively 
shrunken. When most distended the intracellular fat droplets are the 376 
THE DIGESTIVE SYSTEM 
most abundant; as the cells shrink the intercellular droplets increase 
relatively in number (Drago, Richerche d. lab. ant. norm. d. r. univ. d. 
Roma, 1900). The relative size of the epithelial cells and the abun- 
dance of intra-epithelial fat is apparently dependent upon the activity 
of the processes of absorption. 
As to the manner in which the fat enters the epithelium there is 
some doubt. Schafer (Internat. Monatsch. f. Anat. u. Physiol., 1885) 
suggested that the leukocytes by their ameboid activity inclose the 
emulsified droplets in the 
intestinal lumen and convey 
them into the substance of 
the villi. It seems more 
probable that the fats are 
saponified in the intestinal 
tract, and enter the epithe- 
lium in solution (White- 
head, Amer. Jour. Physiol., 
24, 2, 1909). Here they 
are again synthesized into 
neutral fat by the activity 
of the epithelium (Pfliiger, 
Arch. f. d. ges. Physiol., 
1900). Such a process ac- 
counts for the abundance of 
fat within the distal por- 
tions of the cells. The drop- 
lets are then secreted into 
the intercellular and subja- 
cent tissue spaces. 
The second phase of absorption includes the transference of the 
fat particles to the lacteal. This process appears to depend partially, at 
least, upon the activity of the leukocytes, as suggested by Schafer, the 
particles of fat thus finding their way through the diffuse lymphoid 
tissue. According to Reuter (Anat. Hefte, 1902), fat droplets are 
found in the tissue spaces as well as in the lymph corpuscles of the 
diffuse lymphoid tissue, a fact which would seem to indicate that other 
agencies aid in the transit of the fat from the epithelium to the lacteal 
than are accounted for by the purely mechanical theory of Schafer. 
The third phase includes the secretion of the fat into the lumen of 
the lacteal; this is, at least partially, accomplished by the disintegra- 
Fig. 349.-Apex of an Intestinal Villus of a 
Rabbit Which Had Been Fed with Milk. 
The fat droplets have been blackened by fixa- 
tion with picric acid and osmium tetroxid. The 
figure shows the distribution of fat during certain 
stages of absorption. Alum carmin stain. High- 
ly magnified. (After R. Heidenhain, from 
Oppel.) THE ALIMENTARY- CANAL 
377 
tion of fat-laden leukocytes which, by ameboid motion, have found their 
way into the lacteal. Other fat particles may possibly find their way 
into the lacteal without the aid of the leukocytes-a process which 
may be more or less dependent upon the vital properties of the lining 
endothelium. 
The absorption of the products resulting from the digestion of 
the starches, sugars, albumins, etc., probably proceeds along similar 
lines. The peptones enter the epithelium in solution and are then 
secreted, as albumins and globulins, into the tissue spaces, whence they 
find their way into the lacteals and capillaries. Thus the lacteals 
become widely distended even in the absence of the digestion and 
absorption of fat. 
The Large Intestine 
The large intestine includes the cecum, the colon (ascending, trans- 
verse, and descending portions) and the rectum. It measures about 
180 centimeters (5 feet) in length, and from 3 inches at the beginning 
to about 1% inches towards the end of the colon. It connects the 
ileum with the anus. The vermiform appendix represents an atrophic 
vestige of the terminal portion of the embryonic cecum. 
The three outer coats of this portion of the alimentary canal are 
identical in structure with those of the small intestine, with a single 
exception in the irregular distribution of the outer layer of the mus- 
cular coat, which in the large intestine forms three distinct longitudinal 
bands or thickenings, the tenice (linece) coh. At other parts of the 
circumference of the organ the outer muscular layer is slightly thinner 
than in the small intestine. 
Since the teniae are shorter than the other coats of the colon, they 
produce a succession of sacculations or haustra the boundaries of which 
are marked internally by crescentic folds, involving the entire wall, 
the plicce semilunares. These sacculations furnish conspicuous external 
marks by which the large can be differentiated macroscopically from 
the small intestine. Another differential characteristic of the colon 
is the presence generally of fringes and bags of adipose tissue attached 
along the median border to the serosa, the appendices epiploicce. 
The Mucous Membrane.-The mucous membrane of the large in- 
testine may be best described by comparison with that of the small 
intestine. If the mucosa of the latter organ be considered to contain 
two zones, a superficial layer of villi and a deeper glandular layer, that 
of the large intestine may be said to consist of only the deeper of these 378 
THE DIGESTIVE SYSTEM 
zones. It therefore possesses no villi, and its simple somewhat longer 
(about 0.5 millimeter) tubular glands extend from the free surface 
almost to the muscularis mucosae. Villi are present, however, in the 
embryo, but disappear about the sixth month (Johnson, 1913). 
The Lining Epithelium.-The lining epithelium of the large in- 
testine is of the 
simple columnar 
variety and has 
only an indistinct 
cuticular margin. 
That of the glands 
contains both col- 
umnar and goblet 
cells, the latter 
being far more nu- 
merous than in the 
small intestine. 
The large intestine 
contains no plica 
circulares. 
The Lymphoid 
Tissue.-The lym- 
phoid tissue of the 
large intestine oc- 
curs in the corium 
in diffuse form, and 
as solitary nodules, 
which frequently 
break through the 
muscularis mucosa 
and protrude into 
the submucosa. The 
fundus of such 
glands as may occa- 
sionally be inclosed 
within the lymph nodules are frequently prolonged into the superficial 
portion of the submucosa, where they often possess alveolar dilatations. 
Elsewhere the muscularis mucosa forms a complete membrane which is 
nowhere penetrated by the simple tubular intestinal glands. 
Lymph Nodules.-Lymph nodules are especially abundant in the 
Fig. 350.-Section of Large Intestine of Dog, Show- 
ing Intestinal Glands (Crypts of Lieberkuhn) Cut 
Longitudinally. 
Among the columnar cells lining the tubules are numer- 
ous goblet cells. THE ALIMENTARY CANAL 
379 
rectum and in the vermiform appendix. In the latter the nodules are 
more or less confluent, a condition which is not found elsewhere in 
the large intestine. In the appendix the greater portion of the mucous 
membrane is invaded by lymphoid tissue, and the glands are much 
diminished in both number and size (Fig. 352). 
The Vascular and Nerve Supply.-The vascular and nerve supply 
of the large intestine is 
identical in its arrangement 
with that of the small intes- 
tine. The mucous mem- 
brane contains a capillary 
plexus of blood and lym- 
phatic vessels in the corium 
about the glands. The 
nerves of the large intestine 
include both medullated and 
non-medullated fibers. The 
latter supply its muscular 
coats and blood-vessels. The 
former end in naked vari- 
cose or knobbed fibrils be- 
neath and upon the epithe- 
lium of the glands. The 
usual myenteric (Auer- 
bach's) and submucous 
(Meissner's) plexuses ap- 
pear in the large intestine 
with the same structure and location as elsewhere in the alimentary 
canal. 
In the rectum the lining epithelium is continuous at the anus with 
the stratified squamous epithelium of the skin. In this region also, 
the circular fibers of the inner layer of the muscular coat are much 
thickened to form the internal rectal sphincter. Lymphoid tissue 
abounds in the rectal mucous membrane. The glands are less numerous 
but larger than in the colon proper, and the mucosa is thicker. In the 
lower portion of the rectum the mucosa is thrown into a number of 
longitudinal folds, the rectal columns, at which level the columnar 
epithelium changes to stratified squamous type. 
The Ileocecal (Colic) Valve.-The ileocecal valve, which guards 
the orifice by which the small intestine opens into the large, is formed 
Fig. 351.-Section of Portion of Large Intes- 
tine of Dog, Showing the Intestinal 
Glands (Crypts of Lieberkuhn) Cut 
Across, Their Lining Including Columnar 
and Goblet Cells. 380 
THE DIGESTIVE SYSTEM 
by a reduplication of the mucous membrane, which is strengthened by 
a thickening and overlapping of the circular muscular layers of both 
small and large intestines. The valve itself consists of an upper and 
lower segment enfolding the slit-like orifice; laterally the two folds unite 
to form the frenulum, which encircles the colon and marks the boundary 
between it and the cecum. 
The outer longitudinal muscular layer is continued directly from 
the wall of the ileum to that of the cecum, and therefore pursues a 
relatively shorter course than either the internal muscular layer or the 
mucous membrane. Section of only the outer layer of the muscular coat 
The submucosa contains much adipose tissue, and a number of large lymph nodules, 
each with a dense periphery and a large, fighter, germinal center. Photo. X 10. 
Fig. 352.-Transection of the Vermiform Appendix of Man. 
permits one to straighten the fold of the intestinal wall and thus oblit- 
erate the valve. In other words, the outer muscular layer is not included 
in the valvular reduplication. 
The m uscula r is mucosce is slightly thickened at the margin of the 
valve. At this point also, the villi become shorter and at the margin 
of the cecal surface of the valve they entirely disappear. 
The following tabular statement of the more important characteris- 
tics of the several portions of the alimentary tract may be of assistance to 
the student in the identification of microscopic sections of these organs.  
Esophagus. 
Cardiac 
Stomach. 
Fundus 
Stomach. 
Pyloric 
Stomach. 
Duodenum. 
Ileum and 
Jejunum. 
Large 
Intestine. 
Lining epithelium... . 
Stratified 
squamous. 
Columnar. 
Columnar. 
Columnar. 
Columnar 
and goblet. 
Columnar 
and goblet. 
Columnar and 
many goblet. 
Glandular epithelium. 
Columnar, 
mucous. 
Muco-albumi- 
nous, few 
parietal cells. 
Serous, chief 
and parietal 
cells. 
Columnar, 
muco- 
albuminous. 
Columnar, 
muco- 
albuminous. 
Columnar 
and goblet. 
Columnar 
and very 
many goblet. 
' Type.... 
Glands.., 
Branched 
tubulo-acinar. 
Branched 
tubular. 
Branched 
tubular. 
Convoluted 
tubular. 
Branched 
tubulo-acinar. 
Simple 
tubular. 
Simple 
tubular. 
Situation. 
Mucosa and 
submucosa. 
Mucosa. 
Mucosa. 
Mucosa. 
Mucosa and 
submucosa. 
Mucosa. 
Mucosa. 
Lymphatic nodules. . 
Rare, small. 
Many, 
medium. 
Few, small. 
Few, small. 
Many, large, 
confluent. 
Solitary and 
agminated. 
Many, large, 
solitary. 
Muscular coat 
Striated or 
smooth. 
Smooth. 
Smooth. 
Smooth. 
Smooth. 
Smooth. 
Smooth. 
Villi 
None. 
None. 
None. 
None. 
Present. 
Present. 
None. 
381 382 
THE DIGESTIVE SYSTEM 
THE SALIVARY GLANDS 
General Considerations.-The salivary or oral glands include the 
smaller glands of the oral cavity and three pairs of large compound 
tubulo-acinar glands, the parotid, submaxillary, and sublingual glands. 
The three large pairs are commonly 
designated as the salivary glands 
proper, the smaller as the accessory 
salivary glands. All these are of the 
tubulo-acinar type, but certain ones 
secrete a mucous fluid while others pro- 
duce an albuminous secretion which 
contains no mucus. The former are 
known collectively as the mucous, the 
latter as the serous salivary glands. 
Still other salivary glands secrete a 
fluid which is intermediate in compo- 
sition, and as these glands contain cer- 
tain alveoli which resemble those of 
the mucous, and others which are sim- 
ilar to those of the serous glands, this 
type is known as mixed salivary 
glands. 
The salivary glands may therefore 
be subdivided into: 
I. Mucous glands; glands on the 
anterior surface of the hard and soft 
palate (palatine glands) and the mu- 
cous glands of the margins and root of 
the tongue. 
II. Mixed glands; submaxil- 
lary, sublingual, molar, buccal, labial 
and the anterior lingual glands (of 
Nuhn). 
III. Serous glands; parotid, and von Ebner's glands at the base 
of the tongue. 
The form of the salivary glands will be appreciated by examination 
of the accompanying diagram (Fig. 353) which represents one of the 
smaller glands of this type. The larger ones are constructed in the 
Fig. 353.-Semidiagrammatic Rep- 
resentation of a Small Mu- 
cous Gland from the Oral 
Mucosa of a Rabbit. 
a, mucous alveoli; e, epithelium 
of the oral mucosa; m, mouth of 
the glandular duct. X 70. (After 
Kolliker.) THE SALIVARY GLANDS 
383 
same manner, the larger number of their secreting alveoli or acini arising 
through a more complex duct system. 
The larger ducts of the gland are lined by columnar cells, which, 
Fig. 354.-Corrosion Model of an Interlobular Duct and Its Branches, from 
the Human Submaxillary Gland. 
C, interlobular duct; D, large intralobular duct; E, small intralobular duct; F, inter- 
calary duct. X 12. (After Flint.) 
as they approach their termination, become superposed and thus offer 
a gradual transition to the stratified squamous epithelium upon whose 
surface they open. The epithelium rests upon a basement membrane 384 
THE DIGESTIVE SYSTEM 
which, in the larger ducts, is invested with a fibro-elastic coat containing 
a few longitudinal smooth muscle fibers. 
The ducts divide and subdivide in an arborescent manner, the larger 
branches lying in the connective tissue which invests the lobules into 
which the gland is subdivided, while the smaller branches are found 
within the lobule. The duct system is thus divisible into interlobular 
and intralobular ducts; the latter include generally an excretory por- 
tion continuous with the interlobular duct, a modified 'salivary' se- 
cretory portion, and a constricted intercalary or intermediate portion 
connecting with the acinus. 
In the smaller glands of the mouth the number of subdivisions 
of the duct system is relatively small, but in the larger salivary glands 
the small ducts are practically innumerable. Thus, in the submaxillary 
gland, Flint (Amer. Jour, of Anat., 1902) found that the interlobular 
duct system formed 1,500 terminal branches, each of which entered 
a lobule and was further subdivided into intralobular and intercalary 
ducts before terminating in the secreting acini. The larger glands 
may therefore be said to bear to the smaller ones represented in Fig. 
353, a relation which is comparable with that of a full-grown tree to the 
youngest sapling. 
The larger salivary glands are enveloped by a fibro-elastic capsule 
continuous with the adjacent areolar tissue. From this capsule coarse 
trabecula; enter to divide the gland into groups of lobules, the lobes. 
The lobules are invested by more delicate septa from the interlobar 
trabeculae. The ducts of the interlobar connective tissue may be desig- 
nated interlobar ducts to distinguish them from the interlobular ducts 
between the lobules. These are the excretory ducts of the system; the 
'salivary' intralobular ducts have a secretory function. The glandular 
tissue is known as the parenchyma, the connective tissue as the inter- 
stitial tissue of the gland. 
The smaller intralobular ('salivary') ducts are lined by columnar 
epithelium whose cells contain two zones, one on either side of the 
centrally situated nucleus. The distal zone or free extremity of the 
cell is finely granular, the proximal zone or base presents a character- 
istic striated appearance which is apparently due to a fibrillar structure 
of the cytoplasm in this portion of the cell. The basal fibrillae are 
probably, in part at least, the mitochondria which are present in all 
functionally active cells. The epithelium is easily detached from its 
basement membrane by the artificial contraction of the tissues during 
fixation and hardening. THE SALIVARY GLANDS 
385 
The lumen of the ducts is of considerable diameter and contains 
the reticulated or granular particles of the secretion. The larger ducts 
lie in the connective tissue septa which invest the lobular groups of 
acini. Each of these groups is derived from the ramifications of the 
terminal branch of an interlobular duct which enters the lobule to 
divide into numerous intralobular ducts, and secondarily, through a 
short intermediate or intercalary portion, into the secreting alveoli or 
acini. The intercalary ducts are lined by 
low cuboidal epithelium and are the smallest 
tubules of the gland. As the duct passes 
into the acinus the tubule is increased in 
size, and its secretory epithelium becomes 
taller. The tubular acinus is more or less 
tortuous and possesses a sacculated or alveo- 
lar appearance. 
The epithelium differs accordingly as it 
secretes a mucous or a serous fluid. Thus 
the acini are either mucous or serous secret- 
ing. 
The Serous Acini.-The serous acini 
contain pyramidal epithelial cells of sufficient 
height to almost completely fill the tubule; 
hence the lumen is very narrow. The form 
of the secreting cells is somewhat irregular- 
a fact which apparently depends upon their 
crowded condition within the acinus. The 
nucleus is situated in the central portion or in the proximal end of 
the cell, and is spheroidal in shape. The cytoplasm is finely gran- 
ular, the granules being more prominent in the distal portion of the 
cell. 
The epithelium rests upon a basement membrane within which, 
beneath the bases of the secreting epithelial cells, are certain flattened 
'basket-cells' which here and there send short processes between the 
cells of the secretory epithelium and thus provide cup-like depressions 
which receive the bases of the secreting' cells. The function and origin 
of these 'basket-cells' is not at present known. They are readily recog- 
nized by their deeply stained and flattened nuclei which are contained 
within the thin cytoplasmic cell body. They may be immature acinal 
cells, destined to replace worn-out secretory cells. 
The appearance of the secreting epithelium varies with its ac- 
Fig. 355.-Intercalary 
Ducts and Acini of 
the Human Submaxil- 
lary Gland, Corrosion 
Model. 
F, small intralobular duct, 
G, intercalary duct; H;, acini. 
Highly magnified (After 
Flint.) 386 
THE DIGESTIVE SYSTEM 
tivity. During rest the granular secretion accumulates within the cell, 
until the non-granular zone is reduced to a narrow rim at its basal 
extremity and the nucleus is obscured and pushed somewhat basalward. 
The cell becomes therefore much swollen and the alveolar lumen almost 
obliterated. During activity the zymogen granules are discharged into 
the lumen; the cell shrinks and becomes clearer; the nucleus appears 
more distinct, and the granular zone becomes progressively narrower, 
the basal non-granular 
zone being correspon- 
dingly increased in 
breadth. In this basal 
zone elongated gran- 
ules have been demon- 
strated, which in part 
are to be regarded as 
prozymogen ('basal 
filaments' of Solger), 
in part (revealed by 
special technic) as 
mitochondria. 
The serous cells 
are provided with sys- 
tems of secretory ca- 
naliculi which, begin- 
ning at the glandular 
lumen, invest the cell 
with a network of 
canals which lie in the 
intercellular substance 
and may even send short offshoots or intracellular canaliculi into the 
body of the cell itself. These canaliculi are considered to be character- 
istic of the serous acini and are not found in relation with the cells of 
the mucous acini (Fig. 358). 
The Mucous Acini.-The mucous acini may contain only mucus- 
secreting epithelium, or they may also include certain finely granular 
acidophil cells which resemble the epithelium of the serous glands. The 
former variety of acinus is found in the mucous glands at the base 
of the tongue and in the soft palate; the latter in the sublingual gland, 
in the lingual glands of Nuhn, and in the mucous glands of the lips 
and cheeks. 
Fig. 356.-A Group of Mucous Acini, from the 
Human Submaxillary Gland. 
a-a, interlobular connective tissue. Hematein and 
eosin. Photo. X 510. THE SALIVARY GLANDS 
387 
The serous appearing cells of the latter form of mucous acinus are 
frequently arranged as crescentic groups bordering upon the adjacent 
mucous cells. Such groups are known as the demilunes (of Heidenhain) 
or crescents (of Gianuzzi; Fig. 357). They occur at the periphery 
of the acinus, their base being applied to the membrana propria, their 
inner margin sometimes reaching the glandular lumen, but more fre- 
quently separated therefrom by the overlapping of the adjacent mu- 
Fig. 357.-From the Sublingual Gland of Man. 
a, salivary intralobular duct; e, acinus whose cells contain no mucus; s, mucous 
acini, at s' with a demilune; sz, mucous cells in the duct. X 500. (After Kolli- 
ker.) 
cous cells. The demilunes are frequently found at the blind ex- 
tremity of the secreting acinus, but they may also occur along its 
sides. 
The nature of the demilunes is the subject of considerable discussion. 
Heidenhain (Arch. mikr. Anat., 1869) first advanced the theory that 
the mucous cells were destroyed during secretion, and that the function 
of the demilunes was therefore to replace the disintegrated mucinous 
cells. This theory has been practically abandoned, for no one has yet 
demonstrated active cell division in the demilunes, a process which 
would necessarily be concomitant with the rapid development of mucus 
from demilune cells. 
Heboid (1879) is responsible for the theory, strongly supported by 388 
THE DIGESTIVE SYSTEM 
Stbhr, that the demilunes represent an inactive, the mucous cells, an 
active phase of mucus secretion. The easy demonstration of inter- 
mediate stages in many mucus-secreting glands lends strong support to 
this theory, and in the present state of our knowledge it seems beyond 
doubt that such a process actually occurs in at least some of the mucus- 
secreting glands. 
A third theory, more recently advanced by Solger (Anat. Anz., 1894) 
and stoutly supported by Krause (Arch. mikr. Anat., 1895, 1897, and 
1901) and others, considers the demilunes to be 
true secreting cells which form a serous secre- 
tion and are therefore functionally independent 
of the mucinous cells. This theory receives 
strong confirmation in the fact first observed 
by Cajal (1889) and since that time repeatedly 
demonstrated, that the demilunes, like the true 
serous cells, are provided with a system of in- 
tercellular secretory canaliculi by which they 
are placed in relation with the glandular lumen. 
Moreover Krause was able to demonstrate that 
granules of sodium indigo sulphate were se- 
creted by these cells, as also by the true serous 
cells and the striated epithelium of the intra- 
lobular ducts. 
The mucus-secreting cells examined in the 
fresh state present a clear, highly refractive 
appearance. They closely resemble the typical 
goblet cells, but instead of being isolated among 
the granular serous cells, they may invest the 
entire acinus, or even the whole of a small 
lobule may contain only mucus-secreting cells. 
After the customary preparation by fixation and staining, the mu- 
cous cells present a coarse basophilic reticulum which occupies the distal 
portion of the cell. Coarse granules, with proper fixation and in fresh 
tissue as well, can be demonstrated within the meshes of the reticu- 
lum. These granules are readily colored by the so-called specific mu- 
cus stains (Mayer's muchematein and mucicarmin, safranin, and thio- 
nin). 
In the mucous cells the nucleus is crowded to the base or proximal 
end of the cell and flattened against the basement membrane. It is sur- 
rounded by a small remnant of finely granular cytoplasm, which, after 
Fig. 358.-Mucous Acini 
of the Retrolingual 
Gland of the Rat. 
The ducts and secretory- 
capillaries have been black- 
ened. r, demilunes with 
secretory capillaries; s, 
mucous cells. Golgi meth- 
od. X 500. (After Kolli- 
ker.) Fig. 359.-Diagram of the Arrangement of the Cells in a Mixed Salivary 
Gland. 
a, intralobular duct; a', intercalary duct; b, serum-secreting tubules; c, mucus- 
secreting tubules; d, demilune. (After Krause.) 
Fig. 360.-Diagrams of A, Parotid Gland; B, Submaxillary Gland; C, Sub- 
lingual Gland; and D, Pancreas. (After Sobotta.) 
interlobular duct; a2, intralobular duct; sr, salivary intralobular duct; s, inter- 
calary duct; hm, demilune; ts, serous alveolus; tm, mucous alveolus. 
389 390 
THE DIGESTIVE SYSTEM 
the discharge of the mucus during secretion, is presumably capable of 
reloading the cell with its mucinous content. 
We will now consider the more important peculiarities of each of 
the larger salivary glands. 
The Parotid Gland.-This is the largest of the salivary glands and 
in man, sheep, dog, cat and rabbit is purely a serum-secreting organ. 
However, in sheep, dog and cat it contains also a variable number of 
mucous alveoli during 
the first year; these de- 
generate and entirely 
disappear during the 
second year (Brock and 
Trautmann, Anat. Anz., 
47, 17, 1914). 
It is situated in 
front of the external 
ear, and overlaps in- 
feriorly both faces of 
the upper portion of the 
ramus of the mandible. 
A variable number of 
small accessory lobules, 
including mucus-pro- 
l, lumen of a serous acinus; sch, intercalary duct; ducinff alveoli lie aloim 
sr, intralobular duct; T, secreting acini. Hematoxy- 
lin and eosin. X 280. (After Sobotta.) ie course the mam 
parotid (Stenson's) 
duct. The latter opens into the mouth at the level of the second upper 
molar. The parotid is invested by a dense fibro-elastic sheath, septa from 
which divide the gland into lobes and lobules. The lobes and lobules are 
firmly united by the dense but narrow bands of connective tissue; these 
contain the larger ducts, blood-vessels, lymphatics, and a few small gan- 
glia. 
The secreting acini are relatively long and tortuous; they are fre- 
quently branched or forked. Because of the relatively low height of 
. their serum-secreting cells the acini appear slender and their lumen is 
irregular, indistinct, and very narrow. The 'basket cells' upon which the 
secreting cells rest are highly developed in the parotid and often form 
a complete investment for the acinus. 
The acini of the parotid are all of one type. The only other tubules 
within the lobules of this gland are the intercalary and the intralobular 
Fig. 361.-From a Section of the Human Parotid 
Gland. THE SALIVARY GLANDS 
391 
or salivary ducts. The former are characterized by their very narrow 
caliber and low epithelium. They are slender tubules which open on the 
one side from the acini and on the other into the branched terminals of 
the more spacious salivary ducts. The 'salivary' (secretory) portion of 
the intralobular duct has a somewhat greater diameter also than the 
excretory portion, which is histologically similar to the interlobular 
ducts. In the parotid the salivary ducts are relatively short as com- 
pared with the intermediate ducts, but are readily recognized by their 
striated columnar epithelium, 
which is deeply colored by acid 
dyes (eosin, etc.), and are thus 
sharply distinguished from the 
secreting cells of the acini, 
which stain poorly with these 
dyes. 
The Submaxillary Gland. 
-In man and in most mam- 
mals this organ is a mixed sal- 
ivary gland; that of the bear 
and dog contains the largest, 
that of man and the apes the 
smallest proportion of mucous 
acini (Krause, Arch. mikr. 
Anat., 1897). In man the 
proportion of mucous to serous 
alveoli is about one to five 
(Piersol). The submaxillary 
is situated in the floor of the 
mouth under the posterior por- 
tion of the mandible. The main submaxillary (Wharton's) duct opens 
into the mouth one on either side of the frenulum of the tongue, some- 
times joined by the duct of the sublingual gland. 
The serous acini of the submaxillary are shorter and less typically 
tubular than those of the parotid, and they are lined by taller'secreting 
cells. The diameter of the acinus is therefore slightly greater in this 
gland than in the parotid. Its mucous acini contain a relatively large 
proportion of demilunes. 
The intercalary ducts are considerably shorter than in the parotid, 
while the salivary intralobular ducts are much longer in the submaxil- 
lary. The interlobular connective tissue is not quite so delicate as in 
Fig. 362.-From a Section of the Human 
Submaxillary Gland. 
In the center is a small salivary duct, just 
above which are three mucous acini, the 
uppermost one possessing a demilune. The 
other acini are serous. Hematein and eosin. 
Photo. X 370. 392 
THE DIGESTIVE SYSTEM 
the parotid. It contains many sympathetic ganglia of relatively large 
size. Small lamellar corpuscles of simple construction are occasionally 
found in the interlobular connective tissue (Krause). 
The Sublingual Gland.-This is the smallest of the three pairs of 
large salivary glands. It is not invested by a distinct capsule. It lies 
under the floor of the mouth anteriorly, one on either side of the frenu- 
lum. It is a mixed gland in man, dog, cat and 
rabbit. It differs from the submaxillary, how- 
ever, in that all of its acini are mucous. It be- 
comes 'mixed' by reason of the presence of very 
.many demilunes (serous cells). Although iso- 
lated sections which pass through the larger 
collections of demilune cells may appear as sec- 
tions of serum-secreting tubules, if examined 
in longitudinal section or by reconstruction the 
true mucous character of each lobule is ap- 
parent. Many of the terminal acini of the 
sublingual gland, however, although much 
branched, contain no demilunes. The 'basket 
cells' are readily recognized in the acini of this 
gland though they are less highly developed 
here than in the parotid. Its intralobular duct 
system lacks intermediate ducts, and is largely 
of the 'salivary' type. 
Accompanying the sublingual gland proper, 
or larger component, are a variable number (5 
to 20) of accessory sublingual glands of various 
sizes. They consist largely of mucous alveoli, each 
gland opening into the mouth by an independent duct. The duct of the 
sublingual proper (duct of Bartholin) opens at the side of the frenulum. 
Blood Supply.-The salivary glands possess a rich blood supply. 
The arteries accompany the glandular ducts within the interlobar and 
interlobular connective tissue, and thus reach all the lobules of the 
gland. Small arterial twigs enter the lobule from all sides and form a 
rich capillary plexus in the delicate connective tissue coats of the acini. 
The capillaries are thus brought into intimate relation with the secreting 
cells, from which they are only separated by the basement membrane of 
the acinus. The veins return by a similar course, the smallest venules 
passing out of the lobule into the connective tissue septa in which they 
retrace the course of the arteries. 
Fig. 363.-Reconstruc- 
tion Model, of the 
Sublingual Gland of 
Man. 
An intralobular duct 
terminating in salivary- 
ducts and acini. X 285. 
(After Maziarski.) THE SALIVARY GLANDS 
393 
Lymphatics.-Lymphatics are relatively few and are for the most 
part confined to the interlobular septa, where they form cleft-like spaces 
which lead to true lymphatic vessels and so on to the lymph nodes of the 
cervical region. 
Nerve Supply.-The salivary glands are abundantly supplied with 
nerves, which are derived from both sympathetic and cerebral trunks. 
They are distributed to the walls of the blood-vessels and ducts, and 
to the secreting cells of the acini. The nerve trunks are found in the 
interlobular connective tissue where 
they are supplied with small ganglia 
which are most abundant in the sub- 
maxillary and least numerous in the 
parotid gland. 
The sympathetic fibers which inner- 
vate the blood-vessels proceed from the 
superior cervical ganglion. They are 
believed to be vasodilator fibers. The 
cerebral nerves, which supply fibers to 
the gland cells, are the facial and the 
glossopharyngeal. The parotid gland 
is supplied by the glossopharyngeal; 
the fibers (secretory and vasoconstric- 
tor) passing by way of the tympanic 
nerve (nerve of Jacobson), small superficial petrosal, otic (sympathetic) 
ganglion, and the auriculotemporal branch of the inferior maxillary 
division of the trigeminal nerve. The submaxillary and sublingual 
glands receive their secretory fibers and vasoconstrictor fibers from the 
trigeminal nerve, by way of the chorda tympani nerve and the submaxil- 
lary (sympathetic) ganglion. The fibers beyond the otic and submaxil- 
lary ganglia are believed to be true postganglionic fibers; that is, axons 
of cell bodies situated in these ganglia. Sensory fibers are said to pass 
to the ducts. 
Delicate fiber bundles from the interlobular nerve trunks enter the 
lobules and form a plexus of naked fibrils about the walls of the acini, 
known as the epilemmal plexus, from which terminal fibrils pierce the 
basement membrane and as hypolemmal fibers end in contact with and 
between the secreting cells. Small terminal expansions, varicosities, or 
end knobs are found in the course of the hypolemmal fibers. 
Fig. 364.-Nerve Endings in a 
Salivary Gland. 
H, demilune; I, secreting acini; 
n, nerve fibrils. Highly magnified. 
(After Retzius, from Rauber.) 394 
THE DIGESTIVE SYSTEM 
THE PANCREAS 
The pancreas is a flat elongate body lying behind the stomach be- 
tween the loop of the duodenum and the spleen. It arises as two anlages: 
a smaller from the common bile duct (ventral pancreas), and a larger 
from the duodenum (dorsal pancreas). These subsequently fuse to form 
a single organ drained mainly by the duct of the ventral component, 
which has meanwhile made an anastomosis with that of the dorsal com- 
ponent, the latter proximal to the anastomosis nevertheless commonly 
Fig. 365.-Early Stages in the Development of the Pancreas, Illustrating 
Conditions in the 5 and 7 Weeks Old Human Embryos. 
Dp, dorsal pancreas; Vp, ventral pancreas; Pd, pancreatic (Wirsung's) duct; 
Apd, accessory pancreatic (Santorini's) duct; Dch, ductus choledochus; cd, cystic 
duct; Hd, hepatic duct. (Adapted from Kollman.) 
remaining pervious and functional. The pancreas bears a close struc- 
tural resemblance to the salivary glands, more especially the parotid. 
It is a compound tubido-acinar gland which contains an immense num- 
ber of small lobules associated into lobes and which pours its secretion 
into the lumen of the duodenum by means of the chief (Wirsung's) 
and accessory (Santorini's) pancreatic ducts. The lobules are united by 
a delicate and relatively very loose fibro-elastic connective tissue. 
The ducts of the pancreas branch and arborize in the same manner as 
those of the salivary glands. The interlobular ducts are lined by a 
single layer of columnar cells; in the larger divisions (interlobar ducts) 
occasional goblet cells are found. The wall of the interlobular pan- 
creatic ducts is much thicker than in those of the salivary glands, for THE PANCREAS 
395 
they possess a much thicker connective tissue coat, in which are also 
many longitudinal smooth muscle fibers. 
On entering the lobule the duct is immediately transformed into 
Fig. 366.-From a Section of the Human Pancreas, Showing Several Lobules 
and the Broad Interlobular Bands of Connective Tissue. 
a, blood-vessel; b, pancreatic islet; c, intralobular duct; d, interlobular duct and 
accompanying artery. Hematein and eosin. Photo. X 45. 
the intercalary (intermediate; junctional) type; in the pancreas there 
are no specialized intralobular ducts lined by columnar striated epithe- 
lium as in the salivary glands. The intercalary ducts are very slender 
tubules which are lined by low columnar or flattened epithelium. Be- 
cause of the absence of larger intralobular ducts the intercalary portions 
are relatively very long and much branched. 396 
THE DIGESTIVE SYSTEM 
On approaching its termination the lining cells of an intercalary 
duct are still more flattened and often acquire a considerable breadth. 
They are elongated in the direction of the long axis of the tubule, and in 
surface view have an irregularly polygonal outline (Bensley). They 
pass into the acini in a peculiar manner. Instead of offering a direct 
Fig. 367.-Drawing of an Intercal- 
ary Duct of Cat, with Three 
Branches Ending in Acini to 
Form Centro-acinal Cell Groups. 
The acinar cells contain numerous 
basal filaments. X 750. 
Fig. 368.-Reconstruction 
Model of the Human 
Pancreas. 
The intralobular duct gives 
off long intercalary ducts, 
which, after branching, end 
in the acini. X 344. (After 
Maziarski.) 
transition from the duct epithelium to that of the acinus the cells of 
the former frequently appear as if telescoped into the lumen of the 
acinus. Thus the centro-acinal cells (of Langerhans) are produced, 
and consequently the centro-acinal cells correspond closely in appearance 
with those of the intercalated ducts. They seem to occupy the lumen 
of the acinus, and are only separated from the distal ends of the acinal 
cells by the secretory capillaries which place the secreting cells in com- 
munication with the lumen of the duct. The centro-acinal cells are 
characteristic of the pancreatic acini. 
The Acini.-The acini of the pancreas possess an irregular tubular 
form with frequent alveolar dilatations. Their lining epithelium rests THE PANCREAS 
397 
upon a reticular basement membrane within which are thin 'basket 
cells/ A delicate connective tissue stroma invests the acini or alveoli. 
The secreting cells are tall and irregularly columnar or pyramidal 
in shape. Their nucleus lies in the proximal third of the cell and is 
surrounded by reticular or very finely granular cytoplasm. The cyto- 
Fig. 369.-Acini of the Human Pancreas. 
The acinus at a is connected with an intercalary duct, cut in tangential section, 
and occupying the center of the figure. Hematein and eosin. Photo. X 950. 
plasm of the inner zone of the cell, on the other hand, is filled with 
coarse zymogen granules whose number is dependent upon the activity 
of the gland. During fasting the granules accumulate until eventually 
they almost completely fill the cell, but during digestion they disappear 
with the discharge of the secretion, the width of the granular zone 
gradually decreasing, that of the non-granular fibrillar basal zone being 
correspondingly enlarged (Figs. 371, A and B). 398 
THE DIGESTIVE SYSTEM 
With the increased breadth of the basal zone during secretion, there 
appears in this portion of the cell a structure which has been de- 
scribed by Nussbaum (Arch. mikr. Anat., 1885) as the Nebenkern, 
and which has been carefully studied by Mathews (Jour, of Morph., 
1899). This is a spheroidal basophil body which lies near the nucleus 
and is frequently surrounded by a clear area of cytoplasm. Its origin 
and function are undetermined 
and it is possible that several 
distinct bodies have been in- 
cluded under the name. Ogata 
(Arch. f. Physiol., 1883) con- 
siders that it is derived from 
the nucleus by the extrusion 
of its plasmosome, an opinion 
which seems to be shared by von 
Ebner (Kdlliker's Handbuch, 
1902, Bd. iii, 5, 250). The 
studies of Mathews have shown 
that at least in certain instances 
it is distinctly fibrillar and sug- 
gest that it may be concerned 
with the mechanism of secre- 
tion. It most probably repre- 
sents a post-secretion remnant 
of ergastoplasmic basal fila- 
ments. 
In addition to this fibrillar complex of basophilous substance, there 
may be seen in appropriately fixed and stained preparations, another 
group of fibrils, the mitochondria. These can be seen in fresh acinar 
cells and in tissue preserved in fluids which lack acids (mitochondria are 
dissolved by acids), when they also give to the basal portion of these 
cells a striated appearance. These basal bodies have been extensively 
studied by Bensley (Amer. Jour. Anat., 12, 3, 1911) in the pancreas of 
the guinea pig, and their independence from the basal filaments of 
Solger established. Mislawsky also (Arch. mikr. Anat., 81, 4, 1913) 
has recently studied the mitochondria in the acinar cells of the rabbit's 
pancreas. He finds no evidence to indicate that they segment into the 
zymogenic granules. They are described as interstitial elements of the 
protoplasmic reticulum, more probably connected with the general cell 
metabolism. There is apparently no good evidence in support of the 
Fig. 370.-Pancreatic Acinus of Cat 
Cut Transversely near Fundus, 
Showing the Basal (Prozymogen) 
Filaments of the Cells. 
The alveoli of the central portions of 
the cells represent dissolved zymogen 
granules. X 1500. THE PANCREAS 
399 
Fig. 371.-Cells from Pancreas of Necturus. 
A, after rest, and filled with zymogen granules; B, after activity, showing the 
presecretion (basal; ergastoplasmic) filaments, and the so-called nebenkern (2V). 
(After Mathews.) 
idea that either the basal filaments of Solger or the mitochondria give 
origin to secretory granules, by a process of segmentation. 
Pancreatic Islets.-The lobules of the pancreas contain, in addi- 
tion to the acini and ducts, certain larger and smaller spheroidal col- 
lections of polyhedral cells which lie in the inter-acinar connective tissue, 
the pancreatic islets (islands of Langerhans; intralobular or interalveolar 
Fig. 372.-Two Adjacent Acini from the Guinea-pig's Pancreas. 
zThe one at the right shows an entering intercalary duct and two centro-acinal 
cells. The acinar cells are filled proximally with a basophilous substance (basal 
filaments), and contain distally numerous alveoli, the representatives of dissolved 
zymogen granules. X 1200 (After Bensley, Am. Jour. Anat., 12, 3, 1911.) 400 
THE DIGESTIVE SYSTEM 
Fig. 373.-Section of an Acinus from the Guinea-pig's Pancreas, Showing the 
Basal Mitochondrial Content and the Central Zymogen Granules. 
Bensley's mitochondrial technic. X 1200 (After Bensley, Am. Jour. Anat., 12, 3, 
1911.) 
cell groups). The islet cells are arranged in irregular cords, frequently 
only two cells deep, lying in the meshes of capilliform sinusoids, from 
which they appear to be separated by little more than the endothelial 
Fig. 374.-Intercalary Duct with Branches, from Pancreas of Guinea-pig, 
Showing Highly Branched Tubules Connected with the Duct and with 
an Islet. 
Intravitam staining with pyronin and neutral red. X 50. (Bensley, Amer. 
Jour. Anat., 12, 3, 1911.) 
wall. The cells are divisible into two distinct, apparently independent 
types, on the basis of their granular content (Lane, Amer. Jour. Anat., 
7, 3, 1907). The 'A' and 'B' granules differ morphologically and micro- THE PANCREAS 
401 
chemically; it is suggested that they indicate a twofold secretion (Lane). 
The granules of the islet cells of both types differ markedly also from 
those of the acinar cells. The islets are of various sizes, ranging from 
those with only a few or even a single cell to those with many cells 
(3 millimeters in diameter). The number of islets also varies greatly in 
different individuals. Thus De Witt (Jour. Exp. Med., vol. 8, 1906) 
estimated the amount of islet tissue in three apparently normal subjects 
Fig. 375.-Pancreatic Islet of Cat. 
E, endothelial cell; cap, capillary; be, red blood corpuscle. X 750. 
at 1-25, 1-50 and 1-125 of the total volume of the pancreas. By means 
of intravitam stains (neutral red and Janus green), Bensley succeeded in 
staining differentially the islets of the guinea pig's pancreas. He 
counted from 13,000 to 56,000 in different specimens. Clark (Anat. 
Anz., 43, 3, 1913) employed this method in a study of human pancreases 
secured shortly after death, and estimates the average number of islets 
at 12 per milligram. In one male subject of 24 years and 140 pounds 
weight, he estimated the total number of islets at 1,760,000; in another 
of 29 years and 135 pounds weight, only 662, 166. Opie (Johns Hopkins 
Hosp. Bull., 1900) first observed that the islets were more abundant in 
the tail and least abundant in the head of the pancreas; this observation 
is confirmed by both Clark and Bensley. Laguesse (Jour, de Physiol, et 402 
THE DIGESTIVE SYSTEM 
de Path., 13, 1, 1911) described the islets in continuity with the ducts 
of the acini. Such continuity is described also by Bensley for many of 
the islets in the guinea pig's pancreas. Bensley's studies have disclosed 
these further points of relationship between the islets and the zymo- 
a, acini; b, is placed above an interlobular duct; c, a pancreatic islet; a second 
islet, circular in outline, lies near the center of the figure. Hematein and eosin. 
Photo. X 330. 
Fig. 376.-From the Human Pancreas. 
genous parenchyma: Islets may be located (1) in the interlobular con- 
nective tissue, but connected with the duct system; (2) in the lobules, 
also unconnected with the acini (encapsulated), but directly connected 
with the interlobular duct system; (3) in the lobules-these include 
the great majority-and in connection with either acini or ducts or both; 
and (4) islets unconnected with either ducts or acini, both in the inter- 
lobular connective tissue and in the acinar parenchyma. THE PANCREAS 
403 
The tubules (intercalary ducts) are said to branch and anastomose 
freely and to be capable of differentiating either into acini, or islets, or 
both. They may produce also small mucous glands which open into the 
tubules; and single islet cells may be formed along the ducts. Notwith- 
standing their intimate developmental relationship the islets remain 
isolated from the general exocrin parenchyma, since the lumen of the 
connecting tubules does not penetrate its substance. There is no satis- 
factory evidence to show that islet tissue may be increased or diminished, 
or that acinus tissue may change into islet tissue, or vice versa, concom- 
itant with experimentally induced alterations in nutritive and func- 
tional conditions, as has been repeatedly claimed; nor is there evidence of 
a transition between islet and acinar cells. Islets and acini have a com- 
mon embryonic origin, but once differentiated they are not capable of 
transformation one into the other (Bensley). The islets appear in the 
human pancreas about the time the embryo attains a length of 50 milli- 
meters (Lewis). 
The islets are believed to constitute a group of internally secreting 
organs. The evidence for such conclusion is derived from a series of 
experiments by Opie and many others. When the pancreas is removed, 
a form of diabetes follows, characterized by the appearance of sugar in 
the urine. When the pancreatic duct is simply ligated, the flow of pan- 
creatic juice is checked and atrophy of the acinar tissue ensues, but no 
disturbance in carbohydrate metabolism results, nor is any alteration 
produced in the islet tissue. Moreover, in cases of death following 
diabetes mellitus, Opie demonstrated gross degenerative changes. Ho- 
mans' recent experiments (Jour. Med. Research, March, 1914) have ex- 
tended the evidence in support of the conclusion that the islets are con- 
cerned in the metabolism of sugar. When more than three-fourths of 
the pancreas was removed in cats, the main duct being left intact, fatal 
diabetes occasionally followed. Microscopic examination of the islets 
revealed the following conditions: (1) in those instances where diabetes 
did not follow the operation, the islet cells -showed signs of over-activity 
indicated in part by a disappearance of secretory granules; (2) in the 
subjects which died from'diabetes following the operation, the islet cells 
showed degenerative changes, the acinous tissue having remained un- 
altered. 
Blood. Supply.-The large blood-vessels of the pancreas accompany 
the interlobular ducts, but after repeated subdivision these vessels part 
company, and the smaller arteries pursue a separate course through the 
interlobular connective tissue. Thus they reach all portions of the 404 
THE DIGESTIVE SYSTEM 
gland and supply capillaries to the intralobular connective tissue about 
the acini. Certain arterial branches also enter the islets and form a 
specially rich plexus of broad capillaries (sinusoids) within these cell 
groups. The veins return the islet blood by a similar course. 
The Lymphatics. 
-The lymphatics are 
mostly confined to the 
interlobular tissue, 
where they are in re- 
lation with the blood- 
vessels. 
The Nerves.-The 
nerves are derived 
from the sympathetic 
system, and occur as 
small trunks within 
the interlobular con- 
nective tissue. Nu- 
merous small ganglia 
occur in their course. 
As in the salivary 
glands the nerves sup- 
ply the vascular walls. 
About the secreting 
acini they form a del- 
icate network of 
naked fibrils, from 
which end branches 
penetrate the base- 
ment membrane and 
terminate upon the 
secreting cells. Lam- 
ellar corpuscles are oc- 
casionally found in the interlobular connective tissue of the pancreas. 
Resume.-Finally the attention of the student should be specially 
directed to the presence of the pancreatic islets, the centro-acinar cells, 
the very distinct inner granular and outer fibrillar zones of the secreting 
cells, the thick walls of the interlobular ducts, the absence of intralobular 
ducts except of the intercalary type, and the loose character of the inter- 
lobular tissue as the distinguishing characteristics of the pancreas. 
Fig. 377.-Section of a Pancreatic Islet from 
Injected Specimen of Cat's Pancreas to Show 
the Profuse Blood Supply. 
The capillaries were accurately drawn by aid of a 
camera lucida. Only the nuclei of the islet cells are 
indicated; one acinus is shown at the left. X 500. THE LIVER 
405 
THE LIVER 
The liver is the largest gland of the body, and may be classed as a 
peculiar form of compound tubular gland W'hose cells resemble the serum- 
Fig. 378.-A Lobule of the Pig's Liver: the Central Vein Lies in the Middle 
of the Figure. 
a, capsule of Glisson. Hematein and eosin. Photo. X 115. 
secreting type. The organ is invested with a connective tissue sheath, 
the greater portion of which is clothed with peritoneal epithelium. 
From this connective tissue capsule, fibrous bands or septa are continued 
into the substance of the organ and permeate to all its portions. These 
processes of connective tissue, collectively forming the capsule of Glisson, 
are most abundant at the transverse fissure where they contain the large 406 
THE DIGESTIVE SYSTEM 
blood-vessels and hepatic ducts-this fissure serving as a hilum for the 
organ. The liver is very irregular in outline and shape, and comprises 
five so-called lobes of every unequal size. In the adult its weight is 
Fig. 379.-Diagram of Liver Lobules, the Upper Two Cut Transversely, 
the Lower Longitudinally. 
The portal veins are blue striped; the hepatic veins (central with branches, and 
sublobular) are solid blue; the hepatic arteries are red; and the bile canals black. 
(After Merkel.) Cells not indicated. 
about one-fortieth that of the body, about 3 to 3% pounds. The 
parenchyma of the organ arises from a tubular outgrowth of the embry- 
onic duodenum, hence entodermal; the interstitial tissue develops in 
part from the mesenchyma of the caudal layer of the primitive dia- THE LIVER 
407 
phragm (septum transversum) and of the intervening ventral mesentery 
throughout which the entodermal tubules ramify, and in part (the retic- 
ulum) from endothelium of the original venous sinusoids (Mall). 
The liver is dependent for its structural characteristics upon the 
peculiar disposition of the connective tissue of Glisson's capsule, as also 
of the blood-vessels whose branches it contains; for by these tissues the 
substance of the liver is ex- 
tensively subdivided into mi- 
nute collections of hepatic 
cells, each group forming an 
anatomic unit, the hepatic 
lobule, which in addition to 
the hepatic cells contains a 
connective tissue reticulum 
and the smaller blood-vessels 
and secretory capillaries (bile 
canaliculi). 
The hepatic lobules are 
of cylindrical shape, about 2 
millimeters in length and 1 
millimeter in diameter (Bai- 
ley). In transverse section 
they present a polygonal 
(hexagonal or pentagonal) 
outline. In the dog they are 
short polyhedra about 0.7 
millimeter high, and 0.7 millimeter in diameter; the entire liver con- 
taining 480,000 (Mall, Amer. Jour. Anat., 5, 3, 1906). They are anal- 
ogous to the lobules of compound tubulo-acinar glands, inasmuch as they 
contain the secreting parenchyma of the organ, but are very different 
from the latter in the arrangement of the secreting cells which, in the 
human liver, do not present either a tubular or acinar structure, but 
form solid cell columns. Thus in the human liver the tubular character 
of the gland is scarcely apparent, yet in the liver of many of the lower 
animals, notably in that of the turtle and frog, the cells form typical 
tubules within the indistinct hepatic lobules. 
The bile formed by the liver cells is conveyed to the duodenum by 
an excretory system, beginning with innumerable interlobular bile ducts 
which receive the intralobular secretory capillaries, and, leaving the 
lobule from all its sides, find their way through the interlobular con- 
Fig. 380.-From a Section of the Turtle's 
Liver, Showing the Tubular Arrange- 
ment of the Parenchyma. 
a, blood capillary, partially filled with clotted 
blood; b, vascular endothelium; c, darkened 
central portions of the hepatic cells; d, periph- 
eral portion of the hepatic cells. Osmium 
tetroxid; carmin. X 400. (After Shore and 
Jones.) 408 
THE DIGESTIVE SYSTEM 
nective tissue of the capsule of Glisson and unite with their fellows to 
form larger and larger bile ducts, which finally join to form the main 
excretory or hepatic duct; the latter unites with the cystic duct of the 
gall-bladder to form the common bile duct through which the bile 
reaches the intestine. The gall-bladder-which is in principle a diver- 
ticulum from the hepatic duct-is simply a reservoir for the storage of 
bile; it is absent in some animals, for example, the horse and the ele- 
phant. In all their course the bile ducts are in close relation with the 
radicals of the portal 
vein and of the hepatic 
artery - the group of 
vessels which, together 
with their supporting 
(interlobular) connec- 
tive tissue and the in- 
cluded nerve and lymph 
channels, form the so- 
called portal canals. 
The Hepatic Con- 
nective Tissue.-T h e 
hepatic connective tis- 
sue, or the supporting 
tissue of the liver, in- 
cludes the capsule of 
the organ and the cap- 
sule of Glisson-the lat- 
ter forming a frame- 
work throughout the 
liver and inclosing its 
hexagonal lobules-together with the more delicate intralobular reticu- 
lum. These tissues convey the blood-vessels, lymphatics, nerves, and 
bile ducts. 
The fibrous framework, which forms both the outer fibrous capsule 
of the liver and the capsule of Glisson, contains both collagenous and 
elastic tissue, the latter being fairly abundant-a fact which sharply 
contrasts with the complete absence of elastic fibers from the interior of 
the hepatic lobules. 
The intralobular connective tissue is extremely delicate, and consists 
of very fine fibrils and stellate cells (of von Kupfer) which form a deli- 
cate reticulum, in which the capillary blood-vessels and columns of liver 
Fig. 381.-The Reticulum of the Dog's Liver. 
a, central vein; b, capsule of Glisson at the margin 
of the lobule. Gold chlorid. X 120. (After Bohm 
and von Davidoff.) THE LIVER 
409 
cells are suspended. The anastomosing strands of reticulum converge 
from the periphery toward the center of the lobule, thus following the 
course of the blood capillaries and cell columns. This reticular tissue 
(Mall) exists in so small a quantity and is so extremely delicate that 
although it can be readily studied after removal of the liver cells, as by 
artificial digestion, in ordinary preparations-except those of extreme 
thinness-it can scarcely be discovered in the minute clefts between the 
cell columns and the blood capillaries. It differentiates, at least in part, 
from the endothelium of the original venous sinusoids; the stellate cells 
seen in Golgi preparations also represent endothelial elements. The 
endothelial cells of the intralobular capillaries are actively phagocytic. 
The volume of the interlobular connective tissue which forms Glis- 
son's capsule varies greatly in 
different animals. In the liver 
of the pig and the camel this 
tissue is very extensive, and 
forms a complete investment for 
each lobule. In man it is very 
limited in amount and is con- 
fined to minute areas between 
the adjacent angles of the lo- 
bules, with an occasional frag- 
ment separating the lateral sur- 
faces of neighboring lobules. It 
is in the latter portions, viz., be- 
tween the opposed surfaces of 
the lobules, that the branches of the hepatic veins (sublobular veins) 
are found. The interlobular veins, the subdivisions of the portal vein, 
together with the bile ducts and the branches of the hepatic artery 
are found at the angles of adjacent lobules; hence the portal canals, 
which contain these vessels, should always be sought in this location, 
while the sublobular veins, which run alone and form no part of the 
portal canals, will be found between the opposed surfaces of the lobules. 
The capsule of Glisson also contains many lymphatic vessels and non- 
medullated nerve fibers. 
The Hepatic Lobule.-The lobule is the structural unit of the 
liver and consists chiefly of hepatic cells which are arranged in radiating 
cords. In shape the lobule is an irregularly hexagonal pyramid, the 
exact number of its faces being extremely variable. The periphery of 
the lobule is outlined by the connective tissue of Glisson's capsule which 
Fig. 382.-Stellate Cells of von Kup- 
FER IN THE LlVER OF A DOG. 
g, capillary blood-vessel; I, hepatic cells; 
st, stellate cells. Gold chlorid. X 200. 
(After Kolliker.) 410 
THE DIGESTIVE SYSTEM 
either completely invests each lobule, as in the pig's liver, or forms only 
a very incomplete investment, as in the liver of man. 
Blood enters the lobule from the vessels of the portal canals and 
finds its way, through converging capillaries, from the periphery to the 
center of the lobule. Here it enters the intralobular or central vein, 
Fig. 383.-A Lobule of the Pig's Liver in Longitudinal Section, Showing 
the Relation of the Central and Sublobular Veins and the Arrangement 
of the Hepatic Cells. 
a, sublobular vein; b, capsule of Glisson. Hematein and eosin. Photo. X 68. 
which occupies the axis of the lohule and conveys the hlood thence to the 
sublobular veins, which again lie in the interlobular connective tissue of 
Glisson's capsule. 
The hepatic cells occupy the meshes of the intralobular capillaries 
(sinusoids) and are arranged in cords which radiate from the central 
vein toward the periphery. The frequent anastomoses of the capillaries THE LIVER 
411 
as they approach the central vein produce great irregularities in the 
arrangement and length of the cell cords. Each cord, however, reaches 
the periphery of the lobule after a more or less tortuous course, and it 
is here that the secretory bile capillaries, which are found within the 
cell cords, become continuous with the minute bile ducts of the portal 
canals. 
Fig. 384.-A Lobule of the Human Liver, Seen in Transection. 
It is outlined by three small portal canals and contains a single central vein 
Hematein and eosin. Photo. X 50. 
The Bile Capillaries.-The bile capillaries occur as secretory 
canaliculi between the opposed surfaces of the hepatic cells. They are 
thus found within the cell cords and stand in the same relation to the 
hepatic cells as though each cell cord formed a tubule whose capillary 
lumen, the bile canaliculus, was surrounded by only two secreting cells, 
whereas in other tubular glands a larger number of cells encircle the 
lumen of the secreting tubule. Hence the bile canaliculi and the blood 
capillaries are never in contact, but are always separated by at least 
one-third to one-half the diameter of a hepatic cell. The bile canaliculus 
occurs on that surface of the hepatic cell which is in contact with other 412 
THE DIGESTIVE SYSTEM 
cells within the cord; the blood capillary, on the other hand, is in rela- 
tion with that surface of the hepatic cell which forms the periphery of 
the cell cord. 
The blood capillaries are suspended in the fine meshes of the delicate 
reticulum which has already been described as the intralobular connective 
tissue, and which also invests the cords of hepatic cells. This reticular 
connective tissue is of relatively insignificant volume. 
The bile capillaries are true secretory canaliculi by which the bile, 
after secretion by the 
hepatic cells, finds its 
way along the anastomos- 
ing cell cords to. some 
point at the periphery of 
the lobule, where the cell 
cord becomes continuous 
with a minute bile duct, 
the secreting cells within 
the lobule presenting a 
rapid transition to the 
very low columnar or 
flattened epithelium of 
the interlobular bile 
duct. The immediate 
lining of the intralobular 
bile canaliculus is a del- 
icate cuticular mem- 
brane, probably the prod- 
uct of the hepatic cell. 
The Hepatic Cells. 
-These are large poly- 
hedral cells which possess one, or very frequently two, spherical nuclei 
and a coarsely granular cytoplasm. A true cell membrane may be re- 
garded as being absent, yet there is often a sharply defined exoplasm 
which forms the surface of the cell and simulates a true membrane. 
The nuclei of the hepatic cells are rich in chromatin, and stain 
deeply. They are situated well within the cell, but usually in an eccentric 
position. Frequently they contain a distinct nucleolus. 
The cytoplasm of the hepatic cells is finely reticular, the meshes 
being filled with coarse granules of irregular size. Many of these are 
undoubtedly glycogenic granules, and show a decided color reaction when 
Fig. 385.-Section of Liver Tissue of Cat, 
Showing the Liver Cell-Cords, and the Arti- 
ficially Enlarged Sinusoids Lined with Endo- 
thelium. X 375. THE LIVER 
413 
treated with Lugol's solution of iodin after alcoholic fixation. The 
amount of glycogen present varies with the diet. After digestion and 
absorption of a carbohydrate 
meal it is greatly increased, but 
disappears during fasting. Even 
when glycogen is quite deficient, 
the hepatic cells still present a 
granular appearance from the 
presence of other substances, 
possibly zymogens. 
Fat Globules.-Fat glo- 
bules occur in hepatic cells in 
limited numbers, and appear to 
be a normal constituent. The 
globules vary much in size, but 
are all very small. Their number is also dependent upon diet and diges- 
tion. During absorption of a fatty meal, fat globules occur in consider- 
able numbers, and are most numerous in those hepatic cells which are 
Blood capillary 
•Bile capillary 
Lymph space 
Nucleus 
Fig. 386.-Diagram of Four Adjacent 
Liver Cells. 
(Adapted from Merkel. ) 
Fig. 387.-Bile Capillaries of the Hepatic Lobule, from the Liver of a Cat. 
a, a portal canal; b, a small interlobular bile duct. Golgi's stain and hematein. 
Moderately magnified. (After Geberg.) 
at the periphery of the lobule. They are not normally found in the 
vicinity of the central vein. 
The hepatic cells also frequently contain brown or yellowish-brown 414 
THE DIGESTIVE SYSTEM 
Fig. 388.-Showing the Connection Between the Intralobular and Inter- 
lobular Bile Ducts in the Cat's Liver. 
es, interlobular vein; b, interlobular bile duct; c, intralobular bile capillaries. 
Golgi stain and hematein. Highly magnified. (After Geberg.) 
granules of ferruginous pigment, which are more prone to occur in 
the interior of the lobule near the central vein. When present in con- 
siderable amount this pigment can no 
longer be considered a normal constit- 
uent of the hepatic cell. Mitochondria 
have also been described in the hepatic 
cell (Policard, Compt. Rend, de Soc. et 
Biol., 1, 66, 1909). An intracellular 
canalicular apparatus can also be dem- 
onstrated within the cytoplasm. By 
some these channels have been inter- 
preted as intracellular terminals of the 
intercellular (intralobular) bile canal- 
iculi, by others as fixation artifacts, 
and still others regard them as a tro- 
phospongium. Schaffer (1902) inter- 
prets them in part as channels in rela- 
tion with the blood sinusoids. Such in- 
tracellular canaliculi undoubtedly ap- 
pear under certain functional conditions, but it is uncertain whether 
they are definite preformed channels, or simply transient secretory canals. 
Fig. 389.-Types of Cells from a 
Section of the Normal Human 
Liver. 
A, the usual type of liver cell; B, 
fatty, and C, pigmented cells. 
Types B and C were very scarce. 
Hematein and eosin. X 900. THE LIVER 
415 
Moreover, it seems probable that the canals described include structures 
of different significance. 
The Portal Canals.-The portal canals are formed by the ramifica- 
tions of the portal vein, hepatic artery, and hep- 
atic duct, and are characteristic of the liver-the 
peculiarity consisting not so much in the structure 
of the tissue, as in the combination of artery, duct, 
and vein occurring in close relation, in the con- 
nective tissue at the angles of the hepatic lobules. 
The largest vessel in the canal is invariably the 
vein, the smallest the artery. 
The Interlobular Veins.-The interlobular 
veins, branches of the portal, are extremely thin- 
walled sinusoidal vessels. They are formed by 
scarcely more than the endothelial lining, which 
is supported by the connective tissue of Glisson's 
capsule. Their wall contains very little or no 
smooth muscle. 
The Interlobular Arteries.-The interlobular arteries, branches 
of the hepatic, are very small and are 
noted for their highly developed mus- 
cular coat and distinct elastic mem- 
brane. They give off minute vaginal 
branches which supply capillaries to 
the tissue of Glisson's capsule. 
The Interlobular Bile Ducts.- 
The interlobular bile ducts, radicals of 
the hepatic duct, receive the bile from 
the intralobular bile canaliculi and 
convey it, through larger and larger 
branches, to the hepatic duct. They 
are more numerous than the interlobu- 
lar veins and much more numerous 
than the interlobular arteries. Due to 
their frequent branching many of the 
portal canals as seen in transverse sec- 
tion contain two bile ducts. The ducts 
are lined by columnar epithelium 
whose height varies with the size of the tubule, the smallest ducts being 
lined by low columnar, or cuboidal, the largest by tall columnar cells; 
Fig. 390. - Human 
Liver Cell, Show- 
ing Enlarged In- 
tracellular Can- 
aliculi, a Condi- 
tion Characteris- 
tic of Jaundice. 
(Browicz.) 
Fig. 391.-Diagram of a Portal 
Canal, Including a Branch of 
the Portal Vein, Hepatic Ar- 
tery (A), Hepatic (Bile) Duct 
(B), Lymphatic (L) and Non- 
MEDULLATED NERVE TRUNKS. 416 
THE DIGESTIVE SYSTEM 
the lining epithelium of the hepatic, cystic and common bile ducts is 
very tall. The epithelial cells of the ducts possess characteristic spherical 
or ovoid nuclei which are heavily loaded with chromatin. Their cyto- 
plasm is clear or finely reticular. The largest ducts contain a few goblet 
Fig. 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. 
a, interlobular veins; b, central vein; c, central vein from which the injection 
mass had fallen out; the capillaries are dark. Photo. X 70. 
cells; small mucous glands are found in the hepatic and common bile 
duct. 
The epithelium of the interlobular bile ducts rests upon a thin base- 
ment membrane, which is surrounded by a thick fibro-elastic coat. The 
larger ducts are also supplied with circular smooth muscle fibers, which, 
in the largest branches, form a considerable coat. Outside of the liver, THE LIVER 
417 
longitudinal muscle fibers also appear in the walls of the excretory 
ducts, and so accumulate in the wall of the gall-bladder and common 
bile duct as often to form a distinct layer. 
As has been pointed out by Mall (1906) the hepatic lobule cannot be 
regarded as the homologue of the lobule of other glands. For the portal 
canal with its bile duct, the excretory duct of the glandular unit, should 
be axial to the functional lobular unit. Moreover, an interlobular bile 
duct drains not the whole of a particular lobule, but portions of a num- 
ber of adjacent lobules. The functional unit (portal lobule), in contra- 
distinction to the structural unit (hepatic lobule), is accordingly that 
portion of liver tissue (portions of a number of hepatic lobules) sup- 
plied by an ultimate branch of the vessels of a portal canal. Thus a 
hepatic lobule is drained by several bile ducts, and conversely, a single 
ultimate bile duct drains portions of several hepatic lobules. 
Blood Supply.-The liver is supplied with blood from two inde- 
pendent sources, the hepatic artery and the portal vein. That supplied 
by the artery is of minor importance and is destined only for the nutri- 
tion of the connective tissue framework of the organ. 
On entering the liver at the transverse fissure, the hepatic artery 
gives off numerous capsular branches which ramify in the capsule of the 
liver and supply capillaries to its connective tissue. Other branches, the 
direct continuation of the hepatic artery, enter the portal canals and by 
repeated division form the interlobular arteries, which ramify in the 
tissue of Glisson's capsule, and whose vaginal branches supply capillaries 
to this connective tissue. These capillaries, as well as those from the 
capsular branches, become continuous, at the periphery of the lobule, with 
the intralobular capillaries which are derived from the branches of the 
portal vein. 
The Portal Vein.-The portal vein likewise enters at the transverse 
fissure, bringing to the liver the blood collected from the capillaries of 
the organs of digestion and absorption. It divides into numerous 
branches which follow the portal canals, in which they are known as the 
interlobular veins, and in this way reach all portions of the organ. 
The interlobular veins throughout all their course give off small 
branches which at once enter the periphery of the hepatic lobules and 
immediately break into a brush of capillary vessels. These intralobular 
capillaries (capilliform sinusoids, Lewis) converge toward the center of 
the lobule and anastomose to form a capillary network, in the elongated 
meshes of which are the cords of hepatic cells. These capillaries approach 
the center of the lobule where they unite to form the intralobular or 418 
THE DIGESTIVE SYSTEM 
central vein. The central vein frequently begins in the form of a Y, 
its two or more branches finally uniting to form a single vessel which 
pursues its course through the axis of the lobule. The central vein 
makes its exit at the periphery of the lobule and enters the interlobular 
connective tissue where it unite's with its fellows to form larger sub- 
lobular veins. The sublobular are easily distinguished from the inter- 
lobular veins by their thicker walls and by the fact that the former 
Fig. 393.-A Sublobular Vein of the Pig's Liver. 
a, capsule of Glisson between adjacent lobules. Hematein and eosin. Photo. 
X 60. 
pursue an independent course through the tissue of Glisson's capsule, 
being nowhere in relation with either artery or duct. 
The sublobular veins are, as a rule, vessels of considerable size, and 
by frequent union with their fellows become constantly larger. In their 
general direction they tend toward the dorsal surface of the liver and 
finally make their exit as four or five large hepatic veins which enter 
the inferior vena cava. 
The blood supply of the liver, 30 per cent, of which can be ac- 
counted for in the hepatic artery, 60 per cent, in the portal vein (Mac- THE LIVER 
419 
leod and Pearce, Amer. Jour. Physiol., vol. 35, 1914), is peculiar in 
that: (1) the greater portion of its blood has already passed through 
the capillaries of the digestive organs before entering the liver; (2) 
its arterial supply is relatively meager and supplies only the connective 
tissue framework, intermingling with the portal blood at the periphery 
of the lobule; (3) its intralobular capillaries are extremely abundant 
and are in intimate relation with the hepatic cells, each cell coming into 
contact with four to six capillary vessels. 
The course of the blood through the vessels of the liver will be 
readily appreciated by reference to the following table which indicates 
the succession of the hepatic blood-vessels: 
1. Portal vein 
2. Interlobular veins 
3. Branches to lobule 
1. Hepatic artery 
2. Interlobular arteries 
3. Vaginal branches and capillaries 
in Glisson's capsule 
4. Intralobular capillaries 
5. Central vein (intralobular) 
6. Sublobular veins 
7. Hepatic veins 
8. Vena cava inferior 
The three classes of veins, interlobular, central, and sublobular are 
readily differentiated by the fact that the two latter lie alone, while the 
interlobular veins are always in company with the ducts and arteries 
within the portal canals. Moreover the central vein has almost no con- 
nective tissue wall until near its exit from the lobule, where it passes 
into the sublobular branches; the sublobular veins, on the other hand, 
possess a relatively thick connective tissue wall and even some smooth 
muscle, except in the very smallest, which are to be regarded as mere 
interlobular continuations of central veins which soon unite to form 
the larger sublobular vessels. 
Lymphatics.-The lymphatics of the liver may be considered as con- 
sisting of a superficial set which supplies the hepatic peritoneum and 
the capsule of the liver, and which is continuous with a deeper set in 
Glisson's capsule. The lymphatics of the deep set begin as perivascular 
spaces within the lobule, from which the lymph enters larger lymphatic 
vessels in the interlobular connective tissue, which follow the vessels of 
the portal canals to their exit from the liver; the larger lymphatics pass 
to the abdominal lymph nodes. Other lymphatics follow the sublobular 
and hepatic veins and pass to the mediastinal lymph nodes. 420 
THE DIGESTIVE SYSTEM 
Nerves.-The nerves of the liver are mostly of the non-medullated 
variety. They follow the portal canals and are distributed to the walls 
of the blood-vessels, the walls of the bile ducts, and to the capsule of the 
liver. Naked fibrils from these trunks also enter the lobules and form 
a plexus among the hepatic cells (Korolkow, 
Anat. Anz., 1893), in relation with which they 
form fine terminal brushes and varicose end 
knobs (Berkley, Johns Hop. Hosp. Rep., 1895). 
The liver secretes the bile-a fluid which aids 
in the digestion and absorption of fats-and in 
fact probably serves also an excretory role. Bile 
has a greenish-yellow color, due in part to the 
presence of the pigment bilirubin, which is be- 
lieved to be identical with the hematoidin elab- 
orated from the hemoglobin of the erythroplas- 
tids disintegrating in the spleen, and carried to 
the liver by way of the splenic and portal veins. 
Under certain pathological conditions known as 
jaundice, bile finds its way within the liver di- 
rectly into the blood stream where it produces hemolysis of the red 
corpuscles. In addition to its bile-producing activity, the liver functions 
also as an organ of internal secretion, in the conversion of glycogen into 
sugar and the elaboration of urea. Experimental evidence indicates that 
the liver is concerned greatly also with the production of fibrinogen 
(Whipple, Amer. Jour. Physiol., 1914). 
Fig. 394. - Intralob- 
ular Nerve Fibers 
in a Rabbit's Liver. 
a, hepatic cells; b, 
nerve fiber. Golgi stain. 
Highly magnified. (Af- 
ter Berkley.) 
THE GALL-BLADDER 
The wall of the gall-bladder consists of three coats: (1) mucous; 
(2) muscular; (3) fibroserous. The mucous .membrane is markedly 
folded or corrugated, the irregularly polygonal depressions being rela- 
tively broad at the fundus but becoming narrower toward the neck of the 
organ. The lining epithelium is of the tall columnar variety, with 
spheroidal or ovoid nuclei which lie near the base of the cell. The free 
extremity of the epithelial cells presents an indistinct cuticular border. 
The epithelium follows all the folds of the mucosa and lines the inter- 
vening depressions. 
The corium of the mucosa consists of delicate connective tissue and 
contains a few smooth muscle fibers derived from the muscular coat. THE GALL BLADDER 
421 
Fig. 395.-From a Section through the Wall of a Dog's Gall-bladder. 
a, epithelium; b, lymph nodule; c, serous coat. X 80. (After Sudler.) 
It is connected with the muscularis by a thin layer of denser connective 
tissue which contains blood and lymphatic vessels and which simulates a 
submucosa. 
Fig. 396.-Reconstruction of the Wall of a Dog's Gall-bladder. 
a, vein; 6, artery; c, lymphatic vessel; d, epithelium. X 60. (After Sudler.) 
The gall-bladder possesses a distinct muscular wall, consisting of 
numerous interlacing smooth muscle bundles the most of which are cir- 
cularly disposed. Occasionally they form fairly distinct circular and 
longitudinal layers. 422 
THE DIGESTIVE SYSTEM 
The fibroserous coat consists of loose areolar tissue, which contains 
the larger blood-vessels with which the organ is abundantly supplied. 
The free surface of the gall-bladder also receives a peritoneal investment. 
Occasional mucous glands occur in the mucosa of the gall-bladder. 
These are mostly of small size and widely separated, but toward the neck 
of the organ they increase in both number and size. They form short, 
branched, convoluted tubules. 
The blood-vessels form a plexus just outside the muscular coat, from 
which branches are distributed to the peritoneal coat and to a plexus in 
the depth of the mucosa from which capillaries are supplied to the muscu- 
lar layers and to a subepithelial plexus. The nerves are distributed to 
the blood-vessels and to the muscular wall. Minute ganglia occur in the 
muscular coat. CHAPTER XIV 
THE URINARY SYSTEM 
This system includes the kidneys, which are two large bean-shaped 
glands, together with their excretory passages, the ureters, which conduct 
the urine to the urinary bladder, whence it is voided through the urethra. 
THE KIDNEY 
Each kidney is a gland of the compound tubular type, measuring 
about four and one-half inches in length, two and one-half inches in 
width, and one and one-half inches in thickness. Its secretion, the urine, 
is produced by the uriniferous or renal tubules, which are long tortuous 
canals beginning near the surface of the kidney and finally ending at 
the hilum of the organ where they pour their secretion into the calyces 
of the renal pelvis. The uriniferous tubules are in intimate relation 
with the renal blood-vessels which supply rich capillary plexuses to the 
entire extent of the tubules. Each uriniferous tubule consists of both 
tortuous and straight portions, and these are so regularly disposed as to 
produce macroscopical variations in the appearance of the different por- 
tions of the renal parenchyma according as the tortuous or the straight 
portions of the tubules predominate. These variations result in the fol- 
lowing topographical subdivisions. 
Topography of the Kidney 
If the kidney be divided parallel to its long axis by an incision extend- 
ing from its convex surface to the hilum, the cut surface shows that the 
parenchyma is divisible into a superficial cortex and a central medulla. 
The slit-like hilum of the organ opens into a deep excavation, the renal 
sinus, which is occupied by the renal pelvis and its subdivisions, the 
infundibula and calyces, into which the medulla projects in the form 
of several conical pyramids. The pelvis of the kidney, the expanded 
423 424 
THE URINARY SYSTEM 
funnel-form beginning of the ureter, toward the renal parenchyma 
divides into two, sometimes three, infundibula, which in turn subdivide 
into several calyces, each of which incloses the conical apex of a projecting 
medullary or renal {Malpighian) pyramid. 
The Medulla,-The medulla of the kidney consists of a number of 
these conical renal pyramids (usually twelve to fifteen) each of whose 
apices, as already stated, is received 
into the extremity of a renal calyx. 
Occasionally a calyx may receive two 
papillae. The base of each pyramid 
is embedded in the adjacent renal 
cortex, and that portion of the cor- 
tex which is interposed between the 
bases of adjacent pyramids, and thus 
brought into relation with the fi- 
brous and adipose tissue which en- 
velops the pelvis and calyces at the 
hilum of the organ, composes the 
cortical renal columns (of Bertini). 
Each renal pyramid may be sub- 
divided into a central free portion, 
the apical or papillary zone of the 
medulla, which is received into a 
calyx, and an outer or basal portion, 
which is embedded in the renal cor- 
tex and is known as the boundary 
zone of the medulla. These two por- 
tions of the medulla, the papillary 
and boundary zones, can be readily 
distinguished, since the latter con- 
tains only narrow tubules and is 
highly vascular, while the former, 
relatively deficient in blood-vessels, 
contains the broad terminations of 
the uriniferous tubules, the papillary ducts (of Bellini) which converge 
toward the apex of the pyramid where they open into the calyces. 
The Cortex.-The cortex of the kidney, on careful observation, pre- 
sents numerous dark lines or delicate columns which radiate from the 
base of the pyramids outward toward the surface of the organ. These 
radiating columns are the medullary rays (pyramids of Ferrein) or 
Fig. 397.-Longitudinal Section of 
Kidney. 
1, cortex; 1', cortical rays; 1", laby- 
rinth; 2, medulla; 2', papillary portion 
of medulla; 2", boundary layer of me- 
dulla; 3, transverse section of tubules 
in the boundary layer; 4, fat of renal 
sinus; 5, artery; *, renal column of 
transverse medullary rays; A, branch 
of renal artery; C, renal calyx; U, ureter. 
(After Tyson and Henle, from Hill.) THE KIDNEY 
425 
pars radiata of the cortex. They contain straight portions of the urinif- 
erous tubules; these are continuous with the similar tubules in the 
boundary zone of the medulla. These columns lie within the cortex and 
not, as their name might be taken to indicate, in the medulla. They 
are termed 'medullary rays' 
because of their peculiar rela- 
tion to the medulla, from 
which they extend outward in 
a radial direction. It would 
seem more proper to desig- 
nate them 'cortical rays.' 
That portion of the cortex 
which invests the cortical 
rays and which includes all 
the remaining cortical por- 
tions of the organ, consists of 
extremely tortuous tubules, 
and is characterized by the 
presence of small globular 
bodies, each of which con- 
tains a tuft of capillary ves- 
sels. These are the renal 
corpuscles (Malpighian bod- 
ies) which are characteristic 
of the kidney. The portion 
of the cortex in which they 
occur includes the entire cor- 
tical substance with the ex- 
ception of the cortical rays, 
and is known as the renal 
labyrinth or pars convoluta. 
The labyrinth is divided 
into: (1) the renal columns, 
already mentioned; (2) the 
intercolumnar portions, or 
labyrinth proper, which includes that portion of the labyrinth which 
invests the cortical rays, and which, in sections cut parallel to these 
columns (longitudinal sections) appears as a portion of cortex inserted 
between the adjacent rays; (3) a narrow boundary zone of the cortex, 
'cortex corticis' of Hyrtl, which is included between the fibrous capsule 
Fig. 398.-Diagram of the Structure of 
the Kidney. 
a, papillary zone, and b, boundary zone of 
the medulla; c, cortex; 1, apex of a renal 
pyramid; 2, capsule; 3, tubules of the me- 
dulla; 4, vasa recta); 5, vascular arcades; 6, a 
cortical ray; 7, labyrinth; 8, interlobular ar- 
tery; 9, renal corpuscle; 10, 'cortex corticis.' 
(After Testut.) 426 
THE URINARY SYSTEM 
of the organ and the tips of the cortical rays, and in which the renal 
corpuscles, though present, are relatively few in number. 
The Renal Lobule.-In fetal and infantile life the kidney is dis- 
tinctly lobed. This condition is permanent in some animals-e.g., rep- 
tiles, birds, porpoise, ox, bear-each lobe consisting of a renal pyramid 
with its related portion of cortical substance. In 
man, after the first year, the renal lobes com- 
pletely fuse and eventually leave scarcely a trace 
of the early lobed condition. 
Internally this fetal lobed condition is in part 
indicated by the definitive renal pyramids, from 
eight to eighteen in number, each representing the 
product of fusion of from two to nine primitive 
lobes. In certain mammals-e.g., mouse, rabbit, 
cat, guinea pig-neither a primitive nor definitive 
internal or external lobar arrangement appears. 
Such kidneys are designated unipy rami dal or uni- 
papillary, in contradistinction to the multipapil- 
lary type. In certain of the perissodactyls (ele- 
phant, horse) no distinct pyramids are present. 
The term renal lobule or renculus, as applied 
to the adult human kidney, refers to a still smaller 
subdivision of the organ, one which includes a 
single cortical ray together with that portion of the cortical labyrinth by 
which it is immediately invested. Its peripheral boundary is marked by 
the interlobular blood-vessels. This lobule is the anatomical unit of the 
kidney and is thus comparable to the portal and to the pulmonary lobule, 
except that its arterial supply enters at the periphery. The tortuous 
secreting portions of its uriniferous tubules are contained in the laby- 
rinth at the periphery of the lobule, while its straight conducting por- 
tions lie in the cortical ray in the axis of the lobule. The larger inter- 
lobular arteries and veins lie at the periphery, where they supply 
branches to several adjacent lobules. 
Fig. 399. - Recon- 
struction of a Uri- 
niferous Tubule 
of an Infant. (After 
Stoerk.) 
The Renal Connective Tissues 
The kidney is enveloped by a fibrous capsule, the tunica fibrosa, 
which is loosely attached to the substance of the organ and contains the 
usual proportion of elastic fibers together with a little smooth muscle. 
A fatty layer, the tunica adiposa, invests the capsule. At the hilum of THE KIDNEY 
427 
the organ the capsule is continuous with the connective tissue which 
envelops the renal pelvis, infundibula, and calyces, and which, in the 
intervals between adjacent calyces, comes into relation with the cortical 
substances of the renal columns. 
This connective tissue of the hilum is of the areolar variety and 
contains much adipose tissue. It supports the large arteries and veins 
as they pass along the surface of the renal pelvis on their way to and 
from the renal columns, where they enter or leave the parenchyma. 
Sympathetic nerve fibers and a few small ganglia are also found in this 
region. 
The connective tissue of the interior of the organ, interstitial tissue, 
is very scanty, and in most parts consists only of isolated fibrils which 
invest the blood-vessels and the renal tubules. It forms a very delicate 
reticulum by which the walls of the uriniferous tubules are loosely united. 
If the epithelium of these tubules is removed, a delicate fibrous network 
remains; this network incloses a homogeneous basement membrane upon 
which the lining epithelium ordinarily rests. Elastic fibers scarcely 
occur among the tubules of the kidney. The interstitial tissue is slightly 
increased in amount about the larger blood-vessels, the renal corpuscles 
of the cortex, and the small blood-vessels of the boundary zone of the 
medulla. At the apex of the renal pyramid it invests the large papillary 
ducts in considerable quantity. 
The Uriniferous or Renal Tubules 
The uriniferous tubules begin in the cortical labyrinth as the capsules 
of the renal corpuscles. Assuming a tubular form they then pursue a 
tortuous course through the pars convoluta and finally enter the boundary 
zone of the medulla, where, much reduced in size, they form the loop of 
Henle, which consists of a short, descending, thin limb, a U-shaped loop, 
and a long, ascending or thick limb. This last division, after recrossing 
the boundary zone of the medulla, enters a pars radiata and returns 
to the region of its origin, where it becomes again convoluted. A short 
arched tubule connects this convoluted portion with a straight collecting 
tubule of the cortical ray. The collecting tubules traverse the whole 
length of the ray, uniting with their fellows and receiving other arched 
tubules along their entire course. They then cross the boundary zone 
of the medulla, and finally, in the papillary zone, having meanwhile 
received numerous accessions of straight collecting tubules, form the 428 
THE URINARY SYSTEM 
large terminal tubules, the papillary ducts, which pour the urinary 
secretion into the renal calyces. 
Each uriniferous tubule may thus be subdivided into several portions 
Arched collecting 
tubule 
Vas afferens Vas efferens 
Intercalary (dis- 
tal convoluted) 
segment 
Glomerulus 
Cortex 
5 Straight, collect- 
l ing tubule 
Interlobular vein 
Interlobular artery 
Arteriola recta 
Outer stripe 
5 Outer zone of 
' ( medulla 
Inner stripe 
5 Inner zone of 
( medulla 
.Papilla 
Proximal convo- 
luted segment 
Renal capsul 
Vasa arciformia 
Stout, clear por- 
tion of loop of :■ 
Henle ) 
Int erlobarI 
blood-vessels J 
Stout,cloudy por- I 
tion of loop of 
Henle ) 
Slender, clear) 
portion of loop !- 
of Henle ) 
Henle's loop 
Large, straight) 
collecting tu- :■ 
bule ) 
Fig. 400.-Diagram of Uriniferous Tubule of a Mammal. (Adapted from 
Peter and Merkel.) 
which differ from each other, not only in their location, but also in the 
character of their lining epithelium. The successive portions which 
compose a single uriniferous tubule may be enumerated as follows: THE KIDNEY 
429 
1. Capsule of the renal corpuscle. 
2. Neck of the tubule. 
3. Proximal convoluted portion. 
4. Descending limb of Henle's loop. 
5. Loop of Henle. 
6. Ascending limb of Henle's loop. 
7. Distal convoluted portion. 
8. Arched collecting tubule. 
9. Straight collecting tubule. 
10. Papillary duct. 
It should be borne in mind that all of these several portions form 
only successive parts of a single uriniferous tubule. Those portions of 
the urine which are secreted into the capsule of the renal corpuscle 
must therefore find their way through each of these successive portions 
before it can reach the excretory passages of the renal calyces, pelvis, 
and ureter. 
1. The Renal Corpuscle (Malpighian Body).-A renal corpuscle 
consists of a spherical tuft of capillary vessels, the glomerulus, which in 
the course of its development 
is invaginated into the end of 
the uriniferous tubule, and 
thus comes to be enveloped by 
a double-layer of flattened epi- 
thelial cells known as the glom- 
erular capsule (of Bowman). 
The inner visceral layer of 
the capsule closely invests the 
entire surface of the glomeru- 
lus, except at that point where 
the afferent and efferent vessels 
enter and leave the capillary 
tuft; at this point the visceral 
epithelium is reflected outward 
and becomes continuous with 
the parietal layer. The sur- 
faces of these two layers are almost in apposition; the narrow interval 
between them which results from the slightly eccentric position of the 
glomerulus forms the first portion of the lumen of the uriniferous tubule. 
At that pole of the renal corpuscle which is opposite the entrance of its 
Fig. 401.-Reconstruction of a Glomer- 
ulus of the Human Kidney. 
a, afferent arteriole; b, efferent arteriole; 
c, capillaries. X 444. (After Johnston.) 430 
THE URINARY SYSTEM 
blood-vessels the capsule opens, through a narrow neck, into the first or 
proximal convoluted portion of the uriniferous tubule. 
The glomerulus is a true arterial rete mirabile, since it receives an 
afferent artery, which, after forming the capillaries of the glomerulus, 
Fig. 402.-From the Cortical Labyrinth (Pars Convoluta) of the Human 
Kidney. 
A large renal corpuscle is in the center of the figure. At its upper border are 
several sections of distal convoluted tubules. The great majority of the tubules 
shown are from the proximal convoluted portions, a, a portion of a glomerulus; 
b-b, parietal layer of the capsule; c, proximal convoluted tubules; d, just within 
this point is a transection of a junctional tubule having relatively low and clear 
epithelium and a broad lumen. Hematein and eosin. Photo. X 135. 
passes out as an efferent artery to again enter a capillary plexus about 
the neighboring tubules of the renal cortex. The afferent vessel is of 
somewhat larger caliber than the efferent-a noteworthy fact because of 
its relation to the intraglomerular blood pressure. THE KIDNEY 
431 
On entering the glomerulus the artery divides into two vessels which 
immediately subdivide with the formation of five branches (Johnston). 
Each of these branches forms a series of anastomosing capillary loops 
whose convexity is directed away from the entering artery. The capillary 
loops reunite, in a similar manner, to form the efferent vessel, which 
leaves the glomerulus in company with the afferent; but, once out, they 
soon part company, the efferent vessel breaking into a second capillary 
plexus about the neighboring tubules. Within the glomerulus the capil- 
laries are united by a very delicate but scanty connective tissue containing 
no elastic fibers. 
The visceral layer of the capsule is firmly adherent to the walls of 
the glomerular capillaries. It consists of a single layer of flat epithelial 
cells which are intimately blended with each other and with the endothe- 
lium of the capillaries. The epithelial cells possess a clear cytoplasm and 
a flattened ovoid nucleus, which, being thicker than the body of the 
cell, produces a considerable bulging. In fetal and infantile life the 
shape of the cells of this layer is cuboidal or even low columnar, but 
becomes more and more flattened as development progresses, until the 
epithelium finally simulates a layer of endothelial cells. 
The epithelium of the parietal layer is also cuboidal in fetal life, 
but during development becomes nearly as much flattened as that of the 
visceral layer. Its single layer of finely granular cells forms a complete 
lining for the capsule. It rests upon a homogeneous basement membrane 
which is invested by a thin layer of connective tissue. This fibrous layer 
is rather more highly developed about those renal corpuscles which lie 
near the medulla than about those of the more peripheral portions of 
the cortex. 
2. The Neck of the Tubule.-In this portion of the tubule the 
flattened epithelium of the glomerular capsule rapidly changes to the 
low columnar type of the proximal convoluted portion. This section is 
extremely short; it forms a constricted portion which marks the begin- 
ning of the tortuous tubule. This constriction is more apparent than 
real, since the caliber of the tubule in the neck is as great as in the 
succeeding portion whose external diameter is, however, much increased 
by the increasing height of the epithelial cells. This portion of the 
tubule, being in relation with the renal corpuscle, is necessarily found 
in the cortical labyrinth. 
3. The Proximal Convoluted Portion.-This is commonly the 
longest and broadest portion of the uriniferous tubule. Collectively the 
convoluted tubules form the greater part of the cortical labyrinth, in 432 
THE URINARY SYSTEM 
which region only they occur. This portion of the tubule is remarkable 
for the irregularity of its course, it being twisted and bent upon itself in 
a most tortuous manner. Arising at the renal corpuscle, it at first passes 
toward the surface of the organ, but soon turns about and runs toward 
Fig. 403.-From the Cortex of the Human Kidney, Showing a Transection 
of a Cortical Ray in the Lower Left-hand Corner. 
a, glomerulus; b, glomerular capsule; c, proximal convoluted tubule; d, collecting 
tubule; e, ascending limb of Henle's tubule;/, spiral tubule; g, blood-vessel; h, distal 
convoluted tubule. Hematoxylin. X 200. (After Schaper, from Stohr.) 
the medulla, at first with extreme convolutions, but later pursuing a 
rather spiral course {spiral tubule). On reaching the border of the 
medulla the tubule becomes sharply constricted and enters the medullary 
boundary zone at the thin descending limb of Henle's loop. THE KIDNEY 
433 
The epithelium of the convoluted tubule is of the columnar or pyram- 
idal type, its cells having broad, firmly united bases and conical free 
apices. The lateral margins of the cells are often so intimately blended 
at the base as to resemble a syncytium. When isolated, or if outlined 
by impregnation with silver salts, the borders of the epithelial cells are 
extremely irregular and are deeply fluted or serrated, the serrations of 
each cell interdigitating with those of its neighbors. The deep fluted ser- 
Fig. 405.-Cross Section of a 
Proximal Convoluted Tubule 
from the Kidney of a Mouse, 
Showing Basal Filaments 
(Probably Largely Mitochon- 
drial) Breaking up into Gran- 
ules Centrally, and the Cen- 
tral Striated Border of the 
Cells. 
Meves' mitochondrial technic. 
X 1000. 
Fig. 404.-From a Longitudinal Section 
of a Convoluted Tubule of the 
Guinea-pig's Kidney. 
The cell outlines have been blackened by 
the Golgi method. Very highly magnified. 
(After Landauer.) 
rations of the interlocked epithelium gives many of its cells a coarsely 
striated appearance, the striation being more prominent beneath the 
centrally situated nucleus than in the apical portion of the cell. Other 
longitudinal striations in the proximal or basal portion of the cell are 
the result of a linear arrangement of granules and filaments which occur 
in this part. These appearances often give the epithelium of the convo- 
luted tubules a peculiar striated or 'rodded' character. The granules and 
filaments are probably largely mitochondrial in nature. 
The apices of the epithelial cells are very easily destroyed, but when 434 
THE URINARY SYSTEM 
perfectly preserved often present a delicately striated, cuticular border 
('brush border'). The remaining portions of the cytoplasm are finely 
granular. 
The nuclei of the epithelial cells of the convoluted tubules are spheri- 
cal in shape, and do not stain very deeply with nuclear dyes as compared 
with the more distinct and deeply staining nuclei of the collecting 
tubules. Thus they appear as if partially clouded by the granular cyto- 
plasm, an appearance which is greatly exaggerated with the onset of acute 
inflammatory processes, which, on attacking the kidney, are prone to 
involve the convoluted tubules. The chromatin is quite evenly distributed 
throughout the nucleus and the nuclear membrane is not easily demon- 
strated. 
The lumen of the convoluted portion of the uriniferous tubule is of 
variable caliber; it presents frequent slight dilatations. The caliber also 
depends, to some extent, upon the secretory activity of the epithelium, 
whose cells become shrunken, and the lumen correspondingly dilated, 
during active secretion. The diameter varies from 40 to 60 microns. 
The convoluted tubules are most actively engaged in the secretion of 
urine, but the further changes accompanying their secretion have not 
yet been satisfactorily demonstrated. It is generally believed that the 
water and salts of the urine are secreted in the glomerular capsule, the 
urea in the convoluted tubules. 
4. Descending Limb of Henle's Tubule (The Thin or Narrow Tu- 
bule of Henle}.-In this portion, which is, typically, located in the 
boundary zone of the medulla, the uriniferous tubule becomes very much 
narrowed (8-15 p. ), but the decreased diameter is the result of dimin- 
ished height of the lining epithelium rather than of any change in 
the caliber of the tubule. The length of this portion of the tubule is 
very variable; typically it corresponds very nearly with the breadth of 
the medullary boundary zone. 
The lining epithelium of the descending limb is of a peculiar flattened 
shape. Its cells possess an ovoid nucleus which, being thicker than the 
surrounding portions of the cell, projects slightly into the lumen of the 
tubule. The bulging nuclei of opposite sides of the tubule are not in 
apposition but interlock with one another, the nuclei of one side of the 
tubule being opposed to the cell margins of the opposite side. The 
lumen of longitudinal sections through the axis of the tubule thus ac- 
quires a sort of zigzag outline. The nuclei stain deeply but possess an 
evenly distributed chromatin. The cytoplasm of the epithelium is very 
finely granular, and although its cells are intimately adherent at their THE KIDNEY 
435 
lateral margins they do not present the typical striations which are 
characteristic of the preceding portion. 
5. The Loop of Henle.-As the descending limb enters the loop 
of Henle, the tubule makes an abrupt turn and returns toward the cortex. 
The location of the loop, being dependent upon the variable location in 
the cortex of the renal corpuscle and the variable length of the thin seg- 
ment, may be in any portion of the medulla except the extreme tip of the 
pyramids; its most frequent site, however, is near the junction of the 
boundary and papillary zones. 
The structure of the loop may be that of either the descending or the 
ascending limb of the typical loop. It is also subject to great variations, 
since the change in structure from the narrow to the broad type, though 
it typically occurs just prior to the formation of the loop, is frequently 
delayed until well into the ascending limb. As a rule, the change in 
type occurs earlier when the loop lies in the boundary zone, and later 
when it occurs nearer the apex of the renal pyramid; the thick ascending 
limbs do not occur in the papillary zone of the medulla. 
6. The Ascending Limb of Henle's Loop (The Broad or Thick 
Limb).-This portion of the tubule returns through the boundary zone 
of the medulla and enters a cortical ray, its course being parallel to 
that of the descending limb. It then passes toward the surface of the 
kidney, but finally leaves the ray and enters the labyrinth to reach that 
renal corpuscle (close to the vas efferens) from which the uriniferous 
tubule took origin, and in relation to which the tubule again acquires 
a tortuous course (distal convoluted portion). Within the boundary 
zone of the medulla this portion of the tubule is much broader than the 
preceding division, but it becomes somewhat reduced in size in its course 
through the cortical ray. 
The epithelium of the ascending limb is of a short cuboidal form. 
Its cytoplasm resembles that of the lining epithelium of the convoluted 
portion, although the nuclei in the tubule of Henle are rather more dis- 
tinct. Basal striations are also less distinct than in the convoluted tu- 
bule, the lateral serrations less deep, and the cell outlines sharper. The 
cells of this portion frequently possess a slightly imbricated arrange- 
ment. 
The recent careful comparative studies of mammalian kidneys by 
Peter ("Untersuchungen liber Bau and Entwickelung der Niere," Jena, 
1909) have revealed certain important details. Peter divides the medullary 
portion of the renal pyramid into an outer and inner zone; these portions 
have no precise correspondence with the boundary and papillary zones above 436 
THE URINARY SYSTEM 
mentioned. In the outer zone Peter describes an outer and an inner stripe, 
the line of demarcation being the very definite level where the .proximal 
convoluted tubule passes into the thin, clear, narrow limb of Henle's loop 
(Fig. 400). The point of transition from outer to inner zone is marked by a 
change in the character of the epithelium lining the distal limb of the long 
Henle's loops; the epithelium becomes cloudy (granular) and thicker. In 
view of the great variability in the character of the epithelium at the vari- 
Fiq. 406.-A Group of Tubules from a Transection of a Renal Pyramid of 
the Human Kidney; the Section Passes through the Boundary Zone. 
a, collecting tubule; b, ascending limb of Henle's loop; c, descending limb; d, loop 
of Henle. Hematein and eosin. Photo. X 275. 
ous levels in loops of different lengths, and the recognition by Peter of a 
thicker cloudy segment, it seems better to speak of thin clear, thick clear, 
and thick cloudy segments of the loop. In kidneys of the dog and cat 
there are no really short loops, none lying within the outer zone. In the 
kidney of the pig many loops lie in the cortex; such loops lack entirely 
the thin, clear narrow limb. 
7. The Distal Convoluted Portion {Intercalary or Intermediate 
Portion).-This portion of the uriniferous tubule begins close to the 
vascular pole of the renal corpuscle, and, after several irregular contor- THE KIDNEY 
437 
tions which are confined to the region of the cortical labyrinth, enters 
an arched collecting tubule. The distal is much shorter than the proxi- 
mal convoluted portion. Its caliber is subject to great irregularities, so 
much so that its early turns have been characterized as the irregular or 
zigzag portion of the uriniferous tubule. The epithelium of this section 
resembles that of the proximal convoluted portion but is lower, more 
cuboidal, and striations are indistinct. 
This portion terminates the typically secretory portion of the urinif- 
erous tubule. Beyond here the tubule possesses more the function of a 
duct, hence its epithelium shows a decided change in character. Hith- 
erto it has possessed the peculiar character, the typically granular cyto- 
plasm, of a secreting type of cell. Beyond this section the epithelium is 
no longer so granular but possesses a characteristically clear appearance. 
The secretory and excretory portions of the renal tubule have a separate 
embryonic origin, and only secondarily unite to form a continuous duct. 
8. The Arched Collecting Tubule (Junctional Tubule).-This is 
a short portion of the uriniferous tubule which connects the distal con- 
voluted portion in the cortical labyrinth with the straight collecting tu- 
bules of the cortical rays. Its course is characteristically arched. 
The epithelium of the arched tubule consists of clear cuboidal cells 
with distinct outlines and deeply stained, sharply defined nuclei. The 
chromatin of the nucleus is irregularly distributed, forming numerous 
karyosomes, and the nuclear membrane is distinct. The cytoplasm is 
relatively devoid of granules, and unlike that of the secreting epithelium 
does not possess a strong affinity for the acid dyes. 
9. The Straight Collecting Tubules.-These portions of the tu- 
bules begin in the cortical rays, where they receive the arched tubules, 
and, proceeding to the medulla, become considerably increased in size. 
They penetrate the boundary zone of the medulla, all pursuing a parallel 
or slightly convergent course, and occasionally uniting with each other. 
On entering the papillary zone, by frequent union they become rapidly 
larger, and in the apex of each pyramid finally form about a score of large 
terminal papillary ducts. Though shorter than the convoluted tubules, 
the straight collecting portions, because of their direct course, traverse 
a broader area of the renal tissue; beginning near the peripheral end of 
the cortical rays, in these columns they cross nearly the whole breadth 
of the renal cortex and entering the medulla extend from base to apex 
of the renal pyramid. 
Throughout their whole course they progressively increase in size and 
caliber. A corresponding progressive increase in the height of their epi- 438 
THE URINARY SYSTEM 
thelial cells likewise occurs, so that the lumen of the straight tubules 
of the medulla is not only actually greater than that of those of the 
cortical rays, but the walls of the former tubules are also considerably 
thicker. The extreme of this progression is found in the broad lumen 
and tall epithelium of the papillary ducts. 
The epithelium of the straight tubules, like that of the arched, 
possesses a clear cytoplasm, distinct and deeply staining chromatic 
nuclei, and well defined cell outlines. Beginning in the cortical rays with 
a low columnar type, it gradually increases in height in the course of 
the tubule until, in the papillary zone, the epithelium acquires a tall 
columnar form. The clear cytoplasm and distinct nuclear membranes 
of the epithelium of the collecting tubules stand out in sharp contrast to 
the granular cytoplasm and the evenly distributed chromatin in the 
nuclei of the lining cells in the secreting portions of the uriniferous 
tubules. 
10. Papillary Ducts. (Ducts of Bellini).-These are the wide 
mouths of the uriniferous tubules which are formed by the dichot- 
omous union of from ten to thirty collecting tubules, and which empty 
their secretion into the renal calyces at the apex of the renal pyramids. 
They attain a diameter of from two hundred to three hundred microns. 
They are lined by tall columnar cells with an exceptionally clear cyto- 
plasm which has an affinity for the basic in preference to the acid class 
of dyes. The nuclei are spheroidal or ovoid in shape and lie in the 
basal portion of the cell. At their termination several papillary ducts 
frequently open into a common depression or foveola which is lined by 
an involution of the layer of transitional epithelium, derived from that 
of the renal calyx, by which the free papillary portion of the renal pyra- 
mid is clothed. 
It is obvious that the entire renal tubule, from the glomerular capsule 
to the papillary duct, is a continuous canal whose epithelial wall, sup- 
ported by a thin homogeneous basement membrane varies in character 
in each succeeding portion. Thus the proximal and distal convoluted 
portions and the typical ascending limbs of Henle's loops possess a 
granular, rodded or striated, acidophil, secreting epithelium; the capsule 
has thin cells of an endothelioid type; the typical descending limb and loop 
of Henle are lined by flattened finely granular and faintly acidophil 
epithelium; the curved and straight collecting tubules and papillary ducts 
possess a clear columnar epithelium. It should also be noticed that the 
several portions of the renal tubule occur in different topographical sub- THE KIDNEY 
439 
divisions of the kidney and that, therefore, each of the subdivisions 
contains only certain characteristic portions of the renal tubule. Thus 
Renal corpuscle. 
Neck of the tubule. 
are found in the- 
Cortical Labyrinth. 
{Pars Convolutd) 
Proximal convoluted portion. 
Distal convoluted portion. 
Arched collecting portion. 
Cortical Rays. 
(Pars radiata) 
Spiral portion of the convoluted tubule 
Ascending limb of Henle's tubule. 
Straight collecting portion. 
Descending limb of Henle's tubule. 
Ascending limb of Henle's tubule. 
Straight collecting portion. 
Boundary Zone of the 
Medulla 
Descending limb of Henle's tubule. 
Loop of Henle's tubule. 
Straight collecting portion. 
Papillary duct. 
Papillary Zone of the 
Medulla 
The following outline, based upon the investigations of Peter, gives a 
more detailed classification of the different portions of the renal tubule 
in the medulla: 
1. Outer stripe 
(a) straight collecting tubules. 
(b) proximal convoluted tubules. 
(c) thick ascending limbs of Henle's loops, 
including both 
(x) thick cloudy portions, and 
(y) thick clear portions. 
2. Inner stripe 
(a) thin clear descending limbs of Henle's 
loops. 
(b) thick cloudy portion of ascending 
limbs of Henle's loops. 
(c) short loops of Henle, of thick cloudy 
type of epithelium. 
A. Outer Zone 
Medulla 
B. Inner Zone 
(a) straight collecting tubules. 
(b) long loops of Henle, entirely of thin clear type of 
epithelium. 440 
THE URINARY SYSTEM 
The following tabular resume may be of service by emphasizing the 
more important peculiarities of the several portions of the uriniferous 
tubule. 
Portion of Tubule. 
Epithelium. 
Location. 
Renal corpuscle. 
Flattened, endothelioid. 
Cortical labyrinth. 
Neck. 
Changing from flattened 
to low columnar. 
Cortical labyrinth. 
Proximal convoluted. 
Low columnar, granular, 
and rodded. 
Cortical labyrinth. 
Spiral portion of above. 
Low columnar, granular, 
and rodded. 
Cortical rays. 
Descending limb. 
Low cuboidal or flat- 
tened, granular. 
Medulla (boundary and 
papillary zones). 
Loop. 
Varies; like either the 
preceding or following. 
Medulla (boundary and 
papillary zones). 
Ascending limb. 
Cuboidal or low colum- 
Boundary zone of me- 
nar, granular, imbri- 
cated. 
dulla and cortical rays. 
Distal convoluted. 
Low columnar or pyram- 
idal, granular, and rod- 
ded. 
Cortical labyrinth. 
Arched collecting. 
Cuboidal, clear cyto- 
plasm, dark nucleus. 
Cortical labyrinth. 
Straight collecting. 
Cuboidal, changing to 
columnar. 
Cortical rays and both 
zones of medulla. 
Papillary duct. 
Cuboidal, tall columnar. 
Papillary zone of medulla. 
Renal Blood-vessels, Lymphatics and Nerves 
Blood Supply.-The kidney receives its blood supply from the renal 
artery, which, as it enters the hilum, divides into two sets of principal 
branches, of which the ventral set supply one-fourth, the dorsal set three- 
fourths of the renal substance. These principal branches, the arterice 
proprice renales, or interlobar arteries, are embedded in the connective 
tissue of the sinus and follow the walls of the infundibula and calyces, 
upon which they lie, thus reaching the renal columns between the renal 
calyces. Here they enter the cortical substances and divide, each branch 
passing in a curved or arched manner beneath the base of the adjacent 
pyramids. These vessels form an incomplete arterial arcade (arciform 
artery) which lies in the margin of the cortex at the outer border of the 
medullary boundary zone. 
From the arterial arcade, branches are given to the medullary tissue 
of the pyramids on the one hand, and on the other to the cortical sub- 
stance. Those branches which enter the medulla are slender vessels which THE KIDNEY 
441 
pursue a characteristically straight course between the parallel tubules 
of this region and are known as the arteriolce rectce. They branch freely 
at acute angles and form a rich capillary plexus in the boundary zone, 
the longest of the vessels reaching beyond the limits of this region to 
supply a less abundant 
plexus to the papillary 
zone of the medulla. 
The cortical branches 
of the arterial arcades are 
vessels of considerable size 
which enter the labyrinth 
between the cortical rays 
and as interlobular arteries 
(cortical arterioles) pass 
toward the surface of the 
organ, a few of the longest 
branches reaching the fi- 
brous capsule with whose 
vessels they anastomose. 
Throughout their whole 
course the interlobular ar- 
teries give off numerous 
short branches, which 
leave the parent stem at a 
wide angle, and pass di- 
rectly to a renal corpuscle 
as the afferent artery (ar- 
teriole; vas afferens) to its 
glomerulus. Here it sup- 
plies the capillary plexus 
in the manner already de- 
scribed (page 431). 
Certain of the afferent 
arterioles are peculiar in 
that (1) they give off 
small branches which supply capillaries directly to the convoluted tubules 
of the cortical labyrinth; and (2) they occasionally form a small rete 
mirabile before they reach the glomerulus. By far the greater portion 
of the branches of the interlobular arteries, however, pass directly to the 
glomeruli. The capillaries of the glomerulus reunite to form an efferent 
Fig. 407.-The Distribution of the Left Renal 
Artery. 
Of the six arteriae propriae renales, five enter in 
front of the renal pelvis, and, lying upon the wall 
of the calyces, are distributed from the arterial 
arcade to both cortex and medulla, a, ureter; b, 
renal artery; c, arteriae propriae renales; d, the dark 
border is the cortex, within which is the lighter 
medulla. (After Brbdel, from Szymonowicz and 
MacCallum.) 442 
THE URINARY SYSTEM 
vessel which, after leaving the corpuscle, promptly breaks into a second 
capillary plexus about the adjacent tubules. 
The efferent vessels of those glomeruli which lie in that portion of 
the cortex adjoining the medulla, frequently pass to the boundary zone 
of the latter region where they form the arteriae recta? spuriae which, 
though lacking a true arterial structure-they possess no circular mus- 
Fig. 408.-From the Cortex of the Human Kidney. 
The blood-vessels have been injected and appear dark. A cortical ray and the 
adjacent labyrinth is included, a, cortical ray; b, a glomerulus in the labyrinth. 
Moderately magnified. (After Disse.) 
cle fibers-pursue the same course as the true arteriolae rectae and assist 
the latter in supplying the capillary plexus of the medulla. The medul- 
lary capillaries, like those of the rays in the cortex, form a network with 
elongated meshes which surround the parallel tubules of this region. 
The capillaries of the cortical labyrinth, being distributed among irregu- 
lar tortuous tubules, possess a more polygonal mesh. 
The interlobular veins begin near the surface of the organ where THE KIDNEY 
443 
small venules, derived from the cortical capillaries and from occasional 
anastomoses with the capsular vessels, unite to form broad thin-walled 
venous spaces, the stellate veins of Verheyn, just beneath the capsule. 
From these subcapsular vessels the interlobular veins arise, and pass 
toward the medulla in company with the interlobular arteries, throughout 
their course collecting the minute venules which return the blood from 
the capillaries about the tubules of the renal cortex. 
Arriving at the border of the medulla, but still embedded in the 
cortical substance, the interlobular veins turn sharply, at nearly right 
angles to their former course, and by free anastomoses form a venous 
arcade (arciform vein), which receives the venulce rectce coming from the 
capillary plexuses of the medulla, and at the border of the renal pyra- 
mid enters a renal column to unite with similar vessels coming from the 
borders of the adjacent pyramids. The union of these vessels forms 
large venous trunks which leave the renal columns, in company with 
the arteries, as the vents proprice renales (interlobar veins). They enter 
the connective tissue of the hilum, traverse the wall of the calyces, in- 
fundibula, and renal pelvis, and finally unite to form the renal vein. 
TABLE SHOWING THE COURSE OF THE RENAL CIRCULATION 
Renal artery 
Renal vein 
Arteriae propriae renales 
Venae propriae renales 
Arterial arcade 
Venous arcade 
Interlobular arteries 
Arteriolae rectae 
Venulse rectse 
Interlobular veins 
Capillaries of medulla 
I 
Venae steUatae 
1 
Afferent artery to renal corpuscle 
Capillaries of the cortical labyrinth 
Capillaries of the glomeruli 
Efferent vessel from renal corpuscle 444 
THE URINARY SYSTEM 
The venulae rectae are peculiar in their typically straight course, 
and in the fact that the cells of their endothelium are extremely long- 
so long indeed, as frequently to present a somewhat fibrous appearance, 
the elongated axis of the cell being parallel to the long axis of the vessel. 
The capsule of the kidney is supplied by branches of the lumbar, 
phrenic, and suprarenal arteries, which form a rich, capillary plexus. 
These vessels anastomose with the terminal 
branches of the interlobular arteries of the 
kidney in the manner above described-a 
fact which acquires surgical importance from 
its relation to the establishment of a collat- 
eral circulation. 
The table on page 443 may be useful as a 
resume of the more important paths in the 
course of the renal circulation. In it the 
names of the several vessels are arranged in 
order and the arrows indicate the direction 
of the blood current. 
Lymphatics.-The renal lymphatics con- 
sist of a superficial set which forms plexuses 
in the perirenal fat and deeper layers of the 
capsule, and a deep set which supplies the 
parenchyma of the organ. These two sets of 
lymphatic vessels are in communication by 
frequent anastomoses. The vessels of the 
superficial set convey their lymph to the 
neighboring lymph glands of the lumbar 
region. 
The deep renal lymphatics accompany 
the arteries and veins throughout their 
course. They form narrow cleftlike vessels 
of irregular caliber in the scanty interstitial tissue between the urinifer- 
ous tubules of both cortex and medulla. These vessels are relatively few 
in number. They converge to the hilum of the organ where they pass to 
the nearby lymphatic glands. 
Nerves.-The nerves of the kidney include both medullated and 
non-medullated fibers. The sympathetic fibers form a ganglionated 
plexus in the connective tissue about the renal pelvis. From this plexus 
fibers are distributed to the blood-vessels of the capsule and to the 
parenchyma of the organ. The latter accompany the blood-vessels, dis- 
Fig. 409.-Nerve Endings 
in a Convoluted Tubule 
of the Frog's Kidney. 
a, nerve fiber; b, blood-ves- 
sel; c, secreting epithelium. 
Methylene blue; cochineal. 
Very highly magnified. (Af- 
ter von Smirnow.) RENAL PELVIS AND URETERS 
445 
tributing their fibers to the walls of the arteries and veins and to the 
uriniferous tubules of both cortex and medulla. 
The parenchymal branches form an 'epilemmal plexus' in the in- 
terstitial connective tissue about all portions of the uriniferous tubule. 
From this plexus fibrils pierce the membrana propria and anastomose to 
form a 'hypolemmal plexus' about the base of the epithelial cells. Ter- 
minal fibrils penetrate between the epithelial cells where they form 
minute end knobs. 
RENAL PELVIS AND URETERS 
The excretory passages of the kidney include the renal pelvis, the 
ureters, the urinary bladder and the urethra. All of these portions 
possess certain common characteristics. They have three coats, mucous, 
muscular, and fibrous, and are lined by a common type of epithelium, 
Fig. 410.-Cast of the Pelvis, Infundibula and Calices of the Kidneys 
of a Man. 
Showing the expansion of the ureter, the subdivision of the pelvis, and the con- 
cave facets by which the calices fit over the apices of the renal pyramids. (After 
Hauch.) 
transitional, which extends from the renal pelvis to the prostatic por- 
tion of the urethra. 
The mucosa of the renal pelvis and ureter is lined by transitional 
epithelium which rests upon a fibrous tunica propria. The epithelium 
consists of several cell layers, of which the superficial is formed by broad 446 
THE URINARY SYSTEM 
cuboidal cells, or thick flattened plates, whose form varies with the state 
of distention of the organ, and whose deep surfaces are indented by the 
rounded ends of the pear-shaped cells which form the deeper layers. The 
deepest cells are smaller and are irregularly spheroidal in shape. They 
Fig. 411.-Transection of Human Ureter. 
Hematein and eosin. Photo. X 113. 
are firmly attached to the underlying connective tissue which here and 
there projects into the epithelial layer carrying with it the most super- 
ficial capillary vessels. The cells of the deeper layers divide by karyo- 
kinesis and push toward the surface to replace the more superficial cells 
which are gradually desquamated. Direct cell division occurs in the RENAL PELVIS AND URETERS 
447 
large plate-like cells of the superficial layer. The thin transitional epi- 
thelium of the calyces is continuous with the columnar epithelium of the 
papillary ducts. 
The tunica propria, continuous with the renal interstitial tissue, 
contains both col- 
lagenous fibers 
and elastic fibers. 
It is indistinctly 
divisible into a 
superficial denser 
portion, and an 
open-meshed deep 
portion whose fi- 
brous bands loose- 
ly attach the mu- 
cous membrane to 
the muscular coat. 
This deep layer is 
analogous to the 
submucosa of the 
alimentary tract. 
The mucous mem- 
brane is thrown 
into numerous 
deep folds or rugae 
which in the ure- 
ter have a longi- 
tudinal direction; 
this condition 
gives to the canal 
in transverse sec- 
tion a stellate ap- 
pearance. Irregu- 
lar folds or inva- 
ginations of the 
epithelium occur 
in the renal pelvis 
and have been described as glands, but true secreting glands are not 
found. Occasional lymphocytes occur in the mucosa, and small lymph 
nodules have also been found but cannot be regarded as of constant 
-tun lea 
propria 
- turn. 7ca 
/>ro/>ria 
Fig. 412.-Transitional Epithelium of Dog's Ureter. 
A, in the contracted condition; B, in the distended con- 
dition; a, basal layer of cubic cells: b, middle layer of polyg- 
onal cells; c, superficial layer of rectangular and ovoid 
cells. (R. W. Harvey, Anat. Rec., 3, 5, 1909.) X 750. 448 
THE URINARY SYSTEM 
occurrence. The mucosa becomes gradually thinner as it is traced 
through the infundibula and calyces and is reflected upon the surface 
of the renal pyramids. 
The muscular coat of the ureter consists of a well-defined layer 
of circular fibers within which are many discrete bundles of longitudinal, 
smooth muscle. In the lower half of the ureter a third layer, whose 
fibers also have a longitudinal direction, is found outside the circular 
fibers. In this portion of the ureter, therefore, the muscular coat 
consists of three layers, an inner longitudinal, middle circular, and 
outer longitudinal. 
In the renal pelvis and calyces the muscular coat becomes pro- 
gressively thinner toward the renal substance, and at the apex of the 
pyramid consists chiefly of circular fibers which are slightly thickened 
to form a 'sphincter' about the papilla. 
The outer fibrous coat of the ureter consists of areolar tissue which 
blends with that of the surrounding parts. In the renal pelvis this 
coat becomes continuous with the connective tissue capsule of the kidney. 
(For development of excretory passages, see next Chapter.) 
Blood Supply.-The larger blood-vessels lie in the outer fibrous 
coat and distribute branches to the muscular coat and to the mucous 
membrane. In the latter they form a superficial capillary plexus which 
is in unusually intimate relation with the deeper cells of the lining 
epithelium. 
The Lymphatics.-The lymphatics begin in an intramuscular plexus 
and, by scanty vessels, in the deeper part of the mucosa. They pass 
to larger vessels in the outer coat, which possess valves, and convey 
the lymph to the neighboring lymph nodes. 
The Nerves.-The nerves form a coarse plexus in the outer fibrous 
coat which contains many small ganglia. From this plexus motor 
fibers are distributed to the muscular layers, and sensory fibers to 
the mucosa. The latter form a plexus beneath the epithelium from 
which terminal fibers pass to end by minute end brushes in the con- 
nective tissue and by varicose fibrils between the deep cells of the epi- 
thelium. 
THE URINARY BLADDER 
The wall of the urinary bladder closely resembles that of the ureter. 
It consists of mucous, muscular, and fibro-serous coats. Its mucous 
membrane is lined by transitional epithelium like that of the ureter THE URINARY BLADDER 
449 
and renal pelvis. It is therefore impossible to determine from which 
of these portions detached epithelial cells are derived when found by 
microscopical examination of the urine. Epithelium may become de- 
Fig. 413.-Transection of the Wall of a Child's Bladder. 
a, mucosa; b, muscular coat; c, serous coat. Hematein and eosin. Photo. X 128. 
tached from any portion of the excretory passages, and as a result of 
inflammatory changes not only the superficial cells but also the deeper 
pear-shaped cells may be desquamated. 
The character of the epithelium varies with the collapse and dis- 
tention of the organ. When empty the mucous membrane is thrown 450 
THE URINARY SYSTEM 
into deep folds or rugae, whose surface also presents secondary folds 
of irregular direction. The epithelial layer is relatively thick, and is 
thicker on the sides of the folds than upon either their apices or bases 
where the folding of the epithelium increases the tension of its cells. 
When the organ is distended, the folds are more or less completely 
obliterated, the epithelial layer is much thinned, often until it appears 
Fig. 414.-The Mucosa of a Child's Bladder in the Contracted State of the 
Organ. 
a-a, and a'-a', transitional epithelium; b, fibromuscular tissue of the mucosa. 
Hematein and eosin. Photo. X 216. 
to consist of no more than a double layer of cells, and its cells be- 
come much broader and relatively much thinner than in the collapsed 
or empty condition. Hence the transitional variety of epithelium, by 
which the organ is lined, may be said to be remarkable for the extreme 
elasticity of its cells. 
The mucous membrane, except near the urethral orifice, contains 
no glands. In this location, however, the bladder of adult man contains 
a few small mucus-secreting glands, lined by columnar cells (Kbl- THE URINARY BLADDER 
451 
liker). These are not present in infancy. They have been interpreted 
as vestigial prostatic tubules. 
The tunica propria resembles that of the ureter and is loosely united 
to the muscular coat. This latter layer is formed by interlacing 
bundles of smooth muscle. It varies much in thickness according to 
the condition of the organ, being relatively thick when the viscus is 
A, in the contracted condition; B, in the distended condition. (R. W. Harvey, 
Anat. Rec., 3, 5, 1909.) 
Fig. 415.-Transitional Epithelium of Dog's Bladder. 
empty and very thin when it is completely distended. In most portions 
three indistinct layers can be observed, a middle thick layer of circular 
fibers, and an inner and outer longitudinal layer. The outer longitudinal 
muscle is most distinct on the anterior and posterior surfaces of the 
organ. 
The outermost coat of the bladder consists of areolar tissue, having 
very broad meshes; in the lower portion of the bladder this coat blends 
with the connective tissue of the adjacent organs. Over the fundus of 452 
THE URINARY SYSTEM 
the organ its outer fibrous coat is covered by the peritoneum, the con- 
nective tissue of which is indistinguishable from that of the outer coat 
of the bladder; it is clothed by the peritoneal mesothelium. 
Vascular and Nerve Supply.-The vascular and nerve supply of 
the bladder is exactly similar to that of the ureter. The larger blood- 
Fig. 416.-Epithelial Cells from the Bladder of the Rabbit. 
A, as seen from the under surface, showing the depressions made by the under- 
lying polygonal and pyriform cells (P); B, side view of similar cell. (After Klein, 
from Schafer.) 
vessels occur in the outer fibrous coat, whence they distribute branches 
to the muscular coat and mucous membrane. Many small ganglia are 
also found in the outer coat, and motor and sensory nerves are dis- 
tributed to the musculature and to the epithelium and connective tissue 
of the mucosa, as in the ureter. 
THE URETHRA 
The Female Urethra 
The mucosa of the female urethra is lined by a variable type of 
epithelium. Being continuous with the mucosa of the bladder, the 
epithelium of the urethra is at first of the transitional variety, but as 
it approaches the meatus this is changed to a stratified squamous 
type which is continuous with that of the vestibule. In certain indi- 
viduals the superficial cells of the midportion of the urethra are much 
elongated and assume an irregular stratified columnar type. 
The epithelium rests upon a tunica propria of dense areolar con- 
nective tissue whose outer portion blends with a looser connective THE URETHRA 
453 
tissue which contains many broad venous channels and forms a sort 
of spongy erectile tissue. This erectile coat is surrounded by a thin 
muscular coat whose innermost fibers, longitudinal in direction, are 
continued outward to the meatus, and whose outer circular fibers, de- 
Fig. 417.-Transection of the Female Urethra. 
d, gland-like diverticulum; e, urethral epithelium; L, urethral lumen; m, striated 
fibers of the urethral muscle; s, erectile tissue of the tunica propria, containing 
many venous spaces and smooth muscle fibers. X 10. (After Kolliker.) 
ficient toward the meatus, are often slightly thickened near the neck 
of the bladder to form an indistinct sphincter urethrae muscle. This 
coat contains occasional striated muscle fibers. The female urethra 
is scantily supplied with urethral glands which open near the meatus 
and supply a meager mucoid secretion. 454 
THE URINARY SYSTEM 
The Male Urethra 
The male urethra conducts the urine from the bladder to the sur- 
face, its course being through the axis of the corpus spongiosum of the 
penis (Fig. 446). It forms the terminal segment also of the genital 
canal and conducts the semen; it accordingly performs a double func- 
tion, serving both the urinary and the male reproductive system. The 
character of its epithelium is variable, not only in its successive por- 
tions, but it is also subject to great individual variation, and like that 
of the bladder and ureter changes its appearance according as the canal 
is collapsed or distended. In the first or prostatic portion of the urethra 
the epithelium is of the transitional type; in the membranous and penile 
portion its superficial cells are elongated so that the epithelium usually 
acquires a stratified columnar form; near the meatus the type is again 
ex-changed for a stratified squamous epithelium which is continuous 
with that of the glans penis. 
The tunica propria of the urethra consists of areolar tissue in which 
are embedded the small branched tubulo-acinar urethral glands (of 
Littre) lined by columnar, mucus-secreting cells. These glands are 
more abundant along the upper surface. The mucosa also contains 
frequent lacunar invaginations of the epithelium, and is thrown into 
longitudinal rugae, its lumen being obliterated except when distended 
by the passage of urine. 
The tunica propria, and especially that portion which is distant from 
the urethral canal, is permeated by the thin-walled broad venous spaces 
of the erectile tissue of the corpus spongiosum. The septa between 
these venous spaces, in addition to the dense areolar tissue of which 
they chiefly consist, contain many bundles of longitudinal smooth 
muscle. In the deeper portions of the urethra circular muscle fibers 
are also found in the outer part of this coat, and near the orifice of 
the bladder they are somewhat thickened to form the sphincter urethrae 
Moreover, the corpus spongiosum is invested with a thick sheath of 
dense fibrous connective tissue. At the apex of the prostate circularly 
disposed striped muscle fibers form a second urethral sphincter, the 
external vesical sphincter. 
Nerve Supply.-The nerve supply of the urethra includes both 
sensory and motor spinal fibers, and sympathetic fibers for the smooth 
muscle and the blood-vessels. CHAPTER XV 
THE REPRODUCTIVE SYSTEM 
GENERAL CONSIDERATIONS 
The reproductive system differs structurally, widely in the two 
sexes. The several organs involved, however, are in general strictly 
homologous in the male and female organism. The differences result 
from a divergent specialization concomitant with a division of labor 
in the reproductive act and process. The specialization involves both 
progressive and regressive differentiation, the latter producing certain 
Sines pre st et ic ds 
(7rinary 
~]}lAdder. 
.Ampulla- of cfectut 
fef ere ns 
Srminul reside 
_£jacula.tory duct 
- P-OStcute y/antf 
- Pulbourethre! 
"'Sulbus urethrae 
-2>uctus deferens 
Corpus 
Urethral f/eo.de- 
(/ret Are 
Corp. C»< urethra*- 
Pa radu d<f rq < S 
Ductuli. efferentes 
Ductulus abberans 
JDuctus epididymis 
''•'Rete test us 
recti 
''Tabu/i erntnti. 
Pre pace 
Clans penis'' 
fess a. f u-fa jLt 
/ flppendty fastis 
fl pre * 4 i y epididymis 
Fig. 418.-Diagram of Male Genitalia. (Adapted from Merkel.) 
vestigial appendages, of different origin in the opposite sexes. The 
male organs of reproduction include a primarily and essentially in- 
ternal group of genital organs, namely, the testis, and its associated 
455 456 
THE REPRODUCTIVE SYSTEM 
ducts, glands and appendages; and an external genital organ, the penis 
(Fig. 418). The female organs of reproduction likewise include an 
internal group of genitalia, namely, the ovary, with its ducts and the 
Fig. 419.-Diagram of Female Internal Genitalia. 
associated glands and appendages; and a group of external genitalia 
and glands (Fig. 419). The essential sex organs are the testis and ovary, 
respectively. 
DEVELOPMENT 
The primary anlages are the same in both sexes. They include essen- 
tially: a pair of undifferentiated sex-glands or gonads located on the mid- 
ventromesial side of each fetal kidney (Wolffian body or mesonephros); a 
double pair of parallel canals, the fetal Wolffian (mesonephric) ducts and 
the Mullerian ducts. An embryo at this stage of development (13 milli- 
meters, Fig. 210, about 40 days) is said to be in the indifferent sexual stage. 
The ducts communicate terminally with the gonads and the exterior. Sub- 
sequently they undergo a different development, as do also the terminal 
associates (gonads, and urogenital sinus, respectively) in the two sexes. 
For the details of this process reference must be made to a text-book of 
Embryology. But briefly, the primitive gonads in the female develop into 
the ovaries, in the male into the testes. In the female the Mullerian ducts 
become the oviducts, and fuse proximally to form the uterus and vagina; 
in the male, this duct suffers regressive changes and persists only as ves- 
tiges : the appendix testis, and the sinus pocularis. On the contrary the 
Wolffian duct becomes vestigial in the female, persisting as the appendix 
fimbria (hydatid of Morgagni) and the canal of Gartner; while in the male, 
it develops into the main portion of the definitive duct system: ductus epi- 
didymis, and ductus deferens. The tubules of the fetal kidney (Wolffian DEVELOPMENT 
457 
body) also contribute to the excretory duct system. In the male, they per- 
sist in part (10 to 15) to form the ductuli efferentes; several may become 
vestigial forming thus the ductuli aberrentes, the paradidymis and the 
appendix epididymis. In the female, these ducts early disappear for the 
Kidney - 
Mullerian duct " 
Genital gland 
Mesonephros -- 
Ureter - ■ 
Inguinal ligament * 
Mesonephric duc' ~ 
Mullerian duct ~ ' 
•Apex of bladder 
Bladder 
Opening of ureter 
f Opening of mesoneph- 
i ric duct 
{Opening of Mullerian 
duct 
Rectum 
Urogenital sinus 
Cloaca 
Genital tubercle 
Genital ridge 
Opening of cloaca 
Fig. 420.-Diagrams Illustrating the Metamorphoses of the Indifferent 
(A) Urogenital System into the Male (B), and Female (C) Systems. (From 
Polak, after Hertwig.) 
most part-a variable number persisting as vestigial structures: the epo- 
ophoron and the paroophoron. 
The seminiferous tubules (including the recti and rete tubuli) of the 
testis arise as solid cords of cells continuous with the peritoneal epithelial 
covering of the gonad, and apparently as derivatives of this so-called 'ger- 
minal epithelium.' These cords subsequently acquire a lumen, and connect 
with the efferent tubules. In the ovary likewise such cell cords (sex-cords) 
appear, continuous with the peritoneal (germinal) epithelium; from these 
develop the ovarian follicles with their ova, as will be described below. 
The relation of the extra-regional 'primordial germ-cells' to the germinal 
epithelium and to sex-gland derivatives, discussed in the next section, Kidney 
Appendage of testicle) 
Hydatid of Morgagni J 
Epididymis 
Testis 
Paradidymis 
Deferent duct 
Mullerian duct 
Gubernaculum testis 
Ureter 
Seminal vesicle 
Deferent duct 
Epididymis 
Testis 
Gubernaculum testis 
■Apex of bladder 
Bladder 
Opening of ureter 
Urethra 
( Opening of ejaculatory 
( duct 
Prostate 
Urethra Sinus prostaticus 
B 
Kidney • 
Hydatid 
Oviduct) 
(fimbria;) J 
Epobphoron. 
Ovary 
Paroophoron 
Mesonephric) 
duct j 
Oviduct 
Epobphoron 
Ovary 
Ovarian liga- ) 
ment ) 
Uterus 
Round ligament 
.Vagina 
■Apex of bladder 
Bladder 
Ureter 
, Urethra 
{Vestibulum 
vaginae 
458 DEVELOPMENT 
459 
remains in doubt. Felix (Keibel and Mali's "Human Embryology," vol. 2) 
inclines to the view that in man the primordial germ-cells (primitive geni- 
tal cells) disappear, and that they bear no genetic relationship to the primi- 
tive germ-cells (secondary genital cells) of the gonad. 
Table of the Adult Male and Female Derivatives of the Fetal 
(Indifferent) Reproductive System. 
(77te vestigial structures are given in italics, synonyms in parentheses.) 
Internal Genitals. 
Indifferent stage. 
Male. 
Female. 
Genital ridge. 
Testis. 
Gubernaculum (mesor- 
chium). 
Fimbria ovarica. 
Ovary 
Ovarian ligament (meso- 
varium). 
Round ligament. 
Wolffian body (tubules) 
(Mesonephros). 
Globus major of epididy- 
mis (ductuli efferen- 
tes). 
Paradidymis. 
Ductuli aberrentes. 
Appendix of epididymis 
{stalked hydatid). 
Epoophoron (Parovarium, 
organ of Rosenmuller). 
Paroophoron. 
Wolffian duct (Mesonephric 
duct). 
Duct and globus minor 
of epididymis. 
Ductus deferens. 
Seminal vesicle. 
Ejaculatory duct. 
Chief vesicular appendage 
(Hydatid of Morgagni). 
Collecting tubule of epo- 
ophoron. 
Canal of Gartner. 
Mullerian duct. 
Appendix testis {sessile 
hydatid). 
Sinus pocularis (Uterus or 
vagina masculina, or 
utriculus prostaticus). 
Oviducts (Uterine or Fal- 
lopian tubes). 
Uterus. 
Vagina. 
External Genitals. 
Urogenital sinus. 
Genital tubercle. 
Genital folds. 
Genital swellings. 
fProstatic and membra-) 
J nous portions of male > 
I urethra. J 
Penis. 
Scrotum. 
Urethra. 
Vestibule. 
Clitoris. 
Labia minora. 
Labia majora. 460 
THE REPRODUCTIVE SYSTEM 
The outline on the preceding page summarizes in tabular form the 
main facts regarding the development of the reproductive system. 
In both sexes the Wolffian duct proximally sprouts a duct which dilates 
and subdivides distally, meanwhile separating from the parent duct and 
making a secondary connection with the developing bladder. The subdi- 
visions elongate to form the collecting portion of uniniferous tubules, and 
unite with ontogenetically distinct tubules (the secretory portions) to form 
the complete tubules. The dilatation and earlier subdivisions become the 
pelvis and calyces, and the proximal portion of the original anlage persists 
as the ureter. 
GAMETOGENESIS 
The study of the sex or genital glands, the ovary and the testis, 
is perhaps best approached by way of a consideration of the mechanism 
by which they perform their respective specific functions, namely the 
production of ova and spermatozoa ripe for union. The common process 
is known as gametogenesis. The end products are the male and female 
gametes, or sperm and ova. In the male the process is known as 
spermatogenesis, in the female, oogenesis. The act of subsequent union 
.of the gametes is called fertilization, and the fertilized egg is the zygote. 
The result of gametogenesis is the preparation of a primary germ- 
cell for union with a gamete from the opposite sex. The essence of 
the process is known as maturation, and involves prominently mitotic 
cell division. However, the method of division is not of the simple 
homeotypic type, where a chromosome simply divides longitudinally into 
two daughter chromosomes, but is of the type called heterotypic, the 
chief characteristic of which is the formation of tetrads. The latter 
are of various sorts, all, however, characterized by a four-lobed condition 
representing a quadripartite double or bivalent chromosome (Plate B, 
figs. 15-18, page 467). 
Both sperm and egg trace their ancestry back to primordial germ 
cells, indistinguishable in the sexually undifferentiated organism, ex- 
cept for a difference in chromosome content, which difference is com- 
monly indiscernible. In certain instances, e.g., Ascaris, the germ cell 
can be distinguished from the soma cell at the two-cell stage. In a 
number of vertebrates, e.g., dogfish, turtle, etc. (Allen), the primordial 
germ-cell has been traced from a position among the entoderm cells 
lining the gut of the young embryo through a migration into the dif- 
ferentiating gonad, ovary or testis. Swift (Amer. Jour. Anat., 15, 4, GAMETOGENESIS 
461 
1914) has traced the primordial germ-cells in the chick from a crescen- 
tic area in the entoderm in front of the head end of the primitive streak, 
through their migration to the gonad by way of the developing blood- 
vessels. The earlier anatomists, on the other hand, derived the 
primordial germ-cells from the mesothelial covering (germinal epi- 
thelium) of the germ gland region of the primitive kidneys, the meso-1 
nephroi. This mode of origin, either exclusively or in part, is still 
supported by certain investigators. 
Whatever the actual source of origin-whether entodermal or meso- 
dermal, whether specific or otherwise-and whenever the time of dif- 
ferentiation, whether early or relatively late, the primordial germ-cells 
in the gonad undergo extensive proliferation, increasing greatly in 
numbers. The earlier generations may be inclusively designated pri- 
mary spermatogonia or obgonia respectively, the final generation taking 
the term secondary gonia. The question of the origin of the primordial 
germ-cells bears upon the hypothesis of the continuity of germ-plasm. 
Spermatogenesis.-Since gamete production is easier to follow, 
though apparently more specialized, in the male, spermatogenesis is 
advantageously first described. For the purpose we may employ the 
active testis of Schistocerca damnifica, a common grasshopper. Grass- 
hopper material of many species is peculiarly favorable for a demon- 
stration of the process of spermatogenesis. This scheme will apply 
with slight qualification to most grasshoppers. The reduced number 
of chromosomes is the same, namely, 12; moreover, this material shows 
peculiarly well the accessory or sex chromosome, and thus serves as 
a splendid basis for a discussion and comprehension of the salient facts 
and recent theories touching the problems of the determination, control, 
and inheritance of sex. 
The grasshopper testis is a long tubular structure subdivided into 
a number of compartments, or cysts, each filled with cells of ap- 
proximately the same stage of development, the successive stages in 
spermatogenesis being represented in successive cysts from distal to 
proximal pole. For purpose of readiest study there is required, then, a 
median longitudinal section of an entire testis in active condition. As 
is obvious, such material is useful also for illustrating mitosis but, with 
the exception of the spermatogonial and second maturation mitoses, 
cannot be regarded as typical; but for application and extension of a 
preliminary knowledge of simple mitosis it is perhaps unexcelled. It 
must be emphasized that this peculiar type of cell division, charac- 
terized chiefly by the phenomena of synapsis and tetrad formation, in- Proliferation 
Growth 
Maturation 
Fig. 421.-Diagrams Illustrating the Process of Maturation in the Male (A) and Female (B) Gametes. 
( A-ff.or A 
Oogonia J 
Primary oocyte J 
Secondary oocyte 
Mature ovum 
I Proliferation 
\>Maturation 
k Transformation 
•Growth 
Spermatogonia • 
Primary spermatocytes 
Secondary spermatocyte 
Spermatid 
Spermatozoon 
462 GAMETOGENESIS 
463 
volving a reduction as well as an ordinary equation division, is limited 
to the maturation mitoses occurring in active testes and ovaries. The 
appended scheme will serve to show graphically the steps in spermato- 
genesis and oogenesis, and the correspondences and differences between 
the two. 
We may begin the detailed description with the last generation of 
spermatogonia, the secondary spermatogonia. In the early resting stage 
the nucleus is poly-vesicular, each vesicle representing one or several 
chromosomes (Plate A, Fig. 1). Subsequently the separate vesicles fuse 
to form a greatly lobulated nucleus. In Fig. 2 one vesicle is shown still 
separated; this probably represents the accessory or sex chromosome; sub- 
sequently it also fuses with the main nucleus and remains generally 
indistinguishable from the other nuclear elements until early stages 
of the succeeding generation of cells, the primary spermatocytes (Fig. 
8). Figs. 3, 4, 5, 6 and 7 represent successive stages in the karyo- 
kinetic division of the secondary spermatogonia. In the telophase of 
the spermatogonal division and the earliest prophase of the primary 
spermatocytes, as well as subsequently, the sex chromosome (allosome; 
heterochromosome) does not pass through the diffuse and spireme phases 
of the ordinary chromosomes (autosomes; euchromosomes) but remains 
chromatic and relatively compact. Subsequently it condenses consid- 
erably more (Fig. 8) and thereafter persists until late spermatid stages 
as a compact, deeply chromatic body, generally of oval or bilobed form, 
and usually close to or on the nuclear wall (Figs. 10; plate B, 14 and 20; 
and plate C, 27). Following the early growth stages, when the nucleus 
is in the resting or diffusive chromatic stage (Fig. 8), a series of 
changes occur known as synapsis. The most characteristic phase is the 
one in which the spireme becomes closely aggregated and polarized 
(synizesis) and subsequently segmented, the segments becoming looped 
and attached by their open ends to the nuclear wall over a constricted 
area, generally in the vicinity of the sex chromosome. The loops now 
free one attached end and unite in pairs by their free ends forming 
taller loops, oriented similarly to the smaller loops (bouquet figure, 
synaptenic nucleus). The number of loops is now half the original 
number, which represented the full number of chromosomes. This 
chromosome pairing is the essence of synapsis. An end to end union 
as here described is termed telosynapsis (metasyndesis) ; side by side 
union, described in certain forms, parasynapsis (parasyndesis). The 
important point ns the reduction to half (plus one, the accessory) the 
original number (diploid) of chromosomes; the reduced number is 464 
THE REPRODUCTIVE SYSTEM 
termed the haploid group. The loops now lose their polarized condi- 
tion (postsynaptic phase) and become scattered throughout the nucleus, 
which has meanwhile grown in size, and become more or less closely 
united into a more or less continuous thread. This soon shows evidences 
of a longitudinal split (Fig. 12), the diplotene phase; subsequently 
this undergoes transverse segmentation into half the original number 
(23) of chromosomes, irrespective of the ac- 
cessory; thus there are 11 segments. The 
nucleus contains in addition a pale-staining 
plasmosome, and the deep-staining accessory 
chromosome in its characteristic location. 
Figs. 11 to 14 are designed to show these 
two structures in varying relationships. Fig. 
15 illustrates a late prophase condition, in 
which the euchromosomes (McClung) are 
less compant than the heterochromosome 
(accessory), and in the typical tetrad or 
quadripartite condition. 
At this point we may recapitulate our 
facts regarding the chromosomes. The sper- 
matogonium contains 23 (Fig. 423 A). 
With one exception the chromosomes can be 
grouped in pairs; such grouping gives 11 
pairs. Moreover, the chromosomes can be 
arranged in a progressive series from the 
viewpoint of size; the unpaired, or accessory 
chromosome (10x) takes rank between the 
9 and 11 chromosomes. These chromosomes 
represent the original contribution from 
father and mother when the egg was fertilized preceding development. 
At synapsis the chromosomes actually pair and fuse; and obviously in 
the manner indicated in (/I), for the chromosomes can again be ar- 
ranged in a graded series, corresponding approximately in size and range 
to the pairs indicated. Since the accessory has no mate the reduced 
number of chromosomes is 12. 
It is now quite generally believed that the chromosomes of a pair rep- 
resent paternal and maternal contributions; thus from the viewpoint of 
inheritance, assuming that the chromosomes are the vehicles of certain 
hereditary characters and qualities, the offspring of a pair of parents inherit 
Fig. 422.-Primary Sperma- 
tocyte of a Grasshopper, 
Hippiscus Tuberculatus, 
Showing the Compact 
Accessory Chromosome 
(z) Among the Paler 
Mossy Prophase Euchro- 
MOSOMES, AND THE IdIO- 
SOME (l). 
The cytoplasm contains 
many granular and filamen- 
tous mitochondria. Flem- 
ming fixation; iron-hematox- 
ylin stain. X 1800. Plate A. 
Plates A, B, and C.-Successive Stages in the Spermatogenesis of Schisto- 
CERCA DAMNIFICA. 
x, accessory or sex chromosome; p, plasmosome; i, idiosome. 1 to 7, spermato- 
gonia; 8 to 19, primary spermatocytes; 20 to 26, secondary spermatocytes; 27 to 30, 
spermatids, differentiating (31 to 35) into the spermatozoon (36). 10, synapsis 
stage; 18 and 24, metaphase plates of chromosomes; 6 a, diagram of a longitudinally 
split univalent chromosome from the metaphase plate of a spermatozonial mitosis; 
16b, diagram of a bivalent chromosome, in tetrad condition, from the metaphase 
plate of the first maturation spindle, undergoing the reduction division; 23c, longi- 
tudinally split univalent chromosome entering the second maturation spindle for the 
equation division. (Flemming fixation; iron-hematoxylin stain.) X 1750. 
465 Plate B. 
Plates A, B, and C.-Successive Stages in the Spermatogenesis of Schisto- 
CERCA DAMNIFICA. 
467 Plate C. 
Plates A, B, and C.-Successive Stages in the Spermatogenesis of Schisto- 
CERCA DAMNIFICA. 
469 Plate D. 
Plate D (Figs. 1 to 16).-Successive Stages in the Growth (1 and 2, X 2100, 
and 3, X 700), Maturation (4, 5, 6, 7, 8, 9, 10, 11, 12 and 13, X 2100, and 
14, X 700), and Fertilization (15 and 16, X 700) of the Egg of the Star- 
fish, Asterias forbesii. 
In the ripe egg (3) the chromosomes are aggregated in a group connected with 
the nucleolus by a chromatic thread. In 4 the nucleolus is fragmenting (c) and 
the chromosomes (a and 6) are taken onto the first maturation spindle (5). In 
13 two polar bodies are present, and the female pronucleus is forming. In 14, the 
mature egg, three polar bodies are present. In 15 and 16, the male and female 
pronuclei are fusing to contribute their chromosomes to the first segmentation 
spindle. GAMETOGENESIS 
473 
by way of chromosomes only from their grandparents. For their parents 
are simply, as it were, the 'guardians' of their grandparental chromosomes 
which, following the synapsis phase of growth (the final stage of the pre- 
Fig. 423.-Chromosome Groups of Schistocerca damnifica 
(A) Diploid chromosome group of dividing spermatogonium of Schistocerca, 
showing the 11 pairs of chromosomes, and the unpaired (10-x) accessory chromo- 
some. (B) Haploid group of primary spermatocyte, showing 11 bivalent chromo- 
somes and the accessory (10-x). The 11 bivalents fall into a series with the same 
size relationships as the pairs of chromosomes in the diploid group. (C and D) 
Chromosome groups of secondary spermatocytes, one (D) with 11 univalent 
chromosomes, like those of the diploid pairs, the other (C) with similar chromo- 
somes, plus the accessory (x). All mature eggs presumably contain 12 chro- 
mosomes, homologous with C. 
vious fertilization which resulted in the parents) become redistributed in 
various combinations in the maturing germ cells from which the offspring 
develop, and determine their hereditary possibilities. In other words the 
germ-plasm is a continuous substance handed on from generation to gen- 474 
THE REPRODUCTIVE SYSTEM 
eration. Its 'elements' are the same, except in so far as the complement 
is halved during maturation and restored at fertilization by addition of an 
equal quota from another line of descent. This halving and doubling is 
the physical mechanism which underlies the phenomenon of variation in- 
volved in heredity. Offspring thus resemble parents because both have 
had origin largely from the same germ-plasm; lack of resemblance results 
from the fact mainly that the germ-plasm of parents and offspring of neces- 
sity differ in certain elements since different additions are made at fertili- 
zation in the case of successive generations. 
We may now return to the metaphase (Fig. 
16) and follow the further course of the chromo- 
somes. The chromosomes are in typical tetrad 
condition. The first division most probably sep- 
arates the chromosomes that paired at synapsis. 
The unpaired, odd, or accessory chromosome (x) 
passes undivided and in advance of the other 
chromosomes to one pole of the spindle. Thus 
one of the resulting daughter-cells, prespermatid 
or secondary spermatocyte, receives 11 chromo- 
somes, the other, 11 plus the accessory, or 12 
chromosomes. Fig. 17 is a side view and Fig. 18 
a polar view (metaphase plate), of the metaphase 
group, showing all 12 chromosomes. The acces- 
sory is still recognizable at telophase, Fig. 19. 
The chromosomes of the resulting secondary sper- 
matocytes do not pass into a diffuse stage but re- 
main more or less compact and chromatic-a con- 
dition characteristic of the later segmented spi- 
reme stage of mitosis. In half the cells the acces- 
sory appears in its typical shape, staining reac- 
tion, and position, as shown in Fig. 20. This 
shows also a remnant of the original spindle. 
Attention should here be called to the fad that in 
many forms chromatic particles have been de- 
scribed passing from the nucleus into the cyto- 
plasm, during the growth stages of the primary 
spermatocyte, particularly at the synapsis phase. 
Similar conditions have occasionally been de- 
scribed also for the spermatogonia, and in several instances even for the 
secondary spermatocytes. These extrusion products are called chromidia, 
Fig. 424.-Diagrams 
Illustrating the 
Behavior of the 
Chromosomes Dur- 
ing the First (A) 
and Second (B) 
Maturation Divi- 
sions. 
The bivalent chro- 
mosome a + b enters 
the first maturation 
spindle and suffers a 
reductional division, 
chromosome a being 
separated from chro- 
mosome b. In the sec- 
ond maturation divi- 
sion, each chromosome 
undergoes an ordinary 
longitudinal division. 
This division is already 
foreshadowed during 
the first or heterotypic 
division, producing the 
tetrad condition of the 
bivalent chromosome. GAMETOGENESIS 
475 
and are regarded by some as the raw material for mitochondria, to which 
latter certain investigators have attached hereditary significance. 
The further description of spermatogenesis will be confined to that 
half of the secondary spermatocytes containing the accessory or sex 
chromosome; conditions in the other half are closely similar except for 
the absence of the odd chromosome. Figs. 21 and 22 illustrate suc- 
cessive prophase stages. Figs. 23 and 24 illustrate side and polar 
views of the metaphase of the second maturation mitosis; in the latter 
all 12 chromosomes are shown. Plate C, Figs. 25 and 26 show anaphase 
and telophase stages respectively. Fig. 27 is the early spermatid stage, 
the accessory still conspicuous. A conspicuous cytoplasmic element of 
these stages is the idiozome (i), apparently derived from a portion of 
the disappearing spindle. Later stages of the metamorphosis of the 
spermatid are shown in Figs. 28 to 31. The idiozome divides into two 
moieties (Fig. 29). These elongate (Fig. 30) and spread out over a 
filament (Fig. 31), which has grown out from a dark-staining granule 
on the outer surface of the nucleus. The cytoplasm also concurrently 
flows backward around this filament. In conformity with what is 
known of a similar granule with a similar function in various forms, 
this granule represents the centrosome of Fig. 23, but its origin and 
history are obscure. Further steps in the metamorphosis are illustrated 
in Figs. 32 to 36. The mature spermatozoon consists of a long, rela- 
tively lightly chromatic, lance-shaped head, a deeply-staining thimble- 
shaped middle piece (body), and a long gradually tapering tail. The 
latter consists of the central filament ensheathed by the products of 
the idiozome. The entire spermatozoon is furthermore enveloped in a 
close-fitting sheath of cytoplasm. The head originated from the nucleus, 
and the middle piece presumably from the centrosome and a small 
contribution of cytoplasm. 
Determination of Sex.-Anticipating somewhat, we may say that the 
process of oogenesis is essentially similar to that described for spermato- 
genesis. The cardinal difference relates to a numerical inequality between 
the functional descendants of a spermatogonium and an oogonium: in the 
former case the four resulting cells are all functional, and from the stand- 
point of their numerical chromosome content of two sorts; in the latter, 
three of the resulting cells are abortive (polocytes), only one remaining 
functional. Of the two classes of spermatozoa, one has an even number of 
chromosomes, the other an odd number. All mature eggs have the same 
number of chromosomes as that of the spermatozoa with the greater num- 
ber. This description applies strictly only to those instances where an odd 476 
THE REPRODUCTIVE SYSTEM 
or accessory chromosome appears in the male, or where its representative 
is an odd group. Cases are known among insects, where the homologue of 
the accessory may have a mate of smaller size (or possibly even equal size, 
but of typical allosome behavior-idiochromosomes), or where the accessory 
representative may be an even group, in which instances the numerical rela- 
tionships are different, but the principle of sexual relationship remains the 
same. 
Confining our attention then to the simplest case, as. illustrated in our 
specimen of the grasshopper, we may note that all the cells of the female, 
including the obgonia, contain 24 chromosomes. Two of these correspond 
in size to the accessory of the male group, which group in all soma cells 
and all spermatogonia comprises 23 chromosomes. We recall that one-half 
of the spermatozoa received 11 chromosomes, the other half 11 plus the 
accessory, or 12 chromosomes. All mature eggs contain 12 chromosomes. 
When therefore a spermatozoon with 11 chromosomes fertilizes an egg with 
12 chromosomes, the resulting organism will have 23 chromosomes, and 
become a male; when, on the contrary, a spermatozoon with 12 chromo- 
somes fertilizes an egg with 12 chromosomes, the organism will have 24 
chromosomes and become a female. 
An essentially similar relationship is now known to obtain in many 
forms, chiefly insects, but including also various vertebrates, even mam- 
mals and man. According to Winiwarter (Arch, de Biol. T. 27, 1912), the 
white human male produces spermatozoa of two sorts, one with 23 chro- 
mosomes, the other with 24; the male cells containing 47 chromosomes, the 
female 48. There is some uncertain evidence to indicate that the negro 
has half the number of chromosomes possessed by the white man, the 
mulatto consequently possessing numerically intermediate groups. 
With regard to the function of the accessory chromosome in relation 
to sex determination, two obvious possibilities present themselves: (1) it 
may qualitatively determine sex, that is, carry the determiner upon which 
sex depends; (2) it may act in a quantitative way, that is, sexual differ- 
ence may depend upon differences in the amount of chromatin. On the 
contrary the presence of one accessory in the male, and two (homologues) 
in the female may be simply accompaniments of sex in a sense somewhat 
similar to secondary sexual characters (e. g., combs and spurs in poultry), 
these as well as other sexual differences being in common dependent upon 
some more recondite fundamental sex 'determiner.' Experimental evidence 
tends increasingly to show that all organisms carry the potentialities of 
both sexes, and that sex differences are largely differences in degree of dif- 
ferentiation; in other words, that femaleness represents an inhibited male. 
The greater amount of chromatin in the female, due to the presence of 
two sex chromosomes-as against one in the male-may be conceived to 
inhibit the higher grade of differentiation demanded by maleness. 
Attempts have frequently been made recently somehow to bring sex GAMETOGENESIS 
477 
determination in line with our knowledge of inheritance in general, and 
more particularly with the principles of Mendelian inheritance. This ac- 
cordingly would seem to be the logical place for a brief presentation of the 
main facts of Mendelism, and the hypothesis that attributes to the chromo- 
somes the function of vehicles, or determiners for hereditary qualities. 
Barring the sexual numerical differences above discussed, the specific num- 
ber of chromosomes is constant; that is, all cells of the white human male 
have 47, of the female 48 chromosomes. The more variable, superficial, or 
more recently acquired characters are believed by many to depend upon the 
presence in the developing egg-consequently the cells of the organism-of 
certain chromosomes, the so-called 'determiners' The more fundamental 
characters are believed to inhere in the cytoplasm of the egg. For exam- 
ple, the vertebrate condition of a man is thus believed to result from the 
constitution of the egg; the color of his eyes from the presence or absence 
of some determiner or factor in a particular chromosome. 
To elucidate the matter further, we must regard an organism as a 
congeries of almost numberless characters; of these some are like those of 
the mother and her ancestors, others like those of the father and his an- 
cestors, others apparent blends. In Mendelian phraseology these characters 
are called unit characters, and their material basis is located in particular 
chromosomes. We may select a single pair of unit characters in order 
further to present the principles of Mendelian inheritance. Suppose we 
consider the coat color of gray and white guinea pigs. When individuals 
characterized by these coat colors are crossed, the resulting offspring, first 
generation, are all gray in color. The gray color is said to be dominant, 
the white recessive. However, the potentialities or determiners for white 
coat color are still present in the gray hybrid, for if such hybrids are in- 
bred, there result gray and white offspring in the proportion of 3 of the 
former to 1 of the latter. The latter if inbred produces only white off- 
spring, hence called pure recessives, but of the 3 gray only one if bred with 
its own type (pure dominants) will produce gray; two out of the three if 
inbred produce again 3 gray to 1 white. The proportion of 1 pure domi- 
nant to 2 hybrid dominants to 1 pure recessive is the well-known Mendelian 
formula for one pair of unit characters in cross-breeding of specific varie- 
ties. The character of this formula depends upon the fact that no germ 
cell carries both determiners of a pair of unit characters, but only one or 
the other. It thus follows that from the standpoint of a single pair of 
unit characters (e. g., color of iris) there are two categories of eggs and 
likewise of sperm. According to the laws of chance there will then be one 
chance for the determiner of either character (e. g., gray and white coat) 
to meet its like, to two chances that it may meet its opposite, hence the 
formula 1:2:1: 
The central concepts of Mendelian inheritance thus are (1) unit char- 
acters; (2) the phenomenon of dominance; and (3) the principle of seg- 478 
GENERAL CONSIDERATIONS 
regation, producing a purity of the germ cells. The unit characters are 
external features, the hypothecated determiners for these are provision- 
ally located in the chromosomes. 
Sex is of course inherited in the sense that an individual resembles 
either its father or its mother in respect of sex. Moreover, considering a 
species as a group, the two sexes are approximately numerically equal. 
This is the ratio expected when a Mendelian pure recessive (homozygote) 
is crossed with a hybrid dominant (heterozygote)-for again by the laws of 
chance, the chances are equal that a determiner shall meet with its oppo- 
site or its like. On the basis of these considerations mainly, coupled with 
the data of sex-linked inheritance (see Morgan, "Heredity and Sex," 1915), 
sex is conceived by some to be inherited in Mendelian fashion, the indi- 
vidual with a single accessory (male) being regarded as the heterozygote, 
that is, digametic; that with two accessories, the homozygote, that is, the 
homogametic. However, such serious contradictions and difficulties arise 
when the matter is thus strictly interpreted that a simple Mendelian view 
of sex ratios must probably be abandoned. In any event the interpretation 
that regards the heterochromosome, when present in the duplex condition, 
as in the female, as an inhibitor to male sex development from the viewpoint 
of secondary sex characters, accords well with much of the experimental 
evidence from vertebrates. The bulk of the best evidence tends to show 
that sex is determined at fertilization, and that it cannot thereafter be 
altered by control of environmental conditions. Relatively much chro- 
matin may be thought to underlie the anabolic condition characteristic of 
femaleness, relatively less chromatin the katabolic conditions which sub- 
serve the high differentiations of maleness. 
Oogenesis.-We must now return to a detailed description of the 
oogenesis. Splendid material for the presentation of the facts con- 
cerning this process is the egg of Ascaris, or that of certain molluscs, 
or the more easily available egg of some echinoderm, e.g., starfish. This 
description will confine itself to the starfish egg. The essential points 
can be well illustrated with this material (Plate D, Figs. 1-16). In con- 
trast to the spermatozoon, which is relatively minute, highly motile, and 
with a minimum amount of cytoplasm, the egg on the other hand grows 
enormously in size (ratio of sperm to egg 1: 500.000 ±), is non-motile, 
and has a large amount of cytoplasm heavily laden with yolk material. 
This phase of the oogenesis is known as the growth period; during the 
early portions of this period synapsis occurs, and subsequently chro- 
matic material (chromidia) appears in the cytoplasm, presumably ex- 
truded by the nucleus, and in part at least changed into yolk. This 
generation is the primary oocyte, the preceding generation being MALE ORGANS OF REPRODUCTION 
479 
oogonial, primary and secondary, characterized by extensive prolifera- 
tion. The primary oocyte divides in a manner similar to the primary 
spermatocyte, that is by heterotypic mitosis, but the daughter-cells are 
very unequal in size, each, however, with the same number of chromo- 
somes (18) ; the small abortive cell is called the polar body, or better 
polocyte, while the large cell becomes a secondary oocyte. Both polocyte 
and secondary oocyte again divide, the end result being three similar 
polar bodies and one large ootid or mature ovum, now ready for fertili- 
zation. It must be recalled that the maturation process is in essence a 
process of eliminating one-half of the original quota of chromosomes, 
and a quantitative reduction of its original amount of chromatin to 
one-fourth. At fertilization, by fusion of egg and sperm, the specific 
number of chromosomes is reestablished-differing in many cases in 
male and female of the same species-and the chromosomes by growth 
regain or even exceed their original size. With this brief consideration 
of the function of the germ glands in general, we may proceed to a 
description of the structure of the male organs of reproduction and 
subsequently of the female organs. 
MALE ORGANS OF REPRODUCTION 
These organs include the penis and the testes, together with their 
accessory glands, and the excretory ducts which connect the testes with 
the urethral canal. The excretory ducts include the epididymis, ductus 
(vas) deferens, seminal vesicles, and ejaculatory ducts, and with their 
termination in the urethra there are connected the ducts of the prostate 
gland and the bulbo-urethral glands (of Cowper), whose secretion mixes 
with that of the testes to form the semen. The male urethra serves the 
double function of a urogenital canal. 
Internal Genital Organs 
Testis 
The testis is to be regarded as a gland with a double function; it 
produces cells (spermatozoa), hence a cytogenic gland; and an internal 
secretion, hence, in part an endocrin gland. In connection with the 
testis must be considered also its excretory duct system, and the various 
glands accessory to it. The relationship of these various structures 
is shown in diagram, Fig. 418. 480 
THE REPRODUCTIVE SYSTEM 
The testis is encased in a robust fibro-elastic capsule, the tunica 
albuginea, the innermost layer of which is of looser texture and very 
vascular, hence called the tunica vasculosa. External to the albuginea 
is a double-layered sac of peritoneum, the tunica vaginalis, its visceral 
layer closely adherent to the capsule. The human testis measures 
about one and one-half inches in length, one and one-quarter inches in 
width and one inch in thickness. Septa continuous with the capsule 
divide it into a 
number of com- 
partments or lo- 
bules, pyramidal in 
shape, the apices 
converging to an 
anterodorsal mass 
of dense connective 
tissue, the medias- 
tinum testis {cor- 
pus Highmori), 
corresponding to a 
hilum. The lobules 
contain each sev- 
eral, frequently two, 
extensively convo- 
luted tubules, the 
seminiferous tu- 
bules (tubuli con- 
torti). When un- 
coiled they measure 
from one to two 
feet. The entire 
testis contains several hundred lobules; the number has been variously 
estimated at from one hundred to four hundred. 
Bremer (Amer. Jour. Anat., 11, 4, 1911) describes the tubuli con- 
torti of man as tubules that may be single, ending blindly, may branch 
or may anastomose. Huber and Curtis (Anat. Bee., 7, 6, 1913), on 
the contrary, state that in the adult rabbit the seminiferous tubules 
"present no blind ends, diverticula or nodular enlargements." Their 
simplest form is that of an arch beginning and ending in a tubulus 
rectus. The two limbs may lie in adjacent lobules. Complex tubules 
are also described, resulting from the linkage of from three to twelve 
Ductus deferens 
Ductus epi- 
. didymidis 
Lobuli epididymidis- 
.Ductulus 
aberrans 
superior 
Ductuli efferentes - 
testis f 
Corpus epi- 
didymidis 
I 
'Ductulus aberrans 
(inferior) 
Fig. 425.-The Testicle with Its System of Efferent 
Passages. 
Natural size. (After Toldt.) MALE ORGANS OF REPRODUCTION 
481 
simple arched tubules. According to Curtis (1915) branches and 
anastomoses of seminiferous tubules are infrequent in the mouse testis, 
more frequent in dog, and most frequent in rabbit. 
The testis is lodged in the scrotum. The wall of the scrotum is 
essentially like the general integument, except that it may be more 
a and b, interstitial cells, the latter containing coarse granules; c, connective 
tissue cells; d, a mast-cell of the connective tissue. Within the tubule several phases 
of spermatogenesis are well shown. Highly magnified. (After Spangaro.) 
Fig. 426.-Seminal Tubule of a Man in Transection. 
highly pigmented. Its subcutaneous layer, however, is looser in texture 
and contains more elastic tissue and smooth muscle. It is known as the 
dartos. 
The wall of the seminiferous tubules consists of fibro-elastic tissue. 
They are lined with a several layered epithelium, the cells representing 
the several stages of spermatogenesis. In addition to the germ or sex 
cells, the epithelium contains sustentacular cells (Sertoli cells), to which 
the spermatids become attached during process of metamorphosis into 
ripe spermatozoa (spermia). It seems probable that the spermatids also 482 
THE REPRODUCTIVE SYSTEM 
draw nourishment from the sustentacular cells for the work of metamor- 
phosis, hence also known as 'trophocytes' The sustentacular cell is 
roughly of tall columnar shape, tapering somewhat irregularly toward 
the distal pole. The proximal pole contains the nucleus and frequently 
flares somewhat giving the entire cell a tall pyramidal shape. The 
nucleus is pale and contains one or several chromatic nucleoli. The 
spermatozoa are embedded head first, four to eight or more to a cell, 
in the protoplasm of the trophocyte. Such a composite group consti- 
Fig. 427.-Sertoli Cells of the Human Testis. 
A, showing a crystalloid (of Charcot) and lipoid granules and spherules; below 
to the right a spermatogonium with a crystalloid (of Lubarsch). B shows a crys- 
talloid and two accessory rods, and lipoid granules and droplets. C shows at the 
base a crystalloid and one accessory rod, and at the summit two accessory rods. 
X 600. (Winiwarter.) 
tutes a so-called spermatoblast of von Ebner. The sustentacular cell 
contains one or several crystalloids. Their origin and function is un- 
known. They were regarded by Montgomery as probably sustentacular 
cell determinants, having been traced by him from the common mother- 
cells of both trophocyte and spermatogonium into the former, the latter 
being said to lack these elements. However, Winiwarter (Fig. 427) re- 
ports similar crystalloids in both trophocytes and spermatogonia. Tro- 
phocytes more probably have an origin distinct from that of the 
germ-cells, according to certain investigators arising from the Bowman's 
capsule of the Wolffian tubules of the mesonephros. 
Every section of a tubule of an active testis contains several, some- 
times all the stages of spermatogenesis. Since the spermatogenetic 
process generally travels in waves, a longitudinal section is most favor- Spermatozoa 
Secondary sper- 
matocyte 
Sertoli cell 
Primary 
spermatocytes 
Fig. 428.-Portion" of a Transection of a Seminiferous Tubule from the Human Testis, 
Illustrating the Various Stages in Spermatogenesis. 
(From Polak, after Retzius.) 
Spermatid 
Secondary sper- I 
matocytes in 
mitosis 
Spermatogonium 
483 484 
THE REPRODUCTIVE SYSTEM 
able for a study of the continuous process. From wall to lumen of 
tubules can be seen, at successive levels, spermatogonia, primary sperma- 
tocytes, secondary spermatocytes (prespermatids), spermatids, and sper- 
matozoa attached to the tips of the sustentacular cells. Mitoses can 
frequently be seen in spermatogonia, primary and secondary spermato- 
Fig. 429.-Successive Stages in the Metamorphosis of the Spermatid into 
the Spermatozoon. 
(Schematic, from Bonnet, after Meves.) 
cytes. The primary spermatocytes are the largest of the germ cells; 
the secondary spermatocytes are approximately half the size and lie 
distal, while the spermatids are approximately one-fourth the size; the 
spermatids may be at any stage of a continuous process of metamorpho- 
sis involving nuclear, cytoplasmic, and general form changes. The 
spermatogonia are of various sizes, frequently approximating that of 
the primary spermatocytes, but always lie peripherally, on the basement 
membrane between sustentacular cells. The above named marks con- 
stitute the grosser criteria for identifying the several generations of MALE ORGANS OF REPRODUCTION 
485 
cells involved in spermatogenesis. As concerns details, the criteria 
above given for the grasshopper testis, can be applied. 
The Spermatozoon.-Spermiohistogenesis, however, differs some- 
what. The spermatid nucleus becomes progressively more compact, 
chromatic and smaller. At the same 
time it moves toward one pole of the 
cell, the cytoplasm flowing back- 
ward, except for a thin envelope 
(galea capitis) which terminally 
forms a covering for the perfora- 
torium which represents a portion 
(acrosome) of the original idiozome. 
The idiozome is the germ-cell repre- 
sentative of the archoplasmic com- 
plex. Concurrently with the changes 
outlined for the nucleus it liberates 
a centrosome, and centrosome and 
acrosome pass to opposite poles of 
the nucleus. The centrosome di- 
vides into two moieties, a proximal, 
which becomes attached to the nu- 
clear membrane, and a distal, which 
moves peripherally at the same time 
sprouting a flagellum, the central 
filament. Meanwhile a peripheral 
portion separates from the more 
central portion of the distal centro- 
some and moves backward over the 
central filament enclosing an envel- 
oping column of cytoplasm, the mid- 
dle piece, in which mitochondria 
have aggregated. The mitochondria 
fuse to form a filament, the spiral 
filament, which becomes spirally ar- 
ranged about the central filament. The central filament continues to 
grow distally beyond the final locus of the ring centrosome, and together 
with an envelope of cytoplasm constitutes the tail of the spermatozoon. 
A short terminal naked portion of the central filament is known as the 
terminal filament. 
Summarizing the above: The nucleus becomes the head of the 
Aero some 
Galea capitis 
Head 
Neck 
Body 
End ring - 
Anterior knob 
Spiral fibers 
Sheath of axial 
thread 
- Axial thread 
- Capsule 
Main segment of 
taxi 
Terminal filament 
Diagram of Human Sper- 
matozoon. 
Fig. 430.- 
(After Bonnet.) 486 
THE REPRODUCTIVE SYSTEM 
spermatozoon. This is tipped with an acrosome, a derivative of the 
idiozome, and covered by the galea capitis, the two comprising the per- 
foratorium. The other constituents of the idiozome contribute the 
central filament. The extent between distal and 
proximal centrosomes constitutes the neck; the 
portion between distal centrosome and ring cen- 
trosome the connecting or middle piece (body), 
with its spiral filament derived from mitochon- 
dria. The tail or flagellum consists of central 
filament enveloped by cytoplasm. In many forms 
a spiral fin develops on the body. Also, there is 
endless variation with reference to the shape of 
the head. But the development and morphology 
of spermatozoa of all vertebrate forms is essen- 
tially the same. At fertilization only head and 
middle piece-nucleus and centrosome and mito- 
chondria-enter into the egg, the tail being gen- 
erally left behind. 
The human spermatozoon has a length of from 
fifty to sixty microns. Of the total the head con- 
stitutes about 5 p., the middle piece about 5 p. and 
the end-piece about 10 p.. Seen en face the head 
has an ovoid shape; in profile it appears pyriform, 
due to a thinning along its terminal margin. Oc- 
casionally atypical or monstrous, double-headed, 
multiple-tailed, and giant spermatozoa appear; but 
these are probably non-functional. Though flagel- 
late, the spermatozoa are non-motile until they 
reach the epididymis, where they become bathed in 
a secretion. Their motility, however, is not pro- 
nounced until they reach the place in the excretory 
passage where the secretion of the seminal vesicles, 
prostate and bulbo-urethral glands are present. 
The mixture of these secretions with the sperm 
forms the semen. 
The spermatozoa can withstand considerable variations in tempera- 
ture, but they are very susceptible to acid solutions; they survive best 
in slightly alkaline media. Under favorable conditions spermatozoa 
may be kept alive for as long as eight days; it is probable that they 
remain alive for even a longer time in the female genital tract; but 
Fig. 431.-Spermato- 
zoa of Various An- 
imals. 
A, from the badger; 
B, from the bat. Re- 
drawn after Ballowitz. 
X 1200. C, from the 
rat. Hematein and eo- 
sin. X 1200. MALE ORGANS OF REPRODUCTION 
487 
it is uncertain whether they can maintain their functional virility for 
this length of time. The number of spermatozoa per cubic millimeter 
has been estimated at 60,876; and the total in 
an average ejaculation at 200,000,000 (Lode, 
1896). 
The tubuli convoluti pass into short tubuli 
recti and the latter into the rete testis of the 
mediastinum. The rete testis is the beginning 
of the excretory duct, and consist of a meshwork 
of irregular tubules lined with a single layered 
cuboid non-ciliated epithelium. They connect 
with a group of greatly coiled tubules, the duc- 
tuli efferentes, from ten to fifteen in number, 
each terminally winding so as to assume a coni- 
cal shape, hence coni vasculosi-which tubules 
empty into the distal portion of a common duct 
-the ductus epididymis. This portion of the 
duct, together with the efferent ductuli, consti- 
tute the globus major of the epididymis. Con- 
sideration of the duct system will follow below. 
Interstitial Cells of Leydig.-Here should 
be considered the intertubular connective tissue 
of the testis. Fibro-elastic connective tissue acts 
as a supporting stroma for the testicular paren- 
chyma of the seminiferous tubules. Scattered 
throughout this stroma, between the adjacent 
tubules, are peculiar large polygonal cells, inter- 
stitial cells of Leydig, either scattered or ar- 
ranged in masses. The condition of the nucleus 
varies from pale vesicular to dense deeply chro- 
matic. Division figures are exceedingly rare 
among them, though an occasional cell may, in young testes, be seen in 
mitosis. In older testes an occasional nucleus may be seen in what 
appears to be amitotic division. A number of the cells also are bi- and 
multinucleate. However, multiplication of specific interstitial cells is 
evidently exceptional. These cells arise directly through modification in 
shape, and growth from the fusiform and irregular connective tissue 
cells of the stroma. Moreover, this process seems to be reversible. They 
thus represent a transient phase in the life of certain cells of the inter- 
tubular connective tissue. Their cytoplasm contains crystalloids (mito- 
Fig. 432. - Spermato- 
zoa from the Semen 
of Man. 
A, usual type; B, 
'giant' double sperma- 
tozoon. Hematein and 
eosin. X 1200. 488 
THE REPRODUCTIVE SYSTEM 
chondria) and fatty granules. The nature of the lipoid granules is dis- 
cussed by Whitehead (Amer. Jour. Anat., 14, 1, 1912). These cells 
increase in number during senile atrophy of the testis, but later entirely 
disappear. They are rela- 
tively larger and more abun- 
dant also in the testes of 
tuberculous patients where 
there is considerable degen- 
eration and a general infan- 
tile condition of the semi- 
niferous epithelium. Vari- 
ous functions have been 
ascribed to them-that is, 
those obviously dependent 
upon the internal secretion 
of the testes-prominently, 
origin and maintenance of 
secondary sexual characters, 
and origin of sexual in- 
stinct. Obviously other cells 
of the testis might conceiv- 
ably subserve these func- 
tions, namely, the susten- 
tacular cells and the sex- 
cells. However, observa- 
tions on testes of mules (in- 
fertile) and cryptorchid 
horses, and the findings of 
Whitehead (Anat. Rec., 2, 
5, 1908) in a third abdom- 
inal testicle of a horse 
where only interstitial cells 
in great abundance persisted in normal condition, would seem to rele- 
gate these functions to the interstitial cells. 
Kingsbury's careful studies (Amer. Jour. Anat., 16, 1914) of the inter- 
stitial cells of the ovary of the cat (elements presumably homologous with 
the interstitial cells of the testis) strongly support the interpretation of 
these cells in terms of absorbers of degenerating and disintegrating ma- 
terials. In the ovary all of the earliest and many of the later primary 
oocytes disintegrate. In the vicinity of such atretic follicles interstitial 
Fig. 433.-A Group of Interstitial Cells 
from the Testis of a Thirty-five Year 
Old Negro. 
The outlines of three adjacent seminiferous 
tubules are shown. Among the interstitial cells 
are three nuclei of ordinary connective tissue. 
The interstitial cells are filled with lipoid spher- 
ules and granules. Formalin fixation, iron- 
hematoxylin stain. X 1500. MALE ORGANS OF REPRODUCTION 
489 
cells laden with lipoid debris are abundant. Their presence, however, is 
transient, and their abundance reciprocal to the abundance of degenerat- 
ing follicles. This observation, reasoning by analogy, would explain their 
abundance in the testes of cryptorchid horses, mules, and in the third 
abdominal testicle; for here also degenerative processes are going on among 
the sex cells. Testicles of cryptorchid horses and mules are characterized 
by an unusual abundance of interstitial cells, and degeneration of sex cells. 
These animals experience heat, but are infertile; this was true also of the 
stallion from whom two testicles had been removed and in whom subse- 
quently the third abdominal testicle was discovered. These observations 
Fig. 434.-Interstitial Cells from the Human Testis. 
A, B, and C, from a twenty-five year old man; A shows the idiozome, bacillary 
centrosomes, lipoid granules and crystalloids; B, with two nuclei; C, with four 
nuclei (probably the result of amitotic division) and eight centrosomes. D, from 
a 41-year-old man, showing large and small crystalloids. Highly magnified. (Wini- 
warter, Anat. Anz., 41, 11, 1912.) 
would seem to indicate that the sexual instinct depends upon an internal 
secretion on the part of the interstitial cells. The two results can be har- 
monized on this basis: The internal secretion may actually be formed by 
the cells of the seminiferous tubules; when these degenerate the products 
are removed by the interstitial cells; since even in healthy testes there is 
some degeneration of sex cells, all testes contain a few interstitial cells; 
these are more abundant at puberty; the secretory products of degenerating 
sex cells are included among the debris removed by the interstitial cells 
from which they may be passed into the capillaries of the testicular stroma. 
The suggestion that the interstitial cells are in some way connected 
with secondary sex characters seems disproved by various castration experi- 
ments. For example, the spayed hen takes on male secondary sexual charac- 
ters; if these were dependent exclusively upon the interstitial cells of the 
testis, they could not appear in the absence of both ovaries and testes. 490 
THE REPRODUCTIVE SYSTEM 
However, the experiments of Steinach (Zentralblatt f. Physiol., 27, 14, 
1913) cannot be ignored in this connection. Steinach made reciprocal 
transplantations of testes and ovaries in young male and female rats and 
in guinea pigs, and claims to have succeeded in changing a potential 
female, from the view point of secondary sex characters (both physical and 
temperamental), into a male, and vice versa. A male is said to have devel- 
oped functional mammary glands, and even to have suckled young. Stein- 
ach interprets his results to mean that not only do the secondary sex char- 
acters of the male and female depend upon the presence of the 'pubertal 
gland' (interstitial cells), but also the fact whether the undifferentiated 
gonad shall develop into a testis or an ovary. Microscopic examination of 
the transplant showed that everything suffered degeneration except the in- 
terstitial tissue, which underwent extensive hyperplasia. For further in- 
formation on this and related subjects reference should be made to Mar- 
shall's "The Physiology of Reproduction," 1910. 
The Duct System 
Tubuli Recti.-At the apex of the testicular lobule the tortuous 
seminiferous tubules pass into the rete testis of the mediastinum. At 
this point the tubule becomes straight and is abruptly narrowed. Thus 
the short straight tubules, tubuli recti, are formed. In the straight 
tubules the stratified epithelium of the tortuous portions is abruptly 
exchanged for a very low columnar or flattened type of epithelium with 
which the Sertoli cells of the tortuous tubules seem to be continuous. 
The straight tubules are very short and are soon transformed into the 
irregular anastomosing canals of the rete testis. 
Rete Testis.-The connective tissue of the mediastinum is perme- 
ated by a network of irregular channels of varying diameter which 
present frequent dilatations and often have the appearance of broad 
cleft-like spaces. These are the canals of the rete testis which form a 
dense network of anastomosing channels. On the one hand they receive 
the straight tubules, and on the other they pass into the ductuli ef- 
ferentes, which convey the secretion onward to the globus major of the 
epididymis. 
The canals of the rete testis are lined by cuboidal or flattened epi- 
thelium, which rests upon a delicate basement membrane. This in 
turn is supported by the connective tissue of the mediastinum. The 
broad but irregular lumen of the canals is occupied by the secretion 
from the seminiferous tubules and contains many spermatozoa. 
Ductuli Efferentes.-As the tubules of the rete testis leave the MALE ORGANS OF REPRODUCTION 
491 
mediastinum they are abruptly transformed into peculiar efferent ducts, 
10 to 15 in number, which pass into the globus major of the epididymis 
and by means of spiral windings form conical masses, coni vasculosi, 
whose apex projects into the glo- 
bus rhajor. The epithelium of 
these tubules is peculiar in that 
it contains two varieties of cells, 
and in that it is thrown into 
many prominent longitudinal 
folds or rugae. 
In the lining epithelium there 
are short columnar cells which 
rest upon the basement mem- 
brane and carry upon their free 
ends a tuft of short cilia. These 
cells have an ovoid nucleus and a 
very finely granular, eosinophil 
cytoplasm. Between and among the ciliated cells are many broad col- 
umnar or polyhedral cells, having remarkably clear cytoplasm, which 
Fig. 435.-A Small Portion of the Wall 
of an Efferent Ductule of the Tes- 
ticle. 
d, ' glands ' in longitudinal section; d', the 
same in oblique section; F, ciliated epithe- 
lium. X 140. (After Kolliker.) 
Fig. 436.-Efferent Ductules of the Rabbit's Epididymis. 
Hematein and eosin. Photo. X 250. 492 
THE REPRODUCTIVE SYSTEM 
chiefly occur between and at the base of the rugae, and are frequently 
arranged in small groups simulating minute secreting glands. These 
clear cells have spheroidal nuclei and their cytoplasm is filled with large 
coarse granules. They are quite characteristic of this portion of the 
excretory tubules of the testis. The coni vasculosi form a considerable 
The lumen of the tubules contains groups of spermatozoa. Hematein and eosin. 
Photo. X 178. 
Fig. 437.-Several Coils of the Rabbit's Epididymis in Transection. 
portion of the globus major of the epididymis. The epithelium rests 
upon a well-developed basement membrane, outside of which is a robust 
layer of circularly disposed, smooth muscle cells with intermingled 
elastic fibers. The nuclei of the lining cells can frequently be seen in 
some stage of amitotic division. 
Epididymis.-The ductus epididymis forms a long coiled tubule 
whose convolutions, by their regular cylindrical form and their tall 
ciliated epithelium, are sharply distinguished from those of the ductuli MALE ORGANS OF REPRODUCTION 
493 
efferentes, which have much thinner walls. The lining epithelium of 
the epididymis is of the tall, ciliated, simple columnar type with elon- 
gated ovoid nuclei, a finely granular cytoplasm, and a group of non- 
motile cilia which often adhere together to form a peculiar tuft or 
cluster ('brush border'). At the base of the ciliated cells is an in- 
complete layer of basal epithelium, whose flattened cuboidal elements 
are wedged between the bases of the tall columnar cells. The two- 
layered epithelium is thus of the pseudo-stratified type. The cells ap- 
parently multiply largely by amitosis. 
The epithelium rests upon a cellular basement membrane, which is 
supported by a connective tissue tunic of varying thickness. In addi- 
tion to many elastic fibers, this coat contains a few smooth muscle 
cells. The coils of the epididymis are firmly united into a solid mass 
by means of the dense intervening connective tissue. They form the 
whole of the globus minor and a considerable portion of the globus 
major. When unraveled the duct of the epididymis measures about 
twenty feet in length. 
The Ductus Deferens (Vas Deferens).-This duct is a continua- 
tion of the epididymis, whose course now becomes relatively straight. 
It measures about eighteen inches in length. In this portion of the 
excretory duct of the testis the lining epithelium soon loses its cilia, 
and the basal cells become more prominent. Hence in the greater 
portion of its course the ductus deferens is lined by tall, columnar, 
non-ciliated epithelium, with low basal cells between the attached ends 
of the columnar cells. 
The epithelium rests upon a fibro-cellular basement membrane, 
which is supported by a fibrous tunica propria. This, in turn, passes 
almost insensibly into the muscular coat which consists of two layers, 
an inner circular and an outer longitudinal, both of which are highly 
developed. In the lower portions of the ductus deferens, a thin internal 
layer of longitudinal muscle fibers is also found. The fibers of the 
internal and middle circular layers are frequently less regularly ar- 
ranged, in which case their oblique bundles interlace with one another 
in a most intricate manner. The very thick, smooth muscular coat 
and the relatively narrow lumen give this portion of the duct a firm 
consistence and a cord-like feel. 
In its ampulla-the dilated portion near its prostatic termination- 
the mucous membrane of the ductus deferens is more loosely attached 
and the folds or rugae, which elsewhere are few in number, are here 
very pronounced. The lumen of the ampulla is broad, but elsewhere 494 
THE REPRODUCTIVE SYSTEM 
the lumen of the duct is very narrow, especially when compared with 
its exceptionally thick muscular wall. As in other portions of the 
excretory canal of the testicle, the lumen of the ductus deferens con- 
tains many spermatozoa. 
The Spermatic Cord.-The spermatic cord in its scrotal portion, 
Fig. 438.-Transection of the Ductus Deferens of a Dog. 
Hematein and eosin. Photo. X 104. 
in addition to the ductus deferens, contains a mass of connective tissue 
in which are embedded the smooth muscle fibers of the internal cre- 
master muscle, the spermatic artery, veins, and nerve plexus, and the 
vessels of the pampiniform plexus. The whole is invested hy a reflection 
of the tunica vaginalis. 
The pampiniform plexus is a considerable group of venous spaces, 
usually completely collapsed after death, which are characterized by MALE ORGANS OF REPRODUCTION 
495 
very thick, firm, fibromuscular walls. The vessels are embedded in 
dense connective tissue, and the whole plexus in general appearance 
somewhat resembles the erectile tissues. 
Fig. 439.-From a Section through the Wall of a Seminal Vesicle of Man. 
a, mucosa; l>, muscular coat; c, fibrous coat. Hematein and eosin. Photo. X 185. 
The Seminal Vesicles.-The walls of the seminal vesicles consist 
of a thin outermost coat of connective tissue in which are many small 
ganglia, a muscular coat similar to that of the ductus deferens but 496 
THE REPRODUCTIVE SYSTEM 
much thinner, and a characteristic mucosa. The tunica propria of the 
mucous membrane is a thin layer of delicate cellular connective tissue 
which loosely attaches the lining epithelium 
to the muscular coat. The surface of the 
mucosa presents numerous folds which not 
only form longitudinal rugae but also pos- 
sess an intricate network of secondary ridges 
which are both longitudinal and transverse 
in direction. This peculiar arrangement re- 
sults in the appearance of diverticula of 
various forms and sizes which, except that 
their epithelium does not differ from that 
of the surface, might often be interpreted, 
when seen in section, as representing sec- 
ondary secreting glands within the mucosa. 
Slender processes of the corium extend into 
all the folds of the mucous membrane. 
The lining epithelium of the seminal 
vesicles is of the columnar type and usually 
contains but a single layer of cells. Occa- 
sionally basal cells are also found in the 
deeper part of the epithelial layer; in such 
case the epithelium may be said to be of the 
pseudo-stratified type. This variation may 
possibly be partly dependent upon the dis- 
tention or relaxation of the vesicles. The 
cells of the epithelium contain peculiar 
granules of yellowish pigment which are 
present in considerable numbers and are 
quite characteristic of the organ. The su- 
perficial cells appear to be readily desquam- 
ated, and together with coarse granules of 
secretion form the chief contents of the 
lumen. Occasional small concretions of ir- 
regular form, and homogeneous or lamellar 
structure, similar to those of the prostate 
gland, are also found. The seminal vesicles 
usually contain but few spermatozoa. Occasionally these are present in 
large numbers; at other times they may be entirely absent. Their chief 
function is now thought to be secretory. 
Fig. 440.-Model of a 
Reconstructed Pros- 
tate Gland of Man. 
The figure includes one 
lobule. The narrow duct 
expands and terminates in 
a large number of alveoli of 
very varied size and form. 
X 40. (After Maziarski.) MALE ORGANS OF REPRODUCTION 
497 
The Ejaculatory Ducts.-These ducts are formed by the union of 
the ampulla of a ductus deferens and the duct of a seminal vesicle and 
are similar in structure to the ampullae of which they are the continua- 
tion. The ejaculatory ducts, however, possess a thinner wall and their 
mucosa presents the same folded condition as in the seminal vesicles, 
but to a lesser degree. In its prostatic portion the musculature of the 
ductus deferens blends with the muscular stroma of the prostate, so 
that in the ejaculatory duct the smooth muscle no longer forms a 
distinctly lamellated coat. On approaching the urethra, the epithelium 
of the ejaculatory ducts presents a gradual transition to the stratified 
epithelium of the urethral canal. 
Associated Glands 
The Prostate Gland.-This is a compound tubulo-alveolar gland 
consisting of from 30 to 50 lobules investing the urethra and the ejacula- 
tory ducts. It pours its serous secretion, which has a characteristic 
odor, into the neighboring portion of the urethra by means of two large 
and many (15 to 30) small ducts. These open either directly into 
the urethral canal or indirectly through the utriculus prostaticus (sinus 
pocularis). The secreting alveoli are embedded in a very dense fibro- 
muscular stroma which, at the surface of the organ, forms an unusually 
thick capsule in which interlacing bundles of smooth muscle are most 
prominent. This portion of the stroma also contains intrinsic striated 
muscle fibers in limited numbers. Broad bands of fibromuscular tissue 
pass inward from the capsule and form a network of thick septa in the 
meshes of which are the glandular alveoli. These septa converge toward 
the urethra, which penetrates the ventral portion of the organ, their 
muscular fibers finally blending with the sphincter fibers of the prostatic 
portion of this canal. 
The stroma consists of smooth muscle and connective tissue; their 
fibers are intimately blended. The muscle and connective tissue con- 
stitute each about one-fourth of the organ. The muscle cells form 
either groups or bundles of variable size, or are frequently isolated 
within the meshes of the connective tissue. Their extreme abundance 
-in some parts exceeding the connective tissue in volume-is char- 
acteristic of the prostatic stroma. The connective tissue, which is 
sparingly supplied with elastic fibers, is rich in cells. Near the se- 
creting alveoli the muscle fibers are absent and the cellular connective 
tissue becomes more prominent. 
The lining cells are of the tall columnar type, sometimes forming 498 
THE REPRODUCTIVE SYSTEM 
a single, sometimes a multiple cell layer. They possess spherical or 
ovoid nuclei which lie in their deepest third. Their cytoplasm is finely 
granular and often contains small yellowish granules. The epithelium 
rests upon a prominent membrana propria, composed of peculiar coarse 
collagenous fibers, 'B-collagenous' fibers (Ferguson, Anat. Rec., 5, 12, 
1911) somewhat resembling, but not identical with, reticulum. This 
Fig. 441.-Several Alveoli of the Human Prostate Gland, Seen in Section 
Hematein and eosin. Photo. X 160. 
type of fiber is present also throughout the stroma and distinguish- 
able by the Bielschowsky technic from the usual collagenous ('A-col- 
lagenous') fibers. 
The epithelium is remarkably folded upon itself, the narrow interval 
between the two layers of the epithelial folds being always occupied by 
delicate extensions of the connective tissue stroma. The prominence 
of the folds varies greatly in different tubules, some showing scarcely MALE ORGANS OF REPRODUCTION 
499 
any such, the lumen of others being subdivided by deep rugae into 
numerous anastomosing compartments. The amount of the folding also 
varies in different species, being more highly developed in some of 
the lower mammals, e.g., the dog, than in man. 
The lumen of the prostatic tubules is broad, and is beset with numer- 
ous alveolar dilatations and shallow diverticula. It is usually broader 
Fig. 442.-Portion of Prostate Gland of an Old Man, Showing the Prostatic 
Concretions. 
In the upper right hand concretion the concentric lamellae are clearly discernible. 
near the blind extremity and diminishes somewhat in diameter toward 
the duct. The caliber of the lumen also varies greatly in different 
tubules and is possibly dependent in part upon the state of secretory 
activity. The contents of the lumen include the granular albuminous 
secretion, desquamated epithelial cells, and, as age advances, many so- 
called prostatic concretions ('corpora amylacea'; 'prostatic calculi'). 
The concretions vary greatly in size (10 p to 1 mm. in diameter), 
and may be homogeneous, but more frequently present a distinctly 500 
THE REPRODUCTIVE SYSTEM 
lamellated appearance. Prostatic concretions may occur at all ages but 
increase both in number and size in later life. Occasionally they attain 
a large size and may become encysted. 
The prostatic ducts are lined by either a single or a pseudo-stratified 
layer of columnar epithelium, and, except for their narrower caliber 
and more regular contour, they closely resemble the secreting tubules. 
As the ducts approach their termination their epithelium increases 
the number of its cell layers. The larger ducts, just prior to their 
Fig. 443.-Prostatic Genital Corpuscles. 
a, axial nerve fiber; b, peri-axial nerve fiber. Methylene blue. Moderately 
magnified. (After Timofejew.) 
termination, are lined by transitional epithelium similar to that of the 
urethra, into which they open. 
Blood and Lymph Supply.-The prostate gland possesses a rich 
blood supply. Its larger vessels are found in the capsule, whence 
they send branches into all portions of the fibromuscular stroma, and 
form a rich capillary plexus in the connective tissue layer about the 
epithelium of the secreting alveoli, and a second plexus in the substance 
of the stroma itself. The prostate is abundantly supplied, also, with 
lymphatic vessels, which are connected with the deep pelvic lymph 
nodes. 
The capsule of the prostate, as also the neighboring connective tissue, 
both in relation with this organ and with the adjacent seminal vesicles, 
contains many nerve trunks, chiefly sympathetic, and small ganglia. 
The latter are especially numerous. In this region a peculiar variety 
of special nerve ending is found. It was formerly regarded as a Pa- MALE ORGANS OF REPRODUCTION 
501 
cinian corpuscle, but differs somewhat from these bodies. It perhaps 
more nearly resembles the genital corpuscles. These bodies are dis- 
tinctly lamellated and possess a broad axial nerve fiber which some- 
what resembles that of the end bulbs of Krause. This nerve fiber is, 
Fig. 445.-From a Section of the Bul- 
bo-urethral (Cowper's) Gland of Man. 
a, duct; b, tubules; c, stroma. X 130. 
(After Braus.) 
however, accompanied by another and finer fiber 
which, as Timofejew (Anat. Anz., 1896) has 
shown, breaks into a close network of fine fibrils 
surrounding the axial nerve fiber in a peculiar 
basket-like manner. 
The Bulbo-urethral Glands (Cowpers 
Glands).-These are two small tubulo-acinar mu- 
cus-secreting glands which are divisible into 
numerous small lobules. The lobules are sep- 
arated by connective tissue septa containing both 
smooth and striated muscle fibers. The latter 
are continuous with the adjacent compressor urethrae muscle. The se- 
creting acini are lined by columnar cells, some of which are finely 
granular and stain with eosin and acid dyes, while others are apparently 
filled with mucous secretion and react to the specific dyes for mucin. 
Certain other tubular alveoli are lined by low cuboidal or flattened epi- 
thelium. The epithelium rests upon a distinct cellular basement mem- 
brane. 
Fig. 444. - Recon- 
struction of a Bul- 
bo-urethral (Cow- 
per's) Gland of 
Man. 
The tubular ducts 
are closely surrounded 
by the expanded alve- 
oli. X 100j (After 
Maziarski.) 502 
THE REPRODUCTIVE SYSTEM 
The interlobular and the smaller intralobular ducts are also lined 
by a single layer of columnar cells. Their wall is supplied with smooth 
muscle, most of whose fibers have a longitudinal direction. The two 
ducts of Cowper's glands open into the bulbous portion of the urethra. 
Associated Vestigial Structures 
The vestigial structures associated with the male reproductive system 
include the appendices testis and epididymis, the superior and inferior duc- 
tuli aberrentes, the paradidymis and the sinus pocularis. Of these it may 
be said in general that they are more or less variable with respect of gross 
and microscopic structure and even with respect of presence; that they 
resemble histologically the structures with which they are homologous, and 
that they tend to become cystic. 
The appendix testis is the least variable of the vestigial associates. It 
is present in about ninety per cent, of cases. It is a small spherical, fre- 
quently pedunculated, sac attached to the superior pole of the testis; it is 
covered with tunica vaginalis and lined with simple columnar epithelium, 
sometimes ciliated, and represents the end of the degenerated fetal Mul- 
lerian duct. 
The appendix epididymis is a very similar pedunculated structure, much 
less frequently present. It is situated on the globus major of the epididy- 
mis. It is supposed to represent a degenerated Wolffian tubule. By some 
it is regarded as the atrophic end of the Wolffian duct. 
The ductuli aberrentes are blind tubules, the remnants of meso- 
nephric tubules which failed of inclusion among the ductuli efferentes of 
the globus major. The superior ductule opens into the epididymis below 
the globus major; the inferior opens at the globus minor; both lie between 
the testis and the epididymis. They are lined with a single layer of colum- 
nar epithelium, sometimes ciliated. The inferior ductule is the more gen- 
erally present, and has a length of about five centimeters. 
The paradidymis (organ of Giraldes) lies within the spermatic cord 
between the head of the epididymis and the pampiniform plexus. It con- 
sists of a variable number of irregular branching tubules, blind at both 
ends, and lined with a single layer of columnar, ciliated epithelium. These 
tubules also represent persisting rudimentary mesonephric tubules. 
The sinus pocularis (sinus prostaticus) represents the remnant of the 
proximally fused degenerated fetal Mullerian ducts. It is the homologue of 
the vagina in the female. It is a shallow, blind pocket opening into the 
floor of the prostatic portion of the urethra; it may be bifid distally, varies 
in length from six to twelve millimeters, and is lined with a columnar 
epithelium which may be locally ciliated. MALE ORGANS OF REPRODUCTION 
503 
External Genital Organ 
The Penis.-The penis consists of three masses of erectile tissue, 
the two corpora cavernosa penis and the corpus spongiosum or corpus 
cavernosum urethrae, which are firmly united by dense fibrous and areolar 
The two corpora cavernosa (fused in the median line) and the corpus spongiosum, 
the latter containing the urethra, are well shown. The cutaneous surface is not 
included. Hematein and eosin. Photo. X 8. 
Fig. 446.-Transection of a Child's Penis, Just Back of the Glans. 
connective tissue. The outer cutaneous surface is loosely attached over 
the body of the organ; its structure does not differ materially from 
that of the skin of other parts. The subcutaneous tissue is remarkable 
for the extreme looseness of its areolee and the absence of fat. Tn the 
glans penis the epithelial covering, which is continuous with the pre- 
pucial epidermis, is firmly united to the underlying erectile tissue. 504 
THE KEPRODUCTJVE SYSTEM 
Each corpus cavernosum is invested with a thick sheath of very dense 
fibro-elastic tissue, the tunica albuginea, divisible into an inner circular 
and an outer longitudinal layer of fibers, and imperfect between the two 
corpora cavernosa penis where it forms the pectiniform septum. From 
the inner surface of this fibrous coat connective tissue septa, the trabec- 
ulae, pass in all directions and form a reticular framework whose 
fibrous bands contain many smooth 
muscle fibers. In the meshes of this 
framework are characteristic broad 
venous sinuses which possess no true 
wall other than their endothelial 
lining. In the flaccid condition of 
the organ the blood sinuses are com- 
pletely collapsed, their walls are in 
contact, and their lumina almost 
obliterated, which gives them the 
appearance of mere slits in the 
dense connective tissue of the caver- 
nous body. When distended by in- 
jection, or, in the erectile condition 
of the organ, by blood, these spaces 
become widely dilated and form true 
blood sinuses of broad caliber. 
The blood supply of the erectile 
tissue is peculiar. The arteries ter- 
minate either (1) in capillaries, (2) 
by direct anastomosis with the ven- 
ules, or (3) by opening directly into 
the venous sinuses, in which case 
the minute terminal arterioles have a peculiar looped appearance 
and were described by J. Muller (1835) as helicine arteries. The 
capillaries form a superficial plexus beneath the tunica albuginea, which 
opens into a deeper plexus of broader vessels from which the venules 
take origin. Blood following this course through the capillaries and 
into the venules may not enter the venous sinuses-a direction which 
is assumed by the greater portion of the blood in the flaccid condition 
of the organ. The deeper venous plexus communicates freely with 
the venous sinuses so that the least obstruction to the usual venous 
outflow diverts the circulation through these channels. 
The helicine arteries are confined to the corpora cavernosa penis, 
Fig. 447.-Helicine Artery in Sec- 
tion, from the Urethral Bulb of 
Man. 
a, lumen of a helicine artery; b, 
fibrous bands of the erectile tissue; c, c, 
lumen of a venous blood space; m, open- 
ing of the helicine artery into the blood 
space; ms, muscular coat of the artery. 
Hematoxylin and eosin. X 180. (Af- 
ter Kolliker.) MALE ORGANS OF REPRODUCTION 
505 
where they are most abundant near the root of the organ. The ar- 
terioles from which they are derived end by arborization in the con- 
nective tissue framework, their terminal twigs entering fibrous processes 
which project into the venous sinuses and are frequently bound down 
by delicate fibrous bands which unite their extremity to the wall of the 
sinus and produce the characteristic looped condition when the villus- 
like projection is distended by the injection of its arteriole. When 
partially injected the helicine arteries appear to end blindly, but when 
Fig. 448.-The Erectile Tissue of the Penis. 
cr, peripheral capillary plexus; t a, tunica albuginea; vs, venous spaces; z, bands 
of smooth muscle and vascular connective tissue. X 30. (After Kolliker.) 
completely distended they pour their contents into the venous sinuses. 
The venous spaces at the periphery of the erectile body are relatively 
narrow and the intervening trabeculae are thick; toward the axis of the 
body the sinuses become broader and occupy a relatively greater portion 
of the tissue. Here, also, their long axis, except in the corpus spongi- 
osum, frequently lies in the transverse axis of the penis. Both the 
arteries and the veins of the erectile tissue possess very thick muscular 
walls, and in both, the intima becomes locally thickened by accumula- 
tions of longitudinal muscles and elastic tissue bulging into the lumen; 
these modifications are less pronounced in the veins than in the arteries. 506 
TTTE REPRODUCTIVE SYSTEM 
The tunica albuginea and trabeculae of the corpus spongiosum are 
formed by less dense connective tissue than is found in the corpora 
cavernosa penis, and their venous spaces are not so broad. The broad 
anterior end of the corpus spongiosum forms almost the entire body 
of the glans penis, being only indented beneath the corona by the conical 
anterior ends of the corpora cavernosa penis which in this part are 
blended together to form a single median mass. The urethral canal 
occupies the axis of the corpus spongiosum from its bulb forward to 
the urinary meatus at the tip of the glans penis. This canal has already 
been described in the preceding chapter. It should be recalled that its 
lining epithelium differs in the several segments, being transitional in 
its prostatic and membranous portions, and stratified columnar through- 
out the greater length of the spongy portion, changing to stratified 
squamous in the dilated fossa navicularis of the glans penis. 
The skin of the glans penis is peculiar in the relatively moist char- 
acter of its epidermis and the consequent imperfect development of its 
superficial horny layer. Its dermal papillae are conspicuously developed. 
In the region of the corona the derma contains a ring of large sebaceous 
glands, the preputial glands, which open on the free epithelial surface. 
Their secretion forms the smegma, a peculiarly odoriferous sebum. The 
so-called glands of Tyson are shallow, non-glandular epithelia] pockets 
opening near the frenulum preputii (Lewis). 
The medullated sensory nerves (dorsal nerves of the penis; branches 
of the pudic) are abundantly supplied with special nerve end-organs. 
In the skin they form free varicose endings among the epithelial cells, 
and are connected with tactile corpuscles of Meissner in the dermal 
papillae. Deeper in the skin are many end bulbs of Krause, while still 
deeper are the peculiar genital corpuscles. Naked fibrils pass to the 
mucosa of the urethra. Pacinian corpuscles are also found in the loose 
connective tissue and in the tunica albuginea of the corpora cavernosa. 
Sympathetic nerve fibers are abundantly supplied to the walls of the 
blood-vessels and to the smooth muscle of the erectile tissue. Branches 
from the third and fourth sacral nerves also enter the penis as the 
nervi erigentes, supposed to convey the impulse to erection as vasodilator 
fibers. 
The lymphatics of the penis form an abundant superficial set in the 
subcutaneous tissue; these follow the larger blood-vessels and empty 
into the inguinal lymph glands. A less abundant deep set of lymphatics 
in the erectile tissue, also, accompanies the blood-vessels of these parts, 
but are distributed to the pelvic lymph glands. THE FEMALE REPRODUCTIVE ORGANS 
507 
THE FEMALE REPRODUCTIVE ORGANS 
This system includes the ovaries, oviducts, uterus, vagina, and ex- 
ternal genitals. All of these organs are concerned in the reproductive 
function, the ovary producing the germ cell or ovum, and the oviduct 
providing a suitable site for its maturation and fertilization and the 
uterus for the later development of the resulting embryo. 
Internal Genital Organs 
The Ovary 
The ovary also is properly regarded as a gland with a double func- 
tion, namely cytogenic and endocrin. The specific cells involved in the 
production of the internal secretion (exclusive, of the lutein substance) 
are in doubt. As in the testis, the possibilities include the germ cells, 
the general connective tissue and the interstitial cells, homologues of 
the interstitial cells of Leydig of the testis. The genetic and functional 
relationship between the several types of cells are similar to those 
described for the testis. The ovary, however, apparently does not contain 
a homologue of the Sertoli cells. As in the testis the internal secretory 
activity of the ovary sustains a reciprocal relationship to other internally 
secreting glands and in some manner, directly or indirectly, underlie 
normal development and the sexual instinct. The ovary, moreover, 
periodically elaborates still another internal secretion. 
The organ involved is a transient structure, the corpus luteum of 
pregnancy. This will be described below. Its function pertains to 
an inhibition of ovulation during pregnancy (Loeb; Pearl), and a 
stimulation to secretory activity of the mammary glands (Bouin et 
Ancil; Ott and Scott), and apparently in part also to the preparation 
of the uterine mucosa for proper implantation and normal develop- 
ment of the fertilized ovum. As shown by extirpation experiments the 
internal secretions of both ovary and testis influence also the nervous 
system, and seem essential to normal nervous function. 
The ovary is a solid ovoid body, about one and one-half inches 
long, three-quarters of an inch wide and one-half inch thick. It is 
attached to the margin of the broad ligament posteriorly by a short, 
thick connective tissue pedicle, the mesovarium, which transmits the 
blood-vessels with which the ovary is richly supplied. At its ovarian 
attachment the mesovarium becomes continuous with the connective 508 
THE REPRODUCTIVE SYSTEM 
tissue stroma of the ovary. The indentation which is thus produced 
is known as the hilum. 
The substance of the ovary is divisible into a central medulla which 
reaches the surface only at the hilum, and a peripheral cortex which 
invests all other portions of the medulla and is in turn clothed by a layer 
of germinal epithelium, a continuation of the peritoneal epithelium, 
whose cells in this area are peculiar in that they possess a typically 
cuboidal shape, and are thus sharply distinguished from the flattened 
mesothelial cells of the surrounding portions of the peritoneum. 
Fig. 449.-Section of Ovary of Adult Cat, Showing Five Vesicular (Graafian) 
Follicles, Four with the Cumulus Oophorus and the Enclosed Ovum. 
The antrum folliculi is filled with a granular matter, a coagulum of the liquor 
folliculi. Note that the ovarian follicles are in the cortical portion, the medulla 
contains no follicles. Photo. X 7. 
The Medulla.-The medulla of the ovary consists of a fibromuscular 
stroma and large numbers of blood-vessels. Its arteries are characterized 
by their spirally tortuous course and thick muscular walls; its veins are 
numerous and large, and their endothelium rests almost directly upon 
the fibromuscular stroma. This portion of the ovarian stroma consists 
of fibrous connective tissue in which are elastic fibers and considerable 
numbers of smooth muscle cells. The connective tissue is richly sup- 
plied with cellular elements, most of which are ovoid or fusiform in 
shape. 
The Cortex.-The cortex of the ovary likewise contains a vascular 
stroma and also large numbers of ova which are in all stages of develop- THE FEMALE REPRODUCTIVE ORGANS 
509 
ment, from the genetic cells of the germinal epithelium up to the more 
mature germ cells, contained within epithelial sacs and known as ovarian 
follicles. During the menstrual epoch the ovaries also contain peculiar 
yellowish bodies, corpora lutea, resulting from the rupture of the largest 
Fig. 450.-From the Ovarian Cortex of an Infant, Showing Many Ova in 
the Primary Follicular Stage. 
The portion above and to the right is near the free surface; that below and to 
the left adjoins the medulla. Hematein and eosin. Photo. X 200. 
follicles, a phenomenon which marks the climax of the process of ovula- 
tion. 
The stroma of the ovarian cortex is a connective tissue structure 
which contains relatively few elastic fibers and, except near the medulla, 
very little if any smooth muscle. It is, however, abundantly supplied 
with connective tissue cells of large size, most of which are ovoid, fusi- 
form, or even considerably elongated in shape. Many of these cells 510 
THE REPRODUCTIVE SYSTEM 
closely simulate smooth muscle on superficial examination, but are 
readiiy distinguished by careful study, especially if specimens are pre- 
pared by the various differential staining methods. 
In the vicinity of the follicles the stroma is specially rich 
in cellular elements and is otherwise modified to form a concentric coat 
for each of these bodies. This coat, the theca follicula, consists of (a) 
an outer layer, or tunica externa, composed chiefly of connective tissue 
whose interlacing bundles are concentrically disposed, (&) an inner 
layer, tunica interna, which is peculiarly rich in large ovoid cells, and 
(c) an innermost membrana propria, upon which the epithelial cells of 
the follicle directly rest. 
At the surface of the ovary the cortical stroma forms a dense layer 
of fine connective tissue fibers whose delicate bundles interlace in a 
close-meshed network. This layer, which immediately underlies the 
germinal epithelium at the surface of the ovarian cortex, is known as 
the tunica albuginea. It differs greatly in thickness in different mam- 
malian species, in different individuals of the same species, and even 
in different portions of the same ovary. Its deeper surface blends in- 
sensibly with the underlying stroma of the cortex. 
The general appearance of the ovary varies according to the number, 
size, and stage of development of its ova and their follicles. At birth 
the cortex is packed with large numbers of newly formed ova, all of which 
are in approximately the same stage of development. Their number 
has been estimated at between 30,000 and 70,000. No new ova are 
formed after birth. Since in the normal sexual cycle from puberty 
to the menopause (from about the thirteenth to the forty-fifth year), 
a period of about 32 years, only about 400 eggs are liberated, the vast 
majority of potential ova must degenerate. This process of degeneration 
is especially active after the climacteric. 
During childhood the formation of larger follicles goes forward 
at an unequal rate, some ova rapidly approaching maturity, others ap- 
parently remaining almost stationary, and still others undergoing retro- 
grade development, so that at the age of puberty the ovary contains 
germ cells and follicles in all stages of development. After puberty 
the ripe follicles successively rupture and result in the formation of 
many corpora lutea which promptly degenerate, and are finally replaced 
by dense connective tissue in the form of small scar-like masses known as 
the corpora albicantia. Hence throughout the menstrual epoch the ova- 
rian cortex contains many corpora lutea and corpora albicantia in addition 
to ova and follicles in various earlier stages of development. After the THE FEMALE REPRODUCTIVE ORGANS 
511 
climacteric the remaining follicles degenerate and the process of ovulation 
gradually ceases. 
We shall now discuss the structure of the ovum or female germ cell 
and shall then successively trace its development and maturation, the 
formation of its vesicular (Graafian) follicle, the rupture of the follicle, 
and the subsequent history of the corpus luteum. 
The Ovum.-The ovum is a spherical cell of large size (200 to 
300 /a). When fully developed it is surrounded by a thick layer of 
exoplasm, the zona pellucida, which is probably 
derived from the cytoplasm of the follicular epi- 
thelium by which the ovum is closely invested. 
The ovum itself consists of a mass of cytoplasm, 
the vitellus, and a large vesicular nucleus or 
germinal vesicle, within which is frequently a 
single prominent nucleolus or germinal spot. The 
cytoplasm of the mature ovum is inclosed by a 
very delicate cell membrane, known as the vitelline 
membrane, which is not demonstrable in the prim- 
itive ova of the younger follicles. 
The cytoplasm of the ovum at first appears 
finely reticular, but as its development advances 
a fatty material is deposited within its meshes, 
usually in the form of minute irregular spheroids, 
by the accumulation of which the reticular cyto- 
plasm is in great part replaced by a granulofatty 
mass of faint yellowish color known as deuto- 
plasm. Frequently this metamorphosis is not 
quite complete, a remnant of the original cytoplasm persists beneath the 
vitelline membrane and in the vicinity of the nucleus. 
Numerous cytoplasmic structures have been described in these cells, 
chief among which are the accessory nucleus (Nebenkern), and the yolk 
nucleus (Dotterkern). The accessory nuclei, occasionally chromatinic 
and therefore basophil, more frequently stain with cytoplasmic dyes and 
are at times attached, at other times separate from the true nucleus. 
They are more probably remnants of mitotic spindles. The yolk nuclei 
of mammalian ova most frequently take the form of crescentic masses 
of lightly staining chromatin ('chromidia') which partially surround the 
nucleus, forming a so-called nuclear cap. They are often found in 
various stages of disintegration, and the fragments may be transported 
to the peripheral portions of the cytoplasm, or may be irregularly scat- 
Fig. 451.-Ovum, Con- 
taining a Yolk 
Nucleus (Dotter- 
kern) at the Left 
and Above the Nu- 
cleus. 
The peripheral nuclei 
are derived from the 
adjacent stroma. Iron- 
hematoxylin. Highly 
magnified. (After von 
Skrobansky.) 512 
THE REPRODUCTIVE SYSTEM 
tered as small round chromatic granules, which occur throughout the 
cytoplasm. The physiological interpretation of these bodies is uncertain. 
The nucleus of the ovum is a large spheroidal vesicle, the volume 
and distribution of whose chromatin is subject to great variation. Chro- 
matin is present in greatest amount during the period of most active cell 
growth, in which the cytoplasm of the ovum is enormously increased in 
volume. At this time the nucleus often appears as a solid mass of chro- 
matin. Later the chromatin is diminished in volume, portions of its sub- 
stance being possibly extruded into the surrounding cytoplasm; the 
nucleus then acquires a characteristic vesicular appearance. 
The nuclear membrane is sharply defined and is at most times 
prominent, except, as in other cells, during mitosis, a process which 
marks the final maturation of the germ cell. The nuclear matrix or 
nuclear sap abounds in the vesicular type of nucleus and the chromatin 
is scattered in small particles which adhere to the inner surface of the 
nuclear wall or to the delicate achromatic linin threads. 
Each ovum as a rule contains a single nucleus (germinal vesicle), 
though occasionally two nuclei occur. The latter condition is presumed 
to arise either by the fusion of two ova within a single follicle or from 
incomplete cell division during development. 
Each nucleus, during its vesicular stage, usually contains a single 
nucleolus (germinal spot), which forms a spherical mass of chromatin, 
situated, like the nucleus itself, eccentrically rather than centrally. The 
staining properties of the nucleoli vary remarkably. Usually they take 
the basic (nuclear) dyes to a greater or less depth; occasionally they 
exhibit an affinity for the acid (cytoplasmic) dyes; still other nuclei take 
a metachromatic or irregular tint with the ordinary nuclear stains. 
Many nuclei even in the absence of mitosis contain no nucleolus. 
In the development of the ovum from the germinal epithelium, whose 
cells from their homology with the spermatogonia have been termed 
oogonia, there occur several mitoses which result in so-called oocytes; 
these later develop into the mature ovum. At about the time of its 
extrusion from the ripe follicle a final series of mitoses occur, which dis- 
tinguish the maturation of the ovum. In this process there is a series of 
two mitoses which result in the appearance of the polar bodies and pro- 
duce a reduction in the number of chromosomes to one-half the number 
which is characteristic of the somatic cells. By the first mitosis the 
cell produces what may be termed a daughter ovum, together with the 
first polar body, a minute cell of insignificant size. A second mitosis 
ensues giving origin to the mature ovum or ootid and the second polar THE FEMALE REPRODUCTIVE ORGANS 
513 
body. The egg now contains only one-half the specific number of chromo- 
somes ; the full specific number is restored at fertilization by the addition 
of the male reduced complement carried by the sperm. 
Development of the Ovarian Follicle.-The development of the 
ovarian follicle goes hand in hand with that of the ovum and can be 
readily followed in ovaries from individuals of different ages, children 
Fig. 452.-From a Section of the Ovarian Cortex of a New-born Kitten. 
K, Pfliiger's tubes; Ke, germinal epithelium; m, mitosis; Sir, ovarian stroma; 
Ub, primitive follicles. Moderately magnified. (After Kolliker.) 
and adults, the ripe follicles and corpora lutea appearing only after 
puberty. The process begins in the germinal epithelium in which certain 
cells so increase in size that they may be readily distinguished as future 
ova. As noted above, it is still an open question whether the primordial 
germ cells are genetic derivatives of the germinal epithelium or specific 
sex cells which have wandered into and become mingled with the cells of 
the peritoneal epithelium. More frequently, however, the earliest step in 
the process consists in the growth of solid cell columns from the layer 
of germinal epithelium into the cortical stroma of the ovary. These 
cell columns are known as Pfliigers tubes, though, except occasionally 
at the extreme surface of the organ, they lack a true tubular form and 
possess no vestige of a lumen. Felix, however, concludes that PH tiger's 
cords do not occur in the human female. 514 
THE REPRODUCTIVE SYSTEM 
Certain cells in these columns, by their increased size and prominent 
nucleus, become very early distinguishable as the primitive ova; their 
differentiation is rapidly followed by the constriction of the columns, 
through the activity of the surrounding tissue of the stroma, in such 
manner that one, rarely two or more ova, and several undifferentiated 
epithelioid cells are included in each portion whose connection with the 
Fig. 453.-A Primary Ovarian Follicle of the Human Ovary. 
From within outward are seen the germinal spot, germinal vesicle, vitellus, vitel- 
line membrane, zona pellucida, granule cell layer, membrana propria, and theca 
folliculi. The ovarian stroma forms the border of the figure. Hematein and eosin. 
Photo. X 575. 
layer of germinal epithelium is thus severed. In this way the primitive 
follicles {'egg nests') are formed. In the ovary of the new-born hun- 
dreds of such primary follicles occur in all portions of the cortex (Fig. 
450). They are also found persistent in large numbers in the ovary of 
the adult. 
Many follicles never go beyond this primary stage of development, 
but after a time undergo retrograde metamorphosis either by gradual 
atrophy or by a process, known as atresia of the follicle, in which the THE FEMALE REPRODUCTIVE ORGANS 
515 
chromatolysis in the ovum and its surrounding follicular cells is followed 
by growth and organization of the theca folliculi, the connective tissue 
which is thus formed finally replacing the atretic follicle. 
Fig. 454.-A Vesicular (Graafian) Follicle of the Human Ovary, Somewhat 
More Advanced than the Preceding. 
The accumulation of liquor folliculi has separated the granular cells into a discus 
proligerus and a membrana granulosa. The membrana propria is very sharp, and 
the theca folliculi is almost divisible into an inner cellular and an outer fibrous 
layer. Hematein and eosin. Photo. X 460. 
After remaining stationary for a long period, often for years, certain 
of the primitive follicles enter upon a period of rapid growth. This 
process first affects the ovum and results in the appearance of the deuto- 
plasm, zona pellucida, and other accessory structures, as already de- 
scribed. Cell multiplication now occurs in the surrounding epithelial 
cells, so that, instead of the single row of epithelium which surrounds 
the ovum of the primitive follicle, the ripening follicle soon acquires 516 
THE REPRODUCTIVE SYSTEM 
a layer of follicular epithelium several cells deep. This may be desig- 
nated the mantle-layer. 
The rapid multiplication of the epithelial cells is soon followed by 
active secretion, resulting in the formation of a clear fluid by which 
the cells are more and more separated, and the cytoplasm of adjacent 
Fig. 455.-A Nearly Ripe Graafian Follicle from the Ovary of a Dog. 
a, fibrous, and b, cellular layer of the theca folliculi; c, membrana propria; d, mem- 
brana granulosa, which, as a result of contraction during hardening, has retracted 
from the membrana propria, leaving a broad artificial space; E, liquor folliculi; 
f, discus proligerus; g, zona pellucida; h, vitelline membrane; i, vitellus; k, the ger- 
minal spot, lying within the germinal vesicle. Hematein and eosin. Photo. X 150. 
cells is then readily seen to be firmly joined together by numerous deli- 
cate processes which may be regarded as intercellular bridges. Similar 
processes unite the neighboring cells to the zona pellucida which has 
already formed about the ovum. 
The accumulation of the fluid liquor folliculi within the follicle soon 
appears to tear apart certain of the epithelial cells, and a fluid-filled space, •THE FEMALE REPRODUCTIVE ORGANS 
517 
the antrum folliculi, is thus formed. Such a follicle is known as a vesicu- 
lar or Graafian follicle. Follicles intermediate between the primary folli- 
cles with a single or double layer of mantle cells and vesicular follicles 
may for convenience be called intermediate or growing follicles. The 
epithelial cells are separated by the antrum into two layers: the one, 
Fig. 456.-Photomicrograph of a Section of Cat's Ovary, Showing Two Prl 
mary Follicles and One Vesicular Follicle. 
adherent to the membrana propria of the follicle, is known as the mem- 
brana ot stratum granulosum ; the other, adherent to the. zona pellucida 
of the ovum, is designated the discus proligerus. The two layers remain 
in contact at one point, and as the liquor folliculi increases in volume, 
the attached discus proligerus with its contained ovum comes to occupy 
a more and more eccentric position, and the cells of the stratum granulo- 
sum, where the two layers are in contact, appear to pile up about the 518 
THE REPRODUCTIVE SYSTEM 
ovum in the form of a hillock, the so-called cumulus oophorus. The 
latter term is now generally used exclusively in a sense to include and 
displace the term discus proligerus. 
The cells of the cumulus, which adjoin the zona pellucida, become 
somewhat elongated and in this way they form a radiate investment con- 
sisting of one or two rows of columnar cells which surround the zona 
pellucida of the ovum and are known as the corona radiaia. With the 
increase of the liquor folliculi the cumulus with its contained ovum is 
soon separated from its attachment to the stratum granulosum and the 
development of the folliculi is complete. 
During this period of rapid growth and development the follicle 
has increased in size from a diameter which scarcely exceeded that of its 
ovum (about 300/x) to such a size that it occupies the entire breadth of 
the ovarian cortex. It is now ready for the final steps in the maturation 
of its ovum and for the rupture of the follicle coincident with the ap- 
proach of the menstrual period. 
The forces which lead to the rupture of the follicle are not fully 
determined. They are undoubtedly varied, and, in addition to the 
gradual attentuation of the layer of cortical stroma which covers the 
free surface of the follicle and is known as the stigma, they include the 
gradual accumulation of liquor folliculi under increasing tension, the 
marked congestion of the ovary at the approach of the menstrual period, 
which is accompanied by the determination of an undue proportion of 
blood to the theca of the ripe follicle (Clark), and possibly the contrac- 
tion of the smooth muscle contained in the stroma of the deeper part of 
the cortex and adjacent portions of the medulla. In any event, as a 
result of the independent or combined action of these, or other unknown 
forces, the follicle ruptures in the direction of least resistance, viz., at 
the attenuated stigma, and the liquor folliculi gushes forth, carrying 
with it the detached ovum invested with its cumulus. The ovum is 
now free to enter the oviduct and prepare itself for fertilization and the 
development of the future embryo. 
The ovum finds its way from the abdominal cavity into the oviduct by 
aid of currents established in the direction of the orifice by the cilia of 
the cells covering the fimbriae; perhaps assisted by a direct grasping 
activity on the part of the fimbriae. Since spermatozoa are free to wan- 
der out of the oviduct into the abdominal cavity, and since an egg may 
occasionally fail to reach the opening of the oviduct, the possibilities are 
offered for an abdominal pregnancy, a result occasionally consummated. 
Likewise an egg may fail to become expelled from its follicle and may THE FEMALE REPRODUCTIVE ORGANS 
519 
then become fertilized within the ovary; or an egg fertilized in the ab- 
dominal cavity may perhaps subsequently become implanted in an empty 
follicle. Development proceeding under such conditions results in an 
ovarian pregnancy, at least seven well authenticated cases being now on 
record (Bryce, Kerr and Teacher, "An Early Ovarian Pregnancy," 
1908). Ovarian pregnancies cannot proceed normally, and may early 
call for surgical intervention. Occasionally a follicle may contain more 
than one ovum, bi- and triovular follicles being common. Such follicles 
apparently present the possibilities for ordinary twinning and multiple 
births. Arnold (Anat. Rec., 6, 11, 1912) records follicles in the ovary 
of a negress also with from four to ten oocytes, and one each with eleven 
and thirteen oocytes. 
The following table is offered for the benefit of the student as a 
resume of the several structural layers of the ripe Graafian follicle. The 
structures are enumerated in order from without inward: 
tunica externa 
tunica interna 
membrana propria. 
1. Theca folliculi 
2. Stratum (seu membrana) granulosum. 
3. Liquor folliculi-occupying the antrum folliculi. 
4. Discus proligerus-cumulus obphorus. 
5. Corona radiata. 
6. Zona pellucida (seu striata). 
7. Perivitelline space (possibly an artifact). 
8. Vitelline membrane. 
9. Vitellus-egg cytoplasm. 
10. Nucleus or germinal vesicle. 
11. Nucleolus or germinal spot. 
The Corpus Luteum.-The rupture of the follicle is accompanied 
by sudden relief of the intrafollicular tension and consequent hemorrhage 
from the thin-walled capillaries of the theca folliculi. Thus the cavity 
of the follicle is filled with blood; the ruptured follicle is then known 
as a corpus liemorrliagicum. This is the first stage in the formation of 
the corpus luteum. 
Promptly succeeding the formation of the corpus liemorrliagicum, 
lutein cells appear at the periphery of the body. They are large, ovoid 
or polyhedral cells having a clear finely granular cytoplasm and a peculiar 
yellow color due to the presence of a pigment known as lutein. More- 
over, the cytoplasm of the lutein cells becomes very rapidly infiltrated 
with droplets of fat, likewise deeply colored by the lutein pigment which 520 
THE REPRODUCTIVE SYSTEM 
is apparently held in solution. The origin of these cells is still a matter 
of controversy. By certain observers they have been thought to result 
from the growth and multiplication of those cells of the stratum granu- 
losum which remain after the rupture of the follicle (Bischoff, Pfliiger, 
Sobotta) ; by others they are derived from the connective tissue cells in 
the tunica interna of the theca folliculi (Kolliker, His, Palladino). 
Teacher (1908) interprets his preparations to 'indicate quite clearly that, 
Fig. 457.-Section through the Peripheral Portion of a Corpus Luteum, 
Showing Lutein Cells. 
a, the fibrous coat of the corpus luteum; b, lutein cells with bands of newly formed 
connective tissue; c, central blood clot, partially organized. Moderately magnified. 
(After Williams.) 
whatever the source of the cells may be in lower animals, they do not in 
man arise from the membrana granulosa.' Lutein cells may multiply 
by mitosis. 
The lutein cells increase rapidly both in number and in size, and 
gradually encroach upon the margin of the blood clot whose progressive 
absorption precedes the advance of the lutein cells. But not only does 
the lutein mass grow centralward, it also, and especially in the event of 
fertilization of the discharged ovum with the consequently increased THE FEMALE REPRODUCTIVE ORGANS 
521 
vascularity of the reproductive organs, grows at the periphery and in 
this way greatly increases the diameter of the corpus luteum. 
Minute vascular sprouts of embryonic connective tissue now pene- 
trate the lutein mass from the adjacent stroma of the theca folliculi, 
and growing centralward in septa-like processes, finally penetrate as far 
as the central blood clot. Hence the corpus luteum at this stage presents 
a more or less radiate structure. The central ends of the embryonic 
connective tissue septa frequently 
unite to inclose the remnant of the 
central blood clot, or by further 
proliferation they may entirely re- 
place the clot by a mass of newly 
formed gelatinous connective tissue. 
The absorption of the blood clot 
usually proceeds slowly. Remnants 
of the disintegrating blood in the 
form of a central stellate mass, 
which often contains hematoidin 
crystals, frequently persist until the 
corpus luteum has become well or- 
ganized with connective tissue. 
The formation of new connec- 
tive tissue is followed by its con- 
traction. That this process occurs 
very early in the connective tissue 
first formed at the periphery of the 
body, may possibly be held to ac- 
count for the fatty infiltration and final degeneration of the lutein cells, 
because of the consequent interference with their vascular supply. 
By continued development the entire mass of lutein cells is gradually 
replaced by connective tissue, which, by further contraction, finally pro- 
duces a dense white fibrous scar, no longer containing lutein pigment, 
known as a corpus albicans. This body persists for a long period, but 
undergoes progressive contraction until only a minute scar of almost 
microscopical size remains to mark the site of the ruptured corpuscle 
and the highly developed corpus luteum. Such scars persist for years 
in the stroma of the ovarian cortex. 
Finally it must be stated that there are no recognizable histological 
differences, other than those of size and duration, between the corpora 
lutea vera of pregnancy and the corpora lutea spuria whose formation 
Fig. 458.-Portion of Corpus Lute- 
um of Rabbit. 
The lutein cells contain peripherally 
many fat vacuoles. The stroma con- 
sists of fibrous connective tissue. 
X 500. 522 
THE REPRODUCTIVE SYSTEM 
accompanies the extrusion of the unfertilized ovum. The true corpora 
lutea are of relatively large size and persist for many months, the 
spurious are somewhat smaller and persist for little more than one 
month; yet both pass through the same histological process of develop- 
ment and degeneration and both leave their scars in the substances of 
the ovarian stroma. 
Ovarian scars also arise through atresia of the larger follicles, the 
degeneration of whose epithelium is followed by an ingrowth of tissue 
derived from the theca folliculi, and the gradual development, organiza- 
Fig. 459.-A Corpus Albicans, from a Section of the Human Ovary, 
X 75. (After Williams.) 
tion, and final contraction of the connective tissue, forming, as it were, 
a minute but imperfect corpus albicans, in the center of which is often 
the shrunken degenerating remains of the ovum. Certain small acido- 
philic homogeneous bodies, the so-called Call-Exner bodies, of uncertain 
significance are also occasionally present in the stratum granulosa of the 
ovarian follicles. 
Blood Supply.-The blood-vessels of the ovary are derived from the 
branches of the ovarian and uterine arteries. These vessels enter the 
ovary through the mesovarium and divide into numerous branches which 
pursue a peculiar spiral or corkscrew course through the stroma of the 
medulla, and finally enter the cortex. They possess thick muscular 
walls containing bundles of longitudinal smooth muscle fibers. In the 
cortex they supply capillaries to the stroma, and in the theca folliculi of 
the Graafian follicles they form rich plexuses of broad capillaries and THE FEMALE REPRODUCTIVE ORGANS 
523 
thin-walled venules. 
As the follicle ap- 
proaches maturity 
these plexuses be- 
come enormously de- 
veloped and appar- 
ently bear an impor- 
tant relation to the 
rupture of the fol- 
licle and the rapid 
development of the 
corpus luteum. The 
veins, which take 
origin from the ven- 
ules of these capil- 
lary plexuses, con- 
verge toward the 
medulla, where they 
form a plexus of 
large thin-walled 
vessels, the plexus 
venosus ovarii or 
pampiniform plexus,, 
which is embedded 
in the connective 
tissue of the medul- 
la, the mesovarium, 
and the adjacent 
portions of the broad 
ligament. 
Fig. 460.-From a Thick Section 
of the Ovary of a Woman. 
The blood-vessels have been in- 
jected. A, a, and a', arteries; b, cor- 
pus luteum, partially organized; c, 
point where rupture of the follicle 
occurred; d, tangential section of a 
follicle; e, corpora lutea which have 
organized and are already retrogres- 
sive. (After Clark.) Fig. 461.-Transections of the Human Oviduct. 
A, uterine; B, isthmic; and C, ampullar portions. X 15. (After Williams.) 
524 THE FEMALE REPRODUCTIVE ORGANS 
525 
The lymphatics arise in the cortical stroma by anastomosing canals 
and capillaries of irregular caliber, which are especially abundant in 
the walls of the Graafian follicles. These vessels converge toward the 
medulla, where they enter lymphatics which are supplied with valves, 
and find their way to the lymph nodes of the pelvic and lumbar regions. 
The nerves are chiefly derived from the ovarian sympathetic plexus. 
They enter the hilum and are distributed to the walls of the blood- 
vessels, and to the stroma of the ovary; here they form a rich terminal 
plexus in the walls of the follicles. Whether or not the naked fibrils are 
distributed to the epithelial cells within the follicle has not been satis- 
factorily determined. The small ganglia of the medulla include also 
pheochrome cells (Winiwarter); and certain sensory fibers are said to 
end in lamellar corpuscles. 
The Oviduct 
The oviduct, uterine tube, or Fallopian tube is a narrow duct about 
4V2 inches long, 
leading from the 
ovary to the cavity 
of the uterus. It 
consists of a broad, 
funnel - shaped, 
fringed or fimbri- 
ated extremity (or 
infundibulum), a 
constricted neck, 
an intermediate 
ampulla of consid- 
erable diameter, 
and a slender isth- 
mus by which the 
oviduct communi- 
cates with the ute- 
rine cavity. 
Throughout the 
entire tube its wall, 
which becomes 
gradually thinner 
from isthmus to infundibulum, consists of three coats-mucous, mus- 
cular and serous-but the character of its mucous membrane differs 
Fig. 462.-From a Transection of the Ampulla of the 
Oviduct, Showing the Structure of the Mucosa. 
X 280. (After Williams.) 526 
THE REPRODUCTIVE SYSTEM 
somewhat in its several portions. In the isthmus it is relatively smooth 
and usually presents four longitudinal ridges which have few secondary 
or accessory folds; in the ampulla the mucosa is greatly folded, the pri- 
mary rugae possessing small secondary folds which extend in all direc- 
tions, and by their very complexity nearly obliterate the otherwise broad 
lumen. In the fimbriated portion the folds of the mucosa are continued 
into the fimbriae, at the margin of which the columnar ciliated epithe- 
lium of the oviduct becomes directly continuous with the serous mesothe- 
lium of the peritoneum investing the outer surface of the tube. 
The mucosa is lined by columnar epithelium, arranged either in a 
simple or pseudo-stratified manner, the greater portion of whose cells 
are provided with cilia. The ciliary motion is directed toward the uterus. 
The epithelial layer covers all the folds of the mucosa and, extending 
deeply into the crevices, forms invaginations which, in transections of 
the tube, simulate glandular structures. There are, however, no true 
secreting glands in the oviduct. Here and there groups of non-ciliated 
cells with clear cytoplasm occur among the more numerous ciliated cells 
of the mucosa. 
The epithelium rests upon a thin homogeneous basement membrane 
beneath which is a tunica propria consisting of a cellular type of connec- 
tive tissue. Many of the connective tissue cells are of fusiform shape, 
and, unless specially stained or carefully examined, they closely resemble 
smooth muscle cells. The mucosa, however, contains no muscle except at 
the bases of the largest folds, into which occasional fibers from the adja- 
cent muscular coat penetrate. 
The muscular wall of the oviduct is formed by two layers of 
smooth muscle-a broad inner circular layer, and an outer longitudinal 
coat, which is very unequally developed at different portions of the cir- 
cumference, but is relatively thin in all parts, and is entirely wanting at 
frequent intervals. The outer layer is usually broadest at the free mar- 
gin of the oviduct and at its opposite side where the tube is attached to 
the broad ligament. The inner circular fibers are more or less obliquely 
disposed, and, toward the mucosa, the muscular bundles fuse insensibly 
with the cellular connective tissue of the mucous membrane. In gen- 
eral the inner circular layer is thickest at the isthmus and thinnest at 
the infundibulum, while the longitudinal layer is thickest toward the 
fimbriated end. 
The serous coat of the oviduct is continuous with the peritoneum. 
It consists of an outermost layer of mesothelium which rests upon a sub- 
epithelial layer of connective tissue, by which it is firmly united to the THE FEMALE REPRODUCTIVE ORGANS 
527 
muscular wall. This portion of the serous coat contains the larger 
vessels and nerves which are distributed to the inner coats. 
Fig. 463.-Transection of the Uterus of an Ape. 
a, mucosa; b, circular muscle; c, longitudinal muscle; d, serous coat; e, lateral 
ligament; /, Wolffian tube; g, blood-vessels. X 4. (After Sobotta.) 
Blood Supply.-The arteries of the oviduct are derived from the 
uterine and ovarian vessels. The larger divisions find their way through 
the connective tissue of the serosa whence they send smaller branches 
inward to form a plexus between the layers of the muscular wall and 
among the bundles of circular muscle fibers. From this plexus capillaries 528 
THE REPRODUCTIVE SYSTEM 
are distributed to the muscular coat, and to the mucous membrane in 
which they form a rich subepithelial capillary plexus. The veins follow 
a similar course, and like the arteries, form an extensive plexus in the 
muscular coat. The abundance of vessels in the muscular wall of the 
oviduct has led to the description of this coat as the vascular layer of 
the organ. 
The lymphatics arise by anastomosing plexuses in the mucosa, from 
which vessels pass to the serous coat and enter valved lymphatics by 
which the lymph is conveyed to the lymph nodes of the lumbar region. 
The nerves, which are chiefly sympathetic, are distributed from a 
plexus in the serous coat, to the muscular wall, and to the mucosa, in 
which they form a terminal subepithelial plexus. 
The Uterus 
The uterus is a hollow pear-shaped organ, divisible into a deepest or 
fundus portion, the body, and the cervix, about 3 inches in depth, 
in width and 1 in thickness. The cervix opens into the body through 
the internal os, into the vagina through the external os. Its wall consists 
of a mucous membrane, a muscular coat, and an outermost serous coat 
which is derived from the peritoneum and invests the body of the organ. 
The cervix uteri projects into the vaginal canal and the serous coat is 
there replaced by a reflection of the vaginal mucosa. 
The serous coat, or perimetrium, of the uterus consists of meso- 
thelium which rests upon a thin subepithelial layer of connective tissue. 
It presents no peculiarities. 
The muscular coat, or myometrium, of the uterus consists of 
smooth muscle whose fibers are of large size (40 to 60 p. in length) and 
which are disposed in interlacing bundles. In the lower mammals these 
form quite regular layers-an outer longitudinal, a thick inner layer, 
most of whose fibers are circular, and an innermost, but less distinct, 
submucous portion containing oblique and longitudinal fibers. The outer 
longitudinal and circular layers are separated by a fibromuscular stratum 
containing a rich plexus of large blood-vessels. 
In the human uterus the arrangement of muscle fibers is much less 
regular, but follows a similar plan, though there is no distinct sub- 
division into layers. Nevertheless, careful examination reveals three indis- 
tinct strata which are intimately blended with one another. The outer- 
most of these indistinct layers consists of irregularly disposed longitudi- 
nal fibers, the stratum sup rar as cut are. This layer is in most-parts very THE FEMALE REPRODUCTIVE ORGANS 
529 
thin, and is best developed opposite the margin of the lateral ligament 
and in the cervix uteri. Within this is a broad layer of interlacing 
bundles of more or less circular fibers, which, from the slight obliquity 
of their course, frequently cross each other at acute angles. Inter- 
mingled with these circular bundles are many large blood-vessels, from 
which both the mucous and muscular coats are supplied. This broad 
middle layer is therefore known as the stratum vasculare. The inner 
Fig. 464.--Transection through the Body of the Human Uterus, 
g, blood-vessels; I, lumen; ll, broad ligament; Im, longitudinal muscle; m, circular 
muscle (the fibers are mostly oblique); s, serous coat; tp, mucosa. Hematoxylin 
and eosin. X 2. (After Sobotta.) 
portion of this second 'layer passes insensibly into a thin innermost 
stratum submucosum, which again contains many longitudinal fibers, 
and upon which the mucosa directly rests. 
The uterine mucosa, or endometrium, is of considerable thickness 
(1 to 3 mm.). It is clothed with epithelium, and its tunica propria con- 
tains numerous tubular glands. 
The epithelium is of the ciliated columnar type, and consists of a 
single row of cells. Apparently not all of its cells are provided with 
cilia, areas of ciliated alternating with groups of non-ciliated epithelium. 
The epithelial layer is continuous with the epithelium of the uterine 
glands; in the region of the external os uteri it is replaced by the strati- 
fied squamous epithelium of the vaginal mucosa. Ofttimes, and espe- 530 
THE REPRODUCTIVE SYSTEM 
cially in multipart, the stratified squamous epithelium of the vagina is 
continued for some little distance within the canal of the cervix uteri; 
it never clothes more than the lower one-half to two-thirds of the cervical 
canal. The current resulting from the vibration of the intra-uterine 
cilia is directed toward the vagina. 
The tunica propria of the mucosa consists of a peculiar embryonal 
type of connective tissue, similar to that of the oviducts, which contains 
very few collagenous and no elastic fibers, but which is richly supplied, 
Fig. 465.--From a Transection of the Uterine Mucosa. 
X 16. (After Williams.) 
in fact is literally packed, with cellular elements. These cells are ovoid 
or fusiform in shape, and many of them are branched; their nuclei, also, 
are ovoid and somewhat vesicular. Many lymphocytes are found in the 
tunica propria, but these mostly occur in the vicinity of the lymphatics 
and smaller blood-vessels with which the uterine mucosa is abundantly 
supplied. In the mucosa of the cervix uteri the development of the con- 
nective tissue appears to be more advanced, the cellular elements being 
relatively fewer; it also contains many fine fibers which appear to form 
a delicate network. At the external os uteri the tunica propria is con- 531 
THE FEMALE REPRODUCTIVE ORGANS 
tinuous with the similar, though still more fibrous, layer of the vagina! 
mucosa. 
The uterine glands are divisible into two types-those of the body of 
the organ, and those of its cervix. The former are, perhaps, to be re- 
garded as tubular invaginations of the lining epithelium, whose function 
Fig. 466.-From the Cervix Uteri of a Girl of Sixteen Years, Showing the 
Cervical Glands in Section. 
a-a, lining epithelium. Hematein and eosin. Photo. X 102. 
is one of epithelial regeneration rather than of glandular secretion. The 
tubules of the cervix uteri are true mucus-secreting glands. 
The uterine glands proper, those of the body of the organ, are slightly 
branched or forked tubules which traverse the entire breadth of the 
mucosa, presenting a characteristic spiral or corkscrew course; their 
blind extremities are often bent or turned to one side, apparently from 
the proximity of the adjacent muscular coat. The glandular epithelium 532 
THE REPRODUCTIVE SYSTEM 
is of the columnar type and, like that of the free surface, is frequently 
provided with cilia, especially near the mouth of the gland. The epithe- 
lium rests directly upon the connective tissue of the tunica propria. 
The cervical glands (glandules uterinoe cervicales)' resemble those of 
the body of the organ in their tubular form and the columnar shape of 
their epithelium, but here the re- 
semblance ceases. The cervical 
glands are much branched, and their 
tubules present frequent dilatations, 
some of which, apparently from oc- 
clusion of their outlet, attain a 
macroscopic size, and are then 
known follicles (ovula 
Nabothii) ; they are filled with a 
tenacious mucous secretion. The 
glandular epithelium near the crypt- 
like ducts is usually ciliated, like 
that of the surface, but in the 
secreting portions it consists of tall, 
clear, columnar cells which are in 
various stages of secretory activity, 
their product being a viscid glairy 
mucus, strings and granules of 
which are found within the lumen 
of the glands, as well as within the 
canal of the cervix uteri. 
The uterine cavity is a relative 
term. In the virgin, the mucosa is 
considerably folded and its surfaces 
are almost in apposition, being only 
separated by a very limited amount 
of desquamated epithelium and cel- 
lular debris, to which, in the canal 
of the cervix uteri, the mucous secretion is added. During pregnancy, 
the development of the fetus within the uterine cavity distends its walls 
and so dilates the canal that it at last forms a sac of sufficient size to 
contain the fetus, which floats within the amniotic fluid inclosed by its 
membranes. 
The blood-vessels of the uterus enter through the folds of the lateral 
ligament and find their way, through the subepithelial connective tissue 
Fig. 467.-A Gland of the Human 
Cervix Uteri in Longitudinal 
Section. 
X 90. (After Williams.) THE FEMALE REPRODUCTIVE ORGANS 
533 
of the serous coat and the muscular wall, to all portions of the organ. 
In the vascular layer of the muscular coat they form an extensive plexus 
from which branches are distributed to the musculature and to the mu- 
cosa, the branches to the latter penetrating nearly to the surface, where 
they form rich, subepithelial, capillary and venous plexuses. The uterine 
arteries, like those of the ovary, possess a peculiar, spirally tortuous 
course. The veins accompany the arteries, but are less tortuous. 
The lymphatics of the uterus arise by anastomosing channels in the 
mucous and muscular coats. They form a vascular plexus in the serous 
coat and lead outward, through the lateral ligaments and pelvic connec- 
tive tissue, to the lower lymph nodes of the lumbar region. 
The nerves of the uterus are very numerous. They include both 
spinal and sympathetic fibers. They enter the serous coat from the 
ganglionic pelvic plexus, and are distributed to the vascular layer of 
the muscular coat. They there form a rich plexus, from which sympa- 
thetic motor fibers are distributed to the musculature and to the walls of 
the blood-vessels. 
The distribution of nerves within the mucosa has not yet been 
thoroughly worked out. According to von Gawronsky (Arch. f. Gynakol., 
1894) and Kbstlin (Fortschr. d. Med., 1894) sensory nerve fibrils pene- 
trate nearly to the surface and form a scanty subepithelial plexus, whence 
are derived fibrils which terminate between the epithelial cells. 
Since the uterus is subject to extensive structural variations dependent 
upon its functional phase and condition, it becomes important to recog- 
nize the differential marks of the menstruating and of the pregnant 
uterus. Besides general histologic alterations in the wall, especially in 
the mucous and muscular layers, additional structures involved in the 
pregnant uterus are the decidual cells and chorionic villi; these are 
diagnostic of pregnancy. Only the histology of these structures will be 
here described; for a consideration of their embryologic significance and 
relationship reference must be made to a text-book of Embryology. 
The Menstruating Uterus 
The appearance of the phenomena of menstruation is accompanied by 
decided alterations in the structure of the uterine mucosa. In spite of the 
difficulty of obtaining sufficiently fresh and well preserved material, certain 
changes which characterize the menstruating uterus are now definitely 
known. These chiefly consist in increased vascularity, hypertrophy of the 
elementary tissues of the mucosa, epithelial desquamation, and rupture of 
the blood-vessels, with consequent hemorrhages. These changes are fol- 534 
THE REPRODUCTIVE SYSTEM 
lowed by a process of regression and later of regeneration, by which the 
uterine mucosa rapidly returns to its former condition. 
The first or hypertrophic stage involves the epithelium, whose cells are 
elongated, and the tunica propria, in which many of the connective tissue 
cells undergo multiplication and enlargement. Thus the mucous mem- 
brane becomes greatly thickened; its glands, also, are increased in both 
length and breadth, becoming at the same time even more tortuous than 
before. The glandular hypertrophy involves both the uterine and the 
cervical glands; the secretion of the latter is much increased. 
Fig. 468.-From a Section of the Human Uterine Mucosa at the First Day 
of Menstruation. 
e, epithelium; d, disintegrating layer; g, gland; v, blood-vessel; m, muscular coat. 
X 44. (After Minot.) 
At the same time, the blood-vessels become widely dilated, especially 
those near the surface, and broad thin-walled sinuses are formed beneath 
the epithelium. Finally these vessels rupture and hemorrhages occur into 
the substance of the mucosa as well as into the cavity of the organ; des- 
quamation and disintegration of the superficial portions of the mucosa 
result. The menses which are thus formed contain blood, epithelium, con- 
nective tissue cells, and many leukocytes, which wander out from the blood- 
vessels of the mucosa in large numbers. The greatly thickened and hemor- 
rhagic mucosa is known as the decidua menstrualis. 
Regression and regeneration follow rapidly upon one another, the 
mucosa gradually regaining its former condition. During this process fat 
droplets appear in many of the connective tissue cells. The epithelium is 
rapidly regenerated, the new cells arising from the epithelial remnants at THE FEMALE REPRODUCTIVE ORGANS 
535 
the mouths of the uterine glands. In the course of a few days the mucosa 
regains its former quiescent condition. The complete cycle includes 28 
days, of which the menstrual process occupies about seven. 
The Gravid Uterus 
In the event of conception the uterine changes are more pronounced 
than during menstruation. These alterations include the same processes of 
hypertrophy and thickening as occur in the decidua menstrualis; they in- 
volve the musculature as well as the mucosa but are not followed by regres- 
sive changes,-hemorrhage, desquamation, etc.-until parturition occurs. 
The muscular wall undergoes an 
enormous increase both in the num- 
ber and size of its fibers. The rela- 
tively short (30 to 60 /x) smooth 
muscle fibers of the uterine wall 
gradually increase in size to as much 
as eleven times their former length 
and two to five times their breadth 
(Kolliker). The connective tissue of 
the muscular coat also increases in 
volume and becomes more distinctly 
fibrous. After parturition, fat drop- 
lets appear within the muscle cells, 
and the muscular wall by gradual 
atrophy returns to its former condi- 
tion. 
In the mucosa the formation of 
a decidual membrane goes forward 
in a manner similar to the develop- 
ment of the decidua menstrualis, but 
the process is exaggerated. The tu- 
nica propria soon becomes divisible 
into two distinct, though not sharply 
defined, layers, a deeper cavernous portion which is permeated by broad 
vascular channels together with the atrophied remains of the uterine 
glands, and a superficial compact layer in which the vascular channels, 
except for the thin-walled venous spaces, are smaller and the connective 
tissue cells more closely packed. 
Many of the connective tissue cells attain a large size and their nuclei 
are frequently multiple, or they may acquire an irregular polymorphonu- 
clear form. Giant cells are thus produced in the compact layer of the 
mucosa of the gravid uterus; they are highly characteristic of this tissue 
and are known as decidual cells. Though it is frequently asserted that 
Fig. 469.-A Group of Decidual 
Cells from the Human Uterus 
During the Early Stages of Preg- 
nancy. 
One of the cells contains two nuclei 
and a number of fat vacuoles. Three 
nuclei of the connective tissue stroma 
are also shown. X 750. 536 
THE REPRODUCTIVE SYSTEM 
similar cells occur in the decidua menstrualis, this is denied by Minot 
(1903), who states that in a considerable number of menstrual decidua 
examined, no such cells were ever found. 
The superficial epithelium is soon desquamated and the tunica propria 
comes into contact with the fetal chorion. The glandular epithelium is 
also partially degenerated, often becoming flattened and of irregular shape. 
It is frequently desquamated into the glandular lumen; this lumen is thus 
Fig. 470.-Chorionic Villi from the Human Placenta at Full Term. 
Hematein and eosin. Photo. X 114. 
reduced to a narrow crevice, which is so elongated during the dilatation of 
the uterine wall that the axis of the glandular remnant becomes nearly 
parallel to the surface of the decidua. 
The decidual membrane which is thus formed is divisible into three 
portions, according to its relation to the tissues of the embryo: 1, that 
portion upon which the developing ovum directly rests, which is known 
as the decidua serotina or decidua basalis but later forms the placenta 
uterina or maternal portion of the placenta; 2, at the margins of the THE FEMALE REPRODUCTIVE ORGANS 
537 
implanted ovum the decidual tissues close up over the ovum which is 
thus surrounded by the so-called decidua reflexa or decidua capsularis, 
which, after the early months of pregnancy, is gradually obliterated by the 
increasing growth of the fetus, and is finally replaced, its functions being 
progressively usurped by the newly formed placental tissues; 3, all the 
remaining portions of the decidual mucosa, those which line the greater 
part of the uterine cavity, collectively form the decidua vera, with whose 
surface, in the later months of pregnancy, the fetal chorion is intimate in 
relation. 
The mucosa of the cervix uteri meanwhile becomes greatly hyper- 
Fig. 471.-Chorionic Villus at Various Stages of Development 
A, chorionic villus at third week; B, at fourth month; C, at term. (After Wil- 
liams.) X 225. 
trophied and its glands much enlarged. This portion of the uterine mucosa 
does not, however, enter into the formation of the decidua vera; the 
changes occurring in its tissues, though similar, are much less pro- 
nounced. 
The Chorionic Villi.-These innumerable processes form the greater 
portion of the placental tissues. They vary in size from the broad main 
stems to the very slender terminal branches of the floating villi. They 
consist of a core of mesoderm covered with a variable layer of ectoderm. 
In the early condition of the placenta (fourth or fifth month of pregnancy) 
the villi are clothed with a double epithelial layer, of which the superficial 
takes the form of a syncytium (plasmoditrophoblast), while the deeper 
consists of a cellular layer, the cells of Langhans (cytotrophoblast). At 
later periods (seventh month to full term) the syncytium is found to have 
undergone a peculiar alteration, having become much thinner, and having 
even completely disappeared from considerable portions of the villi, it being 
replaced by canalized fibrin; at other points the syncytial cytoplasm is 
much thickened and the nuclei appear to be bunched or grouped within 
the thickened portions; these areas are known as cell-knots or proliferation 
islands. Here and there the degenerated cell-knots have been replaced by 538 
THE REPRODUCTIVE SYSTEM 
canalized fibrin. Wherever the main stems are inserted into the decidua 
the epithelium which formerly covered their tips appears to have also 
degenerated into a peculiar hyalin border zone. Towards the end of preg- 
nancy the cytotrophoblast becomes converted into plasmoditrophoblast. 
Within its syncytium the substance of the villus consists of the super- 
ficial cells of Langhans with their large ovoid nuclei, and a core of con- 
nective tissue of a delicate embryonic type, in which are the fetal blood- 
vessels. Even the smallest villi contain capillary loops of broad caliber, 
which are supplied by fetal arteries, derived from the umbilical arteries, 
which distribute their branches throughout the chorionic connective tissue. 
The fetal veins accompany the arteries. 
The Vagina 
The vagina is a fibromuscular sheath whose wall is divisible into 
three coats-mucous, muscular, and serous. 
The mucous membrane is clothed by a layer of stratified squamous 
epithelium, and is thrown into numerous folds or rugse. The epithelium 
ep., epithelium; p., papilla; c.t., connective tissue. (After Williams.) 
Fig. 472.-Vaginal Mucosa. X 90. 
rests upon a fibrous basement membrane. The tunica propria is 
formed by a close-meshed areolar tissue which, in its deeper and looser 
portion, is permeated by vascular channels of considerable size. This 
deep vascular layer is frequently described as a submucosa; it rests 
directly upon the muscular wall. The surface of the mucosa presents 
numerous conical papillse which project well into the epithelial layer. 
The musculature of the vagina contains smooth or involuntary 
fibers, and is divisible into an inner circular and an outer longitudinal 
layer. The muscle fibers are long and slender. Considerable connective THE FEMALE REPRODUCTIVE ORGANS 
539 
tissue is distributed among the muscle bundles. The latter are arranged 
in more or less parallel layers which are united by the delicate bands of 
connective tissue. 
The outer fibrous coat consists of dense areolar tissue which is 
well supplied with elastic fibers. It loosely unites the vaginal wall to 
the surrounding tissues. In this coat is a plexus of blood-vessels and 
lymphatics, from which branches pass to the muscular coat, and to the 
mucosa, in which they form an abundant plexus. An extensive nerve 
plexus, including spinal and sympathetic fibers, among which are many 
small ganglia, is also found in the fibrous coat; it distributes motor 
branches to the muscular wall and to the blood-vessels, and sensory 
fibers to the mucosa, in which they end in relation with the cells of the 
lining epithelium. 
The vaginal mucosa is reflected upon the outer wall of the cervix 
uteri, and at or near the external os it is continuous with the mucosa of 
the uterine cavity. Though occasional glands have been found in the 
vaginal mucous membrane, lined either by mucus-secreting or by ciliated 
cells, these glands would seem to be properly considered as anomalies, 
since they are usually absent, the mucoid secretions of the vaginal canal 
being chiefly provided by the abundant supply of mucus from the cervical 
glands of the uterus. The vaginal mucosa is continuous below with that 
of the vestibule. 
The Vestigial Structures 
The vestigial structures associated with the female reproductive system 
include the vesicular appendage (hydatid of Morgagni), the epoophoron, 
and the paroophoron. The same general statements made concerning the 
male vestigial structures hold likewise for those of the female. 
The vesicular appendage is attached to the fimbriated end of the ovi- 
duct, its stalk being continuous with the collecting duct of the epoophoron. 
It is a globular pedunculated structure of small size (three to six milli- 
meters diameter) ; it is lined with cuboidal epithelium, and may contain 
fluid. It represents the atrophic end of the degenerated Wolffian duct. 
There are besides a variable number of smaller accessory vesicular appen- 
dages attached to the broad ligament. 
The epoophoron (parovarium; organ of Rosenmuller) lies between the 
layers of the broad ligament in the triangular area between the ovary and 
the ampulla of the oviduct. It consists of a variable number of tubules 
(eighteen to twenty), the homologues of the ductuli efferentes of the male. 
These tubules may be blind at only one or at both ends; they may be lined 
with ciliated columnar epithelium, or their lumina may become obliterated. 540 
THE PEPBODUCTIVE SYSTEM 
Those blind only at one end connect with a longitudinal duct, a variable 
remnant of the Wolffian duct. 
The paroophoron-homologue of the male paradidymis-is a more 
mesial collection of similar tubules of like structure and genetic signifi- 
cance. It is said to be present only in infants. The further extension 
mesially of the longitudinal duct, either in continuation with the collecting 
duct of the epoophoron or paroophoron, or as an isolated blind duct, usually 
in the wall of the uterus and vagina, is known as the canal of Gartner. It 
is the vestige of the lower portion of the fetal Wolffian duct. 
The External Genitals 
The vestibule is supplied with a mucosa which offers a gradual tran- 
sition from the vagina, on the one hand, to the skin on the other. Its 
stratified squamous epithe- 
lium becomes in this way 
gradually more and more 
like that of the skin, eleidin 
granules first, and keratin 
later appearing on the outer 
surface of the labia minora. 
The epithelium of the labia 
majora is identical with 
that of the skin. 
The labia minora or 
nymphae form the lateral 
walls of the vestibule and 
consist of a fold of the mu- 
cosa which is provided with 
exceptionally tall papillse. 
Small sebaceous glands 
open directly upon the sur- 
face of the stratified squam- 
ous epithelium. There are 
no hair follicles in relation 
with these glands, and the 
labia minora contain no 
adipose tissue. They are 
richly supplied with blood-vessels, and with sensory nerve endings. 
The labia majora are formed by similar folds whose inner surface 
resembles the adjacent portion of the labia minora, but whose outer 
Fig. 473.-Transection of a Labium Minus of 
an Infant. 
a, labium minus; 6, border of the labium 
majus; c, adipose tissue of the latter. Hematein 
and eosin. Photo. X 12. THE FEMALE REPRODUCTIVE ORGANS 
541 
surface is cutaneous and is supplied with sebaceous and sudoriparous 
glands and with numerous hair follicles. The subepithelial areolar 
tissue is very dense and its deeper portion contains much fat. 
The clitoris consists of a mass of erectile tissue, homologous with 
the corpora cavernosa and glans penis of the male; it is covered by a 
fold of the mucosa. It is well supplied with nerves, which terminate 
in tactile corpuscles, end bulbs, and genital corpuscles. In this vicinity 
also, as well as in the region of the labia, Pacinian corpuscles are occa- 
sionally found. 
The hymen is formed by a reduplication of the vestibular mucosa. 
Its inner surface is similar to that of the labia minora and vagina; its 
outer is like that of the cutaneous surface, except that it contains no 
hair follicles. 
The glandulae vestibulares minores are a group of small mucus- 
secreting glands, similar in structure to the urethral glands of Littre in 
the male, which occur in the vestibular mucosa in the vicinity of the 
meatus urethrae. 
The glandulae vestibulares majores (glands of Bartholin) form 
a paired tubulo-alveolar mucus-secreting gland which opens by a narrow 
duct into the groove between the hymen and labium minus. The tubular 
alveoli are lined by columnar mucus-secreting cells; the ducts are clothed 
with columnar epithelium, which, as they approach their termination, 
becomes double-rowed, and finally changes to a stratified squamous epi- 
thelium similar to that of the surface upon which they open. These 
ducts frequently present saccular dilatations. 
The Mammary Glands 
From a strictly histogenic standpoint the mammary glands should be 
considered as appendages of the skin, and as such should more properly 
have been considered in the chapter devoted to that subject. ' Yet these 
glands are so closely related to the reproductive functions, attaining 
their full development only in the lactating female, that it seems equally 
proper to consider them at this time as accessory reproductive organs. 
The mammary glands may be regarded as modified sweat glands. 
Though producing a fatty secretion they show no resemblance to seba- 
ceous glands. The mammae undergo the same slight but progressive de- 
velopment in both sexes until the time of puberty when they suffer 
regressive changes in the male, persisting thereafter only in rudimentary 
condition. In the female they continue to grow, but become functionally 542 
THE REPRODUCTIVE SYSTEM 
active only in the event of pregnancy. Upon the hemispherical corpus 
mamma? can be distinguished the central raised nipple or mammilla, and 
the surrounding roughened and pigmented circular area, the areola. 
Each mammary gland consists of fifteen to twenty lobes, each of 
which is of itself a branched saccular gland whose lactiferous duct opens 
Fig. 474.-From the Actively Secreting Mammary Gland of a Woman. 
Several lobules are included, a, interlobular duct; b, interlobular connective 
tissue. Hematein and eosin. Photo. X 52. 
on the surface of the nipple near its apex. The main lactiferous or lobar 
ducts subdivide in an arborescent manner into many interlobular ducts, 
about which are clustered the groups of secreting alveoli, each group 
forming one of the many lobules included in a lobe of the gland. The 
structure of the lobule, as well as the general appearance of microscopi- 
cal sections of the gland, varies according to the stage of development 
and the condition of activity of the organ. THE FEMALE REPRODUCTIVE ORGANS 
543 
The Active Gland.-During lactation the glandular alveoli are so 
numerous as to form by far the most prominent portion of the gland. 
Each lobule consists of a cluster of saccular alveoli which open by short 
alveolar ducts into the interlobular ducts of the connective tissue which 
invests the lobules of the gland. The alveoli are closely packed within 
the lobule. 
The actively secreting alveoli are lined by cuboidal or low columnar 
cells which vary much in height even within the same alveolus, and are 
often considerably flattened. Fat drop- 
lets accumulate within the distal portion 
of their cytoplasm. The droplets in- 
crease, in size as well as in number, 
until they finally occupy the greater 
part of the distal end of the cell and 
are separated from each other by only 
a narrow interval of albuminous cyto- 
plasm. Finally the fat droplets are 
discharged into the broad lumen of the 
alveolus, where they apparently still re- 
tain a thin albuminous envelope which 
prevents their cohesion and consequent 
fusion, and thus permits their suspen- 
sion in the albuminous, fluid portion of 
the milk. The milk may include also 
cytoplasm and nuclear debris. 
The spherical nuclei of the secret- 
ing cells during this process are crowd- 
ed to the base of the cell, and after the discharge of the secretion the 
shrunken but nucleated cell remnants remain in situ; after a period 
of rest the cells apparently resume their secretory function. It appears 
probable that each cell in its life history may repeatedly pass through 
the cycle of secretory changes, though the exact number of such cycles 
which an individual cell may present obviously does not admit of dem- 
onstration. 
As a rule, the active epithelium consists of a single row of cells, 
though here and there they appear as if piled upon one another to form 
a double layer. During pregnancy many of these cells may be seen in 
mitosis. The actively secreting cells contain basal (ergastoplasmic) fila- 
ments. According to Hoven (Anat. Anz., 39, 1911) these filaments 
break up into granules from which minute fat spherules develop. The 
Fig. 475.-Model of a Recon- 
struction of an Intralob- 
ular Duct and Its Acini 
from the Active Mammary 
Gland of a Woman. 
X 200. (After Maziarski.) 544 
THE REPRODUCTIVE SYSTEM 
epithelium rests upon a reticular or homogeneous basement mem- 
brane, within which are occasional basket cells. These have been in- 
terpreted as smooth muscle cells, similar to those of the secretory por- 
tions of the sweat glands. The alveoli of the active gland are so closely 
packed that a connective tissue tunica propria is no more than scarcely 
demonstrable. The thin tunica propria is, however, richly supplied 
with blood capillaries, lymphatic vessels, and nerve fibers. 
The ducts of the mammary gland are lined by either a single or 
double row of low columnar cells. They possess a relatively broad lumen. 
Their membrana propria is supported by a thin connective tissue wall, 
Fig. 476.-Portions of Several Adjacent Lobules, and a Lactiferous Duct, 
of the Active Mammary Gland. 
The alveoli are filled with a stainable milk coagulum in which are many fat spher- 
ules. 
containing both circular and longitudinal elastic fibers but no muscle. 
The elastic fibers of the smaller ducts are poorly developed, but in suit- 
able specimens the longitudinal fibers are readily seen even in very 
small branches. Beyond the lactiferous sinus the duct epithelium 
changes to a stratified squamous variety which is continuous with that 
of the cutaneous surface of the nipple. 
The glandular lobules are firmly united by strong septa derived from 
the dense areolar tissue in which they are embedded. In the deeper 
parts of the gland occasional lobules of fat are found in this tissue. 
Within the nipple and beneath the adjacent portions of the areola, smooth 545 
THE FEMALE REPRODUCTIVE ORGANS 
muscle fibers are also found. These are arranged in circular bundles 
at the base of the nipple, with longitudinal fibers within its substance 
which, at the base of the mammilla, di- 
verge in radiating bundles into the sub- 
cutaneous tissue of the areolar zone. Con- 
traction of these fibers elevates and hard- 
ens the nipple, thus simulating the action 
of the erectile tissues. 
According to Liperovsky (Anat. Anz., 
45, 20, 1914) elastic fibers are more abun- 
dant than was formerly recognized in the 
walls of the alveoli and in the interalveo- 
lar connective tissue, frequently in inti- 
mate association with smooth muscle cells. 
Such 'elastico-muscular apparatus' is well 
developed in the peripheral portion of the 
glands, in the subpapillary layer of the 
skin, and especially in the vicinity of the 
nipple. The elastic fibers, which are super- 
ficially distributed, appear embedded at 
their deeper ends in the muscle fibers. 
This peculiar arrangement of elastic fibers 
in relation to smooth muscle probably aids 
in the expulsion of the secretion. 
Embedded in the subcutaneous tissue 
of the areola are also a number of small 
accessory lactiferous glands known as the 
Glands of Montgomery (Areolar Glands of 
Duval). The nipple and areola contain 
also abundant sebaceous glands; and sweat 
glands are present in the periphery of the 
areola. 
The Resting Gland.-With the cessa- 
tion of lactation the glandular alveoli un- 
dergo a rapid atrophy, and are replaced 
by connective tissue derived from the inter- 
lobular stroma. The ducts contract and 
the epithelium piles up to form a two- 
rowed, or even thicker, layer. The alveoli are reduced to mere buds 
from the terminal ducts, and their lumen is almost obliterated; their 
Fig. 477.-From a Section of 
the Human Mammary 
Gland in the Resting 
Condition. 
a, remnants of the glandular 
alveoli; b, duct; c, connective 
tissue; d, adipose tissue. Hem- 
atein and eosin. Photo. X 10. 546 
THE REPRODUCTIVE SYSTEM 
epithelium is similarly massed into a double layer of small cells. The 
lobules are reduced in size and consist only of a few shrunken alveoli 
clustered about the termination of an interlobular duct. The lumen of 
the alveoli, if any, contains no secretion, and that of the ducts, except 
for a little granular albuminous material and an occasional leukocyte, 
is empty. 
The connective tissue stroma is much increased in volume, and in 
places shows a marked infiltration with fat. The alveolar tissue of the 
mammary gland at all times contains wandering leukocytes, and many 
granule cells, both acidophil and basophil in character. 
With the appearance of pregnancy the gland promptly reenters a 
state of activity; its alveoli multiply; its connective tissue becomes rela- 
tively diminished in volume; its lobules are reformed and their alveoli 
finally begin secretion, a process which is heralded by the formation of 
a granulo-fatty colostrum, a rather serous fluid in which are suspended 
large numbers of colostrum corpuscles, large spheroidal cells, resembling 
leukocytes in their general form and in the character of their nuclei, but 
which possess a broad rim of cytoplasm often containing numbers of fat 
globules of varying size. Their cytoplasm has also been shown to contain 
neutrophil granules of Ehrlich similar to those of the polymorphonuclear 
leukocytes (Michaelis, Arch. mikr. Anat., 1898). 
Colostrum discharge precedes and follows the period of lactation for 
a few days; it appears also in both sexes for several days after birth when 
it is commonly known as 'witch's milk.' 
The origin of the colostrum corpuscles is still somewhat in doubt, 
though modern technic has gradually discredited the theory of their 
origin from desquamated remnants of the alveolar epithelium, and shows 
them to be more probably enlarged leukocytes which have wandered 
through the alveolar wall and have thus found their way into the 
lumen, where they take on a phagocytic activity and continue their 
growth. The following facts may be mentioned in support of this theory: 
a, leukocytes can be readily found between the cells of the alveolar 
epithelium as well as in the lumina of the saccules; b, the colostrum 
corpuscles examined in a fresh condition on a warmed slide have been 
repeatedly shown to possess the property of ameboid motion; c, the 
colostrum corpuscles, when stained, present the same granular and non- 
granular varieties as do the leukocytes of the blood; d, finally, the 
colostrum corpuscles have been shown to undergo mitotic cell division 
(Bizzozero and Ottolenghi), a phenomenon which we should hardly ex- 
pect to find in degenerated and desquamated epithelial cell remnants. THE FEMALE REPRODUCTIVE ORGANS 
547 
The blood-vessels of the mammary gland are specially abundant. 
They form rich capillary plexuses about the walls of the active alveoli. 
Many of the venules coming from these plexuses converge toward the 
areola, where they form an incomplete venous circle (circulus venosus of 
Haller} from which the efferent veins take their origin. 
The lymphatics of the mammary gland are also numerous. They 
take origin from broad channels among the alveoli and enter a rich plexus 
about the interlobular ducts. From here several vessels pass to the lymph 
nodes of the axilla. 
The nerves of the mammary gland include both spinal (sensory) and 
sympathetic fibers. The latter are distributed to the vascular walls, to 
the smooth muscle of the areola and nipple and to the alveolar epithe- 
lium. The sensory fibers supply the connective tissue of the nipple and 
areola where they occasionally terminate in tactile and Pacinian cor- 
puscles. 
Among the secreting alveoli the nerve fibers form an epilemmal 
plexus beneath the membrana propria, from which fibrils penetrate be- 
tween the epithelial cells, upon which they end in minute granular 
varicosities (Arnstein, Anat. Anz., 1895). 
Milk.-Milk, secreted by the active mammary gland, consists of an 
emulsion, in which fat droplets, varying in size from two to twenty 
microns or more, are suspended in a watery albuminous fluid. Water 
constitutes about eighty-six per cent, of the secretion; the protein con- 
stituent (three per cent.), which is largely nuclein, is derived in part 
from degenerating nuclei. Milk contains also a small amount of sugar 
(five per cent.) and a trace of salt. Each fat droplet is presumably 
invested with a thin coat of casein, derived from the cytoplasm of the 
secreting epithelium. Occasionally leukocytes occur in the milk, but 
never in large numbers, and like the similar colostrum corpuscles, they 
are mostly confined to the earlier periods of lactation. CHAPTER XVI 
THE DUCTLESS GLANDS-ENDOCR1N GLANDS 
{Organs of Internal Secretion) 
Under this heading it will be convenient to consider the suprarenal, 
thyroid, parathyroid, thymus, carotid, and coccygeal glands, the hypoph- 
ysis cerebri, the epiphysis cerebri and the paraganglia. This group 
of organs properly includes also the pancreatic islets, the interstitial 
cells of the testis and the ovary, and the corpora lutea already described. 
I. THE SUPRARENAL GLANDS 
The suprarenal glands (bodies or capsules ; also called adrenals') 
are two flattened irregular glandular masses situated close to the cranial 
extremity of each kidney, but without organic or genetic relationship 
with the renal system. On section the adrenal is seen to be readily 
divisible into a bright yellow or brownish-yellow cortex and a more 
vascular, and hence darker and somewhat reddish, medulla, whose central 
portion transmits several large veins which make their exit from an 
indentation in the anterior surface of the organ, known as the hilum. 
Development and Function.-The suprarenal gland is a composite 
structure formed by the intimate association of two embryologically dis- 
tinct anlages: one, the cortical component, of mesodermal, the other or 
medullary component, of ectodermal origin. The cortical component arises 
as a series of buds from the celomic epithelium covering the medial upper 
surface of the cephalic third of the Wolffian body; the medulla develops 
from cells which have migrated from the abdominal sympathetic plexus 
(celiac plexus), and which elaborate peculiar granules having an affinity 
for chromium, hence called chromaffin (or pheochrome) cells. The onto- 
genetic process recapitulates almost precisely the phylogenetic history of 
the suprarenals: In fishes the homologues of the two mammalian com- 
ponents remain separate, and the cortical representative includes a series 
of bodies, the interrenal bodies or organs; the medullary representative, 
548 THE SUPRARENAL GLANDS 
549 
also comprising a series of structures, is known throughout, due to its 
close topographical relationship to the kidney, as the adrenal. The cortex 
of the mammalian suprarenal gland thus represents the product of fusion 
of the ichthyoid interrenals. In the groups between fishes and mammals, 
the association of interrenals (cortical component) and adrenals (medul- 
lary component) becomes progressively more intimate. 
The suprarenal is absolutely essential to life; removal promptly results 
in death. According to Crile (1914) the brain is intimately dependent 
upon the suprarenals; when both glands are excised in the rabbit death 
follows in eighteen hours, the brain cells meanwhile exhibiting loss of 
chromophilic substance. The two portions are believed to have, in part at 
least, a different function, both inhering however in an internal secretion. 
The cortex is generally believed to elaborate an antitoxic secretion for 
neutralization of harmful products of destructive metabolism. The func- 
tion of the medulla is dependent upon the adrenalin (adrenin; epinephrin) 
of the pheochrome granules, probably having to do with maintaining the 
proper tonus of the muscle of the heart and blood-vessels, thus underlying 
blood pressure. Minute amounts of epinephrin in the blood effect a sensi- 
tization of the vasoconstrictor nerve endings so that the efferent impulses 
discharged cause the muscular coats of arterioles to contract vigorously, 
the result being an increase in blood pressure. The most conspicuous 
diseases of the suprarenals involve hypersecretion, perhaps inducing to 
arteriosclerosis; and hyposecretion, frequently the result of tuberculous 
lesions, producing a clinical complex known as Addison's disease. (Refer- 
ence should be made to Vincent's "Internal Secretions and the Ductless 
Glands," Longmans, 1912.) 
The organ is enclosed by a connective tissue capsule of considerable 
thickness. From the inner surface of the capsule delicate fibrous trabecu- 
lae pass inward and subdivide the epithelial parenchyma of the organ 
into cell groups and columns, which vary in their appearance according to 
the distribution of the connective tissue trabeculae. The suprarenal paren- 
chyma is exceptionally prone to post mortem changes. In the medulla 
the connective tissue presents an irregular areolar arrangement; the 
more regular, though varying form of the areolae in the cortex, subdi- 
vides this portion of the organ into three more or less distinct layers, 
which were first described by Arnold (Arch. f. path. Anat., 1866) as the 
zona glomerulosa, zona fasciculata, and zona reticularis. 
In the zona glomerulosa the connective tissue trabeculae subdivide 
the epithelium into spheroidal groups of cells, many of which are con- 
tinuous with the cell columns of the adjacent zona fasciculata. The 
glomerulate layer is relatively thin and lies close beneath the capsule. 550 
THE DUCTLESS GLANDS-ENDOCRIN GLANDS 
The stroma of the zona fasciculata is continued inward from the 
glomerulosa, but is so drawn out as to form elongated areolae, inclosing 
a, central vein; b, capsule; c, zona glomerulosa; d, zona fasciculata; e, zona reticu- 
laris; f, medulla; g, peri-adrenal adipose and areolar tissue. Hematein and eosin. 
Photo. X 45. 
Fig. 478.-From a Section through the Human Adrenal. 
cell columns of considerable length, which are disposed in a radial man- 
ner. This is the broadest of the three cortical zones and is interposed 
between the glomerulosa and reticularis. THE SUPRARENAL GLANDS 
551 
At the inner border of the zona fasciculata the connective tissue 
bundles pass insensibly from the regular columnar arrangement of this 
layer into a reticular maze. The resulting cell groups are of very irregu- 
lar form and compose the innermost cortical layer, the zone reticularis. 
This layer is the 
thinnest and least 
distinct of the 
three zones of the 
cortex. It can 
often be more read- 
ily distinguished by 
the highly pig- 
mented condition 
of its cells, than by 
the mere form of 
its cell columns. 
In man it passes 
almost insensibly 
into the medulla; 
in many animals- 
e.g., the dog, cat, 
and pig-there is a 
sharp demarcation 
between the zona 
reticularis and the 
medulla, produced 
by a thin mem- 
branous layer of 
connective tissue 
which apparently 
results from the 
fusion of the cen- 
tral ends of the 
fibrous bands in the 
cortical stroma. Such a membranous septum is usually wanting in the 
human adrenal. 
The connective tissue stroma of the adrenal consists of a delicate 
vascular network, which in the cortex contains very few if any elastic 
fibers. Flint (1900) has shown that this connective tissue is, in large 
part,- at least, a reticular tissue. The capsule consists of dense bundles 
Fig. 479.-Photomicrograph of Suprarenal Gland of 
Dog. 
A, loose areolar connective tissue of outer portion of 
capsule containing two large (G) and several small gan- 
glia; c, capsule proper; g, zona glomerulosa; F, zona fascic- 
ulata; R, zona reticularis of cortex; M, medulla, showing 
the large central Vein (V). 552 
THE DUCTLESS GLANDS-ENDOCRIN GLANDS 
of white fibrous tissue among which are many elastic fibers. The stroma 
of the medulla is also richly supplied with elastic tissue. 
The epithelium of the zona glomerulosa is arranged in spheroidal 
groups or in hooked or slightly coiled columns which are continuous 
with the straight columns of the fascicular zone. The cells of the zona 
glomerulosa are closely packed within the connective tissue meshes and 
Fig. 480.-More Highly Magnified Region of the Preceding Section, to 
Show the Capsule (C), Zona Glomerulosa (G), and a Portion of the Zona 
Fasciculata (F). 
the cell outlines are very indistinct. Wherever their outlines can be 
readily distinguished the cells are seen to be of columnar shape and are 
arranged in slender columns whose cells are often grouped about an 
indistinct central lumen. The cytoplasm of the cells of this zone is 
finely granular and stains readily with acid dyes. Occasional minute fat 
droplets appear in the innermost cells of the group, but these are never 
so abundant as in the more internal portions of the cortex. The nuclei 
in this zone are spheroidal in shape and rich in chromatin; they present 
frequent mitoses (Canalis, 1877), but these are more abundant in early 
life than in the adult. 
The cells of the zona fasciculata are highly characteristic. They THE SUPRARENAL GLANDS 
553 
are arranged in long straight columns which extend from the zona 
glomerulosa inward to the zona reticularis. The cells are columnar or 
polyhedral in shape; many of them contain minute fatty droplets in great 
abundance. This fat is readily blackened by osmic acid. Arnold (1902), 
by extraction with ether, obtained crystals of palmatin and stearin from 
the suprarenal gland. Plecnik (1902), however, considers that the 
adrenal fat differs in its ultimate chemical properties from the other fat 
of the body. Each columnar group consists of cells which are, as a rule, 
in approximately the same stage of fatty metamorphosis, and the cell 
columns of this zone may be divided into those which are distinctly 
acidophil and those which are distinctly fatty, though between these 
extremes there are many intermediate stages. 
The acidophil cells are ovoid or polyhedral elements which possess 
one or two highly chromatic spheroidal nuclei and a finely granular 
cytoplasm. On careful examination with high magnification, extremely 
minute fat droplets may often be demonstrated even in the most char- 
acteristic of these cells; with lower magnification these are frequently 
invisible. 
The fatty cells possess a spheroidal nucleus which is usually vesicular 
in character; occasionally it is highly chromatic. Frequently the ap- 
parent chromatolysis seems to progress in exact ratio to the accumulation 
of fat; those cells in which the fatty metamorphosis is more advanced 
present the more typically vesicular nucleus. With the progress of the 
fatty metamorphosis the cell outlines are again lost and the granular 
acidophil cytoplasm gradually replaced. The presence of fat in the broad 
zona fasciculata is partially responsible for the bright yellow color of 
the cortex of the organ. 
The cells of the zona reticularis are similar to those of the zona 
fasciculata, though the fatty metamorphosis is less pronounced. In one 
particular, however, the cells of this layer are remarkable. They con- 
tain an abundance of a peculiar brownish-yellow pigment which occurs 
both in the form of coarse granules and as a diffuse coloration of the 
cytoplasm. The spherical nuclei, highly chromatic or only slightly 
vesicular in character, are not invaded by the pigmentation. The vol- 
ume of pigment varies greatly in different individuals; it is usually 
absent in young persons, but is, as a rule, present after the twentieth 
year of life (Maass, 1889). In the suprarenal of the mouse many of 
these cells can be seen in process of amitotic division. 
The epithelial cells of the medulla are ovoid elements with one 
or two spherical nuclei, which in many cases possess a vesicular char- 554 
THE DUCTLESS GLANDS-ENDOCR IN GLANDS 
acter; in other cells they consist of a dense, almost solid, mass of chro- 
matin. The shape of the cell groups in the medulla varies greatly; 
usually they form small spheroidal masses or short columns. The cells 
are frequently arranged in a more or less tubular form but without 
a distinct lumen. Frequently they surround a minute capillary vessel. 
The medullary cells presumably pour their secretion into the blood- 
vessels, whose broad sinusoidal capillaries permeate the delicate connec- 
tive tissue bands which inclose the cell groups. Felicine (Arch. f. mikr. 
Anat., 1904) claims to have demonstrated the presence of minute intra- 
and intercellular secretory canaliculi which open directly or indirectly 
through broader lacuna', into the blood-vessels. 
The cell groups of the medulla, like those of the cortex, are divisible 
into the acidophil and the fatty types; the former are the more abun- 
dant, but the fatty metamorphosis is scarcely ever so advanced as in the 
cortex. There is, however, great variation in the size of the medullary 
cells. The larger ovoid elements form the typical groups; between 
these groups are narrow cell columns consisting of much smaller and 
less highly acidophil cells, which are arranged in slender columns and 
scattered irregular masses. 
The striking feature of the medullary cells is their granular content. 
These chromaffin granules have a special affinity for chromic acid and 
its salts, and stain a light brown or yellow. Their staining capacity in 
chromium solutions is due to the presence of adrenalin (Kingsbury, 
Anat. Rec., 5, 1, 1911). The granules are very readily soluble in acids. 
In the vicinity of the central veins, small nerve trunks are found, 
and occasional minute ganglia or isolated nerve cells occur along their 
course. These are not to be confused with the large ovoid epithelial cells 
of the medulla. 
Blood Supply.-The arteries which supply the suprarenal glands 
form a plexus of vessels in the capsule of the organ and in the neighbor- 
ing connective tissue. Some of the smaller branches of this plexus, the 
capsular arteries, supply the capsule itself, others enter the organ and 
are distributed to the cortex and to the medulla. The blood supplied 
to the capsular arteries, after traversing the capillaries, enters small 
venules which are tributary to the lumbar and phrenic veins. The course 
of the cortical and medullary vessels has been exhaustively studied by 
Flint (Proc. Bost. Soc. of Nat. Hist., 1900). 
The cortical arteries enter the zona glomerulosa where they abruptly 
break up to form a capillary plexus which occupies the connective tissue 
between the cell columns. Capillary vessels are continued from this THE SUPRARENAL GLANDS 
555 
plexus through the intercellular reticulum of the zona fasciculata, where 
they are in intimate relation with the epithelial cells, and reach the zona 
reticularis. Here the capillaries are collected into thin-walled venules 
or sinusoids. These vessels, after some anastomoses, form venous stems 
which are continued, without further anastomosis, through the medulla 
to the central veins. The venules of the cortex possess no walls other 
than their endothelium. 
The medullary arteries are also derived from the capsular plexus. 
They penetrate the cortex, and at the border of the medulla abruptly 
Fig. 481.-Reconstruction of a Dog's Adrenal. 
a, arteries; v, vein. X 25. (After Flint.) 
terminate in a plexus of capillary vessels which lie in the connective 
tissue stroma and come into intimate relation with the medullary cells. 
These vessels possess extremely thin walls, their endothelium often being 
in direct contact with the adjacent epithelium, whose cells frequently im- 
pinge upon the lumen of the capillary vessel (see Fig. 481). The capil- 
lary plexus pervades the entire medulla, its vessels being here and there 
collected into small venules which unite to form the central veins. 
These form two, or sometimes four, main stems (Flint) which make 
their exit at the hilum and enter the lumbar or renal vein, or, on the 
right side, enter the inferior vena cava. 
All of the efferent veins of the adrenal are characterized by a peculiar 
distribution of their smooth muscle fibers, which occur in considerable 
abundance, but are nearly all disposed in the axis of the vessel; the 556 
THE DUCTLESS GLANDS-ENDOCRIN GLANDS 
circular muscle fibers are confined to a very thin coat beneath the endo- 
thelium, or are often entirely absent. Frequently, and especially in the 
central veins of the adrenal, the coarse bundles of longitudinal muscle 
fibers project into the lumen of the vessel in a somewhat rugose manner. 
Whenever two veins unite to form a larger vessel, and at the junction of 
a central vein with any of its branches, these protuberant muscular 
bundles are especially prominent. Moreover, Ferguson (Amer. Jour. 
Anat., 5, 1, 1905) describes anomalous vessels of a venous nature which 
arise in the medulla, penetrate the 
cortex, and enter the venous plexus 
of the capsule; and in these in- 
stances the same peculiar distribu- 
tion of the muscle has been observed 
in the veins of the capsular plexus. 
Lymphatics.-The lymphatics 
of the suprarenal gland, according 
to Stilling (1887), form rich plex- 
uses in the zona glomerulosa and in 
the medulla; elsewhere they are less 
abundant. They follow the course 
of the blood-vessels and are espe- 
cially well developed in the vicinity 
of the central veins. 
Nerves.-The adrenal is well 
supplied with small sympathetic 
nerve trunks from the solar plexus. 
They form a plexus in the capsule 
from which branches are distributed 
to the cortex and to the medulla. 
In the cortex they invest the blood- 
vessels with a delicate plexus, but have not been found within the epithe- 
lial cell columns. In the medulla they are also distributed to the blood- 
vessels and are supplied with occasional small ganglia. Passing from 
the plexus of sympathetic nerve fibers which invests the groups of medul- 
lary epithelium, Dogiel (1894) demonstrated delicate fibrils, supplied 
with minute varicosities, which penetrate between the epithelial cells and 
terminate in a manner very similar to that which is characteristic of the 
epithelial parenchyma of other secreting glands. 
Accessory Suprarenals.-These include bodies of three types of 
structure: (1) bodies consisting exclusively of cortical substance; (2) 
Fig. 482.-Section of Part of an Ac- 
cessory Suprarenal (Chromo- 
phil Body), New-born Child. 
chr, a chromophil cell. (Schaeffer, 
"Quain's Anatomy.") THE THYROID GLAND 
557 
bodies composed exclusively of medullary substance and indistinguish- 
able from paraganglia; and (3) the true accessory (supernumerary) 
suprarenals consisting of both cortex and medulla. These bodies are 
widely distributed in the vicinity of the suprarenal, sometimes embedded 
within its substance, sometimes in the kidney or even in the liver. 
They vary in size from microscopic bodies to such with a diameter of a 
centimeter or more. They are frequently found also in connection with 
the genital system, a rather large representative being almost invariably 
present in the space between the testis and the epididymis, and in the 
broad ligament of the female close to the ovary, where it is known as 
Marchand's gland or Marchand's adrenal. 
II. THE THYROID GLAND 
The thyroid consists of a mass of glandular tubules or follicles, 
supported by a connective tissue stroma and supplied with a thin but 
dense fibrous capsule which closely invests the surface of each of its 
lobes. 
The Connective Tissue Framework.--The capsule of the thyroid 
consists of dense fibro-elastic tissue, from which trabeculae, containing 
the larger blood-vessels, pass inward and produce an indistinct lobular 
subdivision. A network of delicate fibers, among which are very few 
if any elastic fibers, passes from the trabeculae and invests the glandular 
follicles, forming a delicate basement membrane for their epithelium. 
Flint (1903) has shown that much of this interfollicular connective tis- 
sue is of the reticular variety. In it are contained the smaller blood- 
vessels and lymphatics. It also contains a few lymphocytes, which are 
scattered about in a diffuse manner. 
The follicles of the thyroid are ovoid saccules or short branched tu- 
bules with frequent diverticula (Streiff, Arch. mikr. Anat., 1897). They 
vary greatly in diameter and in the caliber of their lumen. Many of 
them present scarcely any lumen; others, by their extreme size (100 to 
200 /*), simulate small cysts. All follicles which possess any consider- 
able lumen contain a peculiar acidophil substance, known as colloid, 
which is apparently formed by the secretory activity of the glandular 
epithelium lining the follicles. 
Colloid is a homogeneous or very finely granular substance which 
stains readily with eosin, taking a very bright tint closely resembling 
that acquired by the hemoglobin of the red blood cells. Frequently, 558 
THE DUCTLESS GLANDS-ENDOCRIN GLANDS 
and especially in specimens which have been fixed and hardened in alco- 
hol, it presents a vacuolated appearance. As a rule the lumen of the 
follicle is not completely filled with the colloid mass, which is then 
adherent to the surface of the lining epithelium by delicate thread-like 
Fig. 483.-From a Section of the Human Thyroid Gland. 
a, thyroid follicles in transection; b, tangential section of the follicular wall. 
Hematein and eosin. Photo. X HO. 
processes; the colloid thus acquires a deceptive appearance of extreme 
contraction, as if its surface, except for occasional delicate strands, had 
been drawn away from the epithelium. 
Occasionally a single large vacuole, often containing basophil gran- 
ules or crystalloid particles, occupies the center of the colloid mass in 
the larger follicles; at other times the colloid material appears to be THE THYROID GLAND 
559 
broken into minute spherules. In general, the ratio of colloid content 
within the follicle, roughly stated, is in proportion to the age of the in- 
dividual. The follicles at the periphery of the lobes of the gland are 
less fully distended than those in the interior. 
Embedded in the colloid mass within the follicle, even in the appar- 
ently normal thyroid, red blood corpuscles and desquamated follicular 
epithelium are frequently found, but never in large quantity. Leuko- 
cytes are of less frequent occurrence and are more rarely found in the 
human thyroid than in that of the lower mammals. 
The follicular epithelium is typically cuboidal in shape; in 
young individuals it is somewhat taller than broad. In those follicles 
which are distended with colloid secretion the epithelium is relatively 
short; in those which are empty it is taller. Each cell contains a single 
spheroidal nucleus which lies in the center of the cell, or somewhat 
toward its basal extremity. This orderly disposition causes the nuclei, 
when seen in sections of the follicle, to appear as a continuous row in 
the wall of the alveolus, a disposition which is noticeable for its ex- 
ceptional regularity. 
The cytoplasm of the epithelium is finely granular and decidedly 
acidophilic. It usually contains some coarse granules and very small 
fatty droplets, which generally occupy the extremities of the cells. Mi- 
nute spheroidal granules which give the color reactions of colloid are 
also found in the cytoplasm of the epithelial cells. Hurthle (Arch. f. d. 
ges. Physiol., 1894), by staining with the Biondi-Ehrlich mixture, suc- 
ceeded in differentiating two types of cell, one lightly staining, the 
'chief cells,' the other a darker colloid-containing type which he designated 
as 'colloid cells.' These variations probably only represent different 
stages of secretion in the same epithelial cell type. Minute intercellular 
canaliculi occur at the angles between adjacent cells. 
In the thyroid of the opossum Bensley (Anat. Rec., 8, 9, 1914) also 
describes two types of cells, namely, the usual epithelial cells and ovoid 
cells. The latter hold a parietal position in the follicle; they are filled 
with fine eosinophilic granules which give to these cells a character strik- 
ingly similar to that of the acidophil cells of the anterior lobe of the hypo- 
physis cerebri. He describes also large needle-shaped crystalloid bodies in 
the epithelial cells similar to those in the interstitial and Sertoli cells of 
the testis. 
The epithelium rests upon a very delicate reticular basement mem- 
brane and is in close relation with the capillaries and lymphatic vessels 560 
THE DUCTLESS GLANDS-ENDOCRIN GLANDS 
of the interfollicular stroma. Colloid material, similar to that within the 
follicles, has been repeatedly found within the lymphatic vessels (Baber, 
Langendorf, Hurthle) and may be readily demonstrated in most sections 
of the thyroid. Un- 
doubtedly this does 
not, however, repre- 
sent the entire 'inter- 
nal secretion' of the 
gland. 
Blood Supply. - 
The arteries form a 
rich plexus in and 
about the capsule of 
the thyroid, from 
which numerous 
branches penetrate the 
organ, lying in the 
connective tissue trab- 
eculee between the lo- 
bules ; they are dis- 
tributed to all parts 
of the gland. They 
supply a rich capillary 
plexus in the walls of 
the follicles. The 
veins retrace the 
course of the arteries. 
The walls of the 
smaller venules consist 
only of endothelium, 
with a very thin coat 
of fibro-elastic connec- 
tive tissue. 
Lymphatics.-The 
thyroid is very abun- 
dantly supplied with lymphatic vessels. These form a plexus of 
very broad lacunar capillaries in the interfollicular connective tissue, 
where they stand in intimate relation with the follicular epithelium. 
From this plexus vessels pass to the interlobular connective tissue, in 
which they form a second plexus, whence lymphatic vessels pass out of 
Fig. 484.-Diagram of Pharynx of Human Embryo, 
Showing the Origins of the Anlages of the 
Thymus, Thyroid and Parathyroids (Epithelial 
Bodies). 
Thy1, earliest position of thyroid anlage; Thy1, sec- 
ondary position of thyroid anlage; Tgd, thyroglossal 
duct; Fc, foramen cecum; LThy, lateral thyroid an- 
lages; Pthy, parathyroid bodies; pb, postbranchial 
body; T, tonsil; I, II, III, IV, V, pharyngeal pouches; 
a, b, first and second branchial grooves ('gill clefts'); 
1, 2, 3, first, second and third aortic arches in the 
cores of the branchial arches. The complete wall of 
the pharynx is only shown at the right, above. (Adapt- 
ed from Kohn.) THE THYROID GLAND 
561 
the thyroid in company with the blood-vessels and enter the deep cer- 
vical lymph nodes. 
Nerves.-The nerves of the thyroid are derived from the sympa- 
thetic system and are mostly non-medullated. They accompany the ar- 
teries and form a delicate terminal plexus in the walls of the follicles. 
The finer fibrils of this plexus end in contact with the epithelium. 
Berkeley (1895) describes also occasional fibrils which apparently pene- 
trated between the epithelial cells. 
Development.-The thyroid develops from three anlages, a median and 
a pair of lateral outgrowths from the primitive pharynx. The median 
anlage sprouts from the floor of the pharynx at the level of the first 
pharyngeal pouches. Its site of origin is marked in the adult by the 
foramen cecum of the tongue. It forms the isthmus and pyramidal lobe 
(process) of the definitive thyroid. The lateral anlages grow down from 
the ventral border of the fourth pharyngeal pouches; they form the lateral 
lobes of the gland. The pyramidal lobe represents the remnant of the 
embryonic thyroglossal duct; it varies greatly in length in different indi- 
viduals; it may even retain a partial lumen which may be filled with col- 
loid, but it does not open upon the surface. The primary anlages consist 
of solid cords of cells; the cords subsequently acquire a lumen, and become 
broken up into lobules and follicles through the invasion of connective 
tissue. According to Grosser the definitive thyroid arises exclusively from 
the median anlage. 
Function.-Removal of the thyroid is followed by serious symptoms 
and frequently fatal results, particularly in the case of the carnivora. Its 
internal secretion is apparently necessary for normal metabolism and devel- 
opment. It governs the conditions favoring tissue oxidation (Crile). The 
essential secretion is probably something apart from the colloid and iodin 
content of the gland. According to Crile the active constituent, thyroidin, 
is iodin in a special proteid combination. The belief that the thyroid has 
also an antitoxic role is based chiefly on the observation that thyroidec- 
tomized animals are extremely liable to certain infections. Gudernatsch's 
experiments with frog tadpoles show that a thyroid diet accelerates differ- 
entiation but inhibits growth: the tadpoles metamorphosed prematurely 
into diminutive frogs-a result the opposite of that obtained when thymus 
is fed. An enlarged thyroid is commonly known as a 'goitre.' Enlargement 
may be due to increase in the amount of the connective tissue or of the 
colloid parenchyma; one results in atrophy of the parenchyma and a condi- 
tion of hyposecretion, associated with myxedema and in extreme cases with 
cretinism-an apparently hereditary defect; and the other in hypersecre- 
tion, associated with exophthalmic goitre (Grave's disease). In man and 
animals the thyroid shows a seasonal enlargement related to the sexual cycle. 562 
THE DUCTLESS GLANDS-ENDOCRIN GLANDS 
Accessory or Aberrant Thyroids 
These bodies, first described by Zuckerkandl (1879), are widely dis- 
tributed through the connective tissue of the cervical region. They 
are most frequently found in the course of the embryonic thyroglossal 
Fig. 485.-From the Border of a Mass of Aberrant Thyroid Tissue of Man, 
Occurring in the Region of the Parathyroid Glands. 
Hematein and eosin. Photo. X 204. 
duct and in the immediate vicinity of the lateral lobes of the thyroid. 
They present the appearance of embryonal remnants of thyroid tissue, 
but are found in nearly all individuals. 
The colloid follicles of the aberrant thyroids are usually small, 
though, in the larger specimens of these bodies, they may attain as great THE PARATHYROID GLANDS 
563 
a size as those of the thyroid itself. The cell columns without colloid 
are more numerous than in the thyroid gland, giving to the aberrant 
bodies a decidedly cellular appearance. Each aberrant mass is usually 
inclosed by a very thin connective tissue capsule which sends delicate 
processes between the cell groups. The epithelial cells retain all the 
characteristics of those of the thyroid gland, and can be readily distin- 
guished from the epithelium of the parathyroid glands with which the 
accessory thyroid bodies have been frequently confused. They are also 
much less vascular than the parathyroids. 
III. THE PARATHYROID GLANDS 
The parathyroids, or epithelial bodies, are small glandular bodies 
of irregular distribution, usually found in relation with the posterior 
margin of the lateral lobes of the thyroid gland. They arise as buds from 
the dorsal pockets of the third and fourth pharyngeal pouches. Typi- 
cally four parathyroids are present, the superior pair situated near the 
lateral, the inferior near the median margin of the lateral lobes of the 
thyroid. The inferior pair in the adult develops from the anterior pair 
of anlages, and frequently becomes embedded in the thyroid tissue. They 
may occur also in relation with the tracheal or laryngeal wall and may 
be found as high as the hyoid bone or as low as the border of the thymus. 
They also vary greatly in size and shape, but usually are of ovoid form 
and about three to five millimeters in diameter. 
Each parathyroid is invested by a thin capsule of dense connective 
tissue and consists of a mass of epithelial cells supported by a delicate 
fibrous reticulum. The epithelial cells are of two chief types, desig- 
nated by Welsh (Jour. Anat. and Physiol., 1898) as the 'principal' and 
the 'oxyphil' or acidophil cells. 
The principal cells are the more abundant. They are ovoid or 
spheroidal elements, with a clear vesicular cytoplasm, a distinct cell 
membrane, and a large spherical nucleus, whose chromatin is irregularly 
distributed and often gives the nucleus a somewhat vesicular character. 
The acidophil cells are of similar shape but are provided with a 
small spherical nucleus, which is very rich in chromatin, and a granular 
acidophilic cytoplasm. The acidophil are less numerous than the 
principal cells. 
The distribution of the epithelial cells is subject to considerable vari- 
ation. Most frequently they form an almost solid epithelial mass, in 564 
THE DUCTLESS GLANDS-ENDOCRIN GLANDS 
which capillary vessels are here and there found, the larger blood-vessels 
occupying the coarser bands of the fibrous stroma. In such glands the 
two cell varieties are either intermingled irregularly, or the acidophil 
cells may occur in scattered groups which are interspersed among the 
more numerous principal cells. 
In certain instances the epithelial cells are arranged in small alveo- 
Fig. 486.-Human Parathyroid Tissue, Moderately Magnified. 
Several blood-vessels are included. Capillary vessels can scarcely be recognized 
with this magnification. Hematein and eosin. Photo. X 300. 
lar groups which are surrounded by a network of capillary vessels. This 
arrangement appears to be more frequent in young individuals. The 
cell groups in this type of gland frequently form branching columns. 
Occasionally, epithelial cells surround a central lumen, in which are 
small masses of an acidophil substance which resembles colloid in its 
reactions. This colloidal material is less abundant in the human para- THE THYMUS 
565 
thyroid than in that of the lower mammals. Likewise the cystic ducts, 
lined by columnar or ciliated columnar epithelium, which have been de- 
scribed by Kohn (1897), though of frequent occurrence in the lower 
mammals are rarely, if ever, found in the human parathyroid. 
The parathyroids and the thyroid are frequently in anatomical con- 
tinuity; this area is characterized by transitional histologic conditions. 
Moreover, after thyroidectomy the parathyroids may alter their structure 
so as to resemble very closely thyroid tissue. The parathyroids are gen- 
erally regarded as having a function absolutely essential to life. How- 
ever, the experimental evidence touching this point is conflicting. But 
in certain forms, e.g., cat and dog, extirpation produces tetany which 
results in death. Vincent interprets the experimental data as indi- 
cating that the thyroid and the parathyroids constitute parts of the 
same apparatus, to which the pars intermedia of the hypophysis cerebri 
may have to be added as. a third constituent. 
The connective tissue of the gland is of variable quantity. It forms 
a thin but dense capsule; occasionally trabeculae extend inward and 
partially outline indistinct lobules. In many instances a hilum trans- 
mits the larger blood-vessels by means of vascular trabeculae which 
radiate to all portions of the organ. A delicate fibrous, or reticular 
stroma invests the individual cells, or the cell groups, when these are 
present. Occasionally the cells are so closely packed that the stroma is 
scarcely demonstrable. 
The blood supply of the parathyroid is exceedingly rich. Ar- 
teries enter from the capsule, or at the hilum, and rapidly break up 
into a plexus of broad capillary or sinusoidal vessels which follow the 
fibrous bands of the stroma and are in intimate relation with the epi- 
thelium. They are collected into thin-walled venules which retrace 
the course of the arteries. 
IV. THE THYMUS 
The thymus was formerly regarded as an organ of fetal and in- 
fantile life., and was believed to attain its maximum development during 
the second year of childhood. After this time it was thought to be- 
come gradually replaced by adipose tissue, its retrograde metamorphosis 
reaching completion at about the age of puberty. However, Waldeyer 
(1890) showed that the thymus may persist even in advanced age as 
a body of considerable size, and apparently functional. The more recent 566 
THE DUCTLESS GLANDS-ENDOCRIN GLANDS 
studies of Hammar (1906) and others indicate that the thymus nor- 
mally continues its development until about the time of puberty. 
Subsequently it loses slowly in weight, but a true atrophy of the 
parenchyma with cessation of function, does apparently not occur until 
about the age of fifty. 
It is still uncertain whether the thymus should be classified with 
Fig. 487.-A Section through Several Lobules of the Thymus of an Infant. 
a, loose fibrous septum between the lobules; &, cortex, and c, medulla of the lobule; 
d, blood-vessels in the connective tissue. Hematein and eosin. Photo. X 60. 
lymphoid organs or with endocrin glands. Recent investigations in- 
creasingly indicate that it is essentially of lymphoid character but func- 
tions, in part at least, as an organ of internal secretion, related to 
normal growth and sexual development. 
At its maximum the thymus forms a large lymphoid mass, embedded 
in areolar connective tissue, the trabeculae of which divide the organ 
into several lobes and innumerable minute lobules. Each lobule is 
surrounded by a thin fibrous capsule, by which it is loosely united to its 
neighbors. 
The lobule consists of a mass of lymphoid tissue, which is dense at 
the periphery but looser in the central portion. Tt is thus divisible 
into a dense cortex and a loose medulla, both composed essentially of 
lymphoid tissue, but between which, because of the difference in density, 
there is a sharp line of demarcation. Frequently, at some point on THE THYMUS 
567 
its circumference, the medulla reaches the surface of the lobule, and 
at such locations a narrow column of medullary lymphoid tissue connects 
it with the adjoining lobule. 
A close-meshed reticulum, within the narrow meshes of which are 
closely packed lymphoid cells, composes the lymphoid tissue of the lobule. 
That of the cortex and the medulla is alike, except for the fact that 
the meshes of the reticulum in the cortex are much more crowded 
with 'lymphocytes' than are those of the medulla. The medulla of 
each lobule is also charac- 
terized by the presence of 
several groups of concen- 
trically arranged epitheli- 
oid cells, the thymic cor- 
puscles (concentric corpus- 
cles of Hassall). 
Each thymic corpuscle 
consists of a large central 
cell or group of cells, which 
is surrounded by two to five 
layers of concentrically ar- 
ranged flat epithelioid cells. 
These groups or cell nests 
are strongly acidophil in 
their staining reactions, 
and therefore stand out in 
marked -contrast to the basophilic nuclei of the surrounding lymphoid 
tissue. A substance simulating the colloid of the thyroid may be present 
among the cells. Since no similar structure occurs elsewhere in the body, 
the concentric corpuscles are absolutely characteristic of the thymus 
lobule. 
The nature of the thymic corpuscles is not satisfactorily understood. 
According to one hypothesis they represent blood-vessels whose lumen 
has been obliterated by proliferation of its endothelial cells. Another 
theory regards them as remains of the epithelial columns from which 
the organ arose in the embryo. They are also interpreted as masses 
of hypertrophied cells of the reticulum. 
The types of lymphoid corpuscle which are found in the thymus 
are similar to those of the lymph nodes, though polymorphonuclear 
leukocytes are rather more frequent here, and giant cells, mononuclear 
or multinuclear in form, may be readily found in the medulla of this 
Fig. 488.-A Thymic Corpuscle from the 
Thymus of an Infant. 
Hematein and eosin. X 665. 568 
THE DUCTLESS GLANDS-ENDOCEIN GLANDS 
organ. Pappenheimer regards the specific cells of the thymus as epi- 
thelial in character, simulating, but not identical with, lymphocytes. 
Blood Supply.-The larger arteries of the thymus are distributed 
within the interlobular connective tissue. They supply branches to the 
lobule which penetrate to the medulla, where they form a plexus of 
sinusoidal capillaries with elongated meshes, and also distribute radi- 
ating capillaries to the cortical portion of the lobule. These sinusoidal 
vessels are highly characteristic of the medulla of the thymus lobule. 
They unite to form venous radicals of considerable caliber, which leave 
the lobule to join the interlobular veins in the loose connective tissue 
between the lobules. 
Lymph vessels, are of frequent occurrence in the interlobular con- 
nective tissue, and their branches occasionally penetrate to the medulla 
of the lobule, but there is nothing corresponding to the lymph sinuses 
of lymph nodes. Small non-medidlated nerve trunks are also found 
in the interlobular connective tissue, but seem to be chiefly distributed 
to the walls of the larger blood-vessels. 
Development and Function of the Thymus.-The thymus arises as 
a pair of tubular outgrowths from the ventral aspect of the third pharyn- 
geal pouch, which subsequently become solid and fuse to form a median, 
flat, bi-lobed organ lying in the root of the neck and the upper portion of 
the thorax. According to certain investigators (Stohr, et al.) the lymphoid 
cells of the definitive organ are derived from the entodermal cells of the 
initial anlages. The recent work of Maximow (Arch. mikr. Anat., 74, 3, 
1909), however, seems to demonstrate that these cells are true lymphocytes 
and that they have their origin in the surrounding mesenchyme, from the 
cells of which they differentiate, and from which location they migrate into 
the thymus anlages-a conclusion confirmed by the still more recent work 
of Badertscher (Amer. Jour. Anat., 17, 4, 1915). The original lymphocytes 
are said to be of the large variety; these give rise through proliferation with- 
in the thymus to the smaller types. Among the invading leukocytes are also 
a small number of polymorphs. The original epithelial anlages continue to 
grow for a time, and gradually become differentiated into the definitive 
reticulum of the thymus. Hassall's corpuscles are believed to represent non- 
reticular remnants of the original entodermal anlages. According to Ham- 
mar, and Bell, these concentric corpuscles are derived from hypertrophic 
reticular cells. They first appear early in fetal life, and continue to form 
and increase in size during infancy. They are interpreted by some as thy- 
mic elements of internal secretion. The thymus is commonly regarded as a 
hemopoietic organ, but its activity is limited to the formation of lympho- 
cytes and possibly a small number of granulocytes. Beard (1900) views it THE CAROTID GLAND 
569 
as the original source of leukocytes. The proliferative foci are the cortical 
portions of the lobules; the medulla does not correspond to the germ cen- 
ters of lymph nodules, but is probably an area of leukocyte dissolution. 
The thymus does not seem to be an organ essential to life. Extirpation in 
dogs and guinea pigs is not followed by death. However, the experimental 
evidence indicates a reciprocal functional relationship between the thymus 
and certain of the organs of internal secretion, especially the sex-glands. 
This suggests a secretory role; a conclusion supported by the results. of 
the recent experiments of Gudernatsch (Amer. Jour. Anat., 15, 4, 1914) 
in which thymus fed to frog tadpoles, accelerated growth, but suppressed 
differentiation. 
V. THE CAROTID GLAND 
This body was first carefully described by Luschka (1862) and, 
from its intimate relation to the blood-vessels and nerves, is also known 
as the glomus caroticum or ganglion inter car oticum. It is about the 
size of a rice grain. It 
consists of scattered 
masses of epithelioid cells, 
usually grouped in small 
spheroidal clumps or 'cell 
balls' embedded in the 
connective tissue at the 
point of bifurcation of the 
common carotid artery. 
Kohn (Arch. f. Mik. 
Anat., 1900) has de- 
scribed four types of the 
gland according to the 
density of its parenchyma 
-the type found in man 
consists of scattered cell 
groups; in the rabbit they 
are even more diffuse. The carotid gland of a cat consists of a single cell 
mass, while that of the ape is intermediate between that of the cat 
and man. 
The glandular elements are derived from embryonal sympathetic 
ganglion cells (Kohn). They are ovoid cells with finely granular 
cytoplasm and a spheroidal, somewhat vesicular nucleus. Many of them 
contain chromaffin granules. Because of its genetic relationship and 
Chrg, a 'chromaffin cell'; s, connective tissue 
septum. Portions of two adjacent lobules are in- 
cluded in the figure. X 200. (After Kohn.) 
Fig. 489.-Carotid Gland of an Ape. 570 
THE DUCTLESS GLANDS-ENDOCRIN GLANDS 
histologic similarity to a sympathetic ganglion, Kohn proposes the 
name, paraganglion caroticum. Its function is obviously similar to 
that of the other organs of the chromaffin system, and probably chiefly 
dependent upon the presence of adrenalin. 
The carotid gland is richly supplied with capillary blood-vessels and 
small non-medullated nerve trunks. The capillaries are in intimate 
relation with the glandular epithelium. 
VI. THE COCCYGEAL GLAND 
This small body-2.5 mm. in diameter (Eberth)-was discovered 
by Luschka in 1860. Its structure closely resembles that of the carotid 
gland. It usually con- 
sists of several minute 
groups of epithelioid 
cells which are in re- 
lation with the ter- 
minal branches of the 
middle sacral artery. 
It is richly supplied 
with broad capillaries 
or sinusoids and hence 
is also known as the 
glomus coccygeum. 
The parenchymal 
cells of the organ are 
ovoid elements which 
are closely packed 
about the walls of the 
blood-vessels in groups or short columns inclosed by delicate sheaths 
of connective tissue. The origin and function of these cells are un- 
known. No chromaffin cells have yet been certainly demonstrated. The 
organ is embedded in the dense connective tissue at the tip of the 
coccyx. Its general structure only suggests an internal secretory function. 
• According to Stoerck (Arch. mikr. Anat., Bd. 69, 1906), the cells 
of the coccygeal body do not give the pheochrome reaction at any period 
of life. They are believed to bear no genetic relation to the sympa- 
thetic nervous system. Schumacher regards the epithelioid cells as 
a transformation of the smooth muscle cells of the arterial vessels; 
Fig. 490.-From a Section of the Coccygeal Gland 
of Man. 
Highly magnified. (After Sertoli.) PARAGANGLIA 
571 
others interpret them as modified endothelial cells of the blood-vessels. 
Vincent suggests that this body may function as a 'safety-valve' in the 
course of the peripheral circulation; he regards the balance of evidence 
as against any function involving an internal secretion. 
VII. PARAGANGLIA 
The so-called chromaffin system includes besides the medulla of 
the suprarenal and the carotid gland, other larger and smaller groups 
of chromaffin cells ('pheochrome organs') derived from embryonal sym- 
pathetic cells and scattered along 
the entire sympathetic nervous 
system, the paraganglia. They 
are therefore present in many 
organs which receive a consider- 
able sympathetic innervation, e.g., 
kidney, liver, uterus, testis, etc. 
Chromaffin tissue composed of 
widely scattered cells is present 
also in the sympathetic trunks, 
particularly the various plexuses, 
among the definitive neurons of 
this system. 
The largest paraganglia (or- 
gans of Zuckerkandl) occur in 
close relation to the inferior mes- 
enteric artery, one on either side. 
Other smaller groups are found 
in relation to the abdominal 
aorta. Busachi has recently 
(1912) described chromaffin tis- 
sue in the human heart; and Thulin (Anat. Anz., 46, 22, 1914) reports 
a paraganglion in the striped muscle of the upper portion of the esoph- 
agus of man. In typical paraganglia the polygonal cells are arranged 
in irregular cords which form a fine-meshed network, the • areolae of 
which are occupied by sinusoidal blood-vessels, upon which the cells rest 
directly without the intervention of a basement membrane. The spher- 
ical nucleus is poor in chromatin; the reticular cytoplasm contains the 
pheochrome granules. The internal secretion of the paraganglia de- 
Fig. 491.-Median Section through the 
Anlages of the Hypophysis Cerebri 
of a 10 mm. Cat Embryo. (Bonnet.) 
Di, diencephalon; Te, telencephalon; 
M, mouth; R, Rathke's pouch (pituitary 
anlage); I, infundibulum. X 50. 572 
THE DUCTLESS GLANDS-ENDOCRIN GLANDS 
pends upon the adrenalin content of the granules. Adrenalin produces 
a contraction of involuntary muscle. Its function appears to be to 
maintain the proper tonus of the blood-vessels. 
VIII. HYPOPHYSIS CERE-BRI 
(Pituitary Body) 
The hypophysis is a gland of the internally secreting (endocrin) 
or ductless type. The secretion passes directly from the specific cells 
into capillaries. This gland is a composite structure, arising from the 
association of two originally distinct anlages; one taking origin as a 
median dorsal diverticulum (Rathke's pouch) from the primitive mouth, 
the other as a medial ventral evagination from the second cerebral 
vesicle (third ventricle) or diencephalon. Both components are thus 
ectodermal. The cerebral flask-shaped element invaginates the buccal 
element and modifies the original bulbar shape of the latter into 
that of a cup. The buccal connection disappears, while the cerebral 
connection persists as the infundibular stalk of the definitive struc- 
ture. 
The hypophysis is present as an essentially similar organ in all 
craniates. In man it measures about 12 mm. in the transverse, about 
7 mm. in the sagittal, and about 5 mm. in the vertical diameter. It 
has an inverted mushroom shape, the stalk or infundibulum, a hollow 
funnel-shaped structure lined with ependyma, attaching it to the brain, 
while its head is lodged in the sella turcica of the skull. The hypo- 
physis was known to the early anatomists as the pituitary gland (Vesal, 
1553), and was supposed to function as an excretory organ in the elimi- 
nation of mucus (pituita') from the brain by way of the nose. The 
term pituitary gland is now generally applied only to the larger anterior 
component or epithelial lobe; the posterior component or neural lobe 
is designated the infundibular process; the term hypophysis is applied 
to the associated elements. But hypophysis and pituitary body are still 
often used synonymously. The neural and glandular tissues are said 
to be connected with each other by means of nerve fibers, probably sym- 
pathetic, connective tissue, and blood-vessels. Certain investigators have 
described accessory pituitary bodies. Thus Haberfeld (1909) finds in 
man at all ages a 'pharyngeal pituitary,' a solid cord of neutrophilic 
cells about 5 mm. in length immediately behind the vomer. This is 
frequently the initial seat of tumors. HYPOPHYSIS CEREBRI 
573 
Function.-Very little is definitely known concerning the function of 
the hypophysis, notwithstanding extensive investigation. Much of the 
recorded clinical and experimental data is contradictory. However, the 
presence of the gland would seem to be essential to health, perhaps indis- 
pensable to the maintenance of life. It appears also that its two funda- 
mental components (anterior and posterior lobes) subserve different func- 
tions, and that pathological alterations in the gland induce marked 
changes in some or all of the other ductless glands, which glands appear 
to sustain reciprocal functional relationships to each other. Absence of 
the hypophysis (apituitarism) in mammals is associated with grave nutri- 
tive disturbances usually leading to death. Disordered function (dyspitui- 
tarism) is accompanied by inordinate enlargement of the extremities 
(acromegaly) and gigantism, mental derangements, disturbances in the 
sexual organs and improper metabolism of sugar. Reduced secretion 
('hypopituitarism') of the posterior lobe leads to an acquired high toler- 
ance for sugars with the resultant accumulation of fat (Cushing; "The 
Pituitary Body and Its Disorders," 1910). Increased secretion may be 
responsible for some types of emaciation and for certain mental distur- 
bances. Deficient secretion of the anterior lobe appears to inhibit com- 
plete development of the skeleton, resulting in dwarfism and infantilism; 
conditions of superabundant secretory activity (hyperpituitarism) are ac- 
companied by acromegaly and gigantism (Cushing). Injection of extract 
of the posterior lobe (pituitrin) into the blood-vessels produces a rise of 
blood pressure accompanied by diuresis, believed to be due to a stimulation 
of the smooth musculature of the blood-vessels. In its effect upon smooth 
muscle, particularly of the uterus, which it stimulates to sharp and pro- 
longed contraction, it resembles very closely the secretion of the suprarenal 
gland. Pituitrin is now extensively used in practical medicine and espe- 
cially in obstetrics. 
The anterior lobe is believed by some to be physiologically inactive, 
except in cases of defective secretion of the gland, while others hold that 
the removal of the posterior lobe gives rise to no symptoms, but that ex- 
cision of the anterior lobe produces all the ill effects of total pituitary 
extirpation. The contradictory results of experimental work may be due 
to failure or inability to completely separate the several portions; more- 
over, certain elements of the supposed symptom complex accompanying 
hypophysectomy may be due to mechanical injury to associated parts of 
the brain. 
Histologic Structure.-The hypophysis is usually described as 
consisting of three portions: (1) the anterior lobe or glandular portion; 
(2) the intermediate portion or boundary zone; and (3) the posterior 
lobe, or nervous portion. The recent more critical investigation of 574 
THE DUCTLESS GLANDS-ENDOCRIN GLANDS 
Tilney (Internationale Monatschrift f. Anat. u. Phys., Bd. 30, 1911), 
including careful reconstructions of a number of mammalian hypophyses, 
shows that this description is incomplete. The form, extent, relation 
and genetic significance of the pars intermedia had apparently hitherto 
not been fully appreciated, though Herring (1908) had already called 
attention to the fact that it comprised two histologically different areas. 
Tilney divides the hypophysis into: (I) pars neuralis (pars nervosa); 
Fig. 492.-Sagittal View of a Wax Reconstruction of the Hypophysis Cere- 
bri of the Adult Cat. 
1, third ventricle; 9a and 6, eminentia saccularis; 6, area premammillaris; 5, cor- 
pora mammillaria; 12, pars tuberalis; 8, recessus infundibuli; 10, infundibulum; 13, 
pars infundibularis; 16, recessus process! infundibuli; 11, processus infundibuli; 
15, lumen residuale; 14, pars distalis; 17. recessus tuberis; 3, optic chiasm. (Tilney, 
Internat. Monatschr., Bd. 30, 1913.) 
and (TT) pars buccalis. The pars neuralis consists of three distinct 
elements: (a) the eminentia saccularis of the tuber cinereum; (b) the 
infundibulum; and (c) the infundibular process. The pars buccalis 
consists of two elements: (a) the pars juxta-neuralis in close relation 
with and investing the neural portion; and (b) the pars distalis. A 
cleft, the residual lumen, remnant of the original cavity in the buccal 
diverticulum, appears between the two. Further analysis of the juxta- 
neural portion of the gland reveals two histologically different parts: 
(1) the pars infundibularis completely investing the infundibulum HYPOPHYSIS CEREBRI 
575 
and the infundibular process; and (2) the pars tuberalis, which sur- 
rounds the eminentia saccularis. 
The following outline presents this analysis in resume: 
HYPOPHYSIS CEREBRI 
1. Pars Neuralis: (Posterior lobe). 
(1) Eminentia Saccularis. 
(2) Infundibulum. 
(3) Processus infundibuli. 
II. Pars Buccalis sen Glandularis: 
(1) Pars juxtaneuralis. (Intermediate portion.) 
(a) Pars tuberalis. 
(b) Pars infundibularis. 
(2) Pars distalis. (Anterior lobe.) 
''The pars infundibularis makes its appearance almost immediately 
after the anlage of the buccal portion of the hypophysis is formed. The 
pars tuberalis arises as a relatively late structure. It has its origin in two 
secondary diverticula or sprouts from the body of the pituitary sac (buccal 
evagination). These sprouts, the lateral processes, ultimately fuse with 
each other across the median line, displace the body of the pituitary sac 
ventrad and thus secondarily assume their juxtaneural position. The 
juxtaneural portion of the hypophysis is intimately connected with the 
neural portion by means of nerve fibers, blood-vessels and connective 
tissue processes. Attempted separation consequently necessarily includes 
laceration of neural elements" (Tilney). Accordingly complete removal of 
the pars buccalis would seem to be impossible without the attendant re- 
moval of portions of the pars neuralis. This must be taken into account in 
interpreting symptoms following removal of the anterior lobe of the hypo- 
physis. 
I. Pars Neuralis : Infundibulum.-This consists of fusiform and 
multipolar neuroglia cells and fibers. A substance resembling colloid is 
also occasionally present. Small nerve cells have been reported, but 
their presence seems doubtful. The glia cells generally have a single 
nucleus, but two or more may appear. The protoplasm is finely granu- 
lar, and occasionally contains pigment granules, which seem to be more 
abundant in aged specimens. Delicate and coarse glia fibers extend 
through the protoplasmic portions of the cells, frequently terminating 
the cell processes (Fig. 49G). 
II. Pars Buccalis Seu Glandularis: (1) Pars juxtaneuralis.- 576 
THE DUCTLESS GLANDS-ENDOCRIN GLANDS 
(a) Pars tuberalis.-The cells of this portion are arranged in large 
tubular acini; the lumina may contain colloidal material. The cells 
are of the cuboidal type, sometimes ciliated, frequently two layers deep. 
The cytoplasm of the cells is sparse, 
homogeneous and deeply basophilic. 
The nuclei are large and vesicular. 
Blood-vessels (sinusoidal capillaries) 
are numerous, and are said occa- 
sionally to contain colloid. 
(b) Pars infundibularis.-Here 
the cells are arranged in a dense 
stratum several layers deep. Occa- 
sional acini (cysts) occur, but they 
are smaller than in the pars tuber- 
alis and are lined with only a sin- 
gle layer of low cuboidal cells. 
These cells contain large vesicular 
centric nuclei surrounded by a con- 
siderable layer of faintly basophilic 
granular cytoplasm. Blood-vessels are very meager and thin-walled. 
(2) Pars distalis.-This portion is surrounded by a robust fibrous 
capsule continuous posteriorly with a thinner investment for the neural 
lobe. Delicate trabeculae traverse 
the parenchyma and support the 
very abundant plexus of arterio- 
venous sinusoidal blood spaces. The 
peripheral cells of the pars distalis 
constitute a narrow zone of almost 
exclusively basophilic cells. The 
cells of the main central portion are 
arranged in dense convoluted anas- 
tomosing cords. The cords com- 
prise axial and parietal cells. The 
parietal cells are the larger, of 
polygonal shape, and with a gran- 
ular cytoplasm deeply acidophilic. 
These are the 'eosinophilic' or acid- 
ophilic ('chromophil') cells. The axial cells are smaller; their cyto- 
plasm contains 'neutrophilic' granules. These are the 'chief,' or 'chrom- 
ophobe' cells. The so-called 'chromophils' and 'chromophobes' of the 
Fig. 493.-Pars Tuberalis, Hypo- 
physis of Cat (Tilney.) 
Fig. 494.-Pars Infundibularis, Hy- 
pophysis of Cat. (Tilney.) HYPOPHYSIS CEREBRI 
577 
earlier terminology (Flesch, 1880), which was based simply upon a 
difference in the degree of tingibility, probably represent merely different 
functional phases of the same cell type. The classification of the cells as 
acidophils and basophils, a distinction based upon a more precise micro- 
chemical difference, accords with a topographical segregation arid more 
probably designates an actual functional division. True chromophobes, 
cells which stain only faintly and with difficulty in either acid or basic 
dyes-and probably functional phases of acidophil and basophil cells- 
appear first only in the higher sau- 
ropsids (Tilney). The nuclei of 
the several cell types are large and 
deeply staining. The cells in great 
part rest directly upon the endothe- 
lial walls of the capillaries. The 
blood-vessels are said to contain 
colloid. 
Comparative histologic studies 
indicate that the pituitary gland 
has a twofold activity, one part de- 
pendent upon the basophils, the 
other upon the acidophils. The 
residual lumen is lined only with 
basophils, and occasionally contains 
colloid. Comparative morphology 
indicates that the neural portion may represent an original special sense 
organ. It has been suggested by Tilney (Mem. Wistar Inst., Biol, and 
Anat., No. 2, 1911) that the basophils contribute their secretion by way 
of the residual lumen and the infundibular process to the cerebrospinal 
fluid, and the acidophils directly through the blood spaces. 
According to Dandy and Goetsch (Amer. Jour. Anat., 11, 2, 1911), 
the pars distalis receives from eighteen to twenty small arteries which 
converge to it from the circle of Willis. Within the lobe no true arteries 
or veins occur. The blood channels are sinusoidal in nature; they drain 
into a venous circle overlying the circle of Willis. 
The above description of the hypophysis is based largely upon dog 
and cat material. Our knowledge of the human hypophysis is less 
complete; but as far as is known, the structural elements are essentially 
closely similar. 
The nerve supply to the hypophysis in the dog is, according to Dandy 
(Amer. Jour. Anat., .15, 3, 1913), derived from the carotid plexus of the 
Fig. 495.--Pars Distalis, Hypophy- 
sis of Cat. (Tilney.) 578 
THE DUCTLESS GLANDS-ENDOCRIN GLANDS 
sympathetic system, which connects with the oculomotor and optic nerves, 
The innervation of the anterior lobe is described as abundant, that of the 
that of the 
Fig. 496.-Section of Hypophysis Cerebri of Dog, Showing Portions of Pars 
Distalis (D) of Anterior or Buccal Lobe, Residual Lumen (7?), Pars Tu- 
beralis (Pars Intermedia) (T), Pars Neuralis (/V), and C, Capsule. 
Note the abundant large blood sinuses in the glandular or buccal portion, and 
the tubules in the pars tuberalis (referring to the portion next the tuber cinereum). 
The pars neuralis is largely of neurogliar composition. 
posterior lobe as very scanty. The fibers are thought to be secretory in 
character. 
Dandy (ibid.) described also a small spherical body which he names 
parahypophysis in connection with the under central surface of the hypo- EPIPHYSIS CEREBRI 
579 
physis, resting in a depression in the floor of the sella turcica. This was 
found in over eighty per cent, of dogs examined. It is interpreted as a 
remnant of the embryonic Rathke's pouch. It is said to vary greatly in 
size and histological character, occasionally extending to the 'pars inter- 
media,' and to have an individual blood supply and possibly also a nerve 
supply. A parahypophysis has not yet been reported for man. 
Fig. 497.-Field from the Center of a Normal Canine (Puppy) Pars 
Anterior Distalis. 
Note the excess of eosinophils lining the sinuses. No basophils in the field, 
as they are more in evidence in the glandular periphery. The central elements in 
the cell columns are neutrophilic. (Hauptzellen.) 
In the hypophysis of the ox, Wulzen (Anat. Rec., 8, 8, 1914) has 
described a cone-shaped structure in connection with the 'pars intermedia' 
resembling in cellular constitution the pars glandularis but differing in 
having finer connective tissue septa and smaller acini. 
IX. EPIPHYSIS CEREBRI 
{Pineal body} 
The epiphysis {pineal body, pineal gland or conarium) may be 
provisionally regarded as an endocrin gland. Its glandular function 
may be of importance only during late fetal and infantile (or pre- 
puberal) life, when it may control normal growth. The mammalian 580 
THE DUCTLESS GLANDS-ENDOCRIN GLANDS 
epiphysis has been known to anatomists as a probable gland since the 
time of Galenus (1562). It has excited interest and been the subject 
of much speculation for centuries. Descartes (1649) regarded it as 
the seat of the 'soul.' Notwithstanding much study, it is still but im- 
perfectly understood, and even its histological makeup is to some extent 
in dispute. 
Development.-The epiphysis cerebri arises as an ependymal diver- 
ticulum from the roof of the diencephalon. The apical cells proliferate 
and undergo differentiation into neuroglia and interneuroglia cells. The 
latter may perhaps assume secretory activities, but no convincing cyto- 
logical evidence appears indicative of such function apart from numerous 
melanic granules,-which, however, are present in all of the cells in early 
stages of development-and certain lipoid granules and spherules. In the 
sheep numerous cysts, lined by tall columnar (ependymal) cells appear at 
half term (21 cm. stage). The cysts contain a coagulum. The cysts pro- 
gressively disappear, apparently through pressure from proliferating cells 
without, only a few persisting to birth and occasionally after. In the sheep 
the cysts arise through accumulations of fluid, compelling a cellular 
arrangement simulating acini, not as tubular outgrowths from the original 
lumen, as is apparently the case in birds. Both melanic granules and 
alveoli (cysts) are more probably to be interpreted as of ancestral signifi- 
cance. As far as is known an epiphysis is present in all vertebrates, with 
the exception of Myxinoides and Crocodilia. No trace of an epiphysis is 
said to appear even in embryos of Crocodilia. The pineal eye of certain 
reptiles is commonly regarded as the homologue of the pineal body of 
mammals. However, in the lower groups of animals the true homologue is 
generally a double structure, the pineal eye developing terminally on a 
secondary anterior evagination from the base of' the primary one. This 
secondary process is not developed in mammals. In Hatteria (a New 
Zealand 'lizard') the pineal eye comes to the surface in the middle of the 
head, and consists of an optic cup with a lens covered by transparent epi- 
dermal scales, forming a cornea. It is believed to function only as a light 
or warmth perceptive organ. An additional structure, the paraphysis, 
found in certain lower forms and in the marsupialia, anterior to the pineal 
body, and arising similarly as an ependymal evagination, is commonly 
regarded as a choroid plexus, evaginated instead of being invaginated, as 
is usually the case in mammals. In sheep the pineal undergoes its greatest 
development during the first year of life, approximately fivefold. 
The pineal body is attached to the posterior portion of the roof 
of the third ventricle by means of the pineal stalk. This contains the 
pineal recess, a cavity continuous with the ventricle. The anterior wall EPIPHYSIS CEREBRI 
581 
of the stalk is limited basally by the habenular commissure, the posterior 
wall by the posterior commissure. The pineal proper thus lies under- 
neath the posterior end of the corpus callosum and rests on the anterior 
pair of the corpora quadrigemina. It is a solid cone-shaped structure 
enveloped by a cap- 
sule of pia mater, and 
more or less distinctly 
lobed (Fig. 498). It 
measures in man 7 
mm. in length by 5 
mm. in transverse 
diameter. The mam- 
malian pineal is per- 
haps rather a meta- 
morphosed than a ru- 
dimentary organ. Its 
size bears no relation 
to the size of the 
brain or the size of 
the body; it is no 
larger in large than 
in small dogs, for example, and no larger in horse than in dog; that 
of sheep is about the size of that of man. 
Function.-Injection of pineal extract of sheep into the blood of cer- 
tain mammals produces only very slight effects. These, however, are fairly 
uniform, but very transient. The most conspicuous effect is a slight fall 
of blood pressure. There is also a slight improvement in the beat of the 
isolated cat's heart, a transient diuretic effect (in rabbit) and a slight ir- 
regular respiratory effect (in dog, cat and sheep-Jordan and Eyster, Amer. 
Jour. Physiol., 1911). These results are, to some extent, the reverse of 
those obtained with extracts of the hypophysis, and suggest a compensatory 
or antagonistic regulatory functional relationship. Extirpation experi- 
ments have not yet yielded perfectly satisfactory results. The evidence, 
however, indicates a functional role which is negligible or nil. Clinical 
evidence combined with autopsy findings indicate symptom complexes asso- 
ciated with pineal tumors or other structural alterations in general like, 
but of reverse relationship, to those present in case of hypophyseal altera- 
tion; i.e., the symptoms of hypopinealism are in general those associated 
with hyperpituitarism, and those of hyperpinealism like those accompany- 
ing hypopituitarism. The symptoms associated with morbid conditions of 
the pineal may possibly be the inherent result of pressure (or undue relaxa- 
Fig. 498.-Semidiagrammatic Representation of a 
Median Longitudinal Section through the Epi- 
physis of a 17 cm. Sheep Fetus. 582 
THE DUCTLESS GLANDS-END OCRIN GLANDS 
tion) upon the hypophysis transmitted through the third ventricle with 
which both pineal and hypophysis are connected. Certain symptoms may 
also be due to a blocking of the aqueduct, and to pressure upon the corpora 
quadrigemina. A conservative estimate of all the evidence indicates very 
meager, if any functional activity, probably never essential to life. The 
practical absence of the pineal body in the opossum adds further support 
to this conclusion; as also its occasional disappearance, except for a mere 
shell, in apparently normal cats. Biedl (1910), however, arrives at the 
conclusion that the pineal body is an organ of internal secretion with 
metabolic significance limited to the young. Its general histological struc- 
ture, and profuse vascularity, certainly suggest a glandular function. On 
the basis of feeding experiments with bullocks' pineals on certain labora- 
tory animals and mentally defective children, Dana and Berkeley (Med. 
Rec., May, 1913) venture to suggest a relationship of pineal function in 
the young to bodily nutrition, including the development of the genital 
organs, the deposit of subcutaneous fat, general growth and mental prog- 
ress. The pineal is a common seat of cysts and tumors, frequently glio- 
mata. 
Histologic Structure.-The epiphysis cerebri is divided imper- 
fectly into lobes by trabeculae of fibro- 
elastic connective tissue provided by the 
pia mater capsule. These support the 
larger blood-vessels. The finer trabeculae 
shade into the fundamental reticular tis- 
sue which supports the parenchyma and 
the capillaries. The larger vessels are 
surrounded by considerable spaces, per- 
haps lymphatics. The parenchyma is 
aggregated into uncertain follicular 
masses and consists of two distinct types 
of cells: neuroglia and interneuroglia 
(secretory cells?). The abundant neu- 
roglia fibers appear to blend intimately 
with the connective tissue framework of 
the structure. The interneuroglia cells 
are oval and polygonal, with a vesicular 
nucleus, and apparently lacking a cel] 
membrane. The neuroglia cells are 
fusiform or stellate, with denser, more 
deeply staining nuclei, and glia fibers in the cytoplasm. Transition 
Fig. 490.-Cells from the Pt- 
neal Body of a 11 cm. Sheep 
Fetus. 
a, two neuroglia and one inter- 
neuroglia cell;/>, various forms and 
sizes of intracellular melanic gran- 
ules X 1500 EPIPHYSIS CEREBRI 
583 
forms are abundant. In young sheep both types of cells are charac- 
terized by pigment granules; in aged specimens the pigment is for 
the most part present in the shape of extracellular clumps. Also in 
these stages the connective tissue is relatively much more abundant, 
Fig. 500.-Photomicrograph of a Peripheral Portion of the Pineal Body 
of a 21 cm. Sheep Fetus, Showing Several Cysts and Vascular Trabecula, 
and an Enormous Number of Intracellular Melanic Granules. X 250. 
and the interneuroglia cells rare. The interneuroglia cells are prob- 
ably less highly differentiated neuroglia cells, both types originally 
arising from ependyma. The interneuroglia cells also contain granules 
and vacuoles of a lipoid nature, perhaps degenerative in significance; 
no pheochrome granules are demonstrable. Involution begins about 
the age of 7 years in man and ends about the age of puberty, though 
regressive histological changes proceed throughout life. Adult corpora 
pinealia present very variable histologic pictures. 584 
THE DUCTLESS GLANDS-ENDOCRIN GLANDS 
Fig. 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. 
Tn older specimens large lamellated masses of brain sand (acervulus 
cerebri) appear, consisting chiefly of calcium carbonate and magnesium 
phosphate. These specimens are also characterized by large edematous 
Fig. 502.-Two Neuroglia and Three Interneuroglia Cells from the Pineal 
Body of a Lamb. X 1500. EPIPHYSIS CEREBRI 
585 
areas. The interneuroglia cells have been variously designated as 
'pineal cells,' 'epithelial cells,' 'lymphoid cells' and 'secretory cells.' Cer- 
tain workers claim to have distinguished, in certain mammals, two types 
of cells, basophils and acidophils. Occasionally smooth and striped 
muscle fibers have also been described in a few forms (e.g., ox). No 
nerve cells are demonstrable. Sympathetic nerves accompany the blood- 
vessels; and a few of the medullated type are found near the attached 
Fig. 503.-Cells from Pineal of Yearling Sheep 
A, neuroglia cell and fibers; B, interneuroglia cell with melanic pigment granules 
X 1500. 
portion, probably taking origin from the habenular and posterior com- 
missures. The blood supply is very profuse. It takes origin from 
the pial vessels which are in union with the blood-vessels of the tela 
choroidea anteriorly. The vessels follow the ramifications of the pial 
septa. In the sheep the capillaries frequently terminate in the form 
of tangled loops or 'glomeruli' within spaces surrounded by more com- 
pact parenchyma ('follicles'). Cross sections of the coarser trabeculae 
show a pair of vascular comites. 
The dependence of normal liver function upon the integrity of the 
ductless glands is indicated by derangements following their removal 
(Whipple and Christian, Jour. Exp. Med., 29, 3, 1914). Many other 586 
THE DUCTLESS GLANDS-ENDOCRIN GLANDS 
organs (e.g., brain, and digestive system) no doubt hold a similar de- 
pendence upon the secretions (hormones) of the ductless glands. More- 
over, the ductless glands themselves seem to sustain interdependent 
relationships among themselves and with the genital glands. 
Fig. 504.-Section of Pineal Body of an Old Sheep, Showing ' Brain Sand ' 
(Acervulus) in the Parenchyma. 
(For recent reviews of literature on the epiphysis cerebri see Kidd, 
"The Pineal Body: a Review," Re. Neur. Psyc., Jan. and Feb., 1913; and 
Jordan, "Results of Recent Studies of the Mammalian Epiphysis Cerebri," 
Trans. Amer. Mier. Soc., 31, 4, 1912.) CHAPTER XVII 
THE NERVOUS SYSTEM 
THE DEVELOPMENT OF THE NERVOUS SYSTEM 
The first external evidence of the beginning of the nervous system is 
the appearance of a median longitudinal furrow in the dorsal (neural) 
ectoderm of the very young embryo 
(about the fifteenth day in man). 
This is known as the neural or 
medullary groove. Still earlier 
stages, as revealed in sections, in- 
clude first an increase in height of 
the ectodermal cells to form an axial 
plate of cuboidal cells, the neural 
plate; and secondly the conversion of 
this simple layered plate into a struc- 
ture of several strata of cuboidal 
cells, which structure meanwhile 
forms the floor and lateral walls of 
the developing neural groove. The 
neural plate apparently grows more 
rapidly laterally causing thus a pro- 
gressive elevation of its borders, the 
neural folds, and producing in con- 
sequence a gradually deepening neu- 
ral groove (Fig. 506). According to 
Glaser (Anat. Rec., 8, 12, 1914), the 
inequality in growth between neural 
plate and the adjacent ectoderm 
which causes folding is due to great- 
er water absorption on the part of 
the plate. By continuation of this 
process of unequal growth medially 
and laterally, the folds finally meet 
in the dorsal mid-line and fuse to form the neural tube. On both sides of 
the line of fusion a group of ectodermal cells appears, the neural or gan- 
glionic crest, from which arise the neurons of the dorsal and sympathetic 
Fig. 505.-Human Embryo 2 Milli- 
meters Long. (Graf Spee.) X 30. 
Am, amnion; C, chorion; C.V., chori- 
onic villi; Bs, body stalk (embryo- 
phore); Mg, medullary groove; Nc, neu- 
renteric canal; Ps, primitive streak; 
Ys, yolk-sac. (From Williams.) 
587 588 
THE NERVOUS SYSTEM 
ganglia, and the neurolemma (sheath) cells of both the afferent and efferent 
fibers of the dorsal and ventral roots respectively. The neural tube (canal) 
is originally of approximately uniform caliber throughout; but shortly the 
Fig. 506.-Transection through the Graf Spee Embryo Shown in the 
Preceding Figure. 
Am, amnion; ect, ectoderm; mes, mesoderm; ent, entoderm; M, medullary groove 
(From Williams.) 
cephalic end, by a series of processes involving dilatations, constrictions, 
foldings and fusions, develops into the brain; while the caudal portion gives 
rise to the spinal cord. 
Ganglionic ridge 
Ectoderm 
Medullary plate 
... Ectoderm 
Ganglionic ridge 
Myotome 
Fig. 507.-Three Successive Stages in the Process of Closure of the Med- 
ullary (Neural) Groove to Form the Medullary (Neural) Canal and 
Neural (Ganglionic) Crests. 
(From Barker, after M. von Lenhossek.) THE DEVELOPMENT OF THE NERVOUS SYSTEM 
589 
These gross developmental changes-more appropriately considered in 
detail in works of Embryology-involve histogenetic processes in the walls 
of the canal. The earlier of these processes are essentially alike in both 
cerebral and spinal portions of the canal. Originally the ectodermal layer, 
which subsequently forms the wall of the tube, 
consists of a single layer of cuboidal cells similarly 
undifferentiated. Shortly spherical and oval ger- 
minal cells appear among the primitive ependymal 
cells. These indifferent cells migrate peripherally 
so that two layers can now be distinguished in the 
wall; an inner nuclear and an outer non-nuclear or 
marginal layer. Cell boundaries have meanwhile 
become obliterated and the entire wall is now essen- 
tially a dense syncytium. Still later the syncytium 
assumes a looser texture, forming the myelospon- 
gium, and the indifferent germinal cells give rise 
to two types of cells: the neuroblasts, from which 
differentiate the neurons; and the spongioblasts, 
from which the neuroglia cells and fibers develop. 
Shortly after the time when neuroblasts and 
spongioblasts first become distinguishable the wall 
of the neural tube can be conveniently divided into 
three zones: (1) the ependymal layer, forming in- 
ternally also a limiting membrane; (2) the inter- 
mediate, middle, nuclear or mantle layer, containing neuroblasts, spongio- 
blasts and indifferent cells; and (3) the outer non-nuclear or marginal 
layer, bounded externally by an outer limiting membrane. A glia frame- 
work pervades the entire width of 
the wall. 
Neuroglia cells differentiate 
from spongioblasts by a process 
involving chiefly the formation of 
glia fibers in their exoplasm. 
These fibers apparently arise from 
spongioplasmic fibrils of the pro- 
toplasm. Many glia fibers subse- 
quently become disposed extracel- 
lularly. The primitive ependymal 
cells become greatly modified into 
stout, slightly branching fibers ex- 
tending through the width of the walls of the neural tube. The main body, 
of columnar shape, with its nucleus and a distal tuft of cilia, retains its cen- 
tral position and forms an ependymal lining for the spinal canal and the 
ventricles of the brain. The several neuroglia constituents (astrocytes and 
Fig. 508.-Cell Lin- 
ing the Neural 
Canal of the New- 
ly-hatched Rain- 
bow Trout, Show- 
ing Mitochondria 
in an Embryonic 
Nerve Cell. 
Meves' technic. X 
2000. 
Fig. 509.-Section through Medullary 
Plate of a Rabbit Embryo. 
The cells include a large round ger- 
minal cell. (After His.) 590 
THE NERVOUS SYSTEM 
glia fibers) form a loose-meshed syncytium, the myelospongium, for the 
support of the developing neuroblasts. Peripherally it is of denser texture 
and relatively free of nuclei, and is designated the marginal velum. Coin- 
cident with this process of neuroglia 
histogenesis, the neuroblasts enlarge, 
proliferate extensively and differentiate 
into neurons, their processes-axon and 
dendrons-arising as sprouts from the 
originally spherical neuroblasts. 
The motor neurons remain located 
in the ventral horn of the spinal cord 
(Fig. 515), their axons (efferent fibers) 
passing out through the ventral root to 
unite with the fibers of the dorsal root 
Fig. 511.-Section through 
Wall of Later Neural 
Tube of Rabbit Em- 
bryo, Showing a Stage 
in the Differentiation 
of the Ependyma Cells 
and the Formation of a 
Myelospongium. 
(After His.) 
Fig. 510.-Section through Medullary 
Plate of Closing Neural Groove of 
Rabbit Embryo. 
Two germinal cells are visible. (After 
His.) 
to form a spinal nerve. The sensory neurons arise external to the cord 
from neuroblasts of the linear neural crests, and migrate some distance 
ventrolaterally, where they aggregate into metameric oval masses which 
differentiate into the spinal ganglia. The differentiation process includes 
both neuroglia and neuron formation. The sensory neuron located in the 
dorsal (spinal) ganglia is also originally spherical or oval; subsequently it 
becomes bi-polar; and finally, by a process involving the retraction of the 
cell body (cyton) from its two processes and the fusion of these processes 
proximally, it, becomes a unipolar cell. The definitive axon thus divides in 
the manner of a T or Y. Its central process, or axon proper, passes into 
the dorsolateral portion of the cord as an afferent fiber and here makes THE DEVELOPMENT OF THE NERVOUS SYSTEM 
591 
contact through a telodendrion either directly or indirectly (through asso- 
ciation neurons) with the dendrons of motor neurons. Its peripheral 
process is to be regarded as the dendron, modified structurally so as to be 
essentially identical with the axon. 
The sympathetic may be regarded as a cenogenetic addition to the 
cerebrospinal nervous system. Ontogenetically it appears in man at the 
Fig. 513.-Diagram of 
a Transection of 
the Spinal Cord of 
an Early Embryo, 
Showing the Migra- 
tion of Neuroblasts 
Toward the Margi- 
nal Veil, and the 
Ventral Nerve 
Root. 
a, neural canal; b, ven- 
tral root. (After His.) 
Fig. 512.-Section of Wall of Fore- 
brain of Four-day Chick Embryo. 
A, apolar neuroblast; B, bipolar neuro- 
blast; a, the beginning of the sprouting of 
the axon; c, axons, showing the terminally 
expanding growth area ('cone of growth'). 
Cajal's silver technic. (Heidenhain, after 
Cajal.) 
beginning of the fifth week (7 mm. embryo). Phylogenetically, it first 
appears in cyclostomes. Kuntz (Jour. Comp. Neur. and Psyc., 29, 3, 1910) 
traces the neurons of the sympathetic trunks and the prevertebral plexuses 
to neuroblasts in both the neural crest and the medullary wall, from whence 
they migrate by both the dorsal and ventral nerve roots. The neurolemma 
cells, as also the neuroglia elements of the sympathetic neurons arise from 
'indifferent' cells which migrate from these same locations and proliferate 
and differentiate along their course. The cardiac plexus and the sympa- 
thetic plexuses in the walls of the visceral organs (terminal plexuses; 'vagal 
sympathetic' plexuses-Kuntz) have their origin, according to Kuntz, in 
nervous elements which migrate from the hind-brain and the vagus gan- 592 
THE NERVOUS SYSTEM 
glia along the fibers of the vagus nerves. Kuntz believes that 'indirect 
embryological and anatomical evidence warrants the conclusion that the 
sympathetic excitatory neurons arise from cells which migrate from the 
neural tube along fibers of the motor nerve roots, while the sympathetic 
sensory neurons, wherever such neurons exist, arise from cells which 
migrate from the cerebrospinal 
ganglia.' However, according 
to Carpenter (1914) the autono- 
mic neurons show no distinct 
differences from the standpoint 
of their chromophilic content. 
Since such differences are con- 
spicuous between the sensory 
and motor neurons of the cere- 
brospinal system (Malone), this 
observation arouses skepticism 
regarding the presence of sen- 
sory sympathetic ganglion cells. 
The primary cerebral divi- 
sions (Fig. 516) and their ma- 
jor adult derivatives are enu- 
merated in the appended out- 
line. The microscopic anat- 
omy of their definitive condi- 
tion lies outside the scope of 
this book. These matters are 
more appropriately treated in 
special text-books of Neurology 
(e.g., Quain's "Anatomy," Vol. 
Ill, 1908; and Villiger's "Brain 
and Spinal Cord," translation 
by Piersol, 1912) and constitute 
the work of a separate course. 
Likewise the developmental history is more advantageously considered in a 
special course in Embryology. 
This work will include only the histology of sections of the spinal 
cord; and that of the cerebellar and cerebral cortex. 
Fig. 514.-Transection of the Spinal 
Cord of a Human Embryo of Four 
Weeks. 
The central canal is immediately sur- 
rounded by ependyma cells. The peripheral 
nerve cells are shown on the left of the figure. 
The ventral nerve roots are already pushing 
outward from the primitive cord, d, dorsal; 
v, ventral nerve roots. (After His.) Fig. 515.-Transection of the Spinal Cord of an Embryo Chick. 
c. rad. ant., axons to the ventral roots; c. rad. post., axons to the dorsal roots; 
col, collateral from an axon back to the gray matter; gg, dorsal root ganglion; rac. 
ant., ventral root; rac. post., dorsal root. (After van Gehuchten.) 
Head fold- 
Neuropore - 
■-■Anterior cerebral 
vesicle, or pros- 
encephalon 
- Middle cerebral 
vesicle, or mes- 
encephalon 
.... Posterior cerebral 
vesicle, or rhomb- 
encephalon 
- Heart 
-Mesodermic 
somite 
Pharynx- 
Vitellin vein*-. 
Medullary groove- 
Fig. 516.-Reconstruction of the Anterior Portion of the Body of a Young 
Chick Embryo, Seen from the Dorsal Surface. (After Kollmann.) 
593 Derivatives of the Neural Tube 
1. Sacral 
region 
2. Lumbar 
region 
3. Thoracic 
(dorsal) 
region 
4. Cervical 
region 
A. MYELON 
(spinal cord) 
(a) MYELENCEPHALON 
(after brain) 
5. Medulla 
Oblongata 
NEURAL CANAL 
I. RHOMBENCEPHALON 
(rhomboid brain) 
(b) METENCEPHALON 
(hind brain) 
6. Pons Varolii 
7. Cerebellum 
8. Region of 
the crurae 
cerebri 
(brain stem); 
corpora 
quadrigemina 
B. ENCEPHALON (brain) 
II. MESENCEPHALON 
(mid brain) 
(c) MESENCEPHALON 
(mid brain) 
9. Region of 
the optic 
thalami 
(basal nuclei) 
10. Optic tract 
(primitive optic 
evaginations) 
11. Posterior 
lobe of 
hypophysis 
cerebri 
12. Pineal body 
(d) DIENCEPHALON 
(interbrain or 
'tween brain) 
III. PROSENCEPHALON 
(fore brain) 
r13. Cerebral 
cortex 
(pallium) 
14. Corpora 
striata 
15. Olfactory lobes 
(e) TELENCEPHALON 
(end brain) 
594 Fic. 517.-Transection of the Spinal Cord of a Child, Seventh Cervical Segment. 
Weigert stain. X 7. 
horn 
Column of 
Clarke 
_Formatio 
" reticularis 
_Central canal 
horn 
Ventral horn 
Ventromedial 
~ fissure 
yDorsomedial sulcus 
and septum 
\\Paramedial sulcus 
and septum 
\ Dorsolateral sulcus 
Dorsal column 
. Funiculus ' 
cuneatus 
Funiculus 
gracilis 
Ventral column 
gelatinosa 
Rolandi 
Lateral white, 
column 
595 596 
THE NERVOUS SYSTEM 
THE SPINAL CORD 
Structure 
Tlie spinal cord (Fig. 517) consists of a considerable mass of central 
gray matter which is surrounded by a layer of medullated nerve fibers, 
the white matter. 
The gray matter comprises two lateral portions united by a central 
commissure (gray commissure) in transverse section resembling the 
letter II. Each lateral portion includes a ventral and a dorsal horn 
with an intervening deeper portion, the central mass or 'intermediate 
zone' of Golgi. Each horn or cornu ends in a head or caput united 
with the intermediate portion or basis cornu by a neck or cervix cornu. 
The ventral is somewhat broader than the dorsal horn. Its cells 
supply axons, which, after uniting into bundles, pass ventralward 
through the white matter to form the ventral (anterior) nerve roots. 
The spinal cord may be considered as consisting of ontogenetic 
segments whose number corresponds to the number of the spinal nerves. 
Hence each segment contains the ventral horn cells whose axons form 
the ventral root of the corresponding spinal nerve. 
In an entirely similar manner the dorsal horns of the gray matter 
receive a large portion of the incoming fibers of the dorsal roots, which 
in large part form end brushes around the cells of the dorsal horns 
and the intermediate zone (Fig. 518). 
The dorsal roots enter through a distinct longitudinal groove, the 
dorsolateral sulcus. At the exit of the ventral roots there is, how- 
ever, only a broad, shallow indentation, these roots making their exit 
in isolated bundles distributed through a vertical plane of considerable 
width. The dorsal root fibers of each segment, on the other hand, enter 
in a single compact mass. 
The gray matter consists of a dense tangle of nerve cells and non- 
medullated fibers, both axons and dendrons, together with neuroglia 
and blood-vessels. The fibers of a given area are derived not only 
from nerve cells in their immediate vicinity, but also include many 
processes which come from very distant regions. The gray reticulum 
is thus supplied from fibers of the ventral and dorsal nerve roots, to- 
gether with innumerable collaterals, not only from the root fibers, but 
more especially from those fibers which collectively form the many 
large tracts passing up and down the spinal cord and placing each seg-  pyramidal 
column 
Direct cerebellar 
column 
Lateral ground 
bundle 
Gower's column 
- 
Fig. 518.-Diagram of the Fiber Paths of the Spinal Cord. 
The black cells are of the sensory or centripetal paths, those on the left are spinal ganglion cells 
whose branches may be traced to their several terminations within the spinal cord. The motor 
cells of anterior horn on the right are white; commissural cells are vertically striped; the small cells 
of the dorsal horns are horizontally striped; a small 'Golgi cell' of the dorsal horn is stippled. 
(Redrawn after the scheme of von Lenhossek.) 
~~ Ventral 
root 
■ Column of Burdach 
Anterior ground bundle 
Direct pyramidal columns 
Column of Goll 
Dorsal root 
I 
597 598 
THE NERVOUS SYSTEM 
merit in communication with many other levels of both the spinal cord 
and brain. 
The center of the gray commissure contains the central canal which 
lies in the axis of the spinal cord and is continuous above with the ven- 
tricles of the brain. It represents the remains of the fetal neural canal; 
and in the young subject is still patent, filled with cerebrospinal fluid, 
and lined by columnar cells which are frequently ciliated. In older 
subjects the cells of the lining epithelium have usually lost their cilia, 
and the lumen of the canal is more or less filled by cell proliferation 
which involves not only the lining epithelium but also the surrounding 
glia cells. The central canal is immediately surrounded by a peculiar 
gelatinous tissue in which are many glia cells. This mass is called the 
substantia gelatinosa centralis. A similar area of gelatinous tissue occurs 
near the extremity of the dorsal horns, and is called the substantia 
gelatinosa Rolandi. The latter, however, is said to contain only a 
scanty supply of neuroglia. 
The white matter forms a covering or shell around the central 
gray mass. It increases in thickness from below upward. This pecu- 
liarity is the result of the progressive influx of centripetal fibers, and 
a corresponding contribution of centrifugal fibers, through the spinal 
nerves of each successive segment. 
The dorsal median septum extends inward from the shallow sulcus 
on the dorsal surface of the spinal cord to the central gray commissure, 
and divides the dorsal mass of white matter into two white columns, 
lying on either side of the median line, and bounded laterally by the 
dorsal horns of gray matter and the dorsal nerve roots. The ventral 
median sulcus in a similar manner, splits the ventral portion of white 
matter into the two ventral white columns. This sulcus, however, 
does not penetrate all the way to the gray commissure but leaves an 
interval of white matter containing many transverse and obliquely 
disposed nerve fibers. The ventral or white commissure thus formed 
connects the two ventral columns of white matter. 
The spinal cord is thus divided into two lateral and symmetrical 
halves by a plane passing through the ventral and dorsal median sulci 
and the central canal. Each lateral half includes a central curved mass 
of gray matter completely surrounded, except at the gray commissure, 
by the white matter. The latter is subdivided into a ventral, lateral, 
and dorsal column, each of which extends the entire length of the 
spinal cord and is apparently (to the naked eye only) continuous above 
with a similar column in the medulla oblongata. THE SPINAL CORD 
599 
The ventral white column is included between the ventral median 
sulcus and the ventral gray horns and nerve roots; the lateral columns 
extend from the ventral roots in front, around the lateral surface of 
the spinal cord, to the dorsal roots; the dorsal columns are included 
between the dorsal horns of gray matter and dorsal nerve roots, and the 
dorsal median septum. 
Each of these columns of white matter is again subdivided by 
neurogliar septa of variable size and number, which extend inward 
from the pia mater for a considerable distance. Such septa may even 
penetrate all the way to the central gray matter. One of these septa, 
the paramedian septum, more constant than the others, subdivides the 
dorsal column into two portions, a dorsomedial and a dorsolateral 
column, or the funiculus gracilis (column of Goll), and the funiculus 
cuneatus (column of Burdach) of the upper portions of the cord. 
In the ventral white column two chief fiber tracts are recognized: 
a narrow median, the anterior or direct pyramidal tract; and a more 
lateral larger anterior ground bundle. In the lateral column four main 
tracts are recognized: three lateral, including an upper crossed pyram- 
idal tract, a middle direct cerebellar tract, and a lower or Gower s 
column; and a large medial lateral ground bundle (Fig. 518). These 
tracts do not possess sharp boundaries. Moreover, the ground bundles 
at least are composite. The several elementary tracts contain fibers 
passing either from the periphery to the brain along the cord {ascending 
fibers') or from the brain through the cord to the periphery {descending 
fibers), or fibers connecting brain and cord or different segments of 
the cord. For a detailed description of the constitution of these fiber 
tracts reference must be made to the systematic text-books on the nervous 
system. 
The larger blood-vessels are distributed along the fibrous septa, 
taking their origin from the vessels of the pia mater; the most of them 
are distributed to the white matter, but to some extent they also supply 
the gray matter. 
The entire surface of the spinal cord presents, just beneath the pia 
mater, a thin superficial layer or marginal veil of glia tissue. In the 
brain this layer is somewhat exaggerated in thickness. 
The varying number of fibers which are given off at different levels 
of the spinal cord results in considerable differences in size in its sev- 
eral portions. By means of these peculiarities, as well as by the spinal 
The Regions of the Spinal Cord 600 
THE NERVOUS SYSTEM 
nerve roots to which they give origin, we distinguish a sacral, lumbar, 
thoracic, and cervical region. Each of these regions presents certain 
more or less important morphological 
characteristics. 
In the sacral region the investment 
of white matter is very thin, the gray 
matter-though actually less in amount 
than in the more cephalad regions-ap- 
pearing large by comparison. Both the 
ventral and dorsal horns of gray matter 
are short and thick. The substantia 
gelatinosa Rolan di is of considerable 
volume. The cell groups in the ventral 
horns of this region are a ventromedial 
and a dorsolateral. 
The cord as a whole is small and its transection nearly circular in 
outline. The five segments of this region contain the neuron centers 
for the urinary bladder, the anus, some of the musculature of the lower 
limbs, and the sensory reflexes 
of the perineum and genito- 
urinary organs. 
Below the sacral region the 
spinal cord tapers rapidly 
(conus medullaris) and is con- 
tinued downward for a consid- 
erable distance as the filum 
terminate. The surrounding 
leash of lumbar and sacral 
nerve roots forms the cauda 
equina. The fibrous mem- 
branes which surround the 
cord continue even farther 
downward in the medullary 
canal to form the central liga- 
ment, which is finally attached to the sacrum or coccyx. 
In the lumbar region there is a distinct enlargement, chiefly in- 
volving the gray substance, which here includes the immense number of 
cells of the ventral horns whose 'motor' fibers enter the large lumbar 
nerve trunks for the supply of the lower limbs. These nerve trunks 
also supply to the cord a great number of centripetal or sensory fibers 
Fig. 519.-Transection of the 
Spinal Cord of a Child, 
Third Sacral Segment. 
Weigert stain. X 7. 
Fig. 520.-Transection of the Spinal 
Cord of a Child, Fifth Lumbar Seg- 
ment. 
Weigert stain. X 7. THE SPINAL CORD 
601 
which enter the dorsal and, later (through secondary neurons), the 
lateral columns; thus both of these columns are of large size in and 
above the lumbar region. The dorsomedial column in this region at- 
tains an appreciable size, and a distinct pial septum marks its lateral 
boundary. 
The spinal cord is now nearly circular in transection, its ventro- 
dorsal being perhaps slightly less 
than its transverse diameter (10 
mm.). The gray commissure lies 
very near the middle of the 
spinal cord, and the ventral me- 
dian fissure is, therefore, quite as 
deep as the dorsal median sep- 
tum. 
Both the ventral and dorsal 
gray horns are long and thick. 
Each dorsal horn contains a 
large apical area of gelatinous 
substance, is somewhat longer on 
its lateral than on its medial 
side, and reaches nearly to the 
dorsal surface of the spinal cord, 
opposite the dorsolateral sulcus. 
The dorsal nerve roots entering at this level are apparently directed 
toward the middle of the tips of the dorsal horns of gray matter; once 
within the spinal cord they pass around to the mesial side of the dorsal 
horns. 
The ventral horns, somewhat larger than the dorsal, present two 
short and broad protuberances, the one at the ventromesial, and the 
other and more prominent at the ventrolateral angle. A similar though 
less prominent protuberance is seen at the base of the ventral horn, 
on its lateral aspect. Each of these projections contains a more or 
less well-defined group of motor nerve cells. The cell groups of the 
ventral horns in the lumbar region are therefore a ventromedial, ventro- 
lateral, and dorsolateral, together with an ill-defined central group oc- 
cupying the deeper 'intermediate zone' of gray matter. 
The nerve centers contained in the lumbar region control the re- 
flexes and musculature of the lower limbs and the lower part of the 
abdominal wall. 
A transection of the spinal cord in the thoracic region is of small 
Fig. 521.-Transection of the Spinal 
Cord of a Child, Eighth Thoracic 
Segment. 
Weigert stain. X 7. 602 
THE NERVOUS SYSTEM 
diameter (eight millimeters), and is very nearly circular in outline. 
The white matter, since it contains the many nerve fibers going to and 
coming from the lumbar enlargement, is much more voluminous than 
the gray matter. The latter is reduced to a comparatively small central 
mass. 
The dorsomedial column attains a considerable size in this region, 
and is distinctly marked off from the adjacent dorsolateral column by 
a fibrous septum derived in part from the pia mater, in part being 
of neuroglia composition. The dorsal and the lateral columns, having 
been much augmented by the influx of fibers from the large dorsal 
roots of the lumbar nerves, form the larger part of the white matter. 
The gray matter consequently appears to be pushed forward, its gray 
commissure lies considerably ventrad of the center of the spinal cord, 
the ventral median fissure is shorter than the dorsal median septum, and 
the tips of the dorsal gray horns are far removed from the surface, 
being only connected with the dorsolateral sulcus by the slender dorsal 
nerve roots. In fact, the dorsal horns of gray matter in this region 
are reduced to a minimum size; they are short and slender and contain 
comparatively few nerve cells. 
At the base of each dorsal horn, on its mesial side, there is a dis- 
tinctly outlined cell group whose transection is of oval or circular out- 
line. Indeed, this cell group, the cell column of Clarice, begins in the 
second or third lumbar segment, and is continued upward to the second 
or third thoracic-at times even into the lowermost cervical segments 
-at which level it has dwindled to a relatively insignificant group. In 
the lower lumbar region an ill-defined group of cells occupying a similar 
position and having the same function is known as the nucleus of 
Stilling. 
The ventral gray horns are very short and narrow, and their cells 
cannot be subdivided into groups as in the other regions of the spinal 
cord. In the upper part of the dorsal region a distinct protuberance 
makes its appearance at the base of the ventral horn, on its lateral 
aspect. This is the precursor of the larger lateral horn of the cervical 
region. In the upper dorsal region it contains a small cell group, the 
dorsolateral. 
The nerve centers of the dorsal segments control the upper abdominal 
region, the thorax, and the viscera. 
In the lower half of the cervical region the spinal cord presents 
a distinct enlargement, within the gray matter of which are the nuclei 
for the upper limbs. The spinal cord in this region is somewhat flat- THE SPINAL COED 
603 
tened, its transverse diameter (14 mm.) considerably exceeding its 
anteroposterior. The major portion of the white matter is still con- 
tained within its dorsal rather than its ventral portion, the gray com- 
missure appearing to lie somewhat ventrad of the center. The dorsal 
median septum dips inward for a much greater distance than does the 
ventral median fissure. 
The dorsal columns are decidedly larger than the ventral, and a 
distinct groove, the paramedial sulcus, from which a fibrous septum 
is continued inward, separates the dorsomedial from the dorsolateral 
column. 
The dorsal gray horns are long, relatively slender, and more divergent 
than in the lower levels. They do not reach the surface of the spinal 
cord, but are connected therewith by the long, slender dorsal nerve 
roots. The gray matter of the dorsal horns in this region is more or 
less invaded by bundles of nerve fibers derived from the lateral and 
dorsal columns; the tips of the dorsal horns are thus almost cut off 
from the deeper portions of gray matter. 
The ventral horns are both long and broad. They present three 
noticeable promontories or processes-a ventral (ventromedial), a medial 
(ventrolateral), and a lateral. The lateral, because of its special promi- 
nence, is frequently called the lateral horn; it is one of the noticeable 
characteristics of the cervical region. 
Each of these processes contains a corresponding cell group; hence 
we distinguish in the cervical enlargement a mesial, a ventral, and a 
lateral group, together with a small intermediolateral, which is partially 
or completely detached from the dorsal portion of the lateral group. 
There is also a small disseminated central group of nerve cells occupying 
the deeper portion of the ventral horn. 
The nuclei of the segments included in the cervical enlargement 
contain the centers for the musculature and sensory reflexes of the upper 
limbs. The partial control of the pupillary movements in the eye is 
also located in the lowermost segments of this region. 
In the upper half of the cervical region a transection of the spinal 
cord, except for its larger size, resembles very closely that of the thoracic 
region. The larger size is due to an increase in the white matter of 
the dorsal and lateral columns, consequent upon the acquisition of 
new fibers which enter the subjacent segments from the nerves sup- 
plying the upper extremities, together with an increased number of 
centrifugal fibers from the cerebrum which are distributed to the gray 
matter of this region. 604 
THE NERVOUS SYSTEM 
The ventral columns are also much increased in size by the addi- 
tion of many fibers coming down from the medulla and cerebellum, 
which place the nerve centers of the spinal cord in close relation with 
those of the cranial nerves and with the association centers of the cere- 
bellum. 
In addition to the large size of its white columns, a noticeable char- 
acteristic of the upper cervical region is the prominence of its lateral 
horns of gray matter. 
Just dorsal to the 
lateral horns is also a 
peculiar reticular for- 
mation which results 
from an invasion of 
the adjacent portions 
of the lateral white 
columns by bands of 
gray matter. The 
gray matter thus 
forms a coarse net- 
work whose meshes 
inclose isolated bun- 
dles of longitudinal 
nerve fibers. 
The ventral horn 
cells of this region are scarcely divisible into groups, but a large and 
distinct cell group, the intermediolateral cell column, occupies the 
so-called lateral horn. 
The nuclei of the upper cervical region innervate the skin and 
muscles of the neck and shoulder, they also supply the diaphragm. The 
nerve cells of this region not only supply the cervical spinal nerves, but 
they also send root bundles to the spinal accessory or eleventh cerebral 
nerve. 
Fig. 522.-Transection of the Spinal Cord of a 
Child, Fourth Cervical Segment. 
Weigert stain. X 7. 
THE CEREBELLUM 
The cerebellum consists of an irregular core of white substance, 
the medulla, and a thick mantle of gray matter, the cortex. It com- 
prises two hemispheres or lobes connected by a third lobe, the vermis. 
Each lobe is a combination of lobules which include a variable number 
of transverse convolutions or folia. Each folium contains a medullary Septum pellucidum 
/ Lamini rostralis 
Commissura anterior 
Lamina terminalis 
Chiasma opticum 
x. Infundibulum 
Hypophysis 
Massa intermedia 
i Foramen interventriculare (Monroi) 
| i Columna fornicis 
Fig. 523.-Median Sagittal Section through the Brain. (After Toldt.) 
I | Tuber cinereum 
| Corpus mammillare 
Pons (Varolii) 
Ventriculus tertius 
Tela chorioidea ventriculi tertii ( 
Corpus pineale I 
Corpus medull. cerebelli 
Medulla oblongata 
Fissura transversa cerebri 
Aquaeductus cerebri 
(Sylvii) 
Corpora quadrigemina \ 
Velum medullare 
anterius , 
Arbor vitae 
Vent, quart. 
Vermis ( 
605 606 
THE NERVOUS SYSTEM 
core and is covered by a cortical layer. The central medulla contains 
four paired masses of gray substance, the internal nuclei. 
The Cerebellar Cortex 
The cortex is divisible into an inner granular layer, and an outer 
molecular layer. The granular layer in a fresh section appears rust- 
colored; in a stained preparation it appears much darker and more 
granular than the molecular layer due to the abundance of nuclei; it 
is thickest over the summit of the folium, and thinnest in the depth 
of the sulcus between adjacent folia. 
a-a, pia mater; b-b, molecular layer; c-c, granular layer; d-d, white matter of 
the medulla. Nissl's stain. Photo. X 38. 
Fig. 524.-From a Section of the Cerebellar Cortex of Man. THE CEREBELLUM 
607 
The most conspicuous and distinctive elements of the cerebellar 
cortex are the Purkinje cells, situated along a line marking the division 
between molecular and granular layers. They are regarded as belong- 
ing to the molecular layer. The remaining cellular elements of the 
cortex cannot be studied in detail in ordinary histologic preparations. 
They must be identified mainly by their relative size and position. Our 
Fig. 525.-A Purkinje Cell from the Human Cerebellar Cortex. 
Moderately magnified. Photo. (After Berkley.) 
knowledge of their finer structure and their interrelationships has 
been gained by use of special staining technics, chiefly the Golgi process. 
By use of this technic two other types of cells can be distinguished 
in the molecular layer: the small cortical cells, and the large cortical 
or basket-cells. 
The Purkinje cells are large flask-shaped elements, with typically 
a robust dendron and a delicate axon at opposite poles. The axon 
passes centrally to contribute to the white matter of the medulla. It 
gives off numerous collaterals, some of which turn back into the molec- 
ular layer and terminate in relation with neighboring cells of Purkinje. 
The dendron passes toward the surface dividing almost immediately 608 
THE NERVOUS SYSTEM 
into two coarse branches, which each divides dichotomously into a suc- 
cession of increasingly more delicate branches forming peripherally a 
dendronic field of extreme profusion of non-anastomosing fibrils. The 
dendron viewed as a whole constitutes a fan- 
shaped structure. Its expansion is in a 
plane at right angles to the long axis of the 
convolution. In sections parallel with the 
long axis of the convolution the dendronic 
field is very narrow, and never wider than 
the diameter of the cell-body. 
The basket-cells, or large cortical cells, 
are multipolar elements with relatively 
short robust branching dendrons, and a 
long axon which passes horizontally in the 
same plane in which the dendronic expan- 
sion of the Purkinje cells are placed. Along 
its course it gives off five or six collaterals 
■which, as also the post-collateral portion 
of the axon itself, pass centrally toward the 
Purkinje cells where each breaks up into a 
profuse terminal arborization which invests 
the cell-body in the manner of a 'basket? 
The basket cells occupy the middle and 
outer portions of the molecular layer; they 
are apparently of the nature of association 
neurons, perhaps coordinating the function 
of a number of Purkinje cells. 
The small cortical cells are distributed 
throughout the molecular layer but are more 
abundant in the outer half. They are mul- 
tipolar and vary considerably in size, some 
being almost as large as the basket cells. 
They possess from two to five delicate den- 
drons distributed for the most part in the 
same plane as those of the Purkinje cells. 
Their short slender axon, which is horizon- 
tally placed, is frequently characteristically 
looped. The axon of some of these cells has numerous collat- 
erals. 
The nuclear or granular layer also contains three distinct types 
Fig. 526.-A Purkinje Cell 
from the Cerebellar 
Cortex of the Rabbit. 
Highly magnified. (After 
Nissl.) THE CEREBELLUM 
609 
of cells: the granule cells, the large stellate cells and the so-called soli- 
tary cells. The latter are small fusiform elements, but of their signifi- 
cance and relationships little is definitely known. 
The granule cells have a general distribution throughout the 
granular layer. They are of relatively small size, multipolar, and pos- 
sess short dendrons (frequently four) which end in claw-like processes. 
These latter are in close relationship with the so-called eosin bodies, 
small spheroidal finely granular masses having a special affinity for 
eosin. The eosin bodies are believed by some to represent synapses 
between the dendrites of the granular cells and the telodendria of the 
centripetal mossy fibers contributed by the medulla. The axon of the 
granule cell is unique among the cerebellar cortical neurons in that it 
passes toward the surface; here it divides in T-fashion, the branches 
passing parallel to the long axis of the convolutions thus coursing at 
right angles to the dendronic expansion of the Purkinje cells, in relation 
with which they probably end. 
The large stellate cells have a limited distribution in the granu- 
lar layer; they are more or less closely confined to the boundary zone 
between the molecular and granular layers. They are large multipolar 
cells, with a profuse dendronic contribution to the molecular layer, 
and an almost equally profuse short axonic and collateral contribution 
to the granular layer where the telodendria end in relation to the 
granule cells. These are typical Golgi cells of the second type. 
The Medulla 
The medulla next the cortex contain three important types of medul- 
lated fibers: the climbing fibers, the mossy fibers, and the axons of the 
Purkinje cells. The latter are centrifugal fibers passing to the internal 
nuclei. The climbing fibers are so designated by reason of their end- 
ing in profuse telodendria which are closely associated with the dendrons 
of the Purkinje cells, apparently 'climbing' over them. The mossy fibers 
owe their designation to the nodular mossy character of their terminal 
branches within the granular layer. Their end-arborizations are in- 
timately related to those of the dendrons of the granule cells prob- 
ably contributing to the formation of the eosin bodies. 
Both cortex and medulla contain an abundant neurogliar supporting 
substance. The astrocytes of the cortex are largely of the short-rayed 
(mossy) type; those of the medulla are exclusively of the long-rayed Axon 
of cell of 
granular 
layer 
Telodendrion 
of collateral 
climbing 
fiber 
Fig. 527.-Diagram of the Cerebellar Cortex. 
A, by ordinary nuclear staining (omitting the layer of Purkinje cells); B, vertical to the sur- 
face of the convolution; C, longitudinal section through the convolution; B and C, by the 
chrom-silver method (slightly modified from Bohm and Davidoff). 
Basket 
cell 
Large 
stellate 
cell 
Purkinje 
cell 
C 
Eosin body 
Climbing 
fiber 
B Axon of cell 
of granule 
layer 
Cell of gran- 
ule layer 
Moss fiber 
A Axon of 
Purkinje cell 
Basket 
cell 
Molecular 
layer 
Granule 
layer 
Medullary 
layer 
610 THE CEREBRAL CORTEX 
611 
type. Next the surface of the cortex the neuroglia tissue is condensed, 
forming a thick peripheral velum. 
The foregoing is summarized in the following outline: 
'Hemispheres 
Vermis 
Cerebellum 
Lobes 
Lobules 
Folia 
I. Cortex. 
A. Molecular layer. 
1. small cortical cells. 
2. basket cells-small stellate cells-large cortical cells. 
3. Purkinje cells. 
B. Nuclear or Granular layer. 
1. granule cells, with dendritic arborizations ending in 
close association with eosin bodies. 
2. large stellate cells. 
3. solitary cells. 
II. Medulla-medullated nerve fibers. 
(a) axon of Purkinje cells. 
(b) mossy fibers, ending in eosin bodies of granular 
layer. 
(c) climbing fibers. 
THE CEREBRAL CORTEX 
The cerebrum consists of two large symmetrically paired lobes or 
hemispheres connected by a bridge of white matter, the corpus callosum. 
Each hemisphere includes essentially a central mass of white substance 
or medulla, containing the internal nuclei or basal ganglia-paired 
masses of gray matter-and a covering of gray substance, the cortex or 
pallium. The cortex is greatly folded, thus becoming marked by con- 
volutions or gyri with intervening fissures or sulci. The surface of each 
hemisphere may be divided into four principal lobes: (1) the frontal 
lobe, bounded posteriorly by the fissures of Rolando and Sylvius; (2) 
the parietal lobe, extending from the fissure of Rolando in front to the 
parieto-occipital fissure behind and the Sylvian fissure below; (3) the 
occipital lobe, bounded anteriorly by the parieto-occipital sulcus; and 612 
THE NERVOUS SYSTEM 
(4) the temporal lobe, lying below the fissure of Sylvius. The cortical 
portion folded under the lips of the Sylvian fissure is known as the 
insula (lobulus insula). The average thickness of the cortex is about 
three millimeters, but in the motor area, of the frontal and parietal 
lobes, it may attain a depth of five millimeters, .while in the occipital 
lobe it may become reduced to almost two millimeters. 
Fissure of Rolando parietal lobe 
Fig. 528.-Left Lateral Surface View of Cerebral Cortex in Man, Show- 
ing the Lobes, Main Sulci, and the Larger Functional Areas. (After 
Oppenheim.) 
The nerve cells which enter into the formation of the gray matter 
of the cerebral cortex present a remarkable tendency to arrange them- 
selves in more or less well-defined layers parallel to the surface of the 
cerebral convolutions. The number and arrangement of these layers 
in the various lobes varies, however, with the peculiar function of each 
of these areas. Thus, in the motor area there is a five layer type, in 
the parietal lobe a seven layer type, in the occipital lobe a six or eight 
layer type. The histologically different areas shade into each other by 
insensible gradations. 
In general, it may be assumed that the nerve cells of all of these 
layers are included in one or two physiologically distinct groups or THE CEREBRAL CORTEX 
613 
types: those whose axons enter the projection paths, and those whose 
axons enter the association paths; also that while these cells intermingle 
with each other in all portions of the cortex, yet certain areas are char- 
acterized by an undue proportion of one or the other type, and may 
accordingly be considered as 
either projection centers or as- 
sociation centers. 
The larger cells belong, as 
a ride, to the projection centers, 
and the peculiar type of large 
cell contained in a given center 
may often be considered as 
characteristic of that particular 
area. Thus the motor area con- 
tains giant pyramidal cells 
(Betz cells), and the visual area 
the giant 'solitary cells' of 
Meynert. 
The larger cells, being of 
Golgi's Type I, are assumed to 
be connected with the projec- 
tion fibers. On the other hand, 
the smaller cells-granule cells, 
polymorphous cells, etc.-which 
more frequently belong to 
Golgi's Type II, are thought to 
supply the axons of association 
paths. Those large areas- 
parietal lobe, frontal lobe, 
lobulus insulae-which consist 
in so large a part of the smaller type of cells, may therefore be supposed 
to contain the larger association centers. 
The cells in any given portion of the cortex are not only arranged in 
layers parallel to the surface of the cerebral convolutions, but the 
passage of fibers of the medulla to or from their terminations within 
the pallium, also separates the cells of the cortex into irregular rows 
or striations, whose axis is perpendicular to the surface of the con- 
volutions. 
Fig. 529.-Large Pyramidal Cell of the 
Cortex. 
(After W. von Bechterew.) (Barker, 
"The Nervous System.") Fig. 530.-Scheme of the Motor Area of the Cerebral Cortex, Showing the 
Effect of Various Staining Methods. 
1, Golgi's stain; 2, Weigert's stain; 3, hematein and eosin; 4, relative depth of 
each layer. A, association neurons; Ag, angular cells of the polymorphous layer; 
As F, association fibers; Ax, axons; C, collateral; C F, centripetal fibers; E, terminal 
fibers; F, fusiform cell of the polymorphous layer; G, Golgi cells, Type II; M, cells 
of Martinotti; P C, collateral of a pyramidal cell; Py, pyramidal cells; Py ax, axon 
of a pyramidal cell; Py S, pyramidal axons passing to the cerebral medulla. (After 
Berkley.) 
614 THE MOTOR AREA 
615 
THE MOTOR AREA 
In the motor area including a para-Rolandic portion of both the 
frontal and parietal lobes, and a mesial supra-Rolandic area, the cortical 
cells form five tangential layers, as follows: 
1. Molecular layer. 
2. Outer polymorphous cell layer. 
3. Small pyramidal cell layer. 
4. Large pyramidal cell layer. 
5. Inner polymorphous cell layer. 
The molecular layer (stratum 
zonale) consists of a net work of fine 
dendronic fibers, derived from the deeper 
layers, which are disposed in tangential 
meshes beneath the pia mater. Occa- 
sionally small cells, apparently displaced 
from the deeper cell layers, are scat- 
tered among these fibers; they are of 
polymorphous form, and their processes 
are confined to the molecular layer. The 
surface of the molecular layer is cov- 
ered by a marginal velum of neuroglia 
homologous with that beneath the pia 
mater of the spinal cord. 
The second, or outer polymor- 
phous, cell layer, is a thin stratum. 
Its cells are frequently clumped, thus 
forming groups of various size. This 
grouping is, however, more distinct in 
some other regions, e.g., the olfactory 
area, than in the motor area itself. 
The THIRD LAYER, SMALL PYRAMIDAL 
cells, is somewhat thicker than the 
above. It consists of numerous small 
cells-triangular, pyramidal, or pyri- 
form in shape-whose pointed apices are 
directed toward the surface. Three sets 
of dendrons are given off by these cells, an apical process which passes 
outward to ramify in the outer molecular layer, and from either side 
Fig. 531.-Disposition of the 
Nerve Fibers in the Cere- 
bral Cortex of Man. 
Between the vertical bands of 
radial fibers are the areas of inter- 
radial feltwork. The supraradial 
jeltwork includes the tangential 
fiber layer or stratum zonale (M. 
P.~), and the stripe of Bechterew 
(Subm.P.'). c.z., subpial neurogliar 
layer; Gt.P.P., outer stripe of Bail- 
larger; Pol.P., inner stripe of Bail- 
larger; W., white matter. (From 
Barker, after L. Andriezen.) 616 
THE NERVOUS SYSTEM 
of the base of the cell a second set, whose processes are distributed in 
a plane nearly corresponding to that in which their cell bodies lie. The 
axon is usually given off from the basal surface 
of the cell, and passes from this point directly 
inward to the white matter of the cerebral 
medulla. 
The fourth layer, that of the large 
pyramidal cells, is also a thick layer. Its 
cells are of the same shape, and distribute their 
processes after the same manner as those of 
the small pyramidal cell layer. The motor 
area is specially characterized by the large size 
of the cells of this layer. The largest of these, 
the Cells of Betz, are about six times as large 
as the small pyramidal cells, which have 
a fairly uniform size of about ten mi- 
crons. 
The fifth, or inner polymorphous cell, 
layer, is thinner than the preceding. Its cells 
are of very varied form-pyramidal, stellate, 
fusiform, and granule cells-and are less 
densely packed than is the case in the more 
superficial layers. They are intermediate in 
size, between the cells of the second and the 
third layers. The axons of the inner polymor- 
phic cells, in large part, pass to the white 
matter of the medulla, though some of them are 
distributed laterally to neighboring convolu- 
tions. Their dendrons are partially distrib- 
uted within the layer in which they arise, but 
by far the larger portion pass to the more su- 
perficial pyramidal cell layers. Many of 
the nerve cells of this layer, e.g., the granule 
cells, are very small, their nucleus being 
covered with an extremely narrow shell of 
cytoplasm. 
It is noticeable that, as a rule, the dendronic processes from the 
cells of all five layers are distributed either in the same plane as their 
cell bodies, or they pass toward the surface, where many of them enter 
the superficial molecular layer. The axons, on the other hand, are di- 
Fig. 532.-Human Cor- 
tex Cerebri, Motor 
Area. 
a, tangential fiber layer; 
b, outer polymorphous 
cells; c, small pyramidal 
cells; d, large pyramidal 
cells; e, inner polymor- 
phous cells. Nissl's stain. 
Moderately magnified. 
(After Schlapp.) THE SENSORY AREA 
617 
rected inward toward the white matter of the cerebral medulla, in 
which they pass, either as association or as projection fibers, to many 
very distant parts. Notable exceptions to this latter rule, however, are 
the so-called cells of Martinotti, which occur to some extent in all 
layers, but which, though found in the pyram- 
idal layers, are especially numerous among 
the polymorphous and granule cells. They are 
small polymorphic cells, which send their axons 
to the superficial molecular layer, giving off 
collaterals on their way. 
The cell types in other portions of the cor- 
tex correspond very closely to those of the 
motor area. There are, however, slight but 
characteristic variations which are worthy of 
notice. 
The cortex of the parietal lobe (also of 
the frontal, temporal, convex surface of the 
occipital lobes, and the insula)-sensory area 
-presents a seven layer type, the additional 
layers resulting from an aggregation of the 
granule cells into one plane, which thus di- 
vides the large pyramidal cell layer. This 
type, therefore, presents the following layers: 
1. Molecular or tangential fiber layer. 
2. Outer polymorphous cell layer. 
3. Small pyramidal cell layer. 
4. Outer large pyramidal cell layer. 
5. Granule cell layer. 
6. Inner large pyramidal cell layer. 
7. Inner polymorphous cell layer. 
The distribution of this cortical type is 
suggestive of a close relation to the great asso- 
ciation centers. Moreover, its most noticeable 
characteristics are the abundance of its granule 
cells and the relative paucity of pyramidal cells, 
especially those of the giant pyknomorphic 
variety. 
In the visual area-median surface of the occipital lobe-the for- 
mation is described as either a six or an eight layer type. The pyram- 
idal cell layers are reduced to extreme thinness, the giant pyramids 
Fig. 533.-Human Cor- 
tex Cerebri, Parie- 
tal Lobe. 
a, tangential fiber layer; 
b, outer polymorphous 
cells; c, small pyramidal 
cells; d, outer large pyr- 
amidal cells; e, granule 
cells;/, inner large pyram- 
idal cells; g, inner poly- 
morphous cells; h, white 
matter of the medulla. 
Nissl's stain. Moderately 
magnified. (AfterSchlapp.) 618 
THE NERVOUS SYSTEM 
being noticeably deficient. The stripes of Baillarger, thin layers of 
tangential fibers on the deeper portions of the cortex, are especially 
distinct. So many granule cells are scattered among those of the pyram- 
idal type that it becomes scarcely possible to distinguish from one 
another the second, third, and fourth layers. When these three layers 
are individually considered, the type presents eight layers; if, on the 
other hand, they are collectively considered as a single stratum, the 
type presents but six layers. With this reservation, the following layers 
may be distinguished: 
1. Molecular or tangential fiber layer. 
2. Outer polymorphous cell layer. 
3. Small pyramidal cell layer. 
4. The layer of granule and large pyramidal cells. 
5. The outer stripe of Baillarger (great pyramidal plexus). 
6. The granule cell layer. 
7. The inner stripe of Baillarger (polymorphous plexus). 
8. Inner polymorphous cell layer. 
The special characteristics of the visual area are the abundance 
of tangential fibers, as evidenced by the prominent stripes of Bail- 
larger, the thick fiber layer in the deeper part of the molecular stratum, 
the abundance of granule cells, the paucity and irregular form of the 
pyramidal cells, and finally the presence in the inner stripe of Baillarger 
and in the outer portion of the deep polymorphous cell layer of numer- 
ous large isolated multipolar cells, the giant 'solitary cells' of Mey- 
nert. 
In the auditory area-temporal lobe-the seven layer type is found. 
The structure in this area is apparently identical with that previously 
described for the seven layer type in the parietal lobe. 
In the olfactory area-hippocampal gyrus-the cells of the outer 
polymorphous layer arrange themselves in groups, and the pyramidal 
cells become largely transformed into polymorphic and fusiform cells; 
these lie between the characteristic outer layer and the inner layer of 
polymorphic cells, giving to the cortex of this region a three layered 
structure of indistinct outlines. 
Fiber Tracts.-The corticifugal axons of the cells of the several 
layers are collected below the upper level of the large pyramidal cell 
layer into vertical columns which pass to the medulla as the bands of 
radial fibers. In these same columns course also the corticipetal axons. 
The cortex thus becomes divided vertically into cell rays and fiber THE FIBER TRACTS 
619 
rays, as was mentioned above. Between the fiber columns the dendronic 
network is known as the interradial feltwork; peripheral to where the 
fiber rays begin, this dendronic network 
forms the supraradial feltwork. At about 
the middle of the large pyramidal cell 
layer, abundant horizontal dendrons pro- 
duce a distinct broad band, the outer 
stripe of Baillarger. Between the large 
pyramidal cell layer and the outer poly- 
morphic cell layer, a similar but narrower 
band is known as the inner stripe of Bail- 
larger. These stripes are most pro- 
nounced in the visual areas as was said 
above. Another band of similar nature 
at about the outer limit of the small 
pyramidal cell layer forms the stripe of 
Bechterew. Beneath the peripheral neu- 
rogliar marginal velum the dendrons of 
the pyramidal cells branch and form thus 
a band of horizontal fibers, the tangen- 
tial fiber layer or molecular fiber layer. 
These fiber bands are conspicuous only in 
specimens prepared with the Weigert 
technic. Both cortex and medulla con- 
tain abundant neuroglia cells. Those 
contributing almost exclusively to the 
marginal velum are fusiform elements 
with lateral tufts of short horizontal 
fibers, and an expanding tuft of delicate fibers passing to the inner 
border of the small pyramidal cell layer. The neurogliar elements of 
the medulla are mostly of the long-rayed type. 
Fig. 534.-Human Cortex Cer- 
ebri, Olfactory Region. 
a, tangential fiber layer; b, 
white matter of the medulla. 
Nissl's stain. Moderately mag- 
nified. (After Schlapp.) 
THE MENINGES AND BLOOD SUPPLY 
The brain and spinal cord are enveloped by the meninges, which 
include three fairly distinct membranes, the dura mater, arachnoid, and 
pia mater, and two cavities filled with lymph or a lymph-like fluid; 
by this arrangement the cerebrospinal axis is, as it were, suspended 
in fluid, and is everywhere surrounded by a watery cushion. 620 
THE NERVOUS SYSTEM 
The dura mater is the outermost of the three coats. Within the 
cranial cavity it is firmly attached to the bony walls, and serves as 
a periosteum for the internal surface of the bones which form the cranial 
cavity. Within the vertebral cavity the dura mater is distinct from the 
periosteum of the vertebrae, with which it is connected by loose fibrous 
tissue and masses of fat, which inclose large lymph spaces or chambers, 
lined by endothelium and collectively forming the epidural space. 
The dura mater is composed of interlacing bundles of fibrous tissue 
containing few elastic fibers. The disposition of its fiber bundles varies 
somewhat in its different portions. In its spinal portion, most of the 
bundles are longitudinally disposed, comparatively few passing circularly 
around the circumference of the vertebral canal; within the cranial 
vault the bundles cross at acute angles; in the falces and in the ten- 
torium cerebelli they are radially disposed. 
The cranial dura consists of two distinct layers, an outer, which is 
very vascular and serves as the bony periosteum, and an inner, which 
is but slightly vascular and may be considered as the dura proper. It 
is the inner layer only which is prolonged inward to form the falx 
cerebri and the falx and tentorium cerebelli. The venous dural sinuses 
of the cranium occupy clefts in the dura along the lines of attach- 
ment. 
Although the dura mater is but poorly supplied with blood-vessels, 
it is relatively rich in lymphatics, which open into the subdural and 
epidural spaces and are continuous with the perivascular and perineural 
lymphatics which leave the cerebrospinal cavities in company with 
the cerebral and spinal nerves and the larger blood-vessels. In this 
way the lymphatics of the dura mater and its adjacent spaces are in 
communication with the lymphatic vessels of the eye, nose, ear, and 
cervical lymph nodes. These communications are of special importance 
as indicating the path followed by certain pathological processes which 
involve the meninges. 
Where the outer surface of the dura is not attached to the surround- 
ing bone or connective tissue, it is covered by a thin endothelioid coat, 
the lining endothelium (mesenchymal epithelium) of the epidural spaces. 
Its inner surface is lined by somewhat thicker endothelial cells, forming 
the wall of the subdural space. The dura contains sympathetic fibers 
for its blood-vessels, and also naked spinal and cerebral sensory 
fibers. 
The arachnoid is a thin membranous sheet which is suspended be- 
tween the dura and the pia mater. It is composed of a delicate areolar THE MENINGES AND BLOOD SUPPLY 
621 
tissue which contains relatively few elastic fibers but is said to contain 
neither blood-vessels, lymphatics nor nerves. This thin fibrous mem- 
brane is covered on either side by a layer of endothelium; that upon 
its outer surface consists of cells of considerable thickness, which are 
derived from the lining membrane of the inner wall of the subdural 
space; the cells upon its 
inner surface are thinner 
and are derived from 
the walls of the sub- 
arachnoid space. 
Delicate septa - like 
bands pass from the in- 
ner surface of the arach- 
noid to the adjacent por- 
tions of the pia mater 
(Fig. 535). These proc- 
esses are likewise invest- 
ed by the endothelial 
lining of the subarach- 
noid space. A similar 
investment clothes the 
processes of the ligamen- 
tum denticulatum of the 
spinal cord which at- 
taches the pia mater spi- 
nalis on either side to the 
adjacent portions of the 
dura mater. Subarachnoid trabeculae support the nerve fibers of the 
dorsal roots. 
A fibrous septum passing from the arachnoid to the pia mater, along 
a line opposite the dorsal median septum of the spinal cord, forms a 
fairly definite partition, the septum posticum. In the cervical region this 
is an uninterrupted septum, but in the thoracic and lumbar regions it 
is incomplete. 
The cranial arachnoid, in the vicinity of the cranial sinuses, notably 
the superior longitudinal sinus, sends outward many villus-like projec- 
tions or arachnoid villi (Pacchionian bodies; granulationes arachnoidales) 
which protrude into the venous sinuses to such an extent as often to 
produce corresponding depressions in the inner surface of the bones of 
the cranial vault, into which they push, carrying before them a much 
Fig. 535.-Section of the Spinal Cord and Its 
Membranes, from the Upper Thoracic Re- 
gion. 
a, dura mater; b, arachnoid; c, septum posticum; 
d, e, f, subarachnoid trabeculae; n, nerve fiber 
bundles; g, ligamentum denticulatum; I, subarach- 
noid space. (From Schafer, after Key and Retzius.) 622 
THE NERVOUS SYSTEM 
attenuated portion of the dura mater. These villi are similar in struc- 
ture to the membranous portion of the arachnoid. They are said to be 
absent at birth, small and inconspicuous in childhood, and to increase in 
size and number as age advances. 
Fluid injected into the arachnoid or into the neighboring portions 
of the subarachnoid space passes readily into the lymph spaces of the 
dura mater, and may even be forced into the venous cavity of the cranial 
sinuses. While fluid thus injected may follow artificial rather than nat- 
ural channels, it seems quite possible that the cerebrospinal fluid may 
during life find its way along such channels into the venous sinuses to 
the relief of excessive intracranial pressure. 
The pia mater is intimately adherent to the surface of the brain 
and spinal cord. It follows all the irregularities of their surfaces and 
sends prolongations into all their sulci. In the larger fissures these in- 
vaginations form a double fold of pial tissue; in the smaller, the in- 
vaginated portions fuse to form a thin septum-like prolongation of the 
pia. In this particular the pia mater differs from the arachnoid, which 
bridges over all the sulci without dipping into any but the largest fis- 
sures. It differs also from the dura mater which, with the exception of 
the falces and tentorium, is not prolonged into any of the fissures or sulci 
of either the brain or the spinal cord. 
The pia mater is a connective tissue membrane and is divisible into 
an inner and an outer layer. The outer layer is composed of coarse 
fibrous bundles the most of which in the pia mater of the spinal cord run 
longitudinally, while the finer fibers of the thin inner layer are cir- 
cularly arranged. 
Between the two layers are many blood-vessels and lymphatics, the 
pia mater being typically a vascular membrane. The larger blood- 
vessels are loosely embedded in the outer surface of the pia, some of 
them projecting into or even lying entirely within the subarachnoid 
space. The outer surface of the pia mater, as also the sheaths of the 
vessels which are loosely attached to its surface, is covered with a layer 
of very thin endothelial cells derived from the lining membrane of the 
subarachnoid space. 
The inner surface of the pia is everywhere firmly adherent to the 
surface of -the brain and spinal cord. The slender trabeculas and septa- 
like processes which extend into the superficial portions of these organs, 
consist of connective tissues whose fibrous bands are continuous with 
those of the membranous pia mater. In the spinal cord many of these 
fibrous bundles extend inward as far as the gray matter, meanwhile be- THE MENINGES AND BLOOD SUPPLY 
623 
coming intimately associated with neuroglia. In both the spinal cord 
and the brain the pial septa serve for the support of numerous blood- 
vessels and perivascular lymphatics which are distributed through this 
connective tissue to all portions of the brain and spinal cord. 
Within the cranium., reduplications of the pia mater, carrying be- 
tween their folds a layer of arachnoidal tissue and an extensive plexus 
of small blood-vessels, push their way into the cerebral ventricles to form 
the superior and inferior telce choroidece. These choroid plexuses are 
separated from the ventricular cavities by an investment of cuboidal 
cells, which in fetal and infantile life are ciliated, and which are derived 
from and are continuous with the ependyma cells lining the walls of the 
ventricles. Thus the blood-vessels of the telae choroidese, in the strictest 
anatomical sense, lie without and not within the cavity of the cerebral 
ventricles, for they are everywhere separated from those cavities by the 
ependyma cells, which, ontogenetically at least, form a portion of the 
wall of these vesicles. The cerebrospinal fluid is supposed to originate 
largely by process of filtration from the blood-vessels of these choroid 
plexuses. 
The pia mater contains mostly sympathetic fibers, but probably also a 
few sensory cerebrospinal fibers. 
The peculiar arrangement of the three constituent membranes of the 
meninges leaves three distinct spaces or connected groups of spaces 
which are filled with fluid. These are the epidural, subdural, and sub- 
arachnoidal spaces. 
The epidural space comprises a connected series of lymph cavi- 
ties, which is of limited extent within the cranium, but of broad extent 
within the spinal canal. These spaces are lined by endothelium which 
is at many points continuous with the perivascular and perineural lym- 
phatics and through them with the lymphatic vessels of the general 
systemic circulation. Obviously the epidural spaces serve as large 
lymphatic vessels and their cavities are consequently filled with 
lymph. 
The subdural space has a complete lining of rather thick endothe- 
lial cells. The walls of this cavity are formed by the dura on the outer, 
and the arachnoid on the inner side. Its cavity is occupied by lymph 
and is continuous with the lymphatic vessels of the dura, and through 
them with the epidural spaces and systemic lymphatics. 
This space is penetrated by the outgoing cranial and spinal nerves, 
which receive an investment from all three of the meningeal coats. The 
three layers composing this investment soon lose their distinctive charac- 624 
THE NERVOUS SYSTEM 
teristics, fuse together, and blend with the epineuriuni of the nerve 
trunks. 
Fluid injected into the subdural space may be readily forced into 
the lymphatics of these epi- and perineural sheaths and may thus travel 
to parts quite remote from the central nervous system. 
The subarachnoid space within the cranium is of limited breadth, 
but within the spinal canal it is much broader and contains not only the 
larger blood-vessels which are loosely attached to the surface of the 
pia, but also the many spinal nerve roots pass downward through this 
space toward their foramina of exit. 
The subarachnoid space is lined by a thin endothelial layer, its 
outer wall being formed by the arachnoid, its inner by the outer surface 
of the pia mater; its cavity is filled with cerebrospinal fluid, which 
closely resembles, yet differs somewhat in chemical composition from the 
lymph. It contains a few lymphocytes, estimated at five per cubic milli- 
meter of fluid. This space is in communication through the foramen 
of Majendie, an opening in the roof of the fourth ventricle, with the 
central canal of the spinal cord and the ventricular cavities of the brain. 
It is also thought to communicate with the cerebral ventricles at several 
other points. 
The spinal portion of the subarachnoid space is crossed by a posterior 
median septum, the septum posticum, laterally by the ligamentum den- 
ticulatum, and by several irregular but incomplete septa which, like the 
ligamentum posticum, connect the pia mater with the arachnoid. 
The ligamentum denticulatum is a dense mass of fibrous tissue 
containing a few elastic fibers, which, beginning at the lateral surface of 
the pia as a complete septum, passes, by about twenty-eight serrations, 
across the subarachnoid space, and pushing the arachnoid before it, is 
attached to the inner surface of the dura mater. The serrations of the 
dentate ligament do not penetrate the subdural space, for around the 
point of their attachment the surface of the arachnoid is firmly adherent 
to the dura mater. Each serration is invested by an endothelial coat 
continuous with the lining of the subarachnoid space. 
Blood Supply.-The blood supply of the central nervous system is 
derived from vessels which lie within the folds of the pia mater, branches 
of the internal carotid and the vertebral arteries. The larger arteries 
form an anterior longitudinal group represented in the spinal cord by 
the anterior spinal artery and its branches, and in the brain by the ves- 
sels of the circle of Willis and their immediate branches. 
Two sets of vessels may be said to be distributed from these sources THE MENINGES AND BLOOD SUPPLY 
625 
-one of which is distributed through the pia mater to the adjacent white 
matter of the spinal cord and to the gray pallium of the brain; the other 
penetrates the spinal cord through the anterior median fissure by a 
series of small fissural arteries to be distributed to the central gray mat- 
ter, and in the brain is represented by the branches of the middle cere- 
bral arteries which penetrate directly to the ganglionic gray matter in 
the interior of the cerebrum. 
In the spinal cord the vessels of the former set are mostly distributed 
to the white cortex, the larger branches, however, penetrate the white 
matter and aid in the formation of the capillary network of the gray 
medulla. In the brain their distribution is similar, the smaller pial 
vessels, the cortical arteries, being distributed to the cortex, which in this 
case is formed by the gray matter; the larger, the medullary arteries, 
penetrating to the white medulla in which they break up into capillary 
vessels. 
The veins trend in the opposite direction and in the pia mater col- 
lect into large vessels, which in the brain open into the sinuses of the 
dura mater, and which in the spinal cord form the ventral and dorsal 
median veins. 
All of the larger vessels receive thin fibrous investments from the 
pia mater; the smaller vessels and capillaries are surrounded by neu- 
roglia. 
There are frequent anastomoses between the larger veins; the arteries, 
however, are all terminal arteries according to Cohnheim's classification, 
possessing no anastomoses with the capillary areas of other vessels. 
Neither brain nor cord possess true lymphatics. The sole lymphatic 
representatives within the central nervous system are pericellular and 
perivascular spaces communicating with subpial spaces and ultimately 
through uncertain clefts and channels with the subarachnoid spaces. CHAPTER XVIII 
THE EYE 
GENERAL CONSIDERATIONS 
The eye may be said to consist of the visual organ, or globe, and its 
appendages-the eyelids, conjunctiva, and lacrimal apparatus-whose 
function is chiefly protective. 
The globe of the eye, or eye proper, is contained within the cavity 
Fig. 536.-Dissection of Eyelids and Lacrimal Apparatus. 
1, upper lacrimal gland; 2, lower lacrimal gland and excretory ducts; 3, mouths 
of excretory ducts; 4, tarsal (Meibomian) glands; 5, puncta lacrimalia; 6, lacri- 
mal canaliculi; 7, lacrimal sac and nasal duct; 8, caruncula. (After Fox.) 
of the orbit, its posterior two-thirds being embedded in a mass of intra- 
orbital fat whose inner surface is covered by a thin fibrous membrane or 
fascia which is clothed with mesenchymal epithelium. The epithelium 
is reflected from this fascia to the surface of the ocular globe, along a 
line just posterior to the border of the conjunctiva, whence it passes 
over the surface of the globe as far posteriorly as the optic nerve, on 
626 GENERAL CONSIDERATIONS 
627 
the surface of which it again becomes continuous with the mesenchymal 
epithelium of the fascia. Thus a serous sac or lymphatic space is formed 
by the parietal layer of this sac, which lines the orbital cavity, in conjunc- 
tion with the visceral layer which covers the posterior two-thirds of the 
globe of the eye; this sac is the capsule of Tenon. 
Fig. 537.-Horizontal Section of the Right Eyeball. 
(From Fox, after Magnus.) 
The anterior third of the globe is covered by a reflection, at the 
fornix conjunctivae, of the conjunctival layer which clothes the inner 
surface of the palpebrae or eyelids. The conjunctiva is a continuation of 
the integument of the lid, modified so as to simulate a mucous membrane. 
The portion associated with the eyelid is known as the palpebral con- 
junctiva, that covering the eye as the ocular, bulbar or scleral conjunc- 628 
THE EYE 
tiva. Where the sclera passes into the cornea, the conjunctival epithe- 
lium becomes continuous with the anterior corneal epithelium, the tunica 
propria blending with the corneal stroma. 
The globe of the eye or eyeball is a spheroidal body whose surface 
consists of three coats, an outer, middle, and inner, and whose contents 
are the vitreous and aqueous humors and the crystalline lens. 
The eyeball is not a true sphere, but may be said to comprise segments 
of two spheres, the smaller of which is inserted into the anterior surface 
of the larger. The anterior or smaller segment consists chiefly of trans- 
parent tissues which permit the entrance of light. Its border nearly 
corresponds to the posterior margin of the ciliary body, and it may be 
approximately indicated by a parallel circle midway between the margin 
of the cornea and the equator of the eyeball. The anterior segment con- 
tains the cornea, the sclerocorneal junction, the anterior and posterior 
chambers, the aqueous humor, the iris, and the ciliary body. The pos- 
terior segment comprises the posterior two-thirds of the eyeball and in- 
cludes the sclera, choroid, retina, and, within these coats, the vitreous 
humor. The crystalline lens with its suspensory ligament forms, as it 
were, a partition separating the two segments. 
The optical or visual axis of the eye is a horizontal, anteroposterior, 
imaginary line, about an inch in length, which extends from the center 
of the cornea through the anterior chamber, the center of the pupillary 
opening of the iris, the center of the crystalline lens, and the center of 
the vitreous humor, and reaches the fovea centralis which lies in the 
middle of a thickened portion of the retina, the macula lutea. The ver- 
tical and transverse axes measure about 1 mm. less than the anteropos- 
terior axis. Toward the inner side, at a distance of 3.5 mm., and about 
1 mm. below the center of the fovea centralis, is the entrance of the optic 
nerve. This nerve pierces the coats of the eye, its fibers spreading out 
in a radial manner, upon the inner surface of the retina. 
The extremities of the visual axis mark the two poles of the ocular 
globe; the anterior extremity, lying in the center of the cornea, is in 
the anterior or smaller spheroidal segment, the posterior extremity, in 
the fovea centralis, lies in the posterior segment of the eye. 
THE EXTERNAL COAT-THE FIBROUS TUNIC 
The outer tunic of the eyeball includes the cornea, the sclera, and the 
sclerocorneal junction. Fig. 538.-The Anterior Segment of a Child's Eye; Meridional Section. 
a, ora serrata; 6, ciliary processes; c, iris; d, crystalline lens; e, ciliary muscle; f, 
ocular conjunctiva; g, cornea; h, the capsule of the lens, partially detached. Hema- 
tein and eosin. Photo. X 10. 
629 630 
THE EYE 
The Cornea 
The cornea is a concavoconvex, transparent, colorless disk of approxi- 
mately equal thickness (1 mm.) throughout all its portions. It is nearly 
circular in outline, its horizontal exceeding its vertical diameter by only 
Fig. 539.-From a Meridional Section of the Human Cornea 
a, anterior corneal epithelium; b, anterior homogeneous membrane; c, substantia 
propria; d, posterior homogeneous membrane; e, posterior corneal epithelium. 
Hematein and eosin. Photo. X 180. 
0.5 mm.; its external surface is convex, its internal surface concave. The 
cornea forms the anterior one-fourth of the tunica externa, and repre- 
sents a spheroidal segment whose radius is somewhat shorter than that 
of the posterior segment of the eyeball. It is inserted into the anterior 
margin of the sclera much after the manner in which a watch-glass is THE EXTERNAL COAT-THE FIBROUS TUNIC 
631 
set in its rim; hence the inner surface of the cornea possesses a slightly 
greater diameter than the outer. 
The cornea may be said to consist of -five layers: 1, the anterior 
epithelium; 2, the anterior homogeneous membrane; 3, the corneal sub- 
stance ; 4, the posterior homogeneous membrane; 5, the posterior epithe- 
lium. 
The anterior epithelium (corneal epithelium, corneal conjunctiva') 
at the margin of the cornea is continuous with the scleral portion of the 
conjunctiva. It consists of a relatively thin layer-six to eight cells 
deep-of stratified squamous epithelium, the deepest cells of which are 
elongated or columnar, the middle cells polyhedral, and the superficial 
cells somewhat flattened. The cells at all levels are nucleated and, like 
the other corneal tissues, perfectly transparent. The columnar cells 
are often slender and much elongated, their pointed apices extending 
well toward the surface of the epithelial layer. 
The epithelium rests directly upon the anterior homogeneous lamella. 
The deeper cells of the epithelium present distinct intercellular lym- 
phatic spaces and intercellular bridges. Between the cells are the termi- 
nal ramifications of nerve fibrils from the plexus in the corneal substance. 
The anterior homogeneous membrane (an/enor basal lamella, elas- 
tic membrane of Bowman) was formerly thought to consist of elastic tis- 
sue, but this supposition is disproved by its ready solubility on boiling 
(His), as well as by the fact that it does not react typically to the spe- 
cific stains for this tissue. Bowman's membrane is apparently a homo- 
geneous or structureless coat except that it is slightly fibrillar at its 
extreme margin where it becomes continuous with the fibrous tissue of 
the sclera. It resembles elastic tissue in that it is highly refractive and 
possesses a shining glassy appearance. It does not stain readily with the 
ordinary dyes. 
The corneal substance (substantia propria) forms the greater por- 
tion of the cornea. It consists of a lamellated connective tissue, which 
forms about sixty fibrous layers, parallel to the corneal surface. The 
fibrous bundles of these lamellae, being arranged in meridional curves 
parallel to the surface, appear to cross one another at right angles 
in the central portion of the circular cornea. Other fibers, arcuate fibers, 
pass from one layer to another; so firmly uniting them that it is im- 
possible to tease the cornea into its component lamellae. 
The intervals between the fibrous layers are occupied by interlamel- 
lar cement, or ground substance, in which lymphatic channels and large 
flattened cells, the corneal corpuscles, can be demonstrated. The cor- 632 
THE EYE 
neal 'corpuscles' are branched lamellar connective tissue cells, which 
occupy the large lymphatic spaces or lacunae of the interlamellar ground 
Fig. 540.-Corneal Corpuscles of the Frog. 
a, as seen in tangential section; b, as seen in transection of the cornea. Chlorid 
of gold. Highly magnified. (After Rollett.) 
substance, and which send fiber-like processes into the interlacing lym- 
phatic channels. 
The posterior homogeneous membrane, or membrane of Descemel 
{posterior basal lamella), is similar in structure to the anterior. Like THE EXTERNAL COAT-THE FIBROUS TUNIC 
633 
the latter, though formerly considered an elastic membrane it does not 
give the specific reactions of elastic tissue. It is somewhat thicker than 
Bowman's membrane. At its margin the membrane is continuous with 
fibrous bundles which are directed outward into the ligamentum pectina- 
tum, and, at least in some animals, through this ligament into the ciliary 
margin of the iris. The membrane of Descemet can be readily detached 
from the corneal substance by teasing. It prevents filtration of fluid 
from the anterior chamber into 
the corneal stroma. 
The posterior epithelial layer 
{corneal endothelium) is a mes- 
enchymal epithelium consisting 
of clear, cuboid al or flattened 
cells, placed edge to edge, and 
bound together by intercellular 
bridges. At the margin of the 
cornea it is reflected over the 
lateral wall of the anterior 
chamber to the anterior surface 
of the iris. Its cells rest upon 
the posterior homogeneous mem- 
brane. 
All the tissues of the cornea, 
during life, are absolutely trans- 
parent. The elements of which they consist are of almost identical 
refractive indices, and about that of water, so that in fresh, or in 
living tissue, it is almost impossible for the microscope to discover any 
of the structure of the cornea. After death the cornea becomes opaque 
and its elements are then easily distinguished. 
Vascular and Nerve Supply.-The cornea itself is an absolutely 
non-vascular tissue, having neither blood nor true lymphatic vessels. 
It is, however, well supplied with nerve fibers, derived from the ciliary 
nerves, which form an annular plexus in the sclera about the margin 
of the cornea, from which point bundles of naked axis-cylinders pass 
into the corneal substance to form a basal plexus, near the anterior homo- 
geneous membrane. From this latter plexus, fibers are distributed to 
the corneal substance and to a subepithelial plexus, anterior to Bowman's 
membrane, whence the terminal sensory fibrils penetrate the anterior 
epithelium. For a distance of several millimeters within the margin of 
the cornea special nerve endings (bulbous corpuscles) may also occur. 
Fig. 541.-Corneal Cells, Isolated. 
Highly magnified. (After Waldeyer.) 634 
THE EYE 
The Sclera 
The sclera {sclerotic coat) is a firm opaque connective tissue mem- 
brane which forms the outermost layer of the posterior segment of the 
eyeball. It consists of two layers, the thick, firm, substantia propria, 
and the very thin, innermost, delicate, Zamina fusca. 
By reflected light the sclera of the adult is of a lustrous white color. 
In the child it has a faint bluish tint, due to the presence of pigment in 
the deeper layers of the child's eye which shows indistinctly through 
the relatively clear superficial tissues. The anterior portion of the 
sclera is covered by the bulbar conjunctiva and is familiarly known as 
the 'white of the eye.' A yellowish patch in the vicinity of the corneal 
margin, known as the pinguecula, may be present, especially in old 
age. It is believed to be due to irritation from dust, leading to colloid 
infiltration of the conjunct! vat-stroma. 
That portion of the sclera which is posterior to the ocular equator 
is covered by the visceral layer of the capsule of Tenon except at the 
insertions of the straight and oblique muscles. The tendons of these 
muscles pierce the capsule and are obliquely inserted into the surface of 
the sclera in a line nearly corresponding to the equator of the eye. The 
tendon bundles of the muscles are directly continuous with the fibrous 
bundles which compose the sclera. 
The Substantia Propria.-The collagenous fibrous tissue of the 
sclera is disposed in bundles which are arranged along meridional and 
equatorial lines; they interlace with one another to form a dense net- 
work. A few elastic fibers are interspersed among the bundles of this 
network. Stellate connective tissue cells, the scleral corpuscles, lie in the 
interfascicular clefts. Occasional pigmented cells are also sometimes 
present. 
The Lamina Fusca.-The inner surface of the sclera presents a fine 
gauzy membrane which can be readily detached by teasing. This is the 
lamina fusca sclerae. It consists of delicate interlacing fibrous bundles 
and numerous pigmented connective tissue cells. The lamina fusca near 
the posterior pole is firmly adherent to the scleral substance. 
At the posterior pole of the eye the sclera is pierced by the optic 
nerve, whose numerous bundles penetrate the coats of the eyeball and 
give to this portion of the sclera a cribrose appearance. This area of the 
sclerotic coat is known as the lamina cribrosa sclera. It is a circular 
zone whose border is outlined by the entrance of the posterior ciliary 
arteries and the ciliary nerves. This is the thickest portion of the sclera, THE EXTERNAL COAT-THE FIBROUS TUNIC 
635 
the coat becoming progressively thinner toward the equator of the eye; 
near its anterior margin it is again thickened by the tendinous insertions 
of the extrinsic muscles. 
The sclera is chiefly supplied by branches from the posterior ciliary 
arteries, which form a wide-meshed plexus in its substance, its vessels 
anastomosing freely with those of the choroid coat. 
The Sclerocorneal Junction 
The sclerocorneal junction (Fig. 543) is a narrow circular zone at 
the margin of the cornea, where it is inserted into the sclera. Across 
this narrow zone the fibrous bundles of the opaque sclera are continued 
directly into the similar, though perfectly transparent, bundles of the 
corneal substance. 
The anterior or outer surface of this zone is covered by the ocu- 
lar portion of the conjunctiva. Its epithelium is of the stratified squam- 
ous variety and is continuous with the anterior epithelium of the cor- 
nea. 
From the inner surface of this junctional zone the anterior extremi- 
ties of the muscle fibers composing the ciliary muscle take their origin. 
The fibers of this muscle intermingle with the marginal fibers of the 
posterior homogeneous layer of the cornea to form the ligamentum 
pectinatum, which connects the sclerocorneal junction with the base of 
the iris. This pectinate ligament is very much more highly developed in 
certain animals, e.g., cow and horse, than in man. 
Toward the inner side of the scleral margin and near the border 
of the cornea is the canal of Schlemm (sinus venosus sclera). 'fhis 
is an annular venous channel (or network of channels), draining into 
the anterior ciliary veins. Though venous in character it serves also 
as a drainage channel for the lymphatic spaces of Fontana, which lie in 
the lateral wall of the anterior chamber and between the fiber bundles 
of the ligamentum pectinatum. The spaces of Fontana are true lym- 
phatic spaces and are in communication with the anterior chamber of 
the eye. 
Through the canal of Schlemm, the aqueous humor of the anterior 
chamber is put into communication with the veins of the sclera, and 
a system is thus formed by which the intra-ocular pressure is maintained 
at normal. A blocking of the canal of Schlemm interferes with the 
drainage of the anterior chamber, and is believed to produce the serious 
pathologic condition of the eyeball, known as glaucoma, due to progres- 636 
THE EYE 
sive increase of intra-ocular tension which causes atrophy of the optic 
nerve and the retina. 
Blood Supply. -The sclerocorneal junction is abundantly supplied 
with blood from the anterior ciliary vessels, which, with the posterior 
conjunctival vessels, form loops at the margin of the cornea and anasto- 
mose freely with the vessels of the ciliary body. The sclera contains no 
true lymphatic vessels. 
THE MIDDLE COAT-THE VASCULAR TUNIC 
The middle tunic (uvea, uveal tract) includes the choroid coat, 
ciliary body, and iris. The latter is perforated centrally by an approxi- 
mately circular aperture, the pupil. 
The iris divides the cavity of the anterior segment of the eye into an 
anterior chamber, included between it and the posterior or inner surface 
of the cornea, and a posterior chamber, which is bounded by the iris in 
front and the crystalline lens and its suspensory ligament behind. 
The free or pupillary margin of the iris is in light contact with the 
anterior surface of the lens. The posterior chamber is therefore an an- 
nular compartment. 
The Choroid Coat 
The choroid coat (tunica choroidea) consists of three layers: 1, the 
lamina suprachoroidea; 2, the lamina vascularis; 3, the lamina capillaris. 
The function of the very vascular choroid is to supply nutrition to the 
outer portions of the retina. 
The lamina suprachoroidea (suprachoroid layer) is a very delicate 
membrane which contains many pigmented cells and is similar in struc- 
ture to the lamina fusca of the sclera. 
The flattened pigmented cells are brownish-black in color from the 
many coarse granules which they contain, and are irregularly disposed, 
either separately or in groups. Lymphatic spaces occur between this 
layer and the sclera and communicate through the interfascicular lym- 
phatic clefts of the sclera with the capsule of Tenon. 
The fibers of this layer are not only distributed in its own plane but 
pass obliquely to the lamina fusca, thus loosely attaching the supracho- 
roid layer to the sclera. Similar, obliquely disposed fibers pass to the 
deeper portions of the choroid, with the fibers of which they blend. 
The lamina vasculosa (vascular layer, choroid proper), so called THE MIDDLE COAT-THE VASCULAR TUNIC 
637 
because it contains the ramifications of the ciliary arteries and veins, 
is by far the thickest of the three layers of the choroid. It may be ar- 
bitrarily separated into an outer stratum, consisting chiefly of dense 
interlacing bundles of connective tissue fibers which inclose only the 
larger blood-vessels, and an inner stratum of similar structure, but every- 
where permeated by a close network of small vascular twigs. So dense 
is this network near the posterior pole of the eye, as to give the layer 
the appearance of an almost continuous sheath of small blood-vessels. 
The Lamina Capillaris.-Within the vascular layer is the capillary 
membrane (lamina capillaris, lamina choriocapillaris, tunica Ruyschi- 
Fig. 542.-From a Meridional Section of the Choroid Coat. 
a, membrane of Bruch; b, the inner margin of the vascular layer. Between a 
and b is the capillary layer or choriocapillaris; c, venule containing blood cor- 
puscles; d, fibrous layer of the choroid or lamina suprachoroidea. Highly magni- 
fied. (After Cadiat.) 
ana), which contains an exceedingly close-meshed capillary network. 
This network is specially dense near the macula lutea at the posterior pole 
of the eyeball. Its inner surface forms a very thin homogeneous mem- 
brane, the lamina basalis, lamina vitrea or membrane of Bruch, which 
increases somewhat in thickness as age advances. The inner surface 
of the lamina basalis is indented by the bases of the adjacent pigment 
cells of the retina. Anteriorly the vessels of the choriocapillaris, like 
those of the vascular layer, become continuous with the vessels of the 
ciliary body and iris. 
Between the pars vascularis and the choriocapillaris may be distin- 
guished a narrow dense fibro-elastic boundary zone, free of pigment. 
In ruminants this layer becomes pronounced, due to the presence of ro- 
bust connective tissue fibers, and is known as the tapetum fibrosum. 
This layer gives to the eyes of ruminants their characteristic metallic 
luster. In the eyes of carnivora and certain fishes the tapetum is com- 
posed of rectangular epithelioid cells, filled with peculiar glistening 638 
THE EYE 
crystals giving to these eyes an iridescent sheen, and is known as the 
tapetum cellulosum. 
The Ciliary Body 
The ciliary body (corpus ciliare) represents the thickened anterior 
border of the choroid coat. It is, therefore, of annular shape and occu- 
pies a zone whose posterior border blends with the choroid at a 
point opposite the ora serrata of the retina, and whose anterior 
margin is continued into the iris opposite the sclerocorneal junction. 
It may be said to consist of three structures arranged in layers of vary- 
ing thickness: 1, the ciliary muscle; 2, the fibrous layer with its ciliary 
processes; and 3, that portion of the pigmented epithelium of the retina 
which constitutes the pars ciliaris retinae or ciliary epithelium, and 
covers the inner surface of the ciliary body. The suspensory ligament of 
the crystalline lens is attached to the inner surface of the retinal epithe- 
lium of the ciliary processes and grooves. 
The ciliary muscle consists of an annular mass of non-striated fibers 
which arise from the inner surface of the sclera near the sclerocorneal 
junction, and are inserted into the entire breadth of the fibrous mass 
of the ciliary body as far back as the anterior margin of the choroid. 
The muscle fibers are divisible into three sets, according to the direction 
of their long axis; these are the meridional, the radial, and the 
circular. 
The meridional fibers form the outer and greater portion of the mus- 
cle. They begin just posterior to the corneal margin, taking their 
origin from the inner surface of the sclera, and radiate backward in a 
meridional direction for a variable distance, to be finally inserted into 
the fibrous bundles of the posterior half of the ciliary body (ciliary ring), 
the longest fiber bands passing as far back as the choriociliary junction, 
where they are attached to the anterior margin of the choroid. 
The radial fibers simulate the meridional fibers in that they radiate 
from the corneal margin. They pursue, however, a shorter course. 
From their origin they pass backward with a sharp inward curve to 
assume a. direction which approaches that of the radii of the ocular globe 
(hence their name) ; they are inserted into the anterior half of the fibrous 
layer of the ciliary body. Their radial disposition becomes progressively 
more apparent toward the axial margin of the ciliary body. These 
fibers are far less numerous than the meridional. 
The circular fibers comprise numerous small non-striated muscle 
bundles which are interspersed among the bundles of radial fibers. a, circulus major of the iris; C, cornea; Ch, choroid; c, c, and cr, lymphatic 
clefts in the anterior surface of the iris; ci, anterior ciliary vein; f, f, f, con- 
traction furrows on the anterior surface of the iris; h, posterior layer of iridal 
pigment epithelium, partially detached; i, i, spacia zonularis; k, zone of nuclei 
of the lens fibers; L, lens; I, ligamentum pectinatum; M, longitudinal, and 
Mu, circular fibers of the ciliary muscle; 0, flattened portion or orbiculus of 
the ciliary body; o, ora serrata; P, ciliary processes; p, pupillary margin of the iris; pc, inner, non-pigmented 
layer of the ciliary epithelium; Pc, retinal pigment epithelium; pc, outer or pigmented layer of the ciliary 
epithelium; P, retina; r, radial fibers of the ciliary muscle; S, sclera; s, canal of Schlemm; sp, circular muscle 
of the iris, the sphincter pupiltee; v, outer pigmented layer of the retinal epithelium; z, z, z, suspensory ligament 
of the lens. X 16. (After Fuchs.) 
Fig. 543.-The Ciliary Body and the Adjacent 
Structures; Meridional Section. 
639 640 
THE EYE 
They are disposed in a circular direction about the axial margin of the 
ciliary body on its outer surface, and hence are in relation with the inner 
surface of the sclerocorneal junction and the outer margin of the 
base of the iris. The circular muscle fibers are also interspersed among 
the fibers of the ligamentum pectinatum, which pass in a radial manner 
from the margin of the posterior homogeneous membrane of the cornea 
to the base of the iris and anterior margin of the ciliary body. The 
circular fibers are said to be deficient or even absent in myopic eyes, but 
are exaggerated in hypermetropic eyes. 
The disposition of the ciliary muscle fibers is such that during con- 
traction the fibrous ciliary body and the base of the iris are drawn 
forward, the choroid is made tense, and the suspensory ligament of the 
lens is relaxed. The lens then becomes more nearly spherical because 
of its own elasticity. 
The fibrous layer of the ciliary body consists of connective tissue, 
and connects the fibrous portion of the choroid to the similar tissue of the 
iris. It is formed by a reticulum of the fine fibers in the meshes of 
which are numerous lamellar and a few pigmented cells. Buried within 
the outer portion of this fibrous mass and intermingling with its fibers 
are the fiber bundles of the ciliary muscle. Into the inner portion of the 
fibrous layer a vascular plexus is continued from the vascular and capil- 
lary layers of the choroid; branches of the ciliary arteries communicate 
with this plexus. 
Appended to the inner surface of the fibrous layer are numerous 
meridionally disposed folds of connective tissue which radiate from the 
base or outer margin of the iris to the margin of the choroid opposite the 
ora serrata. These are the ciliary processes. Their inner or free surface 
is covered by the pigmented retinal epithelium, and within these proc- 
esses are contained the greater portion of the pigmented connective tissue 
cells of the ciliary body. Each fold is much deeper (about 1 mm.) 
toward its axial margin and becomes progressively diminished in height 
toward the choroid. 
The pigmented epithelial layer is here and there invaginated into 
the fibrous tissue of the ciliary processes to form ampullate recesses 
(the ciliary glands'), which somewhat resemble true secreting glands. 
These so-called glands have been supposed to be concerned in the secre- 
tion of the aqueous humor. They are probably not true secreting glands, 
but represent mere invaginations of the epithelium. 
The ciliary epithelium (pars ciliaris retinae) consists of a double 
layer of epithelial cells, continuous posteriorly with the retina, and in THE MIDDLE COAT-THE VASCULAR TUNIC 
641 
front with the pars iridica retinae. The superficial (innermost) cells 
present a clear or slightly granular cytoplasm with a centrally situated 
nucleus. Their cytoplasm is but slightly pigmented, and ofttimes is 
indistinctly rodded or fibrillated. In shape, these cells are of the low 
columnar type, but they become progressively flattened toward the iris, 
where they are continuous with the pars iridica retinae. They represent 
a continuation of the sustentacular cells of the retina. 
The cells of the deeper (outer or anterior) layer vary in height from 
a low columnar at the ora serrata to a somewhat flattened cell near the 
iridal margin, and are continuous with the pigmented cell layer of the 
retina. This cell layer is deeply pigmented, the entire cytoplasm being 
filled with the dark brown pigment granules. The nucleus, however, 
as in the pigmented cells of the choroid, contains no pigment, and 
therefore, in unstained preparations, appears under the microscope as 
a clear opening in the dark background of pigmented cytoplasm. 
The Iris 
The iris (Figs. 538 and 543) forms an annular curtain which pro- 
jects from the anterior margin of the ciliary body toward the axis 
of the eye. It presents a central circular opening, the pupil, which lies 
in the visual axis. 
The iris is suspended in the aqueous humor, its pupillary margin 
resting gently upon the anterior surface of the lens, its base or ciliary 
margin being separated from the lens by an interval, the posterior 
chamber, which is also filled by the aqueous humor. 
The iris may be said to consist of three layers: 1, the external 
epithelium; 2, the fibrous stroma; 3, the internal epithelium. 
The external epithelium (endothelium of the iris) is a mesen- 
chymal epithelium continuous at the margin of the anterior chamber 
with the posterior epithelial layer of the cornea, which appears to be 
reflected upon the anterior surface of the iris. At the pupillary border 
it is also continuous with the internal epithelium of the iris (pars iridica 
retinas). The cells of the anterior or external epithelium are very much 
flattened and almost endothelioid in appearance; at occasional intervals 
the epithelium is incomplete. These intervals occur either near the 
pupillary or the ciliary margin, and correspond to recesses which open 
directly into the fibrous stroma of the iris and become continuous with 
its lymphatic interstices. 
To the naked eye the anterior surface of the iris presents an uneven 642 
THE EYE 
appearance, which is apparently due to the presence of slight meridional 
ridges, with shallow intervals, which extend from the pupillary margin 
of the iris to its outer border. The lighter radial and circular markings 
are due to the blood-vessels. 
The fibrous stroma of the iris {pars choroidalis iridis, pars uvealis 
iridis) consists of a loose spongy connective tissue of an almost embry- 
onal type. Its fibers are scanty and are gathered into small bundles, 
which interlace somewhat, but which are for the most part disposed in 
a meridional direction. This disposition is especially noticeable near 
the ciliary margin. 
The fibrous stroma is very rich in connective tissue cells, which are 
mostly stellate and branch and interlace freely. They contain more or 
less brownish pigment, which is most abundant near the posterior (in- 
ner) surface. The color of the iris, when viewed with the naked eye, 
is dependent upon the depth of pigmentation in these connective tissue 
cells, as well as in the cells of the internal epithelial layer, and to the 
relative transparency of the stroma. In dark blue and black eyes the 
stroma pigment is scanty, and the very dark epithelial pigment shows 
through the more anterior clear layers of the iris. In the brown eye 
the stroma pigment is dense and opaque. A gray color is produced by 
a scanty stroma pigment clouded by a rather dense fibrous stroma. In 
the eyes of albinos the iris lacks pigment altogether; the pink color 
of the iris is due to the blood in the numerous vessels of the stroma. 
Embedded in the fibrous stroma, near its pupillary margin, is a 
small bundle of non-striated muscle fibers, which are circularly disposed, 
to form the so-called sphincter muscle of the iris. Its fibers are distrib- 
uted in a plane parallel to the surface of the iris, and within the inner 
(posterior) part of its fibrous stroma. They are most abundant near 
the pupillary margin, and become progressively thinner toward the 
base of the iris. Internally to the sphincter muscle, and in contact 
with the basement membrane of the internal epithelium, is an incom- 
plete layer, more distinct toward the ciliary margin of the iris, w'hich 
contains radially disposed smooth muscle fibers, the dilator muscle of 
the iris, apparently of ectodermal origin. Mydriatics (e.g., atropin) pro- 
duce an enlargement of the pupil, presumably through inhibition of 
the constrictor and stimulation of the dilator muscles; mitotics (e.g., 
morphin) produce a contrary effect. 
The stroma of the iris is exceedingly vascular, the arteries and veins 
being meridionally disposed, the capillaries forming an irregular plexus. 
Near the pupillary margin the vessels form a rich capillary anastomosis, THE POSTERIOR CHAMBER 
643 
the circulus minor. The entering arteries likewise form a cir cuius major 
by anastomoses at the ciliary margin of the iris. 
The internal epithelium (posterior epithelium, pars iridica retince) 
resembles that of the ciliary body or pars ciliaris retinae, with which 
it is continuous. The innermost (superficial) layer of epithelial cells, 
in the iridal epithelium, is deeply pigmented and somewhat flatter than 
in the ciliary body. The pigmentation is so deep that in the adult iris 
it is scarcely possible to distinguish the two epithelial layers. These can, 
however, be readily seen in the fetal eye, and even in that of the child. 
THE ANTERIOR CHAMBER 
The anterior chamber is bounded in front by the posterior (internal) 
surface of the cornea, and behind by the anterior surface of the crystal- 
line lens and the anterior (external) aspect of the iris; it contains the 
aqueous humor presumably largely a filtration product from the numer- 
ous blood-vessels of this region, in part a secretion product of the ciliary 
epithelium. Its anterior boundary is convex, its posterior concave, and 
its circular margin is limited by an area which is known as the irido- 
corneal angle. 
At this angle the mesenchymal epithelium is reflected from the poste- 
rior surface of the cornea upon the anterior surface of the iris. The 
latter portion of the epithelial layer is incomplete, since it presents nu- 
merous openings which communicate with the lymphatic spaces between 
the fibers of the ligamentum pectinatum and ciliary muscle. These lym- 
phatic recesses are the spaces of Fontana. 
The ligamentum pectinatum consists of fibers which arise from 
the margin of Descemet's membrane, and pass backward and inward, 
in a radial direction, to the fibrous stroma of the iris and ciliary body. 
Viewed from the cavity of the anterior chamber the fibers of this liga- 
ment, with the intervening spaces of Fontana, present a toothed appear- 
ance; the ligament derives its name from this peculiarity. 
THE POSTERIOR CHAMBER 
The posterior chamber is an annular cavity, somewhat triangular or 
trapezoidal in transection, whose lumen, like that of the anterior cham- 
ber, is occupied by aqueous humor, suspended in which are the fibers 
of the suspensory ligament of the crystalline lens. 644 
THE EYE 
It is limited anteriorly by the internal surface of the iris, and an- 
tero-externally by the ciliary processes. Its postero-internal boundary 
is formed by the marginal portion of the lens, together with the adjacent 
portion of the hyaloid membrane, which incloses the vitreous humor. 
THE INTERNAL COAT-THE NERVOUS TUNIC 
The internal coat of the eyeball is divisible into three portions: 
1, the pars optica retinae or retina proper; 2, the pars ciliaris retinae, 
and 3, the pars iridica retinae. 
The last two portions, though morphologically continuous with the 
pars optica retinae, differ therefrom in their physiological function; they 
respectively form the innermost layer of the ciliary body and iris. As 
such they have already been described. 
General Consideration of the Betina 
The retina {pars optica retince) may be said to be formed by the 
radial expansion of the fibers of the optic nerve which enter the eye at 
the inner side of its posterior pole, piercing the sclera and choroid and 
spreading out over the inner surface of the eyeball. 
These nerve fibers arise from groups of nerve cells which are disposed 
in layers to form the optic and retinal ganglia {ganglion nervi optici 
and ganglion retinal). The association of nerve cells and fibers with 
their supporting tissues forms the inner, cerebral, or neural portion of 
the retina. The dendritic arborizations of many of these nerve cells lie 
within the outer half, or neuro-epithelial portion of the retina. 
The retina may be said to extend forward from the entrance of the 
optic nerve (optic disk) as far as the posterior margin of the ciliary 
body, where it apparently ends abruptly with an indented border, the 
ora serrata. From this border the retina is continued farther forward, 
but only as the dark pigmented layers of the ciliary processes and iris. 
In the usual preparations these layers contrast intensely with the opaque 
white color of the true retina. Like all the other tissues which are 
placed in the optical axis of the eye, the retina, during life, with the ex- 
ception of its pigment layer, is perfectly transparent, but becomes 
opaque immediately after death or local injury. 
The retina presents on its inner surface a slightly elevated yellow 
spot, the macula lutea, which lies exactly at the posterior pole of the THE INTERNAL COAT-THE NERVOUS TUNIC 
645 
visual axis. The fovea centralis is the slight depression in the center 
of the macula lutea, and is the result of an apparent thinning of the 
retinal layers at this point. 
The papilla optica, or entrance of the optic nerve, also forming a 
slight elevation with a central depression, the physiologic excavation, 
is placed 3.5 to 4 mm. to the nasal side of the macula lutea, and at a 
slightly lower horizontal plane. 
Development of the Eye 
A word as to the development of the organ will make clearer the 
description of the several layers of the retina. The retina is developed 
as an evagination of the first cerebral vesicle, and is, therefore, to be re- 
garded as a detached lobe of the cerebrum itself. The evagination or 
optic vesicle grows forward 
in the embryo, and soon 
forms a flask-shaped process 
whose expanded extremity 
is early infolded in a cup- 
like manner forming the 
optic cup. The peripheral 
layer of the cup becomes 
the pigmented layer, the 
lining layer differentiates 
into the neural layers, of 
the retina. The inferior 
surface of this optic cup 
and the connecting optic 
stalk at first presents a 
slit-like deficiency, the 
choroidal fissure, into which 
grows the mesoblastic tis- 
sue which ultimately forms 
the vitreous humor and 
conveys the central artery 
of the optic nerve. The 
indented extremity of the optic cup is soon occupied by the developing 
lens, which arises, under the influence of the optic cup itself (Lewis, 
Amer. Jour, of Anat., 1904), but is formed from the overlying area of 
the epidermal ectoderm. 
Fig. 544.-The Developing Eye in Merid- 
ional Section; Diagrammatic. 
A, early; B, later stage. E, E, ectoderm; L, 
lens; M, M, mesoblast; a, optic vesicle, pro- 
truding from, b, the first cerebral vesicle; c, a 
thickening of the ectoderm, anlage of the lens; 
o, constricted pedicle of the optic cup; p, outer 
coat of the optic vesicle, anlage of the retinal 
epithelium; r, inner wall of the vesicle, anlage 
of the neural portion of the retina. (After 
Fuchs.) 646 
THE EYE 
According to certain investigators (Szily, 1908, et al.) the definitive 
vitreous humor is preceded by a primitive structure in the form of a loose- 
meshed reticulum of protoplasmic fibers (cytodesmata) derived from, and 
in continuity with, both the lens and the retina, 
hence ectodermal in origin. This primitive vi- 
treous body is subsequently invaded by vascular 
mesenchyma, the two tissues uniting to produce 
the definitive vitreous. The hyaloid membrane, 
surrounding the vitreous body, and the fibers of 
the suspensory ligament of the lens are thought 
by some to represent the persistent peripheral 
remains of the original ectodermal stroma. 
Others, among them most recently Baldwin 
(Arch. mikr. Anat., vol. 80, 1912), describe the 
origin of the suspensory ligament from mesen- 
chyme. 
Failure of closure on the part of the chor- 
oidal fissure gives rise to various degrees of a 
defect known as coloboma. This condition may 
appear simply as a shallow cleft in the iris, or as a more or less extensive 
fissure in the retina or even the optic nerve, w7hich seriously interferes with 
vision. 
Fig. 545.-Schematic Re- 
construction of THE 
Developing Eye. 
a, optic cup; s, choroidal 
fissure; sb optic nerve; L, 
developing lens. (After 
Fuchs.) 
Layers of the Betina 
The retina may be said to consist of ten layers, which from without 
inward are: 
1. The pigment epithelium. 
2. The layer of rods and cones. 
3. The external limiting membrane. 
4. The outer nuclear layer. 
5. The fiber layer of Henle. 
6. The outer reticular layer. 
7. The inner nuclear layer. 
8. The inner reticular layer. 
9. The ganglion cell layer. 
10. The nerve fiber layer. 
To these several layers an additional one, the internal limiting mem- 
brane, is frequently added. The first five of these layers are contained 
within the neuro-epithelial portion of the retina, the last five form its 
cerebral or neural portion. 
1. The pigment epithelium (layer of pigmented cells') consists of THE INTERNAL COAT-THE NERVOUS TUNIC 
647 
a single layer of columnar epithelial cells whose bases, of generally hex- 
agonal outline, rest upon and are firmly adherent to the inner surface 
of the choroid coat, and from whose free borders irregular processes 
extend inward between the ele- 
ments of the rod and cone layer. 
These epithelial cells have a finely 
granular cytoplasm. Their nucle- 
us is oval, somewhat flattened, and 
placed near the base of the cell; 
it is, however, obscured or even 
entirely hidden by the mass of 
dark pigment granules (fuscin) 
by which the cytoplasm of the cell 
is more or less completely filled. 
The disposition of the pigment 
within the epithelial cell appar- 
ently corersponds to, and is de- 
pendent upon, the effect of light 
upon the retina. In an eye ex- 
posed to the action of light at the 
instant of death, the pigment 
granules accumulate in the irreg- 
ular processes of the cells which 
surround the rods and cones, the 
outer or basal portion of the cell 
being relatively free from pig- 
ment. In an eye which is shaded from the light, or in one removed in 
comparative darkness, the pigment has apparently retracted until it lies 
entirely with the body of the cell. Even under 
these conditions the extreme base of the cell fre- 
quently presents a narrow zone which is rela- 
tively free from pigment. Similar changes in 
the disposition of the pigment undoubtedly occur 
in the living eye under the influence of exposure 
to varying degrees of light. 
The function of this pigment and of the pe- 
culiar changes in its disposition is still somewhat 
speculative, but it may, without doubt, be safely 
asserted that these phenomena are concerned with the renewal of 
the visual purple of the outer segments of the rods after the same has 
Fig. 546.-The Retina of a Child's 
Eye; Meridional Section. 
a, nerve fiber layer, the broad bases of 
Muller's fiber cells show distinctly; b, 
blood-vessel; c, large ganglion cell layer; 
d, inner reticular layer; e, inner nuclear 
layer; f, outer reticular layer, with a 
prominent fiber layer of Henle; g, outer 
nuclear layer; h, layer of rods and cones; 
i, layer of pigmented epithelium; k, 
choroid coat. Hematein and eosin. 
Photo. X 225. 
Fig. 547.-Pigmented 
Epithelium of the 
Retina, Viewed in 
Transection. 
X 500. (After Fuchs.) 648 
THE EYE 
been bleached by exposure to light. Possibly these changes possess a 
stimulant action upon the neuro-epithelial elements. 
2. The rod and cone layer (bacillary layer) consists of a series 
of columnar elements which are disposed in a palisade-like manner, and 
whose narrow extremities are embedded in the surface of the layer of pig- 
ment epithelium. The rod and cone layer contains elements of two dis- 
tinct types, the rods and the cones, specialized receptors of the rod and 
cone visual cells, and very similar to each other in their structure. Each 
Fig. 548.-Isolated Rod and Cone Visual Cells of the Pig. 
a-e, cones; f-i, rods; za, outer segment; zi, inner segment of the cone, the latter 
consisting of an ellipsoid, ze, and a more or less elongated neck, m; zk, cone nucleus; 
zf, cone fiber; sa, outer, and si inner segment of the rod; sk, rod nucleus; sf, rod 
fiber. (After Kblliker.) 
rod and each cone visual cell consists of two distinct portions, the outer 
of which, alone, lies in the bacillary layer; the inner portion is included 
in the outer nuclear layer of the retina. The outer portion is cytoplas- 
mic, and its broad base rests upon the external limiting membrane; the 
inner portion is narrow, nucleated near its center, and extends entirely 
through the outer nuclear layer. 
The Bods.-The outer, cytoplasmic, or bacillary portion of each 
rod visual cell consists of a somewhat thickened spheroidal base, the inner 
segment, and an outer filamentous extremity, the outer segment. These 
two segments are quite as distinct in fresh unstained tissue as in fixed THE INTERNAL COAT-THE NERVOUS TUNIC 
649 
and stained preparations, the distinction being due to the fact that the 
inner segment of each rod, while finely granular and easily stained, is 
also singly refractive; the outer homogeneous segment, on the other hand, 
not only stains with difficulty but is 
doubly refractive or anisotropic. The 
outer, therefore, under all conditions 
appears bright and lustrous as com- 
pared with the isotropic inner seg- 
ment. The outer segment is said to 
be covered by a delicate sheath of 
neurokeratin, and to consist of a sub- 
stance chemically very similar to 
that of the myelin of medullated 
nerve fibers. 
The outer segment contains the 
visual purple or rhodopsin which, 
during life, is rapidly bleached by 
exposure to light, and is as rapidly 
renewed through the agency of the 
pigment epithelium. 
Both segments, but especially the 
inner, under favorable conditions, 
present slight longitudinal striations. 
These striations, when present, are 
most distinct in the outer half of the 
inner rod segment where they form 
the so-called ellipsoid; they are gen- 
erally interpreted as due to linear 
surface grooves in the outer segments, 
and to fibrils in the ellipsoid. The 
outer filamentous segment of each rod 
sometimes exhibits transverse mark- 
ings, possibly indicating a minute 
structure which is comparable to a 
series of superposed disks. 
The rods have an average length of 60 microns, and an average 
diameter of 2 microns; of the entire extent, the outer cylindric seg- 
ment and the inner spheroidal segment contribute approximately equal 
portions. 
The inner or nucleated portion of each rod, the rod fiber, is found 
Fig. 549.-Diagram of the Rod 
and Cone Visual Cells, and 
Their Respective Bipolar Neu- 
rons. (Schwalbe.) 
m.l.e., external limiting membrane; 
n.l.e., external nuclear layer; r.l.e., 
external reticular (molecular); layer; 
n.l.i., internal nuclear layer (layer of 
rod and cone bipolars). 650 
THE EYE 
in the outer nuclear layer and is continued as a fine filament, which, 
having penetrated the external limiting membrane, extends as far as the 
border line between the outer nuclear and outer reticular layers, at which 
Fig. 550.-A Rod and a Cone 
Visual Cell from the Fun- 
dus of the Human Re- 
tina, Outside the Macula 
Lutea. 
a, outer segment; b, inner seg- 
ment; c, rod- or cone-fiber; d, 
nucleus; e, rod- or cone-foot; f, 
ellipsoid; g, myoid (of cone); 
h, external limiting mem- 
brane. (Schafer, Greeff.) X 
1000. 
Fig. 551.-Two Cones from the Human 
Retina. 
A, from close to the ora serrata; B, from 
near the margin of the forea centralis. The 
fiber (f) is cut short beyond the nucleus. Be- 
tween the ora and the fovea cones of inter- 
mediate lengths are found, forming a series 
from A to B. In the central part of the 
fovea, the cones are still longer than B, the 
increase being due mainly to an elongation 
of the outer segments (os) to about twice 
the length in B. (Greeff.) X 1000. THE INTERNAL COAT-THE NERVOUS TUNIC 
651 
level the rod filament ends in a knob-like expansion. Similar knobs may 
appear along its course. At some point in its course through the nuclear 
layer the rod fiber presents a nucleated enlargement, which, under some 
conditions, shows one to three alternate light and dark transverse stria- 
tions, the optical expression of the distribution of the chromatin in the 
1, outer nuclear layer; 2, outer reticular layer; 3, inner nuclear layer; 4, inner 
reticular layer; a, external limiting membrane; b, rod cell nuclei; c, cone cell nuclei; 
d, cone bipolars; e, rod bipolars; f, an exceptionally long process of a rod bipolar. 
Methylene blue. Highly magnified. (After Dogiel.) 
Fig. 552.-From the Human Retina. . 
form of bands. The nuclei of the rod fibers are placed at various levels 
in the nuclear layer, and collectively occupy nearly its entire thickness. 
Its outer border, however, contains relatively few rod nuclei. 
The Cones.-The cones resemble the rods in structure, but their 
cytoplasmic portion is shorter, the inner segment of which is several 
times as broad (35 p by 7 g. ). The outer anisotropic segment is espe- 
cially short and does not contain visual purple, while the isotropic basal 
segment, whose fibrillated ellipsoid occupies a somewhat greater propor- 652 
THE EYE 
tion of its length than is the case with the homologous rod segment, rests 
directly upon, and may even project through the external limiting mem- 
brane. The inner or nucleated portion, therefore, begins as a broad 
nucleated mass, equal in diameter and continuous with the bacillary por- 
tion of the cone element, to which it is ofttimes united by a slightly con- 
stricted neck. In this inner portion, just within the external limiting 
Fig. 553.-Diagrams of the Human Retina, Showing the Relationships to 
Each Other of the Retinal Neurons, and Their Disposition in the Dif- 
ferent Layers. 
(From Fox's "Ophthalmology.") 
membrane, is the cone nucleus; it differs from the rod nucleus in that 
it stains less deeply, presents no transverse striations, and frequently 
incloses a distinct nucleolus. From its nucleated portion the cone fiber 
is continued as a rather broad cytoplasmic filament straight inward to the 
border of the nuclear layer, where it terminates in an expanded portion 
or cone foot, from the flattened inner surface of which the fine filaments 
penetrate the margin of the outer reticular layer. 
The outer segments of both rods and cones are embedded in the cells 
of the pigment layer, whose delicate filamentous processes project between 
the rods and cones, frequently extending almost to the external limiting THE INTERNAL COAT-THE NERVOUS TUNIC 
653 
membrane. Both rods and cones are hexagonal or nearly circular in 
transection. The slight intervals between the neighboring elements and 
the processes of the pigment epithelium are occupied by a homogeneous 
fluid, probably a somewhat modified lymph. The rods far outnumber 
Fig. 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. 
1, pigment layer; 2, bacillary layer; 3, external limiting membrane (indistinct); 4, 
outer nuclear layer; 6, outer reticular layer; 7, inner nuclear layer; 8, inner reticular 
layer; 9, ganglion cell layer; 10, nerve fiber layer; 11, internal limiting membrane; 
a, choroid coat. Hematein and eosin. Photo. X 400. 
the cones; three to four rods generally appear between two successive 
cones. The total number of cones in the human retina has been esti- 
mated at 70,000,000; that of rods at 130,000,000. 
3. The external limiting membrane (membrana limitans externa) 
consists of the flattened and amalgamated extremities of the sustentacular 
cells (Muller's fibers), which form the chief supporting tissue, the neu- 654 
THE EYE 
roglia element, of the retina, and which extend from the extreme inner 
surface outward to the external limiting membrane. It will therefore 
be more convenient to defer further description of this membrane until 
the remaining layers have been described, and the Mullerian fibers can 
be considered in their entirety. 
4. The outer nuclear layer (outer granular layer) consists, for 
the most part, of the nucleated portions of the rod and cone elements. 
The outermost zone of this layer contains only cone nuclei; the inner 
portion, comprising about three-fourths of its thickness, contains only rod 
nuclei. The former, with occasional exceptions (Stbhr), are situated in 
only one relatively narrow plane; the latter are distributed at various 
levels, though they occur more abundantly in the mid-region of the 
nuclear layer. In addition to portions of Muller's fibers which serve for 
the support of the nucleated elements, this layer contains the terminal 
filaments of the distal processes of some of the small bipolar nerve cells 
of the inner nuclear layer. 
5. The fiber layer of Henle is formed by that portion of the cone 
fibers which is internal to the layer of rod nuclei. It is a thin layer and' 
only acquires importance in the neighborhood of the macula lutea, where 
the cones are most abundant. In this portion of the retina it is easily 
distinguished from the outer reticular layer by the somewhat radial 
disposition of its fibers, the fibers of the reticular layer having an irregu- 
larly meridional direction. 
6. The outer reticular layer (outer molecular layer; outer plexi- 
form layer) presents a dense tangle of neural tissues consisting of sup- 
porting neuroglia fibers and interlacing processes from the horizontal 
and bipolar nerve cells of the inner nuclear layer. Terminal fibrils from 
this network intermingle in the fiber layer of Henle with terminal fibrils 
from the cone feet; more externally they are in intimate relation with 
the end knobs of the rod fibers. This arrangement permits the transmis- 
sion of stimuli from the neuro-epithelium to the retinal ganglion. 
7. The inner nuclear layer (inner granular layer, ganglion retince, 
outer ganglionic layer) contains a mass of nerve cells, together with the 
nucleated portion of the sustentacular fiber cells of Muller. The nerve 
cells may be described as corresponding to one of three types, which, 
from the plane in which they are distributed may be termed the outer, 
middle, and inner. 
The Outer Nerve Cells.-The outer nerve cells (horizontal cells, 
basal cells) possess pyramidal, stellate, or flattened cell bodies whose 
dendrons are distributed to the horizontal plexus of the outer reticular 655 
THE INTERNAL COAT-THE NERVOUS TUNIC 
layer. These cells vary in size; the dendritic or distal processes of the 
smaller cells on reaching Henle's layer are in relation with the terminal 
fibrils of the cone feet; those from the larger nerve cells are in relation 
with the terminal knobs of the rod fibers. The axis cylinders or central 
processes from all these cells after traveling horizontally-viz., in a plane 
parallel to the layers of the retina-for a greater or less distance, turn 
inward and pass to the inner reticular layer, where they come into 
Fig. 555.-Horizontal Cell from the Retina of a Calf. 
a, cell body; b, axon; c, terminal arborizations of the axon. Golgi's stain. X 150. 
(After Marenghi.) 
relation with the dendrons of the large nerve cells of the ganglion cell 
layer. Other processes, mostly from the smaller cells, terminate in the 
outer reticular layer, probably serving the purpose of association neu- 
rons. 
The Middle Type.-The nerve cells of the middle type are usually 
of bipolar form, and are the most abundant elements of the outer 
nuclear layer. The one set of their processes is directed outward (periph- 
eralward) ; they pass to the outer reticular layer where they eventually 
come into relation with either the rod fibers or the cone fibers. Hence 
those cells which are in relation with the visual rods are classified as 656 
THE EYE 
rod bipolars, those in relation with the visual cones as cone bipolars 
(Fig. 552). The terminal fibrils of the cone bipolars are horizontally, 
those of the rod bipolars radially, disposed. 
The central processes, axons, of the bipolar cells are directed inward 
(centralward), and on entering the inner reticular layer terminate in 
an end brush which is in relation with the dendritic processes from the 
large ganglion cell layer. 
The Inner Nerve Cell Type.-The inner nerve cell type (amac- 
rine cells of Cajal) are large nerve cells which occupy a narrow zone 
at the inner margin of this nuclear layer. These are large stellate cells 
whose dendritic processes extend into the inner reticular layer and take 
part in the formation of the dense feltwork of which that layer consists. 
The course of the axis-cylinders of these cells is still a matter of some 
Fig. 556.-Two Amacrine Cells from a Transection of the Retina of a Calf. 
Golgi's stain. X 260. (After Kolliker.) 
doubt. Banion y Cajal, believing these cells to possess no axon, desig- 
nated them 'amacrine cells' and subdivided them according as their den- 
drons were distributed in either one of several horizontal planes (the 
number varying in different species) or diffusely throughout the inner 
reticular layer. 
Some of the amacrine cells, however, send an axon in a horizontal 
direction to the inner reticular layer, and are also in relation with the 
terminal arborizations of centrifugal nerve fibers which enter from the 
nerve fiber layer. These have been regarded by some observers as 'dis- 
located nerve cells' of the ganglion cell layer; Cajal named them 'associa- 
tion amacrins* 
8. The inner reticular layer (inner molecular layer, inner plexi- 
form layer) is a densely tangled network of nerve-cell processes, a neuro- 
spongium. To these are added a much branched portion of Muller's 
fibers, which form the chief supporting tissue of this layer. The cell proc- 
esses entering into this formation are derived from the cells of the inner 
nuclear and ganglion cell layers, and it is here that the processes of these 
cells interlace so closely as to permit the transmission of impulses from 
the one neuron to the other. Their terminal arborizations are, for the THE INTERNAL COAT-THE NERVOUS TUNIC 
657 
most part, disposed in horizontal planes, though a few spread throughout 
the entire thickness of the reticular layer. 
9. The ganglion cell layer (ganglion nervi optici, inner ganglionic 
layer, layer of large nerve cells) is of variable thickness. Its greatest 
depth is in the region of the macula lutea, where it consists of five or 
six superposed ganglion cells. Toward 
the equator of the eye it becomes progres- 
sively thinner, until near the ora serrata 
its single layer of cells only forms an in- 
complete stratum. 
The cells comprising this layer are 
mostly large, stellate, pyriform, or sphe- 
roidal nerve cells, from whose peripheral 
border dendrons pass to the inner reticu- 
lar layer, and from whose central border 
an axon passes to the nerve fiber layer to 
eventually become the axis cylinder of a 
fiber of the optic nerve. 
These cells, though varying much in 
size and shape, possess a body of the usual 
structure with neurofibrils and chromo- 
philic granules, and a pale vesicular nu- 
cleus with a distinct chromatic nucleolus. 
Intermingled with the nerve cells are 
many fine branches of the sustentacular 
cells which here form an open-meshed 
network within whose spaces the nerve 
cells are inclosed. 
10. The nerve fiber layer, in inti- 
mate relation with the preceding, forms 
the innermost of the retinal zones. It 
consists of naked axis-cylinders passing 
from their origin in the ganglionic layers 
to their immediate destination, the optic nerve. They are, therefore, 
mostly if not wholly centripeetal fibers. A few centrifugal fibers have been 
demonstrated in this layer, but they would appear to be probably vaso- 
motor in function, a few possibly ending in relation to the amacrine cells. 
The nerve fibers of this layer converge from all portions of the retina, 
follow a meridional course through the open meshes of the network of 
branching sustentacular cells, and converge toward the optic papilla, the 
Fig. 557.-A Nerve Cell of 
the Large Ganglion Cell 
Layer; from the Retina of 
a Cat. 
n, n, axon; c, c, collaterals. 
Golgi's stain. X 325. (After 
Kolliker.) 658 
THE EYE 
entrance, or rather the point of exit, of the optic nerve. Hence the 
nerve fiber layer, being augmented by the constant acquisition of new 
axons from the ganglion cells, becomes pro- 
gressively thicker toward the posterior pole 
of the eye, and is thickest at the margin of 
the optic papilla, where it is so highly de- 
veloped as to almost exclude the other 
retinal layers. 
The course of these non-medullated 
nerve fibers is not straight; on the contrary, 
they interlace to form a delicate fibrillar 
network. At the margin of the papilla op- 
tica the nerve fibers bend outward with a 
sharp curve almost at right angles to their 
former course. At this point also they grad- 
ually acquire a medullary sheath and, unit- 
ing into many bundles, penetrate the nu- 
merous openings of the lamina cribrosa of 
the sclerotic and choroid coats to form the 
optic nerve. 
The Supporting Tissues of the Retina 
These consist of a gliaform reticulum 
distributed throughout the cerebral portion 
of the retina, and of a special supporting 
tissue, Muller's fibers, which may also be re- 
garded as glia tissue, though they are com- 
mon to both the neural and epithelial por- 
tions. 
The fibers of Muller {radial fibers; 
sustentacular cells') comprise numerous large 
glia cells whose processes begin with an ex- 
panded base at the inner surface of the 
nerve fiber layer, and can be traced all the 
way through the retina to the membrana 
limitans externa, which is likewise formed 
by the terminal expansions of these cells. 
The nucleus of the fiber cell lies in the mid-region of the inner nuclear 
layer. 
Fig. 558.-A Fiber Cell of 
Muller, or Sustentacu- 
lar Cell, from the Dog's 
Retina. 
1, nerve fiber layer; 2, gan- 
glion cell layer; 3, inner retic- 
ular layer; 4, inner nuclear 
layer; 5, outer reticular layer; 
6, outer nuclear layer; a, a 
process extending into the 
inner reticular layer; b, nu- 
cleus of the cell; m.l.e., exter- 
nal limiting membrane; m.l.i., 
internal limiting membrane. 
Golgi's stain. Highly mag- 
nified. (After Cajal.) THE INTERNAL COAT-THE NERVOUS TUNIC 
659 
The expanded and flattened bases or inner extremities of these glia 
cells are so closely approximated to one another as to form a complete 
investment for the inner surface of the retina, which is known as the 
internal limiting membrane (membrana limitans interna) and is fre- 
quently classed as the innermost layer of the retina. Under low magnifi- 
cation it appears as a continuous membrane, but under higher powers it 
is readily resolved into the broad, conical, basal expansions of which it 
consists. From these initial expansions the glia cells may be traced 
outward through the nerve fiber and ganglion cell layers by means of 
the numerous coarse processes or glia fibers. 
The glia fibers then pass in a fairly straight course through the 
inner reticular layer. In this portion numerous short, fine, lateral off- 
shoots from the main stem support the neurospongium of the reticular 
layer. Continuing through the inner nuclear layer the glia substance 
is somewhat thickened; it sends off fewer but coarser lateral processes, 
and in the mid-region of this layer presents an enlargement which is 
almost entirely occupied by the large ovoid nucleus. 
The fiber cell, somewhat narrowed, may then be traced through the 
outer reticular to the outer nuclear layer, where its processes form a 
dense network about the nucleated segments of the rod and cone visual 
cells. 
The terminal processes of the fiber cells become again flattened, some- 
what after the manner in which the internal limiting membrane is 
formed, and are so closely approximated as to form an external limiting 
membrane, a distinctly membranous structure which derives a reticular 
appearance from being pierced by each of the innumerable rod and 
cone elements. 
From the outer surface of the expanded ends of the Mullerian 
fiber cells which form the external limiting membrane, minute fibrils 
are continued between the bases of the non-nucleated portions of the 
rod and cone cells to form shallow sockets, the rod and cone sockets, into 
which the bacillary portions of these elements are fixed. The neuroglia 
supporting tissue includes also the ordinary long- and short-rayed astro- 
cytes, limited, however, to the cerebral portion of the retina. 
The Macula Lutea 
(Yellow Spot) 
The macula lutea being apparently the most highly developed portion 
of the retina, deserves some special consideration. The macula is a cir- 660 
THE EYE 
cular elevation about 2 mm. in 
diameter, in the center of which 
is a marked depression, the fovea 
centralis. It is yellow in color, 
due to the presence of a pigment. 
The elevation results from an in- 
creased thickness of all the ret- 
inal layers, but especially of the 
ganglion cell layer, which in this 
portion of the retina is five or six 
cells deep. The reticular layers 
are also much thickened in this 
area. In the bacillary layer, 
within the area of the macula, 
the cones are far more numerous 
than elsewhere, especially when 
considered in relation to the rods, 
which are greatly diminished 
peripherally and absent centrally. 
The cones of the macula are al- 
most twice as long as those of 
the equatorial region of the re- 
tina, the increased length being 
due to elongation both of the in- 
ternal and external segments, 
but mainly the latter; they are 
also somewhat more slender, and 
their nuclei may be placed some 
distance beyond the external lim- 
iting membrane. 
Toward the fovea centralis 
the inner layers of the retina be- 
come very much thinned, until 
at its center the nerve tissues are 
merely represented by scattered 
cells of the inner nuclear and 
ganglion cell layers. Rod ele- 
ments are not found in this area; 
the bacillary layer consists en- 
tirely of elongated, slender cones. 
Fig. 559.-Transection through the Fovea Centralis Retinas. 
ak, outer nuclear layer; f, outer reticular layer; g, large ganglion cell layer; 
gl, membrane of Bruch; i, inner reticular layer; ik, inner nuclear layer; le, 
external limiting membrane; Ih, internal limiting membrane; n, nerve fiber 
layer; p,'pigment cells; z, bacillary layer. (After Schafer.) THE INTERNAL COAT-THE NERVOUS TUNIC 
661 
The much elongated nuclear portion of the cones deviates in a slanting 
direction toward the margin of the macula, and the cone nuclei are 
further removed from the external limiting membrane than elsewhere 
in the retina. 
The pigment of the epithelial layer is much diminished and may 
even be absent at the fovea. Because of the diminution in the number 
of ganglion cells in this area the nerve fiber layer is greatly diminished 
in thickness on approaching the margin of the fovea, and toward its 
center entirely disappears. 
The fovea centralis lies at the posterior pole of the anteroposterior 
axis. The light stimulus here meets least obstruction in passing to the 
neuro-epithelial elements; this is the point of acutest vision. 
Since the fovea centralis contains no rods, it lacks the visual purple; 
and since vision is sharpest at this point, the visual purple would seem 
unessential to sight. The 
visual purple is said to be 
absent in the eyes of the 
pigeon, the hen, some rep- 
tiles and some bats. It is 
supposed to enhance the 
irritability of the rods in 
dim lights. 
In the eyes of birds 
and reptiles the cones out- 
number the rods; and in 
certain reptiles, e.g., liz- 
ards, rods are entirely 
lacking. In sharks and 
rays, most nocturnal ani- 
mals, and the owl, cones 
are either absent or few in 
number or rudimentary in 
structure. According to 
the view of Kreis (1895) 
the cones function in the 
perception of color, the rods are sensitive only to light and darkness. In 
color blindness the cones are defective; in night-blindness the rods are 
affected. 
Development of Rods and Cones.-The rods cones arise and by an 
essentially identical mode of differentiation from apparently similar em- 
bryonic cells. A protoplasmic bud is pushed beyond the external limiting 
membrane towards the layer of pigmented cells. The cone bud is from 
Fig. 560.-Developing Rod and Cone Visual 
Cells, from the Retina of a 345 mm. (6 mos.) 
Human Fetus. 
M, diplosome in a Muller's fiber at the level of 
the external limiting membrane; C, diplosome in a 
cone cell; F, fiber growing out from the cone diplo- 
some; R, diplosome in a rod visual cell. (Seefelder.) 
X 1000. 662 
THE EYE 
four to five times as stout as that of the rod cell. These processes carry 
apically a diplosome, surrounded by a lighter cytoplasmic halo. From each 
member of the diplosome a fiber-process grows out, the one passing towards 
the elongating distal, the other towards the proximal, pole of the cell. The 
distal process thus becomes enveloped by an extension of the cell cytoplasm, 
the two constituents, fiber and investing cytoplasm, uniting in the forma- 
Fig. 561.-Two Early Stages in the Development of the Rod and Cone 
Visual Cells in the Chick. 
A, from 12-day embryo, showing the visual cell buds containing mitochondria; 
L.e., external limiting membrane; C.V., visual cell; R.e., external reticular layer; 
C.p., bipolar cells; B, from 1-day-old chick, showing two complete rods and one 
cone, both elements containing a large lipoid spherule (<7) and mitochondria. The 
cone contains an ellipsoid (A); seg. int., internal segment; seg. ext., external segment. 
(Leplat.) X about 2000. 
tion of the outer segment of the rods and cones. Seefelder ("Atlas zum 
Entwickslungsgeschichte des Menschlichen Anges," Leipzig, 1914) has re- 
cently confirmed the essential points in the earlier descriptions of rod and 
cone differentiation by Leboucq (1909) and by Magiott (1910). Leplat 
(Anat. Anz., 45, 8, 1913) has investigated the role of the mitochondria in 
connection with this process. He desbribes the migration of the 'plasto- 
somes' into the external segment where they become chemically altered 
and disappear as such in their contribution to the homogeneous cytoplasmic 
sheath of the centrosomal filament of the external segment. Leplat inclines 
to regard the transverse striation of this segment and its cleavage into THE INTERNAL COAT-THE NERVOUS TUNIC 
663 
discs by maceration as the expression of its mode of construction from 
mitochondria. It remains uncertain whether the longitudinal fibrillation 
of the internal segments is likewise the probable result of an arrangement 
of mitochondria in the developing cell; the complete history of these mito- 
chondria has not yet been traced. 
The Inversion of the Retina.-The receptive cells of the vertebrate 
retina exhibit, in contrast to all other neuro-epithelial cells, a reversed 
polarity with respect to the source of their special stimulus, the ether 
waves; the transmitting end of the cells is nearer the source of the light 
than the percipient end. The human retina is appropriately described as 
Visual cell 
Retinal layer 
Pig nent layer 
Infundibulum 
Neural ectoderm 
Neural canal (forebrain) 
Epidermal ectoderm 
Optic cup 
Optic stalk 
Rathke's pouch 
Buccal cavity 
Fig. 562.-Diagram Illustrating Balfour's Theory to Account for the 
Inversion of the Visual Cells of the Vertebrate Retina. 
Transverse section through the head of a hypothetical vertebrate embryo, to 
show the morphological relations of the surfaces of the ectoderm of the integument, 
the neural tube, and the forming retina. In each of these situations a single sense 
cell is indicated. (After Parker, Amer. Nat., 42, 501, 1908.) 
an inverted sense-organ. The most plausible theory yet proposed in ex- 
planation of this inversion of the visual cells seems to be the one outlined 
by Balfour (1881), expressed in terms of the ancestral history of the verte- 
brate eye. (Among the invertebrates an inverted retina is known only in 
certain mollusca, e.g., Pecten, and in certain spiders and the scorpion.) 
'According to this view the vertebrate retina originated on the outer sur- 
face of the ancestral vertebrate in much the way that the eyes of many 
invertebrates have been produced. The primitive retinas thus formed 
were implanted in that portion of the surface of the animal from which 
the central nervous system was destined to develop, and when this was 
infolded these retinas were carried in with it and came thus to be involved 
in the central organ. If the morphological position of a sensory cell, such 
as may have existed in the primitive external retina, is supposed to have 
been thus retained as this organ was carried from its superficial location 
into the central nervous system and out again almost to the external sur- 664 
THE EYE 
face, the resulting retina would be composed of inverted elements (Fig. 
562). Thus this theory at once offers an explanation for the two most 
striking features of the vertebrate retina, namely, its formation as an 
apparent outgrowth from the central nervous system and the inverted con- 
dition of its receptive cells' (Parker). The difficulties of this theory are 
discussed, and an alternative 
theory, based upon the direc- 
tion eyes of Amphioxus, is 
presented by G. H. Parker 
(Amer. Nat., 42, 501, 1908). 
The Optic Nerve 
The optic nerve is a 
large nerve trunk, com- 
posed, like the white mat- 
ter of the brain of which it 
is an ontogenetic portion, 
of medullated nerve fibers 
without a neurolemma, sup- 
ported by a neurogliar net- 
work containing long-rayed 
astrocytes. It receives an 
investing sheath from each 
of the cerebral membranes, 
septa from the pia mater 
enveloping the several funi- 
culi. These sheaths are 
continued as far forward 
as the eyeball, at which 
point they become contin- 
uous with the sclera. 
Though the choroid corre- 
sponds to the pia mater, the 
two are not apparently in 
direct continuity. 
Lying in the axis of the 
nerve, the arteria centralis 
retvnce with its accompany- 
ing vein enters the eye and 
appears on the inner sur- 
Fig. 563.-Entrance of the Optic Nerve. 
ak, outer granular layer of the retina; ch, choroid coat; d, sclera; ds, dural sheath; e, depressed center of the optic 
papilla,/, fovea centralis; g, layer of ganglion cells; gf, blood-vessels; ik, inner granular layer; ler, lamina cribrosa; 
n, nerve fiber layer; p, pigment layer; ps, pial sheath; sn, funiculi of optic nerve fibers. X 17. (After Kolliker.) THE OCULAR CONTENTS 
665 
face of the retina at the porus opticus (physiologic excavation; optic 
disk) in the center of the optic papilla. Here it divides, its two branches 
at first pursuing a meridional course between the hyaloid membrane and 
the retinal surface; soon they pierce the latter to supply the cerebral 
portion of the retina. No vessels penetrate the neuro-epithelial portion 
of the retinal layers; these are nourished by the choroid. The -vena cen- 
tralis retince pursues a course exactly similar to that of the artery. 
The Ora Serrata 
At the ora serrata (Fig. 538) the typical layers of the retina, already 
much thinned, abruptly cease. The first elements to disappear are the 
rods and cones; the cones, which become much shorter, practically lacking 
the outer segment, extend farther toward the ora than the rods. The 
remaining layers are continued forward only as the double layer of 
epithelial cells belonging to the pars ciliaris retinae, the inner stratum 
of which appears to be analogous to and continuous with the cerebral 
portion of the retina, apparently the sustentacular cells; while the outer, 
deeply pigmented layer apparently represents the pigmented layer of the 
retina. For some distance toward the ora serrata, the retina becomes 
modified by the presence of large vacuoles, probably lymph spaces. 
THE OCULAR CONTENTS 
Within the ocular globe, whose walls are formed by the three coats 
of the eye, are certain structures which may be collectively considered as 
its contents. They are : 
1. The aqueous humor. 
2. The crystalline lens. 
3. The vitreous humor. 
4. The hyaloid membrane. 
5. The suspensory ligament. 
The Aqueous Humor 
The aqueous humor is a fluid, closely allied to lymph, which occupies 
the anterior and posterior chambers of the eye. Microscopically it is 
structureless. Occasional leukocytes, migrants from adjacent lymph 
channels, may be encountered. 666 
THE EYE 
The Crystalline Lens 
The crystalline lens with its suspensory ligament forms a sort of 
diaphragm which separates the ocular cavity into two compartments, 
of which the anterior is occupied by the aqueous humor, the posterior 
by the vitreous humor. 
The lens is a biconvex transparent body having a somewhat greater 
convexity on its posterior than on its anterior surface; its curvature 
is greater at its margin than toward its center. It has a transverse 
diameter of from 8 mm. to 9 mm., and an anteroposterior diameter of 
from 3.5 mm. to 4 mm. according to the degree of accommodation. It 
consists of a capsule, epithelium, and a substantia lentis. 
The capsule of the lens is a homogeneous membrane which covers 
its entire surface and receives the attachment of the suspensory liga- 
ment. It presents faint meridional striations and may sometimes be 
separated into several lamellae (Berger, 1893) ; this lamellation may be 
purely artificial, but appears to be somewhat dependent upon the attach- 
ment of the fibers of the suspensory ligament to the surface of the 
lenticular capsule. 
The capsule is about twice as thick over the anterior as over the 
posterior surface of the lens. On the former surface it is in relation 
with the lenticular epithelium, but on the posterior surface the capsule 
rests directly upon the substantia lentis. The anterior surface of the 
capsule is in gentle contact with the free margin of the iris. 
The lenticular epithelium consists of a single layer of cells which 
covers the entire anterior convexity of the lens, extending as far back as 
its equator. The height of these cells varies with the age of the indi- 
vidual. In fetal life they are distinctly columnar, in youth short colum- 
nar or cuboidal, in adult life low cuboidal or flattened. Toward the mar- 
gin of the lens the epithelial cells become progressively lengthened, and 
at its equator are transformed directly into the fibers of the lenticular 
substance. This definitive structure of the lens recalls its manner of 
development from the original lens vesicle; the hollow vesicle becomes 
solid by the elongation of the cells of the posterior wall. 
The substantia lentis is, therefore, the product of the epithelium 
of the lens, whose cells become greatly elongated to form slender hexag- 
onal prisms, known as the lens fibers. When it is first formed each 
prism exhibits a nucleus which persists for some time, but gradually 
disappears as in the process of growth the older fibers become farther 
and farther removed from their source of nutrition, the lymph and the THE OCULAR CONTENTS 
667 
aqueous humor in which the surface of the lens is bathed. This change 
is accompanied by a hardening or cornification and slight shrinkage 
of the lens fibers, so that those prisms which come to occupy the center 
of the lens form a dense, hard mass of non-nucleated fibrous cells with 
faintly serrated margins; the peripheral fibers retain their smooth edges 
and their nuclei, and form a protoplasmic mass of much softer con- 
sistency. The hardened central mass is 
the so-called nucleus of the lens. Any 
opacity of the lens or its capsule is known 
as a cataract. 
The nuclei of the lens fibers remain in 
the neighborhood of the equator, where 
they are first formed, and are thus con- 
tained within a narrow, superficial, equa- 
torial zone, the nuclear zone. 
Each lens fiber is disposed along a 
meridian of the lens, and extends from 
its anterior to its posterior hemisphere; 
the fibers are so arranged that they abut 
upon one another, end to end, along V- 
shaped lines which radiate from either 
pole. This union is often quite firm, and 
thus are formed long fibrous bands which 
can be traced from the anterior to the 
posterior hemispheres of the lens. These 
bands are distributed in a peculiar man- 
ner. Near each pole along the line of 
abutment, the band may be said to bend 
upon itself with a sharp curve-making 
an angle of about 60 degrees-whose convexity is directed toward the pole, 
the parallel fibers being so arranged as to form a sector whose apex is 
also directed toward the pole. The corresponding sectors of opposite 
poles overlap one another so that the fibrous bands are continued from 
one side of one polar mass to the reverse side of the overlapping sector 
and so back, on the farther side, to the adjacent sector of the former 
hemisphere. By teasing, fibrous bands can sometimes be traced suc- 
cessively through all of the polar sectors and thus back to a sector be- 
neath that from which the start was made. Obviously no individual 
lens fiber is of sufficient length to extend from pole to pole of the 
lens. 
Fig. 564.-Lens Fibers. 
1, in profile, from the crystal- 
line lens of the ox's eye; 2, in 
transection, from the human crys- 
talline lens. X 350. (After 
Kolliker.) 668 
THE EYE 
The polar figures formed by the lines of terminal union of the lens 
fibers are known as lens starts; these are at first three-rayed, but later 
become six- and even nine-rayed. 
During the earlier stages of the development the lens is invested 
Fig. 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. 
a, lens fibers; b, lenticular epithelium; c, capsule of the lens; d, suspensory liga- 
ment. Hematein and eosin. X 273. 
by a delicate vascular membrane, the tunica vasculosa lentis (designated 
pupillary membrane in front), supplied by the hyaloid artery continued 
from the central artery of the retina. This tunic normally disappears 
before birth; its atypical persistence in whole or in part seriously inter- 
feres with vision. THE OCULAR CONTENTS 
669 
The Vitreous Humor 
The vitreous humor {vitreous body) is a soft jelly-like mass which 
fills the entire cavity of the eye behind the line of the ora serrata and 
crystalline lens. About 98 per cent, of its composition is water. It is 
completely invested by the hyaloid membrane. Its anterior excavation 
which holds the posterior convexity of the lens is known as the hyaloid 
or patellar fossa. The vitreous humor appears to be a peculiarly deli- 
cate form of very loose gelatinous connective tissue whose scanty fibers 
present a somewhat concentrically lamellated arrangement and are so 
very delicate as to be recognized under ordinary conditions only with the 
greatest difficulty. 
Occasionally stellate and fusiform cells, remarkable for their large 
vacuoles and varicose processes, have been'demonstrated in small num- 
bers within the vitreous body. Small rounded cells somewhat resembling 
leukocytes are also found, but for the most part they are flattened against 
the hyaloid membrane; they occur in very limited numbers. 
These various cells, as well as occasional filamentous remnants of 
the original mesenchymal constituents of the vitreous humor, may cast 
shadows upon the retina within the visual field. Such shadows, called 
muscce volitantes, on account of their 'flitting' motion when the eyes 
are moved, are seen when looking at a bright light, or frequently in 
looking through the microscope. In advanced age crystals may form 
in the vitreous which are observed to settle to the bottom of the eye 
when the eyes are held still. 
The Hyaloid Membrane 
The hyaloid membrane is a very thin structure which surrounds the 
vitreous humor and unites it to the inner surface of the retina and the 
crystalline lens. It consists of delicate glassy fibers so disposed as to 
form an extremely thin reticular membrane. It passes forward over the 
inner surface of the retina, to which it is loosely united, until at the ora 
serrata its fibers leave the retinal surface and pass inward to the margin 
of the lens to become inserted into the lenticular capsule. 
The Suspensory Ligament 
(Zonula Ciliaris) 
Certain fibers from the hyaloid membrane pass forward from the 
ora serrata and are firmly adherent to the ciliary processes, or become 670 
THE EYE 
attached in the grooves between the processes. From the sides of these 
processes fibers diverge at frequent intervals and pass to the margin 
of the lens, where they are attached on either side of the equator, spread- 
ing over a zone which is somewhat narrower posteriorly than anteriorly. 
These fibers form the suspensory ligament of the crystalline lens (Figs. 
543 and 565). They occupy an annular zone which is included between 
the ciliary processes and the margin of the lens, and which is known 
as the zonula ciliaris (of Zinn). 
The glassy fibers of this ligament take origin from the sides of the 
ciliary processes along which they are firmly attached, becoming free only 
near the apices of these processes. They pass thence to the margin of 
the lens and spread out upon the surface of the capsule to which they 
are intimately adherent. The fibers arising more posteriorly are said 
to be attached to the lens anteriorly to the equator, those arising from 
the more anterior ciliary processes becoming attached posteriorly to the 
equator of the lens. 
The most anterior of these fibers form a somewhat plicated but in- 
complete membrane which serves as the anterior boundary of an annular 
series of connecting lymphatic spaces collectively forming the spatia 
zonularis (canals of Petit). This irregularly sacculated, annular canal 
is bounded posteriorly by the hyaloid membrane, anteriorly by the in- 
complete membranous wall of the posterior chamber through which the 
aqueous humor readily diffuses, internally by the margin of the crystal- 
line lens, and antero-externally by the ciliary processes. Besides sup- 
porting the lens, the suspensory ligament assists in the accommodation 
of the lens to far and near vision, a process involving a change of con- 
vexity, and dependent upon the activity of the ciliary muscle. 
BLOOD-VESSELS OF THE EYE 
The circulation of blood in the globe of the eye is maintained through 
four sets of vessels: 
1. The arteria and vena centralis retinae. 
2. The short ciliary arteries and venae vorticosse. 
3. The long ciliary arteries. 
4. The anterior ciliary arteries and veins. 
1. The arteria centralis, destined for the supply of the retina, en- 
ters the optic nerve about midway between the optic commissure and 
the ocular globe, and arriving at the center of the nerve runs in its axis BLOOD-VESSELS OF THE EYE 
671 
to the papilla optica, 
at which point it 
divides into two 
branches, an inferior 
and a superior branch, 
which, by rapid dicho- 
tomous division, radi- 
ate from the optic 
papilla to all parts of 
the retinal surface, 
thereby forming a 
plexus of small ar- 
teries within the 
nerve fiber and gan- 
glion cell layers. 
From this plexus ca- 
pillaries are distrib- 
uted to all the cere- 
bral layers of the re- 
tina. No blood-vessels 
are found within the 
neuro-epithelial lay- 
ers. The retinal ar- 
teries, like those of 
the brain, do not anas- 
tomose with one an- 
other ; they are ter- 
minal arteries. 
The retinal veins 
follow a course exact- 
ly similar to that of 
Fig. 566.-Schematic Representation of the Intrinsic Blood-Vessels of 
the Eye. 
Arteries in outline, veins in solid black. A, choroid; a, central artery, and vein 
of the retina; B, conjunctiva; b, retinal arteries; b1; retinal veins; c, c, short ciliary 
arteries; d, long ciliary artery; e, e„ anterior ciliary arteries and veins; f, chorio- 
capillaris; g, capillaries of the ciliary body; H, cornea; h, circulus major of the 
iridal arteries; i, arteries, and ii, veins of the iris; k, circulus minor of the iridal 
arteries; L, crystalline lens; I, venae vorticosse; m, anastomosis of ciliary and an- 
terior ciliary veins; N, retina; n, canal of Schlemm; 0, optic nerve; o, posterior 
conjunctival artery, and Oi, vein; p, anterior conjunctival vessels; q, vascular loops 
at the margin of the cornea; R, internal rectus muscle; S, sheath of the optic nerve; 
Sc, sclera. (After Leber.) 672 
THE EYE 
the arteries; they converge to form a single efferent vessel, the vena cen- 
tralis retinas. The retinal veins are peculiar in that their walls contain 
no muscle. The optic nerve is supplied with small branches from the 
arteria and vena centralis retinae in their passage through its substance. 
In the fetus a small branch, the hyaloid artery, apparently the 
direct continuation of the arteria centralis retinas, passes forward through 
the vitreous humor to the posterior surface of the lens, whence capillary 
vessels pass around the margin of the lens and are connected with the 
anterior ciliary vessels at the margin of the iris. The hyaloid artery 
supplies blood to the fetal tunica vasculosa lentis for the nutrition of 
the developing lens. Before birth these vessels disappear; the hyaloid 
artery remains for a time as a delicate fibrous strand, occupying the 
persistent canalis hyaloideus or canal of Stilling, which lies almost in 
the visual axis and extends from the papilla optica to the posterior 
surface of the lens. The hyaloid canal (also called the canal of Cloquet) 
establishes a channel between the aqueous humor and the lymphatic 
spaces of the retina. In adult life both the vitreous humor and the 
crystalline lens are bloodless tissues. 
2. The short ciliary arteries, twelve to fifteen in number, enter 
the globe of the eye in a circle (circle of Zinn} which surrounds the 
optic nerve. They supply branches to the meningeal sheaths of the optic 
nerve and to the sclera, their main stems penetrating this coat to enter 
the choroid. Here they subdivide to form the plexus of arteries in the 
lamina vasculosa from which the vessels of the choriocapillaris are 
supplied. The capillaries of the last-named layer unite to form small 
venous radicals which converge toward the equator of the eye, where they 
unite in a whorl-like manner to form the four or five vence vorticosce, 
which pass obliquely backward through the sclera, receiving additional 
branches from this coat, and finally emerging from the eye to empty 
into the ophthalmic vein. 
The vessels of the choroid communicate posteriorly with those of 
the optic nerve, and anteriorly, by a free anastomosis, with those of 
the ciliary processes. 
3. The long ciliary arteries, two in number, enter peripherally at 
the circle of Zinn on either side of the optic nerve, and pass horizontally 
forward upon the outer surface of the choroid to the ciliary muscle. 
Near the base of the iris they divide, and by anastomosis with each 
other and with the anterior ciliary arteries form a vascular circle, the 
circulus major, about the base of the iris. 
From this circle recurrent branches supply the ciliary body and 673 
THE LYMPHATIC SYSTEMS OF THE EYE 
anastomose with the vessels of the choroid; other branches pass into 
the iris and, converging toward the visual axis form, just outside the 
pupillary margin, a second circle of anastomosis, the cir cuius minor. 
The veins of the iris and ciliary body follow closely the distribution 
of the arteries, the greater portion of their blood returning through 
the veins of the choroid and the venae vorticosae. Some, however, is 
returned by means of anastomoses with the anterior ciliary veins. 
4. The anterior ciliary arteries, derived from the muscular and 
lacrimal branches of the ophthalmic, distribute branches to the con- 
junctiva and sclera, and within the latter membrane, about 2 mm. outside 
of the corneal margin, pass to the circulus iridis major and partially 
supply the iris and ciliary body as already described. 
The anterior ciliary veins follow the course of the corresponding 
arteries. They empty into the vessels of the ocular conjunctiva. 
THE LYMPHATIC SYSTEMS OF THE EYE 
The lymphatic systems of the eye include very few true lymphatic 
vessels, but consist rather of a series of channels which may be arbitrarily 
considered as an anterior and a posterior set of intercommunicating 
spaces. The former set includes the lymphatic spaces of the cornea, 
the spaces of Fontana, the anterior and posterior chambers, the lymphatic 
clefts of the ciliary muscle and iris, and the zonular spaces or canals of 
Petit. The posterior set includes the subdural and subarachnoid spaces 
in the sheath of the optic nerve, the capsule of Tenon, the lymphatic 
spaces of the lamina suprachoroidea, the perivascular spaces of the 
choroid and retina, the irregular clefts between the pigmentary and 
bacillary layers of the retina, the similar clefts of the ganglion cell 
layer, the lymphatic spaces of the hyaloid membrane, the hyaloid canal, 
and the interstices of the vitreous humor. 
These two sets of lymphatic channels communicate with each other 
by means of the perivascular spaces of the two outer tunics, as well as 
through that portion of the hyaloid membrane which forms the posterior 
wall of the spatia zonularis, through the clefts of which and the hyaloid 
canal the lymph of the vitreous body communicates freely with the 
aqueous humor of the spatia zonularis and posterior chamber. Conse- 
quently, if the cornea be penetrated either accidentally or otherwise, 
and the anterior and posterior chambers be emptied, their aqueous 
humor is rapidly replaced, not only from the adjacent spaces of the 674 
THE EYE 
anterior set of lymphatic vessels, but from the vitreous humor and 
posterior set as well. 
It is also important to note that the posterior set of lymphatic 
spaces is directly connected through the meningeal sheaths of the optic 
nerve with the subdural and subarachnoid spaces of the cerebral 
meninges. 
THE NERVES OF THE EYE 
The nerves of the eye, in addition to the optic, are the long and 
short ciliary branches of the ophthalmic nerve. The former, two or 
three in number, and the latter, six to ten, after supplying a vasomotor 
branch to the arteria centralis retinae, pierce the sclera in company with 
the corresponding ciliary arteries and pass meridionally forward on the 
inner surface of the sclera, supplying branches to this tunic and to the 
vessels of the choroid, and finally reaching the ciliary muscle, where 
their branches form an annular plexus containing a few ganglion cells. 
From this plexus fibrils are supplied to the blood-vessels and mus- 
cular tissues of the ciliary body and iris, and to the cornea. The corneal 
branches pass to the annular plexus at the sclerocorneal junction, whence 
they are distributed to the corneal tissues, as already described (page 
633). 
APPENDAGES OF THE EYE 
The appendages of the eye include the eyelids, conjunctiva, and 
lacrimal glands. 
The Eyelids 
The eyelids are developed in the embryo through an invagination of 
the skin, which, leaving a slit-like aperture (the palpebral fissure) 
between its involuted margins, covers the inner surface of the lid to 
form the palpebral conjunctiva, and is reflected over the globe of the 
eye as the ocular conjunctiva and anterior corneal epithelium. 
The lids, therefore, may be said to consist of two membranous por- 
tions, the cutaneous (outer or anterior) and the conjunctival (inner or 
posterior). Between these two portions the orbicularis palpebrarum 
forms a septum of striated muscle fibers. 
The cutaneous portion of the eyelid differs from other portions APPENDAGES OF THE EYE 
675 
of the skin only in that its subcutaneous tissue contains no fat. The 
derma is loosely connected with the muscle by . a wide-meshed areolar 
tissue. Fine hairs are distributed over the cutaneous surface, their 
follicles extending well down through the derma. Small sebaceous 
a, sweat glands; ai, primary tarsal arch; as, secondary tarsal arch; b, conjuncti- 
val epithelium; c, eyelashes; co, rugated portion of the conjunctiva; d, epidermis; 
e, fine hairs; j, process of the levator palpebrse superioris which is inserted into the 
skin; g, Meibomian gland; h, internal angle of the margin of the fid; I, levator palpe- 
brae superioris; m, duct of a Meibomian gland; o, orbicularis palpebrarum muscle; 
p, superior palpebral muscle of Muller; r, ciliary muscle of Riolan; s, glands of 
Moll; t, fibrous tissue of the tarsus; v, external angle of the margin of the fid; w, 
posterior tarsal glands; z, sebaceous glands. (After Fuchs.) 
Fig. 567.-Vertical Section through the Upper Eyelid 676 
THE EYE 
glands open into the hair follicles and occasional sudoriparous glands 
pour their secretion upon the epidermal surface. 
At the margin of the lid its cutaneous portion is reflected inward, 
and at its inner angle becomes directly continuous with the palpebral 
conjunctiva. The free margin of the lid presents, therefore, an outer 
angle, an inner angle, and an intermediate surface. 
Two or three rows of large stiff hairs, the eyelashes or cilia, project 
from the outer angle, and large sebaceous glands open into their follicles. 
Other smaller sebaceous glands open directly upon the free surface. 
These sebaceous glands are sometimes called the glands of Zeiss. 
The intermediate surface of the margin of the lid retains the char- 
acter of the skin, though no hairs are found in this portion. Peculiar 
sweat glands, the glands of Moll, occur in the derma of this part. 
At the inner angle of the lid the epidermis abruptly changes its char- 
acter to that of the conjunctiva, the derma of the cutaneous surface 
being continuous with the submucous connective tissue of this membrane. 
At the inner angle also, are the openings of the peculiar large sebaceous 
glands, the tarsal glands (of Meibom), their orifices forming a con- 
tinuous punctate row of pores barely visible to the naked eye. 
The tarsal (Meibomian) glands are long compound saccular 
glands, about thirty in the upper, and about twenty in the low'er lid, 
whose secreting saccules open into a common, axially placed duct which 
extends the whole length of the gland. Each saccule is filled with cells 
in various stages of fatty degeneration and is exactly similar in structure 
to the saccules of the ordinary sebaceous glands. The glands are em- 
bedded in the connective tissue of the conjunctiva and are so large as 
to form projecting ridges on its surface, which are disposed in vertical 
lines radiating from the row of glandular orifices at the margin of the 
lid. At their blind extremities the glands are often slightly bent or 
curved upon themselves, and this portion is embedded in a dense mass 
of fibrous tissue known as the tarsus. 
The tarsus in each eyelid forms a very dense plate-like mass of areolar 
connective tissue which is so dense and resistant as to erroneously 
suggest a cartilaginous structure. It is inserted between the conjunctiva 
and the orbicularis muscle. It is thickest toward the free margin of 
the lid, but becomes progressively thinner in the opposite direction, until, 
as a mere fibrous membrane, the palpebral fascia, it is continued to the 
margin of the orbit. 
The conjunctival portion of the lids, the palpebral conjunctiva, 
consists of a peculiar stratified epithelium and a thin connective tissue APPENDAGES OF THE EYE 
677 
corium. Its epithelium comprises four or five layers of cells, the deeper 
of which are small and spheroidal, and the superficial elongated or coni- 
cal, their blunt ends forming the free surface of the conjunctiva, their 
pointed extremities buried between the cells of the deeper layers. The 
bases of these elongated cells become somewhat expanded and broader 
from the increased tension of the conjunctiva when the lids are closed; 
they retract and become narrower when the lids are separated and the 
conjunctiva relaxed. 
The cells of the superficial layer are often so distinctly elongated 
as to possess a columnar form. They may, however, be spheroidal or 
even somewhat flattened, in which case they very closely resemble the 
ordinary type of stratified squamous epithelium. The epithelial layer 
rests almost directly upon the connective tissue corium, the basement 
membrane being imperfectly developed. 
The corium of the conjunctiva is thin. With the aid of a thin layer 
of submucous areolar tissue it unites the epithelium to the tarsus and 
to the fibers of the orbicularis muscle; near the margin of the lid its 
submucous tissue incloses the Meibomian glands. Opposite the plane 
at which the blind ends of the Meibomian glands are embedded in the 
free margin of the tarsus, the conjunctival surface is thrown into eight 
to twelve horizontal folds, beneath which, in the connective tissue, are 
a few minute tubulo-alveolar glands, the posterior tarsal glands {glands 
of Waldeyer; glands of Henle). Their ducts open upon the free surface 
of the conjunctiva near the fornix conjunctivae. 
At the attached base of the lid a narrow band of smooth muscle ex- 
tends from the levator palpebrae and inferior oblique muscles into the 
body of the lid. These fibers have been described by H. Muller (1858) 
as the superior and inferior palpebral muscle of the upper and lower 
lid, respectively, and have come to be known as the muscle of Muller. 
The fold by which the palpebral conjunctiva is reflected upon the 
globe of the eye to become continuous with the ocular portion of the 
membrane is known as the fornix conjunctiva. The extremely loose 
attachment of the conjunctiva of the fornix to the underlying connective 
tissue and intra-orbital fat permits the great freedom of motion which 
is characteristic of the ocular globe. The small accessory lacrimal glands 
{glands of Krause} open into the margin of the fornix conjunctivae. 
The superior fornix contains from eight to twenty, the inferior from 
two to five. In this region, also, occasional goblet cells occur in the 
superficial layers of the epithelium. 
The ocular conjunctiva is likewise very loosely attached to the sclera. 678 
THE EYE 
The scleral portion of the conjunctiva is nearly identical in structure 
with the palpebral portion already described. Near the margin of the 
cornea the superficial cells of the epithelium become at first spheroidal 
and then, as the cornea is approached, they are progressively flattened, 
so that, just outside of the corneal margin, the conjunctival epithelium 
conforms to the stratified squamous type which forms the anterior epi- 
thelium of the cornea. 
The blood supply of the eyelids is derived from the internal palpe- 
bral artery which furnishes a branch to each lid; these two branches 
anastomose at the external angle 
with the lacrimal branch of the 
ophthalmic, through the external 
palpebral artery. These trans- 
verse arterial vessels (primary 
tarsal arches) lie near the free 
margin of the lids between the 
tarsus and the orbicularis palpe- 
brarum muscle. Each tarsal arch 
sends pre-tar sal twigs forward to 
supply the muscle and integu- 
ment, and post-tarsal twigs back- 
ward to supply the tarsal fascia, 
the tarsal glands and the conjunc- 
tiva. At the basal end of the tar- 
sus, just back of the levator pal- 
pebrae muscle, a second arch (the 
(secondary tarsal arch) may be present, more commonly in the upper 
lid; this second arch represents a larger branch of the palpebral artery, 
and it anastomoses freely with the primary arch. The veins follow an 
essentially similar course. The lymphatics likewise include a pre- and 
post-tarsal set, which unite to form larger tarsal tributaries which drain 
along the facial vein toward the submaxillary lymph nodes. 
The nerve supply includes sensory, motor and sympathetic fibers. 
The main trunks lie between the tarsus and the orbicularis palpebrarum 
muscle. The sympathetic fibers supply the blood-vessels, the smooth 
muscle of Miiller, and the glands. Motor fibers contributed by the facial 
nerve, supply the annular sheet of striped muscle; the oculomotor 
nerve contributes motor fibers to the levator palpebrae muscle. The 
sensory fibers, which are derived from the trigeminal nerve, end in naked 
fibrils among the cells of the external integument and the internal con- 
Fig. 568.-Arterial Supply of the Eye- 
lid. 
(After Fox.) APPENDAGES OF THE EYE 
679 
junctiva, and in the subcutaneous connective tissue and the tarsus. 
Numerous sensory fibrils end also in special end-bulbs, especially along 
the inner margin of the lids; similar endings occur in the palpebral and 
bulbar conjunctiva. 
The Lacrimal Lake 
In the Q -shaped area of the internal canthus, the lacus lacrimalis, 
lies a roughened irregular reddish mass of delicate modified skin, the 
caruncle lacrimalis'). It is embedded in fat and contains 
a number of very delicate hairs, large sebaceous glands and a few sweat 
glands. Where the borders of the lake pass into the palpebral margins 
there appears a slightly raised papilla lacrimalis, each of which contains 
an apical opening, the puncta lacrimalia, leading into the two canaliculi 
lacrirnales, which conduct the excess of lacrimal secretion or tears into 
the nasolacrimal duct. To the outer side of the lacrimal lake there 
appears a vertical crescentic fold of delicate skin, the plica semilunaris, 
which is the homologue of a functional third eyelid (nictitating mem- 
brane) of birds and reptiles. 
The Lacrimal Gland 
The lacrimal glands are two flattened, lobulated, glandular masses 
situated at the upper and outer angle of the orbit, one in relation with 
each eye. They secrete a clear watery fluid, the tears. These glands 
are somewhat molded to conform to the shape of the orbit and the globe 
of the eye, between which they are inserted. 
Each lacrimal gland is a secreting gland of the compound tubular 
type (Marziarski) (Fig. 257, page 258), and consists of eight to twelve 
small lobules which open into the fornix conjunctivae by about as many 
minute ducts. The lobules are aggregated into two fairly distinct 
lobes, separated by a denser fascia, the superior lobe or orbital portion 
and the inferior lobe or palpebral portion, and are united by thin fibrous 
fasciae which contain the larger ducts. 
Each lobule of the gland contains many serum-secreting acini and 
numerous small intralobular ducts. The secreting acini are lined by 
tall, columnar cells, resting upon a thin basement membrane, which 
is supplied with 'basket cells' and is invested with a delicate fibrous 
tunica propria. The appearance of the secreting epithelium differs some- 680 
THE EYE 
what according to its state of activity. After a period of rest, and 
in the ordinary condition of relative inactivity, the epithelium becomes 
distended with secretion and is either clear in appearance or at most 
is only very finely granular, the nuclei are crowded to the base of the 
swollen cells, and the lumen of the acinus is very small. After a period 
of excessive activity the secreting cells become shrunken and more dis- 
Fig. 569.-Section through a Lobule of the Lacrimal Gland of Man. 
a, small duct branching within the lobule; b, intercalary ducts; c, connective 
tissue; f, fat cells. A, transection of an interlobular duct. Hematoxylin and eosin. 
X 112. (After Kolliker.) 
tinctly granular, and the lumen of the acinus appears much dilated. 
The secreting acini empty into narrow intercalated ducts which lie 
within the lobule, have a considerable lumen, and are lined by tall 
columnar cells resting upon a second incomplete layer of small, some- 
what flattened basket cells. 
These intralobular ducts unite at the margin of the lobule to form 
the larger interlobular ducts, which are contained in the interlobular 
connective tissue. Here the duct is lined by low columnar or even 
somewhat flattened cells, at first disposed in a single, but later in a APPENDAGES OF THE EYE 
681 
double layer. As the duct approaches the conjunctival surface the 
number of cell layers increases until their lining epithelium finally 
conies to resemble 
the stratified epi- 
thelium of the con- 
junctiva with which 
it is continuous. 
Minute collec- 
tions of diffuse 
lymphoid tissue 
and even small 
lymph nodules are 
occasionally found 
just beneath the 
epithelium of t h e 
conjunctiva in the 
neighborhood of the 
lacrimal glands of 
the fornix; occa- 
sionally the lym- 
phoid tissue is 
quite abundant. 
In animals pos- 
sessing a membrana 
nictitans ('third 
lid') a small, mu- 
cus-secreting gland 
occurs at the inner 
angle of the orbit; 
this is known as the 
gland of Harder. 
It is well developed 
also in some mam- 
mals, e.g., rabbit, 
but in man and 
other primates it is 
usually absent, though in an extremely vestigial condition it may occa- 
sionally be found within the basal portion of the plica semilunaris. 
Fig. 570.-Portions of Two Adjacent Lobules of the 
Lacrimal Gland of the Rabbit, Showing Two Stages 
in Secretory Activity of the Tubules. 
In the upper lobule the cells are filled with minute, in 
the lower lobule with large, secretion spherules. CHAPTER XIX 
THE EAR 
This organ may be subdivided for description into the external, 
the middle, and the internal ear. The first two portions serve for the 
collection and transmission of sound waves, the last for the transforma- 
tion of the sound waves into nerve stimuli which are then transmitted 
through the path of the auditory nerve to the cerebrum. 
THE EXTERNAL EAR 
The external ear includes an auricular or free portion and an ex- 
ternal acoustic (auditory) meatus. 
The Auricle 
The auricle, or pinna, contains a thin cartilaginous plate of peculiar 
form which is covered on both sides by the skin. The cartilage is of 
the elastic variety, but differs from the similar cartilages of other parts 
in the abundance of its large cartilage celjs; in occasional areas the 
elastic reticulum is deficient. This reticulum is closely connected with 
the fibrous perichondrium, beneath which it forms a complete layer. 
The extrinsic muscles of the ear are inserted into the perichondrium 
and the fibrous tissue by which it is surrounded. 
The skin of the external ear does not essentially differ from that 
of other parts. It is supplied with fine hairs and with many large 
sebaceous glands; sweat glands also occur on the outer surface. The 
derma is united to the underlying cartilage by connective tissue; on 
the concave surface this union is very firm and permits but little motion. 
The subcutaneous tissue, except in the lobule, contains but little fat. 
The lobule does not contain cartilage. 
682 THE EXTERNAL EAR 
683 
The External Acoustic Meatus 
The external acoustic meatus (or auditory canal) is divisible into 
an outer cartilaginous and an inner bony portion; the walls of the two 
Fig. 571.-Transection of the Lobule of the External Ear of an Infant. 
a, cartilage; b, skin; c, adipose connective tissue. Hematein and eosin. Photo. 
X 20. 
portions, except for this difference, are quite similar in structure. The 
cartilage is continuous with that of the auricle, and is of the cellular 
elastic variety. The skin of this portion contains large stiff hairs and 
both sebaceous and ceruminous glands. The former, as in the auricle, 684 
THE EAR 
open either upon the free surface of the skin or into the adjacent portion 
of the hair follicles. 
The Ceruminous Glands 
The ceruminous glands resemble in structure the sweat glands of 
other portions. They are coiled tubular glands which open upon the 
surface of the skin by means of a narrow duct. The coils of their se- 
creting portion are lined by columnar cells with spheroidal, basally 
Fig. 572.-From the External Acoustic Meatus of Man. 
a, sebaceous gland; b, ceruminous gland; c, cartilage. Hematoxylin and eosin. 
X 15. (After Sobotta.) 
situated nuclei and a clear cytoplasm containing many small brownish 
granules of pigment and a few fatty particles. The cytoplasm is often 
diffusely colored by the brownish pigment. Between the lining cells 
and the basement membrane appear slender fusiform elements re- 
sembling similarly placed elements in the sweat glands, and likewise 
interpreted as muscle cells. The secretion of these glands, the cerumen, 
in addition to the pigmented and fatty secretion of the glands, contains THE MIDDLE EAR 
685 
sebum, desquamated epithelial cells and occasional fine hairs, together 
with foreign particles of a very varied sort. 
In the bony portion of the meatus the corium or derma is firmly 
adherent to the periosteum of the bone, and all the layers of the skin 
are much reduced in thickness. The scanty hairs are very fine, and, 
with the glands, are continued inward to the tympanic membrane only 
in the superior portion of the wall of the canal. Papillae are present 
as far as the margin of the tympanic membrane. Upon the surface of 
this membrane, which closes the inner end of the external acoustic 
meatus and separates it from the cavity of the middle ear, the skin is 
reduced to an extremely thin cutaneous coat, devoid of hairs, glands, 
and papillae. 
THE MIDDLE EAR 
General Considerations 
The middle ear or tympanum ('ear-drum') is an irregular cavity, 
broad above and behind, narrow below and in front, which lies just 
within the external acoustic meatus. Its outer wall is largely formed 
by the tympanic or drum membrane, its inner by the osseous wall of the 
internal ear. 
The contour of the tympanum is very irregular, its cavity being 
encroached upon by numerous bony elevations which are most pro- 
nounced on its internal wall. Externally the tympanic membrane is 
attached to a bony and fibrocartilaginous ring, the annulus tympanicus, 
which projects somewhat into the tympanic cavity. In front, the orifice 
of the auditory (Eustachian) tube is marked by a slight cartilaginous 
projection near the floor of the cavity. 
Above and behind, the tympanic cavity is prolonged into a deep 
recess, the epitympanic cavity, in the upper part of whose posterior 
wall are the orifices of the mastoid cells. The upper portion of the 
cavity contains the rounded heads of the malleus and incus, the two 
largest of the auditory ossicles. The internal wall of the tympanum 
presents anteriorly a bulging prominence which is known as the promon- 
tory, and which indicates the position of the first or broadest turn of 
the spiral canal of the cochlea. Beneath this prominence is a recess 
leading to a bony 'window,' the fenestra cochlea (or fenestra rotunda), 
which, in life, is closed by a delicate membrane, the secondary tympanic 
membrane. Behind the promontory and at a slightly higher level a 686 
THE EAR 
deep recess, the pelvis ovalis, leads inward to the fenestra vestibuli (or 
fenestra ovalis), which is closed by the base of the stapes; the body of 
this ossicle is contained entirely within the pelvic recess, and near its 
mouth the stapes articulates with the orbicular extremity of the long 
process of the incus. The superior portion of this deep recess is en- 
croached upon by the projecting wall of the aqueductus Fallopii which 
transmits the facial nerve, and posteriorly, near the point where it 
merges with the general tympanic cavity, a low, conical, bony projection 
known as the pyramid transmits the stapedius muscle. The canal of the 
tensor tympani muscle contained within a still more prominent, conical, 
bony projection, the processus cochleariformis, is found near the antero- 
internal angle of the tympanic cavity just above and parallel to the 
auditory tube. The narrowest portion of the tympanum is, perhaps, 
almost its very center, and is included between the promontory on 
the inner and the tympanic membrane on the outer side. Extending 
from this narrowed central portion upward, backward, and inward, are 
expanded recesses which are partially occupied by the three auditory 
ossicles; the remaining portions of the tympanum are filled by air which 
gains access to the cavity through the auditory tube. 
The Tympanic Mucosa 
The tympanic mucosa consists of a thin but dense tunica propria 
which is firmly attached to the underlying periosteum and softer parts 
by loose connective tissue, and is clothed with a layer of flattened ento- 
dermal epithelium, which, in the vicinity of the origin of the auditory 
tube, is of low columnar form and is provided with cilia, but in most 
other portions of the tympanum is squamous in character and of the 
tessellated type, closely resembling endothelium. The floor of the tym- 
panum and the lower portions of its anterior, internal, and posterior 
walls also possess a partial clothing of low ciliated cells (Kessel). Occa- 
sional gland-like folds of the mucosa occur near the orifice of the audi- 
tory tube, though the true glandular character of these folds is very 
questionable. 
The Mastoid Cells 
The mastoid cells (cellules mastoidees seu pneumaticcs) are numer- 
ous small spaces situated within the mastoid process of the temporal 
bone; they are lined by a continuation of the tympanic mucosa, which 
is everywhere clothed by flattened epithelium. The corium is closely 
attached to the periosteum of the bony wall, the periosteum also serving THE MIDDLE EAR 
687 
as a vascular layer of the mucosa in the mastoid cells, as well as in 
the general tympanic cavity. 
The Tympanic Membrane 
The tympanic membrane is a 
thin delicate partition which is 
formed by a reflection of the 
cutaneous layer of the external 
acoustic meatus on the one hand, 
the tympanic mucosa on the 
other, and between these two 
membranes a layer of dense fi- 
brous tissue whose tendinous 
bands are disposed in radial and 
circular directions. The margin 
of the tympanic membrane is in- 
serted into a fibrocartilaginous 
ring which rests upon a bony ele- 
vation, the annulus tympanicus. 
The slender manubrium or 
handle of the malleus projects 
from the superior margin of the 
ring and is inserted between the 
folds of the tympanic membrane, 
extending downward to about the 
center of the membrane, at which 
point is the deepest part of its 
concavity, its umbo. The bony 
handle of the malleus, lying be- 
tween the cutaneous and mucous 
layers of the tympanic membrane, 
is covered by a thin cartilaginous 
layer, and receives the insertions 
of the tendinous fibers. These 
fibers are divisible into an outer 
radial layer which extends from 
the fibrocartilaginous ring at the 
periphery inward to the manubrium mallei, and an inner circular layer 
whose thickest portions are found close to the manubrium and near the 
Fig. 573.-Transection of the Tym- 
panic Membrane of a Child. 
a, a', fibrocartilaginous ring; b, b', bone; 
c, c', skin of the external acoustic meatus; 
d, d', tympanic mucosa; e, cutaneous layer 
of the tympanic membrane; f, fibrous 
layer, obliquely cut at g, layer derived 
from the tympanic mucosa; h, handle of 
the malleus; i, blood-vessels. Hematoxy- 
lin and eosin. X 11. (After Kolliker.) 688 
THE EAR 
periphery of the membrane; between these points the circular layer of 
fibers is partially or entirely deficient. Just within the fibrocartilagi- 
nous ring at the periphery 
of the membrane the cir- 
cular layer of fibers 
abruptly ends. 
The cutaneous layer 
of the tympanic membrane 
forms a very thin coat, its 
epidermis consisting of a 
germinal layer one or two 
cells deep, which is cov- 
ered by several flattened 
non-nucleated cells of the 
horny portion. The derma 
or coriuni is very thin, 
contains no papillae, and 
is intimately adherent to 
the fibrous layers of the 
membrane; it contains 
neither glands nor hairs. 
The mucous layer of 
the tympanic membrane 
is even thinner than the 
cutaneous. It consists of 
a flattened entodermal 
epithelium which rests al- 
most directly upon the 
layer of circular fibers. 
A few connective tissue 
fibers pass irregularly 
from the mucous, through 
the fibrous, to the cu- 
taneous layer, thus firm- 
ly uniting the several lay- 
ers into a compact mem- 
brane. 
In the upper quadrant of the tympanic membrane, above the at- 
tachment of the malleus, the fibrous layers are wanting; the mucous 
and cutaneous layers are therefore in contact, and the membrane presents 
Fig. 574.-Section through the Margin of the 
Tympanic Membrane of a Child. 
a, fibrocartilaginous ring; b, bone; c, derma of 
the external auditory canal; d, tympanic mucosa; 
e, e', epidermis; f, radial fibers, and f, circular 
fibers of the tympanic membrane; g, mucosa of the 
membrane; h, epithelium of the tympanum; i, 
blood-vessels. X 55. (After Kolliker.) THE MIDDLE EAR 
689 
a flaccid appearance in comparison with the tense condition of its other 
parts. This portion is known as the membrana flaccida or Slirapnell's 
membrane. 
The Auditory Ossicles 
These are three in number, the malleus, the incus, and the stapes; 
they form a continuous bony chain, extending from the insertion of 
the manubrium mallei in the tympanic membrane to the fenestra vestib- 
Fig. 575.--The Auditory Ossicles. 
I, ossicular chain of the left ear; 1, malleus; 2, incus; 3, stapes. II, ossicular 
chain of the right ear; 1, malleus; 2, processus gracilis; 3, manubrium; 4, long process 
of the incus; 5, short process of the incus; 6, stapes. (After Riidinger.) 
uli, with whose margin the foot of the stapes articulates. The ossicles 
consist of compact bony tissue containing loosely packed Haversian sys- 
tems; they are united with each other by firm •fibrocartilaginous ar- 
ticulations. With the exception of the stapes, none of the ossicles contain 
a marrow cavity. 
The manubrium of the malleus is firmly fixed in the tympanic mem- 
brane, as already described, the head of the bone articulating with 
the head of the incus in the epitympanic recess. The long process of 
the incus, circular in transection, extends downward along the tympanic 
wall in a course nearly parallel to that of the manubrium mallei, being, 
in a portion of its course, contained within a recess in the osseous wall 
of the tympanum. Finally, at the level of the stapes it makes a sharp 
bend, almost at right angles with its former course, to articulate, by 
means of a rounded end or orbicular process, with the head of the 690 
THE EAR 
stapes. This latter bone is deeply placed within the recess of the pelvis 
ovalis, and continues the bony chain to the fenestra vestibuli, where 
the foot plate of the stapes is in relation, by its inner surface, with the 
vestibular perilymphatic space of the internal ear. 
The course of the chain of ossicles is such that they form a lever; 
the long process of the incus being shorter than the manubrium mallei, 
the vibrations of the tympanic membrane in response to sound waves 
are transmitted to the internal ear diminished in amplitude but ex- 
aggerated in intensity. 
The combined activity of 
the tympanic membrane 
and the auditory ossicles 
is said to reduce the am- 
plitude as much as sev- 
enty-six times, and to 
increase the force of the 
vibrations thirty times. 
Two muscles and sev- 
eral ligaments are con- 
nected with the ossicles. 
The tensor tympani 
muscle is mostly con- 
tained within a canal 
which is parallel to and 
lies just above the audi- 
tory tube, and from its 
bony wall the muscular 
fibers arise. The wall of 
the canal forms a conical 
projection known as the 
processus cochleariformis, 
which projects well into 
the cavity of the tympanum, being directed toward the neck of the mal- 
leus. Leaving its canal at the apex of this conical process the tendon 
of the muscle bends sharply over the margin of the processus cochleari- 
formis and passes directly to its insertion into the neck and the adjoin- 
ing part of the manubrium of the malleus. Hence the naked tendon of 
the muscle lies within the tympanic cavity. 
The stapedius muscle is similarly contained within the cavity of 
the pyramid, from whose bony wall its fibers take origin. Passing for- 
Fig. 576.-The Cavity of the Tympanum, Viewed 
from Above. 
i, the body of the incus; I, ligamentous fold of the 
mucosa; l.a.m., anterior ligament of the malleus; 
l.e.m., external ligament of the malleus; l.i., pos- 
terior ligament of the incus; M, mastoid cell; m, 
head of the malleus; m.m., mucous membrane; n, 
chorda tympani nerve; pr. o., orbicular process of the 
incus articulating with the stapes in the depth of 
the cavity; R, beneath this space is the flaccid por- 
tion of the tympanic membrane; s.l.m., cut end of 
the superior ligament of the malleus; sp, spina tym- 
panica anterior; st, st', tendon of the stapedius 
muscle; tt, tendon of the tensor tympani muscle. 
X 4. (After Schafer.) THE MIDDLE EAR 
691 
ward, the muscle makes its exit at the apex of the pyramid, and is di- 
rectly inserted into the neck of the stapes close to the articulation 
of the orbicular process of the incus. 
The ligaments of the malleus are the anterior, the external, and 
the superior. The anterior ligament firmly attaches the head of the 
malleus to the margin of the Glaserian fissure in the anterior wall of 
the tympanum. The processus gracilis of the malleus is inclosed by 
the fibers of this ligament. It is also in close relation with the chorda 
tympani nerve, which, being clothed by the tympanic mucosa, trav- 
erses this portion of the tympanic cavity and enters the iter chordae 
anterius. 
The external ligament connects the neck of the malleus with the 
upper portion of the external wall of the tympanum. It is somewhat 
fan-shaped. The space lying between the external ligament of the 
malleus and the membrana flaccida is known as Prussak's space. The 
superior ligament is a looser fibrous band which passes from the head 
of the malleus to the superior wall of the tympanum. 
The ligament of the incus is decidedly fan-shaped, its straight, coarse, 
fibrous bands radiating from the short process of the ossicle to the ad- 
jacent portion of the posterior wall of the tympanum. 
The articulation of the malleus with the incus, as also that of the 
latter bone with the stapes, is supplied with a delicate capsular liga- 
ment. 
The annular ligament of the stapes connects the margin of the 
foot plate of this bone with the adjacent portions of the cartilaginous 
and bony wall of the vestibule at the margin of the fenestra vestibuli. 
The articulation which is thus inclosed is directly formed by an an- 
nular plate of cartilage investing the margin of the oval foot of the 
stapes, and a similar annular plate of hyaline cartilage which lines the 
borders of the foramen vestibuli. The fibers of the annular ligament 
are continuous with those of the perichondrium and adjacent periosteum. 
The Auditory (Eustachian) Tube 
The auditory or Eustachian tube connects the cavity of the tym- 
panum with that of the nasopharynx. Its first portion, including 
about one-third of its entire length, is surrounded by a bony wall; be- 
yond this it is supplied with a cartilaginous plate; its pharyngeal ostium 
is entirely membranous. 
The mucosa consists of an entodermal epithelium, which is of the 692 
THE EAR 
columnar ciliated variety, continuous with, and similar to ihe respiratory 
epithelium of the nasopharynx, together with a fibrous membrana 
propria which is loosely connected with the surrounding bony, car- 
tilaginous, and muscular walls. The lower portions of the tube are 
richly supplied with mucus-secreting, tubulo-acinar glands, and toward 
Fig. 577.-Transection of the Eustachian Tube; Diagrammatic. 
1, cartilaginous plate; 2, median or hooked end of the cartilage; 3, 'dilator tubas' 
(tensor palati); 4, levator palati; 5, fibrocartilage at the base of the skull; 6 and 7, 
mucous glands; 8, adipose tissue; 9, 11, lumen of the tube; 10, 12, connective tissue. 
Low magnification. (After Riidinger.) 
its pharyngeal end the mucosa is much infiltrated with lymphoid tissue, 
thus forming the tubal tonsil of Gerlach. 
The cartilage of the auditory tube is firmly adherent to the bony wall. 
At the point of attachment it has a hyaline structure, the fibers of 
the perichondrium penetrating only the surface of the cartilaginous 
plate. Lower down the cartilage becomes infiltrated with fibers and 
conforms to the typical elastic, variety. Like the cartilage of the auricle 
it is rich in cellular elements. Its transection presents a peculiar hook- 
like form, by means of which the posterior surface, the superior margin, 
and the upper portion of the anterior surface are invested by cartilage, THE INTERNAL EAR 
693 
while the remaining portions of the anterior surface and the whole 
of the inferior margin are entirely membranous. Closely associated 
with the auditory tube are the tensor and levator palati muscles, lying 
medially and ventrally to the tube. These muscles serve also as dilators 
for the tube. 
Vascular Supply 
The Blood-vessels.-The mucosa of the middle ear is richly sup- 
plied with blood-vessels, the larger of which lie in the deeper part of the 
membrane and supply capillary vessels to the tunica propria. The blood- 
vessels of the auditory tube are especially numerous. 
In the tympanic membrane the arteries and veins form an annular 
plexus at the margin; and a group of similar vessels surrounds the 
manubrium mallei, lying in the deeper layers of the cutaneous portion 
of the membrane. 
The mucosa of the tympanum is peculiar in the relative deficiency 
of capillary vessels (Prussak, 1869) ; the veins are numerous. The 
veins of the auditory tube empty into the internal jugular; they also 
communicate with the cavernous sinus by a trunk of considerable size 
(Dench, 1895). 
The lymphatics of the middle ear form plexuses in the connective 
tissue of the mucosa and in a general way follow the course of the 
smaller veins. They lead in part to the lymphatic nodes behind the ear, 
and in part to the parotid group (Kblliker). They also communicate 
with the perilymphatic spaces of the internal ear. 
THE INTERNAL EAR 
General Considerations 
The internal ear includes a series of membranous structures together 
with the terminal fibers of the acoustic nerve; these are contained within 
a series of connected cavities hollowed out of the petrous portion of 
the temporal bone, and in relation with the mesial wall of the tympanum. 
The central portion of this bony cavity, an ovoid space, is known as 
the vestibule; its outer wall presents the orifice of the fenestra vestibuli 
which leads to the tympanum, but during life is closed by the base of 
the stapes. Opening from the vestibule, at one end, are the bony cavi- 
ties occupied by the three semicircular canals which, in a general way, 694 
THE EAR 
project from the posterodorsal aspect of the vestibule; at the other end 
the bony cochlea containing its series of spiral canals projects anteriorly 
from the vestibule. Collectively these spaces, with several diverticula, 
form the bony labyrinth, and within them in life are contained a num- 
ber of membranous sacs whose general form corresponds more or less 
1, round window; 2, osseous lamina spiralis; 3, osseous cochlear canal; 4, floor of 
internal acoustic meatus; 5, vestibule; 6, 7, 8, 9, semicircular canals. The figures 
are placed at that portion of the margin which is nearest the structure indicated. 
(After Rudinger.) 
Fig. 578.-The Bony Labyrinth. 
closely to that of the bony cavity; these sacs collectively form the mem- 
branous labyrinth. 
The vestibule contains two of these membranous sacs, the sacculus 
and the utriculus, which are connected by means of the slender utriculo- 
saccular canal, from which a much prolonged diverticulum enters the 
aqueductus vestibuli to penetrate to the posterior surface of the petrous 
bone where it conies into relation with the cerebral meninges; this di- 
verticulum is known as the ductus endolymphaticus. Its dilated terminal 
portion constitutes the endolymphatic sac, which lies upon the dura and 
probably opens into the subdural space. The utricle and saccule, as also 
all other portions of the membranous labyrinth, contain a watery fluid, THE INTERNAL EAR 
695 
the endolymph; they do not entirely fill the bony cavity of the labyrinth 
in which they lie, the intervening space being occupied by a retiform 
connective tissue with broad interstices which are permeated by an 
aqueous fluid, the perilymph. 
The Saccule 
The saccule is a rounded membranous cavity which is connected, 
on the one hand, by means of the slender canalis reunions, with the 
cochlear duct or scala media, and on the other hand with the ductus 
endolymphaticus and utricle, as already stated. Its wall consists of an 
Fig. 579.-Diagram of the Membranous Labyrinth in Lateral View. 
A, ampullae; U, utricle; S, saccule; SM, scala media or cochlear duct; CR, canalis 
reunions; C, crus, or common canal; SE, saccus endolymphaticus; DE, ductus endo- 
lymphaticus; dss, dsp, dsl, superior, posterior and lateral (external) semicircular 
ducts. The utricle and saccule are connected by the utriculosaccular duct. The 
cochlear duct terminates in the ceca vestibulare and cupulare. (After Gray.) 
ectodermal epithelium, a membrana propria and a fibrous coat. The epi- 
thelium consists of flattened squamous cells; it completely lines the 
cavity. The epithelial surface is somewhat irregular from the papillary 
elevations of the fibrous coat. On the antero-inferior surface of the sac- 
cule the epithelium is peculiarly altered so as to form a layer of col- 
umnar cells, many of which are provided with stiff cilia. This neuro- 
epithelium is distributed over an oval area (3 mm. by 2 mm. in extent) 
beneath which the fibrous coat is much thickened by the entrance of 
many fibers derived from the vestibular portion of the acoustic nerve. 1, utricle; 2, superior semicircular canal; 3, posterior semicircular canal; 4, ex- 
ternal semicircular canal; 5, saccule; 6, endolymphatic duct; 7 and 7', canals con- 
necting utricle and saccule respectively with the endolymphatic duct; 8, endo- 
lymphatic sac; 9, cochlear duct; 9', its vestibular cul-de-sac (cecum vestibulare); 
9", its terminal cul-de-sac (cecum cupulare); 10, canalis reunions. (After Testut.) 
Fig. 580.-Diagram of the Right Membranous Labyrinth. 
Fig. 581.-The Isolated Membranous Labyrinth. 
1, utricle; 2, saccule (opened); 3, location of the macula acustica sacculi; 4, am- 
pulla of a semicircular canal; 5, canalis communis. Low magnification. (After 
Rudinger.) 
696 THE INTERNAL EAR 
697 
This elevation with its neuro-epithelial covering is known as the macula 
acustica sacculi. 
The neuro-epithelium contains two varieties of cells, the sustentacu- 
lar and the hair cells. The former, fiber cells of Retzius, form a layer, 
two or three cells deep, which rests upon the basement membrane, 
and whose broad basal portion contains a spheroidal nucleus. Beyond 
the nucleated portion the cytoplasm of the sustentacular cell is con- 
Fig. 582.-Transection of the Margin of the Macula Acustica Sacculi of a 
Guinea-pig. 
a, otolithic membrane; b, hairs; c, cuticular membrane; d, hair cells; e, susten- 
tacular cells; /, epithelium of the saccule; g, tunica propria; h, nerve fibers; i, bone. 
Hematoxylin and eosin. X 325. (After Kolliker.) 
tinned inward between the bodies of the hair cells to the surface of 
the epithelial layer, this portion of the cell being relatively slender. 
The hair cells occupy the superficial part of the epithelial layer 
by their broad nucleated portions, which carry upon their free extremity 
a single tuft of long stiff cilia, having the appearance of a delicate hair- 
like process which projects into the endolymphatic cavity. That por- 
tion of the endolymph which immediately overlies the macula, and 
into which the hair-like processes project, though not essentially dif- 
ferent in microscopic appearance in fresh tissues, appears to possess a 
somewhat gelatinous consistence, and in it are suspended various forms 
of minute crystals of calcium carbonate which are known as otoconia 
or 'otoliths' The free surface of the neuro-epithelium is also provided 698 
THE EAR 
with a reticulated cuticular membrane which presumably is formed by 
the amalgamation of the free ends of the sustentacular cells. Through 
the openings in this reticular membrane the ciliary tufts of the hair 
cells project. 
The central ends of the hair cells, beneath the nucleated enlarge- 
ment which is found near the middle of the epithelial layer, are pro- 
longed outward between the nucleated portions of the sustentacular cells 
and frequently terminate in small knobbed extremities. This portion 
of the cells is in intimate relation with the terminal fibrils of the vestibu- 
lar portion of the acoustic nerve, which, coming from nerve plexus in 
the fibrous wall of the saccule, 
forms an intra-epithelial plexus 
of delicate varicose fibrils. Fre- 
quently the epithelial coat con- 
tains coarse granules of a brown- 
ish pigment which, at times, also 
produces a diffuse coloration of 
the cells. 
The lining epithelium of the 
saccule rests upon a thin homo- 
geneous basement membrane and 
is further supported by a delicate 
fibrous coat or tunica propria. 
The connective tissue of this coat forms interlacing bundles the most 
of which are distributed in a circular manner about the wall of the 
ovoid sacculus. At the macula this coat is much thickened by the en- 
trance of the fibers from the vestibular nerve. It also contains the 
minute blood-vessels which supply the organ. 
As is the case with the other divisions of the membranous labyrinth, 
the fibrous wall of the saccule is in contact on one aspect of its surface 
with the periosteum which lines the osseous labyrinth; elsewhere it is 
separated from the periosteum by the perilymphatic cavity. 
Fig. 583.-Nerve Endings in the 
Macula Acustica of a Guinea-pig. 
a, epithelium; b, tunica propria; c, three 
terminal nerve fibers. Golgi stain. X 
about 200. (After Retzius.) 
Tiie Utricle 
The utricle is somewhat larger than the saccule. It lies behind 
and somewhat above the saccule, is of a very irregular oblong form, and 
receives the insertions of the semicircular canals. Its anterior portion 
the fibrous wall of the saccule is in contact on one aspect of its surface 
of its wall differs in no wise from that of the saccule; both of these mem- THE INTERNAL EAR 
699 
branous sacs are contained within the irregular cavity of the vestibule. 
The structure of the utriculus, therefore, requires no further description. 
The Semicircular Canals 
The semicircular canals or ducts are three in number, the posterior, 
superior, and lateral. The last is also horizontal in its position; the 
first two are vertical, but are so placed as to form a right angle with 
one another. The posterior lies in the long axis of the petrous bone 
and its plane is therefore more nearly sagittal, while that of the superior 
canal is more nearly coronal. Each canal forms something more than 
half a circle, its two ends opening separately into the cavity of the vesti- 
bule, with the exception of the posterior and superior canals whose in- 
ternal ends open by a common orifice, the canalis communis. The un- 
joined orifices of the posterior and superior canals, as also the outer 
extremity of the lateral canal, present a marked dilatation at their 
termination in the vestibule. These dilatations are known as the am- 
pulice. They lodge the neuro-epithelial patches, the cristae acusticae. 
The osseous and membranous canals are of similar shape; the 
latter is, of course, contained within the former. 
The membranous semicircular canals open into the utricle. They 
do not entirely fill their bony canal, but, like the utricle and saccule, 
lie in contact with the periosteum at one surface only, this surface being 
that of the outer wall or periphery of the semicircle, while in the re- 
maining portion of the circumference of the cylindrical bony duct, the 
membranous canal is loosely united to the periosteum of the osseous 
wall by a retiform connective tissue whose loose meshes are filled with 
perilymph and lined with mesenchymal epithelium. 
The wall of the membranous canal is similar in structure to that 
of the saccule and utricle and consists of an ectodermal epithelium, a 
membrana propria, and a fibrous tunic. Each of the three ampulla? 
presents a marked differentiation of the epithelial lining, which is there 
raised in the form of a prominent crescentic fold, inappropriately termed 
by the older anatomists the crista acustica, from its supposed connection 
with the auditory function. Like the maculae of the saccule and utricle, 
the cristas are supplied by the vestibular nerve and are concerned with 
the function of equilibration. 
The utricle and saccule represent the original anlage of the ear- 
the otocyst-from which the canals and cochlea arise as evaginations; 
they correspond most closely also to the 'ear' of certain invertebrates, 700 
THE EAR 
e.g., Crustacea, which is simply an equilibrating organ. They are be- 
lieved to function as static organs of equilibration, giving information 
as to position at rest or during progressive movements; the semicircular 
canals on the other hand are commonly conceived of as dynamic or- 
gans of equilibration and are thought to furnish information regarding 
the direction and extent of rotatory movements. 
1, bone; 2, retiform connective tissue membranes; 3, at this point a band of con- 
nective tissue joins the periosteum; 4, membranous semicircular canal; 5, liga- 
mentous attachment of the canal; 6, at this point the membranous and osseous 
canals are in contact. Moderately magnified. (After Riidinger.) 
Fig. 584.-Transection of a Human Semicircular Canal. 
The cristae are clothed with tall columnar cells which, though some- 
what taller, are otherwise similar in structure to those of the maculae, 
and are similarly divisible into sustentacular cells and hair cells. They 
are also covered by a gelatinous cuticular formation, containing otoliths, 
which is here known as the cupola. The vibratory stimulus is trans- 
mitted from the endolymph to the hair cells through the medium of 
the otolithic membranes. THE INTERNAL EAR 
701 
The Cochlea 
The cochlea, like the vestibular portion of the internal ear, consists 
of a bony case which incloses a membranous organ. 
Structure.-The bony cochlea possesses a peculiar flat pyramidal 
shape. The base of the pyramid is in contact with the anterior aspect 
of the vestibule; its apex or cupola is directed forward, outward, and 
slightly downward. The pyramid is hollow and contains in its axis a 
conical bony support, the modiolus, which tapers from a broad base to 
a pointed apex beneath the broader, 
blunt, and rounded cupola of the 
outer bony wall. The modiolus con- 
tains a broad canal which receives 
the cochlear division of the acoustic 
nerve as it enters from the internal 
meatus. 
The outer surface of the modio- 
lus supports a bony shelf, the lam- 
ina spiralis ossea, which winds in a 
spiral manner from its base to its 
apex, and ends in a hook-like proc- 
ess, the hamulus. This shelf only 
partially spans the interval between 
the modiolus and the outer wall of 
the cochlea. In life the remaining 
interval is completed by a firm fi- 
brous membrane, the basilar membrane (lamina spiralis membranacea). 
Thus the cylindrical canal of the cochlea, which is wound spirally around 
the modiolus making two and one-half turns from the base to the apex, is 
subdivided into two parallel longitudinal divisions, which are respectively 
known as the scala vestibuli and the scala tympani. They are so dis- 
posed that in a given turn of the canal the former is always nearer the 
apex, the latter nearer the base of the cochlea. According to Wieder- 
sheim (1893) the human cochlea has nearly three turns, the pig four, 
the cat three, the rabbit two and one-half, the ox three and one-half, 
and cetacea one and one-half turns. 
The osseous lamina spiralis presents a grooved margin or sulcus, 
from the basal or tympanic lip of which the lamina basilaris is con- 
tinued to the opposing surface of the bony wall. The lamina spiralis 
ossea is hollowed out in a diploic manner for the transmission of the 
Fig. 585.-Axial Section through 
the Cochlea of a Fetal Calf. 
a, internal acoustic meatus in which 
is the cut end of the cochlear nerve as it 
enters the modiolus. X 6. (.After Kol- 
liker.) 702 
THE EAR 
branches of the cochlear nerve, which are continuously given off all the 
way from the base to the apex of the osseous spiral lamina, and which 
pass outward through the foramina nervosa upon the basilar membrane 
Fig. 586.-Axial Section through a Turn of the Cochlea of a Guinea-pig, 
a, bone of the outer wall of the cochlea; b, membrane of Reissner; d, membrana 
tectoria; De, cochlear duct or scala media; f, stria vascularis; g, organ of Corti; h, 
spiral ligament; i, cells of Claudius; k, scala tympani; I, scala vestibuli; m, vestibular 
lip of the Embus spirale; n, internal spiral sulcus; o, nerve fibers of the cochlear 
nerve, contained within one of the radiating canals within the osseous spiral lamina; 
p, nerve cells of the spiral ganglion; q, blood-vessel; r, external spiral sulcus, upon 
which open Shambaugh's glands; s, prominentia spiralis, containing the vas prom- 
inens. X 90. (After Bohm and von Davidoff.) 
to be distributed to the epithelium of the spiral organ (of Corti). This 
organ is a peculiar spiral group of neuro-epithelial cells which extends 
the whole length of the basilar membrane from the base to the cupola 
of the cochlea. THE INTERNAL EAR 
703 
The margin of the osseous spiral lamina is much thickened by 
the fibrous and epithelial tissues by which it is invested, so that a mem- 
branous sulcus of considerable depth is formed between the two lips 
(vestibular and tympanic lips) of the bony sulcus spiralis internus. 
This is further thickened by a marked elevation of fibrous tissue cov- 
ered by columnar cells, from the outer margin of which a delicate mem- 
brane, the membrana tectoria, extends outward and overhangs the epi- 
thelium of Cortfs organ. From the inner margin of the elevation of 
fibrous tissue, the limbus spiralis, which is supported by the vestibular 
lip of the bony lamina, a delicate membrane, the vestibular membrane 
(of Reissner), passes obliquely outward to the bony wall of the cochlea, 
and in transections appears to cut off a corner of the scala vestibuli, 
thus marking off a triangular space whose base is formed by the outer 
wall of the cochlea, its sides by the membrane of Reissner and the 
basilar membrane upon which rests the organ of Corti; its blunt apex 
is found at the sulcus spiralis internus. Since these membranes ex- 
tend the entire length of the bony spiral canal of the cochlea, the 
space which is thus apparently cut off from the scala vestibuli must 
form a spiral canal, included between the scala tympani on the one side 
and the scala vestibuli on the other; this canal is the scala media or 
cochlear duct. 
The scala media is an endolymphatic canal. At the apex of the 
cochlea it ends in a blind extremity which is known as the lagena or 
cecum cupulare; its opposite end forms a blind pouch between the fenes- 
tra cochleae and the fenestra vestibuli, at the base of the cochlea, which 
is termed the cecum vestibulare. The scala media is connected with 
the saccule and utricle by means of the canalis reuniens, as described 
above. 
The scala tympani and scala vestibuli, on either side of the scala 
media, extend spirally from the base to the apex of the cochlea. At 
the apex they are united by the helicotrema, a continuation of these 
canals which curves around the hamulus. At the base of the cochlea 
the two canals diverge, the scala tympani ending abruptly at the fenestra 
cochleae, which is closed by a fibrous membrane, clothed on its tympanic 
surface by the flattened epithelium of the tympanic mucosa, and on its 
cochlear surface by the epithelium of the scala tympani. This secondary 
tympanic membrane Serves for the relief of tension in the cochlea when 
the perilymph is set into motion by the stapes. The scala vestibuli, on 
the other hand, is continued backward into the vestibule, where it is 
in relation with the external surface of the saccule and utricle, and, 704 
THE EAR 
since it is in contact with the outer wall of the bony vestibule, this por- 
tion of the scala vestibuli receives the opening of the fenestra vestibuli, 
which is closed by the foot plate of the stapes. Corresponding to the 
relative positions of the fenestra vestibuli and fenestra cochleae, the scala 
vestibuli in the first turn of the cochlea lies above the scala tympani, 
and being somewhat the longer it also extends farther backward. 
Having traced the general form and relations of the several portions 
of the cochlea, we are now in a position to study more carefully the 
finer structure of its more important parts. 
The membranous wall of the scala tympani and scala vestibuli is 
clothed by a mesenchymal epithelium of flattened endothelioid cells, 
which rest upon a double layer of fibrous tissue. Thus the tunica propria 
also serves as a periosteum for the inner surface of the bony wall of the 
cochlea, and conveys the blood and lymphatic vessels. The scalae are 
perilymphatic canals. They communicate with the subdural space 
through the aqueductus vestibuli and the aqueductus cochleae. The latter 
opens from the scala tympani near its beginning at the fenestra coch- 
leae, and passes below the pyramid to the dura transmitting a small 
vein. 
The vestibular membrane (of Reissner) is an extremely delicate 
structure which consists of a thin central substantia propria, covered 
on either surface by epithelium, that on the one surface being con- 
tinuous with the mesenchymal epithelium of the scala vestibuli, that 
on the other with the ectodermal epithelium of the scala media. It is 
non-vascular in the adult. 
The outer wall of the scala media is lined by a continuation of the 
epithelium in that portion which adjoins the membrane of Reissner, 
and this rests upon a fibrous membrane similar to that which forms 
the walls of the other scalae. Toward the attachment of the membrana 
basilaris, however, the tissue of the outer fibrous wall of the scala media 
is much thickened, and forms a dense ligamentous structure, triangular 
in shape as seen in a longitudinal section of the cochlea, which receives 
the insertion of the membrana basilaris at its apex, and being, like 
the basilar membrane, continued from the base to the apex of the cochlea, 
is known as the spiral ligament. Its dense fibrous bands radiate from 
the attachment of the basilar membrane to all portions of the ligament, 
and are firmly attached to the bony wall of the cochlea, with whose 
periosteum the deeper fibers of the spiral ligament are blended. 
The surface of the spiral ligament, which forms the outer wall of 
the scala media, slopes gradually away from the attachment of the basilar THE INTERNAL EAR 
705 
membrane; that which impinges upon the scala tympani slopes more 
abruptly. The greater portion of the spiral ligament, therefore, is con- 
tained within the scala media. Here it is lined by low columnar or 
cuboidal epithelium whose cells blend, without demarcation, with the 
underlying vascular connective tissue, so that the minute blood-vessels 
frequently appear as if lying within the epithelial layer, although they 
probably are always contained within the connective tissue processes 
which project into the attached surface of the epithelial layer. 
This very vascular subepithelial portion of the spiral ligament is 
known as the stria vascularis. A short distance above the point of 
attachment of the basilar membrane to the spiral ligament appears a 
prominent spiral ridge, the prominentia spiralis, the intervening groove 
constituting the sulcus spiralis externus. The larger blood-vessel 
(venous) within the prominence is the vas prominens. From the ex- 
ternal sulcus there extend into the subjacent ligamentous tissue numer- 
ous large clear clumps of epithelioid cells. These have been variously 
interpreted as neuro-epithelial elements and as smooth muscle cells. 
But Shambaugh (Archives of Otology, 37, 6, 1908) has shown that they 
contain tubules which open into the sulcus, and that they are in reality 
branched tubular glands. He ascribes to them the function of pro- 
ducing at least a portion of the endolymph of the scala media; the stria 
vascularis is probably also an important source of endolymph. 
The tympanic wall or floor of the scala media presents for examina- 
tion several structures, which, from within outward (viz., from the 
modiolus to the ligamentum spiralis), are the limbus spiralis, membrana 
tectoria, sulcus spiralis internus, basilar membrane, and the organ of 
Corti which rests upon the basilar membrane (Fig. 587). 
The vestibular lip of the limbus spiralis presents a distinct eleva- 
tion, which is formed by a peculiar cellular variety of connective tissue, 
and is covered by columnar epithelium, whose cells are not sharply de- 
fined from those of the underlying connective tissue. The surface of 
the epithelium presents a distinct cuticular formation of considerable 
thickness, which seems to be prolonged outward from the margin of 
the vestibular lip, and forms the membrana tectoria. 
The surface of the limbus spiralis, when viewed from the scala 
media, presents slight elevations which, at the margin of the vestibular 
lip, are prolonged into prominent ridges whose indented borders over- 
hang the sulcus and are known as the auditory teeth (of Huschke). 
The Membrana Tectoria (Membrane of Corti).-This is an exo- 
plasmic or cuticular tissue, formed by the epithelium of the inner or 706 
THE EAR 
limbus portion of the embryonic cochlear duct. It has a gelatinous 
fibrillar structure, but lacks nuclei; and, unlike the otherwise very simi- 
lar otolithic membranes of the maculae and cristae, it contains no calca- 
reous products. Its free margin overhangs, or rests lightly upon, the hair 
cells of Corti's organ. 
The tectorial membrane has been very carefully studied by Hardesty 
(1908) in the pig, from whose cochlea he has been able to remove it entire. 
It is said to measure about 30 mm. in length, to occupy the four turns of 
the cochlea, to be about five times as wide and five times as thick in the 
apical turn as at the basal end, and to have a section area in the apical 
turn approximately twenty-one times and a volume ninety-five times the 
area and volume of its basal end. It is described as consisting 'of a hyaline 
matrix, probably keratin, in gelatinous form, in which are embedded the 
very numerous fine fibers or threads of uniform size' (Anat. Rec., 8, 2, 
1914). The membrane has a slight amount of elasticity, is of a semi-solid 
character and possesses 'marked adhesiveness'; its specific gravity is said 
to be but little greater than that of the endolymph. None of the fibers 
extend the entire width of the membrane, none are attached at both ends, 
and the greater number are attached at neither end (Hardesty, Amer. Jour. 
Anat., 8, 2, 1908). Hardesty describes a stripe {Hensen's stripe) on the 
under surface of the tectorial membrane opposite the row of inner hair 
cells, which he explains 'as a line of intercrossing ends of fibers of the 
under surface resulting from the process by which the growth of the mem- 
brane terminates.' He describes also a thin, exceedingly delicate, 'acces- 
sory tectorial membrane' along the under surface of the outer portion of 
the chief membrane; only its outer edge is attached to the latter, and it is 
bounded internally by Hensen's stripe, thus covering only the outer hair 
cells. 
The Sulcus Spiralis Internus.-This is a deep groove included be- 
tween the vestibular lip of the limbus and the basilar membrane which 
is attached to the tympanic lip. The sulcus is lined by flattened epi- 
thelial cells, which are apparently continuous with those of the vestib- 
ular lip, and like them are not readily distinguished from the under- 
lying connective tissue. The epithelium is continued outward upon the 
basilar membrane to the margin of Corti's organ, with the innermost 
cells of which it is continuous. 
The Basilar Membrane (Membrana basilaris).-This is a thin but 
resistant membranous structure, upon which rests the epithelium of 
Corti's organ. Hardesty (1908) describes it as a'flat tendon . . . whose 
purpose is merely to strengthen the floor of the ductus cochlea ris and Fig. 587.-A Radial Section Through Corti's Organ in the First turn of the Human Cochlea. 
a, vestibular lip of the lamina spiralis; 5, sulcus spiralis internus; c, epithelium of the sulcus; d, nerve fibers penetrating a for- 
amen nervosum; e, mesenchymal epithelium of the scala tympani; f, fibrous layer of the basilar membrane; g, cuticular layer; h, 
spiral ligament; i, inner, and k, outer pillars; I, Deiters' cells; m, Hensen's cells; n, cells of Claudius; o, inner, and p, outer hair 
cells; q, Corti's tunnel; r, Nuel's space; s, nerve plexus among the inner hair cells; t, plexus jvithin the tunnel; u, tunnel fibers; 
v, plexus about the outer hair cells; w, x, y, z, membrana tectoria. X 465. (After Kolliker.) 
707 708 
THE EAR 
the position of the organ of Corti, and the fibers of which are too rigid 
and firmly associated to allow of resonant vibration.' Its tympanic sur- 
face is clothed by a continuation of the lining membrane of the scala tym- 
pani, consisting of a mesenchymal epithelium, resting upon a very thin 
and delicate connective tissue layer. The substantia propria of the bas- 
ilar membrane consists of tendinous bands which, being radially disposed, 
span the interval between the margin of the tympanic lip of the osseous 
spiral lamina and the opposed margin of the spiral ligament. 
Because of the great breadth of the modiolus at the base, and its 
rapid diminution in thickness toward the apex of the cochlea, this 
interval is relatively narrow at the beginning of the first turn of the 
spiral scala media, but progressively widens as the apex of the cochlea 
is approached. Consequently, the shortest tendinous fibers of the basilar 
membrane are found at the base of the cochlea, the longest at its apex. 
The shortest fibers are also the coarsest. It has been estimated that 
there are 24,000 distinct fibers or 'auditory strings' in the basilar 
membrane. 
The substantia propria is covered upon that surface which faces 
the scala media by a thin homogeneous membrane, a cuticular forma- 
tion or exoplasmic derivative, upon which rests the epithelium of the 
organ of Corti. 
The Organ of Corti.-This organ consists of a highly differenti- 
ated neuro-epithelium whose specialized cells are disposed according to 
a very regular arrangement. The flattened epithelium of the sulcus 
spiralis interims is continued for a short distance upon the basilar mem- 
brane. Suddenly, at the margin of Corti's organ, it alters its char- 
acter. Here the epithelium becomes abruptly changed to a tall columnar 
variety, the first cells, known as the inner sustentacular cells, being ap- 
parently piled upon one another and resting against the inner hair cells, 
which form a single row of neuro-epithelium; these, like all the suc- 
ceeding rows of cells, can be traced as a continuous line in the spirally 
wound scala media, from the base to the apex of the cochlea. 
The inner auditory or hair cells have a broad body which is con- 
fined to the superficial third of the epithelial layer and which is nu- 
cleated at its deeper end. Its free surface forms an expanded oval 
plate from which about twenty stiff cilia project through a cuticular 
membrane toward the cavity of the scala media. These end plates 
interdigitate with the phalanges of the inner pillar cells, which are to 
be shortly described. The bases of the inner hair cells are thin and 
slender, and are in relation with a nerve plexus of fine fibrils derived THE INTERNAL EAR 
709 
from the terminal processes of the cochlear nerve. These nerve fibrils 
make their exit in small bundles from the bony spiral lamina, through 
the foramina nervosa and passing outward upon the basilar membrane 
are distributed in a plexus beneath the epithelium, some of their .naked 
processes almost immediately penetrating the epithelial layer to end 
between the bases of the inner hair cells. 
The inner hair cells rest against the inner pillar cells, or rods, of 
Cortis arch. This arch is formed by two rows of highly specialized 
cells, the inner and the outer piltars, which are widely separated where 
their bases are attached to the basilar membrane, but are in contact 
at their free ends; in fact, the free extremity of the inner pillar is pro- 
longed into a broad flattened plate-like process whose inner margin in- 
terdigitates with the head plate of the inner hair cells, as stated above, 
and whose outer margin is so prolonged as to almost, though not com- 
pletely, cover the rounded head of the outer pillar. The head of the 
outer pillar, being similarly flattened, expanded, and prolonged outward 
beyond the margin of the head plate of the inner pillar cell, comes into 
contact with the phalanges of Deiters' cells and with the cilia of the 
outer hair cells which lie next without; they leave a space between 
the outer pillars and the outer hair cells which is known as Nuel's space, 
filled by a semi-fluid intercellular substance. 
The inner pillar cells are rather more numerous than the outer 
-in the entire length of the scala media, according to Retzius, there 
are 5,600 of the former to 3,850 of the latter-so that about three of 
the expanded head plates of the inner pillars overlap two of the rounded 
heads of the outer pillar cells. The arch formed by the opposed pillar 
cells, being succeeded by similar arches of successive pillars, forms a 
continuous tunnel, triangular in transection, which extends the whole 
length of the scala media, and is known as the canal of Corti. This 
canal is also filled with a semi-fluid substance. 
Each pillar cell is differentiated into two portions, the pillar proper 
and the basilar cell, the latter containing the nucleus. The pillar 
presents a fibrillar appearance, the fibrils being disposed in the long axis 
of its body. This portion of the cell reaches from the basilar membrane 
to the free surface of the neuro-epithelium. 
The basal part of the cell, the basilar cell, probably represents the 
undifferentiated portion of the primordial pillar cell. It consists of a 
clear, finely granular cytoplasm and contains the spheroidal nucleus. It 
lies on that side of the pillar which faces the canal of Corti, the bases 
of the opposed cells being expanded until they meet, thus forming a 710 
THE EAR 
cuticular floor for the tunnel. This undifferentiated basilar portion 
occupies only the deeper half of the pillar cell. 
The outer hair cells form three to five rows of ciliated cells which 
are similar in structure to the inner hair cells, and which are sup- 
ported by the sustentacular cells of Deiters. Their cylindrical cell 
bodies occupy the superficial third of the epithelial layer and at the 
deeper extremity present a nucleated enlargement, beyond which they 
are continued only as an extremely slender basal process. The free 
ends of the outer hair cells present an expanded oval surface from which 
the hairs project. The outer hair cells are about five times as numerous 
as the inner, that is, there are about 3,600 of the inner to 18,000 of 
the outer (Waldeyer). According to certain authorities the hair cells 
lack the delicate basal process in the adult condition. 
The outer sustentacular cells (Deiters' cells') are cylindrical cells 
whose expanded bases rest upon the basal membrane and whose distal 
portions extend toward the surface between the outer hair cells. The 
superficial portion of these cells, being encroached upon by the broad 
outer hair cells, is very slender; the broader basal portion occupies the 
deeper two-thirds of the neuro-epithelium, the spheroidal nuclei being 
found at the level of the middle third. Each sustentacular cell contains 
a cuticular filament (fiber of Retzius) which begins in contact with the 
cuticle of the basal membrane, and extends through the axis of the 
cell to its free border, where it expands to form a broad flattened 
plate of peculiar shape, known as the phalangeal process. These cuticu- 
lar processes surround and overlie the margins of the head plates of the 
hair cells, thus forming a reticular layer through the openings of which 
the cilia of the hair cells project. 
The cells of Deiters are succeeded by the sustentacular cells of 
Hensen. These are tall columnar cells about eight rows broad, the inner- 
most of which equal in height the tall cells of the preceding type, but 
which at their outer border become abruptly shortened. Here they pass 
into the cuboidal cells of Claudius, and are thus continued outward to the 
spiral ligament. 
The nuclei of the cells of Hensen are found in their superficial 
third, those of the cells of Claudius in the center of the cell. Beneath 
Hensen's cells other small nucleated elements are occasionally found; 
they give to this layer somewhat the appearance of a two-rowed epi- 
thelium and are known as the cells of Bottcher. 
Both the cells of Hensen and those of Claudius are provided with 
a cuticular margin which, with the similar cuticle of the cells of Deiters, THE INTERNAL EAR 
711 
forms a continuous, membranous, cuticular layer known as the lamina 
reticularis. The inner portion of this cuticular membrane is pierced by 
the cilia of the three to five rows of outer hair cells, as already described. 
A fibrillar axial core is a common feature of all of the sustentacular 
elements of Corti's organ. This fiber of Retzius becomes progressively 
Fig. 588.-Diagram of the Organ of Corti. 
A, surface view, from the direction of the scala media; B, as seen 
in section, profile view, a, the vestibular lip of the lamina spiralis; b, margin of 
same; c, sulcus spiralis internus; d, inner sustentacular cells; e, inner hair cells; f, 
pillar cells; g, outer hair cells and phalanges of Deiters' cells; h, cells of Hensen; i, 
cells of Claudius. Very highly magnified. 
less pronounced in passing from the pillar cells, where it is very highly 
developed, to the cells of Claudius, where it is barely discernible. 
In the above description we have directed attention to the appear- 
ance of transections of the organ of Corti. In the study of this organ 
in the fresh condition, and occasionally in fixed and stained preparations, 
it is possible to obtain a surface view of this organ from the direction 
of the scala media. In such preparations the polygonal outlines of the 
columnar cells of the limbus spiralis, beneath which are the auditory 
teeth, are seen on the outer side of the attachment of Reissner's mem- 712 
THE EAR 
brane. Beneath the overhanging vestibular lip of the limbus the mosaic 
of large polygonal epithelial cells of the internal sulcus comes into 
view. At the margin of the organ of Corti these are exchanged for the 
broader cell ends of the inner sustentacular cells and the adjacent single 
row of inner hair cells. 
The flattened rectangular head plates of the inner pillar cells form 
the next row, the heads of the outer pillars projecting from beneath, 
and extending beyond the heads of the inner pillar cells. These are fol- 
lowed by the interdigitating phalanges of the cells of Deiters, which 
enter into the formation of the reticular membrane, through the fenestra 
of .which the cilia of the three to five rows of outer hair cells project. 
This- cuticular membrane is continued outward, and beneath it are 
successively seen the ends of the cells of Hensen, and of the cells of 
Claudius. 
The Acoustic Nerve 
The acoustic nerve presents two distinct divisions both of which are 
sensory, but which differ greatly as regards their central termination. 
They likewise differ in their peripheral distribution. Within the inter- 
nal acoustic meatus the nerve divides, each branch consisting of numer- 
ous bundles. The vestibular (superior or anterior) division is supplied 
with a ganglion of considerable size, the vestibular ganglion (of Scarpa), 
beyond which the nerve separates into three branches which supply, re- 
spectively, the macula of the utricle, and the cristae of the superior and 
lateral semicircular canals, in the neuro-epithelium of each of which 
their terminal fibrils end in relation with the bases of the hair cells (Figs. 
582 and 583). The remaining nerve fibers which are distributed to the 
vestibule are derived from a branch of the cochlear (inferior or poste- 
rior) division, and they supply in a similar manner the macula of the 
saccule and the crista of the posterior semicircular canal. According to 
Streeter (Amer. Jour. Anat., 1906), the vestibular nerve contributes also 
the innervation to the posterior canal and to the saccule, the cochlear 
nerve supplying only the cochlea. 
The cochlear branch proper, cochlear nerve, enters the modiolus, 
where it becomes abruptly narrowed by giving off numerous fine branches 
which pass outward between the layers of the bony spiral lamina. Here 
they form a continuous spiral succession of small nerve trunks, supplied 
with many bipolar ganglion cells, which collectively form the spiral 
ganglion (Fig. 586). They penetrate the margin of the bony sulcus 
through the foramina nervosa, a succession of perforations, in the tym- THE INTERNAL EAR 
713 
panic lip of the sulcus. Here the nerve fibers lose their medullary 
sheath and come almost at once into relation with the inner hair 
cells. From this point the path of the non-medullated fibers varies, most 
of them passing for some distance along a spiral course through the 
organ of Corti. One such spiral bundle is found on the inner, and 
another on the outer side of the inner pillars, the latter lying within 
the canal of Corti. Still other fibers, the tunnel fibers, cross the canal 
of Corti to form a spiral plexus beneath the outer hair cells and the cells 
Fig. 589.-Axial Section through Corti's Organ of the Guinea-pig, Showing 
the Terminal Nerve Fibrils. 
B, cells of Bbttcher; D1, D2, D3, three rows of Deiters' cells; H, cells of Hensen; 
i.b., inner border cell; i.h., inner hair cell; i.p., inner pillar cell; n, terminal branch of 
the cochlear nerve; o.h.-l, 2, 3, three rows of outer hair cells; o.p., outer pillar cell; 
p., phalangeal process of the outer sustentacular process. Very highly magnified. 
(After Held.) 
of Deiters. Terminal fibrils from these spiral plexuses end in relation 
with both the inner and the outer hair cells. 
The relation of the nerve cells of the spiral ganglion and the vestibu- 
lar ganglion to the termination of the nerve fibrils about the hair cells 
of the organ of Corti, the maculae, and the cristae, is essentially the same. 
The ganglia contain the cell bodies of the peripheral sensory neurons 
of the eighth cerebral or acoustic nerve. These are bipolar cells, of 
which the central process or axon enters a medullated nerve fiber of the 
acoustic nerve, while the peripheral process is distributed to the hair 
cells of the several areas of specialized neuro-epithelium, as above de- 
scribed. 714 
THE EAR 
The Vascular Supply 
Blood. Supply.-The internal ear is supplied by the internal audi- 
tory artery, a branch of the basilar artery, which enters the labyrinth 
along with the acoustic nerve, and at once divides into two main stems, 
the vestibular and the cochlear (arteria cochlearis communis, Sieben- 
Fig. 590.-Scheme of the Vascular Supply of the Internal Ear. 
C1, first turn of the cochlea; S, saccule; Sup.S.C., Ext.S.C., and Post.S.C., superior, 
external, and posterior semicircular canals; U, utricle. The arteries are in heavy 
black, the veins somewhat fighter; a, central vein, and b, central artery of the cochlea; 
c, vestibular artery; d, vestibulocochlear artery; e, arteria proprise cochleae; f, vena 
aqueduct us cochleae; g, vena aqueductus vestibuli. 
mann). The vestibular artery accompanies the branches of the vestibular 
nerve to the saccule, utricle, and semicircular canals, supplying these 
structures in the posterior portion of the vestibule, and forming a rich 
plexus in the connective tissue of the maculse and cristse, and a more 
scanty network in the remaining portions of the membranous labyrinth. 
The cochlear division of the internal auditory artery, according to 
Siebenmann, promptly subdivides into the cochlear artery proper, which 
appears as the continuation of the vessel, and the vestibulocochlear THE INTERNAL EAR 
715 
artery, which supplies the macula sacculi, the posterior ampulla, and the 
adjacent portions of the utricle and posterior semicircular canal. This 
vessel also supplies the early portion of the first turn of the spiral 
cochlea. 
The true cochlear artery enters the modiolus and supplies a branch 
to the remaining portion of the first cochlear turn, and a terminal 
branch which passes as far as the apex of the cochlea, distributing its 
Fig. 591.-Scheme of the Vascular Terminations in the Wall of the Coch- 
lear Canals. 
c, capillary vessels in the spiral ligament; De, cochlear duct or scala media; d, 
capillaries in the limbus spiralis; f, scala tympani; g, arteriole; h, spiral ganglion; 
i, vena spiralis inferior; v, scala vestibuli; j, vena spiralis superior. (After Bohm 
and von Davidoff.) 
branches to the last two turns. All of these vessels are characterized 
by their peculiarly tortuous course. They distribute terminal branches 
to the limbus spiralis and to the connective tissue of the membranous 
scala vestibuli, extending as far around this canal as the spiral ligament. 
No vessels cross in the basilar membrane. 
The veins collect the blood from the limbus spiralis and the wall of 
the scala tympani and form venous trunks within the modiolus, which 
correspond more or less closely with the arteries. Two of the cochlear 
radicals of the venous tributaries are important by reason of their posi- 
tion and relative size: the vas prominens of the prominentia spiralis of 
the stria vascularis, and the vas spiralis beneath the organ of Corti. 716 
THE EAR 
Those veins coming from the wall of the scala tympani unite to form 
superior and inferior spiral veins in the inner wall of the scala tympani. 
These vessels chiefly empty into the vena aqueductus cochlea which 
finds its way. through the aqueduct to the internal jugular vein. Other 
branches from the interior of the cochlea unite to form the central vein 
of the cochlea, which becomes the chief radical of the internal auditory 
vein, and thus enters either the transverse or inferior petrosal sinus. 
The veins from the utricle and semicircular canals mostly enter the 
vena aqueductus vestibuli, which follows its aqueduct to the superior 
petrosal sinus. 
It will be perceived that the blood has three chief avenues of exit from 
the labyrinth: 1, by the vena aqueductus vestibuli; 2, by the vena aque- 
ductus cochleae; and, 3, by the internal auditory vein. The greater 
portion of the blood pursues the second course and thus finds its way to 
the internal jugular vein, the smaller remainder entering the petrosal 
sinuses by one of the other two avenues. 
Lymphatics.-The internal ear contains relatively few lymphatic 
vessels but is richly supplied with broad lymphatic spaces. Anastomosing 
vessels are found in the periosteum and membranous wall of the laby- 
rinth. These communicate with the perilymph spaces between the peri- 
osteum and the membranous wall in the vestibule, and with the vestibular 
and tympanic seal® in the cochlea. The perilymphatic spaces are con- 
nected with the subdural space of the meninges by means of lymphatic 
channels in the aqueductus cochleae. The perilymph of the vestibule also 
communicates with the subdural space through vessels which follow the 
sheaths of the nerves. 
The endolymph cavities of the several divisions of the membranous 
labyrinth communicate freely with one another; by means of the ductus 
endolymphaticus a connection is also established though the aqueductus 
vestibuli with the subdural space, the blind terminal saccule of this 
canal, the saccus endolymphaticus lying upon the posterior surface of 
the petrous bone and in contact with the dura mater. 
FUNCTION OF THE COCHLEA 
The cochlea is the essential organ of hearing. The fundamental struc- 
ture concerned in audition is the spiral organ of Corti. The physiology 
of sound perception involves proximally the stimulation of the hair cells 
of Corti's organ by the tectorial membrane. This membrane is thrown DEVELOPMENT OF THE EAR 
717 
into synchronous vibrations by the undulations in the endolymph of the 
cochlear duct transmitted through the vestibular membrane from the peri- 
lymph. The latter receives the sound waves through the foot-plate of the 
stapes. 
The Helmholtz (1896) theory of tone perception, until recently widely 
accepted, postulated sympathetic vibrations, in resonance with atmospheric 
waves, on the part of the fibers of the basilar membrane. This view has 
been shown to be untenable, notably by Shambaugh (Archives of Otology, 
37, 6, 1908) and by Hardesty (Amer. Jour. Anat., 8, 2, 1908). The basilar 
membrane contains only a little more than half as many fibers as the 
maximum number of vibrations (40,000 double vibrations per second) com- 
monly audible; moreover, it does not possess the physical and histologic 
properties demanded by the 'resonance theory' of tone perception. Har- 
desty has shown that the tectorial membrane on the contrary does answer 
the requirements of an alternative theory, a modification of the earlier 
'telephone theory' of Rutherford (1886) ; and he has succeeded in construct- 
ing an apparatus which simulates the cochlea, and imitates its presumed 
functional activity at least in the lower ranges of the tone scale. 
Hardesty suggests 'that notes up to a certain pitch throw the entire 
natural tectorial membrane into vibrations of corresponding frequencies 
and that sensations of pitch are determined by the frequency of impinge- 
ment of the membrane upon the auditory hairs, intensity being determined 
by the amplitude and quality by the quality of the wave motion imparted. 
Further, that the highest notes within the range of the auditory apparatus 
throw, according to their frequency, only varying extents of the smaller, 
basal end of the tectorial membrane into vibration, being so damped out 
in passing toward the apex of the cochlea, overcoming friction, the inertia 
of the endolymph and that of the membrane itself, as not to produce vibra- 
tions in the heavier, apical portions.' (Anat. Rec., 8, 2, 1914). 
In essence, the tectorial membrane is conceived to respond in its sev- 
eral parts in the manner of a physical resonator to tones of different pitch 
(Shambaugh). According to this conception, tone analysis is accomplished 
peripherally, the specific stimulus being carried to the brain by the special 
sets of cochlear nerve fibers. 
DEVELOPMENT OF THE EAR 
The external ear develops in connection with the first branchial fur- 
row: the meatus from the deepened groove, the auricle through the fusion 
of definite tubercles on the adjacent branchial arches. 
The middle ear and auditory tube arise from the corresponding pharyn- 
geal pouch, the process involving a ventral elongation of the groove to form Fig. 592.-Semidiagrammatic Illustrations of Successive Stages in the De- 
velopment of the Internal Ear of the Chick. 
A, 45 hour embryo; B, 60 hour embryo; C, 5 day embryo; D, 7 day embryo; M, 
wall of neural canal at level of metencephalon; E, epidermal ectoderm; op, otic pit; 
oc, otocyst (otic vesicle); DE, ductus endolymphaticus; SE, saccus endolymphaticus; 
cd, cochlear duct; u, utriculus; dss, superior semicircular duct; dsl, lateral semi- 
circular duct. 
Fig. 593.-Wax Reconstructions of Three Early Stages in the Develop- 
ment of the Internal Ear (Membranous Labyrinth) of Man. 
A, lateral view, from a 6.6 mm. embryo; B, lateral view from an 11 mm. embryo; 
C, front view from a 20 mm. embryo (these correspond approximately to stages 
B, C, and D of the preceding figure). DE, ductus endolymphaticus; SE, saccus 
endolymphaticus; VP, vestibular pouch; cp, cochlear pouch; ap, absorption focus; 
c, crus; s, sacculus; u, utriculus; cd, cochlear duct; dss, dsp, and dsl, superior, pos- 
terior, and lateral semicircular ducts. (After Streeter.) 
718 DEVELOPMENT OF THE EAR 
719 
the tube and a subsequent dorsal dilatation, expanding as the tympanum 
to include the auditory ossicles which have meanwhile taken form in the 
adjacent mesenchyma. The mastoid cells are formed by a late erosion and 
invasion of the bone by the mucous membrane of the tympanum. 
The internal ear develops from a thickening in the epidermal ectoderm 
at the level of the third primary cerebral vesicle. This auditory anlage 
becomes invaginated to form an otic pit, the aperture of which subse- 
quently closes and thus separates an auditory vesicle or otocyst from the 
overlying parent ectoderm. At the point of closure medially a dorsal 
evagination arises to form the endolymphatic duct. At the upper pole of 
the vesicle appear the semicircular ducts through a process involving the 
elevation of three circular folds, the lateral walls of which fuse proximally, 
and subsequently disappear leaving a peripheral duct dilated at one end 
to form an ampulla. The cochlea arises at the opposite pole as a tubular 
evagination which becomes spirally disposed. The original vesicle persists 
as the utricle; on its anteromedial border is formed an alveolar evagina- 
tion, the saccule, which remains connected by a constricted duct, the utric- 
ulosaccular canal, to which is attached the ductus endolymphaticus. 
Each ampulla differentiates an elongated patch of neuro-epithelium, 
the cristce; in both utricle and saccule a similar oval patch appears, the 
maculce; the spiral organ of the cochlea develops in like manner through 
a specialization of the ectoderm along the floor of the membranous duct. 
The bony labyrinth develops from the mesenchyma originally envelop- 
ing the membranous labyrinth. The mesenchyma immediately surround- 
ing the membranous labyrinth becomes converted into a mucoid tissue 
which eventually disappears, leaving the perilymphatic spaces; these are 
bounded by periosteum, the innermost layer of which becomes modified into 
a mesenchymal epithelium. CHAPTER XX 
HISTOLOGIC TECHNIC 
The satisfactory examination of the tissues with the aid of the mod- 
ern microscope requires certain preparatory steps which are in certain 
cases very simple, in others very complicated. The present chapter deals 
briefly with the more important and simpler methods, and the general 
principles upon which they are based. 
THE EXAMINATION OF FRESH TISSUES 
Certain tissues may be examined immediately after they have been 
removed from the body. This method is applicable to blood, lymph, 
scrapings from the spleen, liver, uterus, and similar organs, small frag- 
ments of muscle, connective tissue, etc. 
A small drop of blood may be collected upon the under surface of a 
cover glass, which is then quickly dropped upon a glass slide and 
examined at once. The glass must be thoroughly cleaned, otherwise a 
thin preparation can not be obtained. Slides and covers should be 
washed in very dilute hydrochloric acid (about 10 per cent.), then 
washed in running water for several hours, and finally rinsed in 95 per 
cent, alcohol. Ordinarily slides and cover glasses can be sufficiently 
cleaned by simply dipping in alcohol and drying with a linen cloth. 
Scrapings from the epithelium of the mouth, or from similar mucous 
membranes, may be prepared in the same manner as blood, and ex- 
amined while still suspended in their own fluids. Most tissues, however, 
are not sufficiently well moistened for examination after this manner; 
the preparation must then be diluted with some inert fluid. Normal 
saline solution may be used for this purpose; the following formula is 
recommended : 
Sodium chlorid 0.75 to 0.9 grm. 
Distilled water 100 c.c. 
720 THE DISSOCIATION OF TISSUES 
721 
Some histologists regard a 0.6 per cent, solution preferable. Normal 
salt solution has become quite generally displaced by Ringer's Solution, 
which corresponds more nearly to blood plasma and is less likely to 
produce distortion. This is prepared, adjusted to tissues of warm- 
blooded animals, according to the following formula: 
Sodium chlorid 90.0 
Potassium chlorid 4.2 
Calcium chlorid (anhydrous) 2.4 
Potassium bicarbonate 2.0 
Distilled water 10000.0 
In order to render the nuclei more conspicuous a drop of a 5 per 
cent, aqueous solution of acetic acid may be added. This, however, will 
dissolve the collagenous fibers and albuminous granules. The nuclei 
may be stained by the addition of a drop of a 1 per cent, aqueous solu- 
tion of methylene blue. 
A 40 per cent, solution of glycerin in distilled water also is useful 
as an examining medium; better still, the tissues may be suspended 
in a mixture of equal parts of 95 per cent, alcohol, glycerin, and dis- 
tilled water. This mixture is especially useful, for in it tissues may be 
kept for a long period without deterioration. 
Amniotic fluid obtained from pig fetuses is also valuable as a medium 
for the examination of fresh tissues. 
Hogan (Jour. Amer. Med. Assoc., 64, 9, 1915) has devised a normal- 
salt-gelatin mixture with a colloidal constitution like that of blood serum, 
which serves as a favorable indifferent medium for the examination 
of fresh blood and other delicate tissues. For the method of preparation 
reference should be made to the original article. 
THE DISSOCIATION OF TISSUES 
It is frequently desirable to dissociate tissues to a certain extent into 
their component elements prior to microscopical examination. This is 
accomplished by teasing, or by the solvent action of relatively strong 
acids or alkalies. Isolation by the latter method is known as maceration. 
For teasing, minute fragments of tissue are separated by the aid of 
needles or scissors and placed on a clean slide, where they are to be 
kept always moistened with normal saline solution or other isotonic 722 
HISTOLOGIC TECHNIC 
fluid. For their further manipulation a dissecting microscope is useful, 
though not essential. Two sharply pointed needles, mounted in wooden 
handles, are to be used. 
The fragment of tissue is pinioned with the needle held in the left' 
hand, and with that in the right the tissue is gently torn by a rhythmic 
combing motion, being very careful to avoid squeezing the tissue between 
the needle and the slide. With a little practice bundles of fibers, groups 
of cells, etc., are readily isolated sufficiently to be studied under moder- 
ate magnification. During the teasing, the fragments of tissue should 
be kept well moistened, and are to be frequently inspected under low 
magnification to determine the progress of the operation. When satis- 
factorily prepared, a cover glass may be applied, and the preparation 
examined under higher magnification. 
In applying a cover glass care should be taken to permit one edge 
of the cover to first touch the slide while being held at an angle of 30 
degrees to 40 degrees. If the cover is then gently lowered into place, the 
air is forced out before the advance of the fluid, and the many air 
bubbles which would otherwise be included are not found in the prepara- 
tion. 
The method of teasing is particularly applicable to the study of the 
connective, and peripheral nervous tissues. Collagenous fibers, elastic 
fibers, fat cells, and nerve fibers are readily isolated in this way. If 
desired, they may be stained by the addition of a drop of a solution of 
methyl green, picrocarmin, etc. 
Chemical Dissociation.-It is necessary to dissociate many tissues 
by chemical means, either because of the firm union of the elements 
composing the tissue or because they may be too delicate and fragile to 
withstand the mechanical teasing. Epithelial cells, nerve cells, and 
muscle fibers are readily macerated in this way. 
For the dissociation of muscle fibers small cubes (0.25 to 0.5 c.c.) 
are placed for ten to thirty minutes in the following solution: 
Strong nitric acid100 c.c. 
Potassium chlorate, sufficient to saturate. 
The fragments of tissue should be handled with glass rods. After 
some minutes they begin to disintegrate at the surface, and should then 
be transferred to running water, where they are left to wash from three 
to twelve hours. The pieces of tissue are then transferred to a mixture 
of equal parts of alcohol, glycerin, and water, and thoroughly shaken. FIXATION 
723 
Muscle fibers isolated in this way may be kept for months or even 
years. 
Caustic potash (potassium hydroxid) is also a valuable dissociator 
for muscle tissue. The solution commonly used is made by dissolving 
40 grams of the potash in 60 c.c. of water. Cardiac muscle is suffi- 
ciently macerated in twenty minutes. The tissue must then be thor- 
oughly washed, and may be preserved in the alcohol-glycerin mixture. 
Epithelium may be dissociated by teasing or by the action of a 40 
per cent, solution of potassium hydroxid, or by means of a 10 or 20 
per cent, aqueous solution of 'lysol/ and preserved, if desired, in the 
mixture of alcohol, glycerin, and water. 
Nerve cells may be isolated from the anterior horns of the spinal cord 
or other gray matter of the central nervous system by teasing. They 
may also be isolated by immersion in a 0.2 per cent, aqueous solution 
of formalin in normal salt solution for two to twenty-four hours, or in 
a 0.2 per cent, aqueous solution of potassium bicarbonate, two to five 
days. Afterward they are transferred to a normal saline solution or to 
a mixture of alcohol, glycerin, and water, and isolated by shaking, 
assisted, if necessary, by gentle teasing. 
Similar preparations may also be made by placing small fragments 
of tissue in 30 per cent, alcohol (Ranvier's alcohol; 2 parts water, 1 
part 95 per cent, alcohol) for two days or more; then shake thoroughly, 
allow the debris to settle, remove a drop of the fluid with a pipette, and 
examine. 
For the isolation of the elements of the epidermis, hair and nails, 
stronger solutions are required. Concentrated sulphuric acid may be 
employed. After maceration is complete, the cells must be thoroughly 
washed in water and may then be preserved in the alcohol-glycerin 
mixture. A caustic potash solution, acting for two to three hours, is 
also serviceable with these tissues. 
Any of the above preparations may be stained by the addition of a 
small drop of a solution of eosin, picrocarmin, or methyl green to the 
fluid in which they are examined. 
FIXATION 
For the preservation of tissue, and as a preparation for further 
manipulation, most tissues require to be 'fixed.' Innumerable formulas 
have been advocated for this purpose, many of them having as their 724 
HISTOLOGIC TECHNIC 
object the demonstration of certain structural features by the after ap- 
plication of special staining methods. 
The action of the fixing fluids is in most cases dependent upon the 
combination of the reagent with the chemical elements of which the 
tissue consists; very elaborate compounds are thus formed. 
The distinction between a physical and a chemical combination of 
a dye with particular tissue elements must be emphasized. 
The following reagents are recommended for general use. The choice 
of a fixative is in great measure determined by the staining method 
which is to be afterward applied. 
Alcohol.-This is especially useful for the fixation of the glandular 
organs. Tissue may be placed directly in 95 per cent., or in absolute 
alcohol. The fluid is to be changed in twenty-four hours, and again in 
five to seven days. This method of fixation is desirable for after-staining 
of the nervous tissues with methylene blue and for the demonstration 
of glycogen in the hepatic cells, cartilage, etc. Alcohol causes consider- 
able distortion of the internal architecture of the cell by its rapid and 
forceful diffusion from the surface toward the center of the tissue, the 
cytoplasmic granules often being in this way forced to one side of the 
cell. This result may be partially avoided by the use of 'graded alcohol," 
viz., 67 per cent, alcohol for three to twelve hours, 82 per cent, for 
twenty-four hours, and finally 95 per cent, alcohol, which should be once 
changed after a few days. Glycogen, however, is partially dissolved 
by the action of the dilute alcohols. 
The graded alcohols may be derived from the 95 per cent, stock 
supply by the following dilutions: 
95 per cent, alcohol, 1 part; distilled water, 1 part=48 per cent. 
95 per cent, alcohol, 3 parts; distilled water, 1 part=67 per cent. 
95 per cent, alcohol, 5 parts; distilled water, 1 part=82 per cent. 
For practical purposes these grades may be regarded as 50, 70 and 80 
per cent, respectively; they may be derived also by the use of the fol- 
lowing formula: 
265 c.c. 95% ale. -j- 235 c.c. aq. dist. = 50% ale. 
370 c.c. 95% ale. % 130 c.c. aq. dist. - 70% ale. 
425 c.c. 95% ale. -j- 75 c.c. aq. dist. = 80% ale. 
The distortion from the use of strong alcohol, as well as the disso- 
ciation which follows the use of the weaker strengths, may also be par- FIXATION 
725 
tially avoided by the addition of a little iodin to the stronger alcohol, 
or by combination with acetic acid, thus: 
Glacial acetic acid 5 c.c. 
95 per cent, alcohol 60 c.c. 
Distilled water 35 c.c. 
After fixation for three to twenty-four hours the tissues are washed, 
and hardened by immersion for twenty-four hours in each strength of 
graded alcohol (50, 70, 80 and 95 per cent.), and may be kept indefinitely 
in 80 per cent, alcohol. Tissues should always be stored in 80 per cent, 
alcohol. Lower grades tend to macerate, higher grades to harden unduly. 
Carnoy recommends also a mixture of glacial acetic acid and abso- 
lute alcohol in the proportion of 1 to 3; this gives excellent results with 
muscular tissues. 
Tissues for fixation by these or any subsequent method are pref- 
erably cut into small cubes; a size not exceeding 0.5 to 1 cm. is most 
desirable. If larger pieces of tissue are necessarily used, the reagents 
will each require increased time to insure complete penetration. 
Mercuric Chlorid (Corrosive Sublimate).-This salt is to be used in 
saturated aqueous solution. As it dissolves with difficulty in cold water, 
the use of a hot, normal saline solution hastens the operation. 
Mercuric chlorid is an excellent fixative for cytoplasm, but gives still 
better results when combined with a nuclear fixative such as acetic acid. 
The following is an excellent method for general use: 
Mercuric chlorid 7 grm. 
Sodium chlorid 0.75 grm. 
Distilled water 95.0 c.c. 
Just prior to use add 5 c.c. of acetic acid. 
Small pieces of tissue remain in this corrosive acetic mixture for 
two to twenty-four hours, and are then transferred to graded alcohol, 
beginning with 70 per cent, and remaining twenty-four hours in each 
strength. Most dyes will act perfectly on tissue fixed in this way. If, 
however, the presence of mercury interferes with the action of a dye, 
this salt can be readily removed by the addition of a few crystals of 
iodin to the higher grades of the graded alcohols, renewing the iodin if 
necessary until it is no longer decolorized. 
Formalin.-Tissues may be fixed in formalin (formol), a 40 per 726 
HISTOLOGIC TECHNIC 
cent, solution of formaldehyd gas, which is to be used in strengths vary- 
ing from 5 to 20 per cent. Small pieces should be left in the weaker 
solutions (5 to 10 per cent.) from six hours to two days, not longer. 
In the stronger solutions (10 to 20 per cent.) tissues should remain 
for only two to six hours. More prolonged immersion in the fixative 
causes considerable swelling. As a rule, the stronger solutions are pref- 
erable; this is especially true for the fixation of the cells of lymphoid 
tissue. The 10 per cent, formalin solution is valuable for the fixation of 
human embryos. For the hardening of nervous tissues, also, the 10 per 
cent, solution is very serviceable. 
After fixation, the tissues are transferred directly to 80 per cent, 
alcohol, with one or several changes. This method gives excellent re- 
sults with lymphoid and epithelial tissues, but does not bring out the 
finer details of cytoplasmic structure. 
Potassium Bichromate (Bichromate').-This salt has been used in 
all sorts of combinations; those which follow may be specially recom- 
mended. Muller's solution is employed for the fixation of the tissues 
of the central nervous system, and must be used when fixation is to be 
followed by any of the Weigert hematoxylin staining methods. Applied 
to the fixation of other organs, Muller's fluid is apt to produce some 
maceration and better results are usually obtained with Muller-formol or 
with Tellyesniczky's solution. 
For the special fixation of cytoplasmic granules, and also for after- 
staining with Mallory's connective tissue stains, Zenker's solution yields 
better results. 
Muller's Solution: 
Potassium bichromate 2.5 grm. 
Sodium sulphate 1.0 grm. 
Water 100.0 c.c. 
Pieces of tissue are left in the fluid for one to six weeks; large 
pieces of the spinal cord or brain require four to six weeks. If left too 
long the tissues will become brittle. After fixation, the tissue is washed 
thoroughly in running water for twelve to twenty-four hours, and 
hardened in graded alcohol. 
A relatively large volume of the fixing fluid should be used, and 
it should be frequently changed. It should not be allowed to become 
turbid nor to deposit crystals: this is avoided by frequent changes and 
by keeping the jars in the dark, or at least in such a position that 
they are not exposed to a bright light. FIXATION 
727 
Tellyesniczky's Fluid: 
Potassium bichromate 3 grm. 
Water 100 c.c. 
Glacial acetic acid (added just before use) 5 c.c. 
Pieces of tissue are placed in a considerable volume of the fixing 
fluid and left for three to seven days. They are then washed in run- 
ning water for twelve to twenty-four hours, and hardened in graded 
alcohol. (Where tissues are first washed in water, the graded alcohols 
must begin with the 50 per cent, strength.) This fluid yields excellent re- 
sults with muscular and glandular tissues, and is particularly serviceable 
where pieces of considerable size must be used, e.g., whole embryos. 
Orth's Fluid (Muller-formol) : 
Muller's fluid 95 to 90 c.c. 
Pure formalin 5 to 10 c.c. 
This is an excellent fixative for general use, for by it most tissues 
are well preserved. Small pieces of tissue are left in a considerable 
volume of the fluid for one to five days, washed thoroughly in running 
water for twelve to twenty-four hours, and hardened in graded alcohol. 
The washing should be so thorough as to remove all excess of the 
chromium compounds, otherwise difficulty will be experienced in obtain- 
ing satisfactorily stained preparations. 
Chrom-Acetic-Formalin Mixture.-This makes an excellent fixing 
fluid for general embryologic work. 
Mix and keep in stock the following solution: 
1 per cent, chromic acid 16 volumes 
Glacial acetic acid 1 volume 
At the time of using add to 2 volumes of the stock mixture, 1 volume 
of formalin. 
Wash in water from twenty minutes to two hours according to size. 
Zenker's Solution: 
Potassium bichromate 2.5 grm. 
Sodium sulphate 1.0 grm. 
Mercuric chlorid 5.0 grm. 
Distilled water 100.0 c.c. 
Just prior to use add 1 c.c. of glacial acetic acid to each 20 c.c. of the 
fluid. 728 
HISTOLOGIC TECHNIC 
Small pieces of tissue, only, should be used. They remain in a con- 
siderable volume of the solution for three to twenty-four hours, after 
which they are thoroughly washed in running water for twelve to 
twenty-four hours, and hardened in graded alcohol. The corrosive 
sublimate deposits crystals in the tissue. These may be removed by the 
addition of a crystal of iodin (or tincture of iodin) to the stronger alco- 
hols until decolorization no longer occurs. If the mercury is not thus 
removed it will be difficult to obtain well stained specimens, and the 
presence of the crystals may cause much confusion. In obstinate cases 
Lugol's solution is recommended in place of tincture of iodin (alcoholic 
solution of iodin), to be added until the alcohol has a 'port wine' color. 
(See page 758.) 
This is probably the best fixing fluid for general routine histologic 
work. The presence of the acetic acid, however, dissolves the more deli- 
cate albuminous granules. To avoid this, formalin may be substituted 
in the same proportion, and added in the same way, for the acetic acid. 
This modified Zenker's fluid (Helly's fluid) is particularly valuable 
for the preservation of tissues where it is desired to investigate the 
granular cytoplasmic contents, e.g., blood cells in embryos, etc. 
Flemming's Fluid (strong solution) : 
Chromic acid, 1 per cent, aqueous solution 15 parts 
Osmic acid, 2 per cent, aqueous solution 4 parts 
Glacial acetic acid 1 part 
The mixture should be newly made, from stock solutions of the 
ingredients, immediately before using. The stock mixture undergoes a 
deteriorating chemical transformation. 
Pieces of tissue should not be more than 2 to 3 mm. in thickness 
and should be left in the solution and kept in the dark for one to twenty- 
four hours, according to the results desired. For mere fixation a short 
immersion is sufficient; for blackening fat and the myelin of medullated 
nerve fibers the longer period is necessary. After fixation the tissues 
are to be washed in running water for three to twenty-four hours, and 
hardened in graded alcohol. 
This fluid gives splendid results for the fixation of the finer cyto- 
logical elements of glandular epithelium; and for • the demonstration 
of nuclear constitution, chromosomes, and mitotic figures, it is unex- 
celled. It serves also to demonstrate the presence of fat and myelin, 
which are blackened by the osmium tetroxid. When used for the dem- 
onstration of fat in sections, chloroform should be substituted for FIXATION 
729 
xylol in the embedding process. It does not penetrate the tissues very 
readily, and the surfaces of the piece are usually destroyed by over- 
fixation. 
Kleinenberg's Fluid: 
Saturated aqueous solution of picric acid 99 c.c. 
Sulphuric acid 1 c.c. 
Shake well, filter and dilute the filtrate with 200 c.c. of distilled water. 
Small pieces of tissue should be left in the fluid for about three 
hours and then transferred to 70 per cent, alcohol, which is changed 
two or three times during the first day. Hardening is continued in 
80 and 95 per cent, alcohols, which are to be frequently changed. The 
picric acid will be slowly dissolved by the alcohol, but will not be en- 
tirely removed even after a considerable time; a trace does no harm. 
This fluid gives excellent results with small pieces of embryonic 
tissue, and possesses the additional advantage of removing the calcareous 
salts from partially calcified bone; it is not, however, a strong decalcify- 
ing reagent. 
When a fixative is employed which contains picric acid, the tissue 
must never be washed in water, but is transferred directly to 70 per 
cent, alcohol. 
Bouin's Fluid: 
Picric acid, saturated aqueous solution 75 c.c. 
Formalin 20 c.c. 
Glacial acetic acid 5 c.c. 
Small pieces of tissue are fixed from three to twelve hours, trans- 
ferred to 70 per cent, alcohol, and then passed through the higher 
grades. This is an excellent fluid for the fixation of embryonic ma- 
terial. For chromosome studies it is probably surpassed only by Flem- 
ming's fluid. 
Van Gehuchten's Fluid (Carnoy's fluid, No. I) : 
Absolute alcohol 60 c.c. 
Chloroform 30 c.c. 
Glacial acetic acid 10 c.c. 
Very small pieces of tissue should be used. They should be left in 
the fluid three to twelve hours, and the vessel tightly closed to prevent 
evaporation of the volatile fluid. The tissues are then transferred to 730 
HISTOLOGIC TECHNIC 
several changes of absolute alcohol to remove the fixing fluid and com- 
plete the dehydration. 
This fluid is especially valuable for the fixation of lung tissue. It 
can be advantageously applied only to perfectly fresh, viz., living tissues. 
Gilson discovered that this fluid could be advantageously modified 
for cytologic purposes by saturation with mercury bichlorid. About .20 
grams should be added to the above mixture. As thus modified the 
solution is commonly known as Carnoy's fluid, No. II. Its penetrating 
properties are very high and the degree of fixation delicate. Tissues 
should not be left in the fluid for more than an hour. The after- 
treatment is the same as with the simple solution, except that tincture of 
iodin must be used with the alcohols. 
Gilson's Fluid (Mercuro-nitric mixture) : 
Bichlorid of mercury 5 grm. 
Nitric acid (approximately 80 per cent.) 4 c.c. 
Glacial acetic acid 1 c.c. 
Alcohol (70 per cent.) 25 c.c. 
Distilled water 250 c.c. 
Fix small pieces of tissue from three to twelve hours, transfer 
directly to 70 per cent, alcohol, and pass through the higher grades, 
with the addition of tincture of iodin. This fluid has a high degree 
of penetration, and produces faithful and delicate fixation. 
Heat.-This is a useful agent for the fixation of blood, marrow 
cells, and scrapings from glandular and other organs, which are not 
to be afterward stained with methylene blue or its compounds. For 
this purpose smears made upon glass slides or cover glasses are quickly 
dried in the air, heated to 110 degrees C. for twenty to thirty minutes, 
and are then ready for immediate staining. 
The smears are made in the following manner: Slides or cover 
glasses should be thoroughly cleaned with a final rinsing in equal parts of 
absolute alcohol and ether. A small drop of blood or other fluid is 
collected by quickly touching the center of a cover glass to a drop of 
ordinary size. This cover glass is then immediately dropped upon the 
surface of a second one, and the two are drawn apart by a rapid sliding 
motion, the two surfaces being maintained parallel to one another during 
the motion. The success of the maneuver depends upon its rapidity, and 
to obtain very thin preparations some little dexterity is required. 
Fairly good smears are more easily made with slides. A drop of blood 
is collected upon the end of one glass slide whose edge must have been DECALCIFICATION 
731 
ground. The end of the slide with the drop of blood is then touched to 
the middle of a second slide, the drop spreads out between the two, and 
the first slide is rapidly drawn over the surface of the second, while 
being held at an angle of about 45 degrees. A broad smear is thus 
left upon the surface of the second slide, some portions of which are 
sufficiently thin, other portions too thick for use. Like the former 
maneuver the success of this depends upon rapidity, cleanliness, and the 
use of a sufficiently small drop of fluid. 
Fixation by Vapors.-Smears of fluids or very thin pieces of tissue 
may be fixed by a very brief exposure to the vapor of osmium tetroxid, 
formalin, etc. This method is only useful in occasional instances. Os- 
mium tetroxid vapor has been shown to preserve faithfully the mito- 
chondria in young cells from tissue cultures (M. R. and W. H. Lewis, 
Amer. Jour. Anat., 17, 3, 1915). 
In all methods of fixation where pieces of tissue are immersed in 
the fixing and hardening fluids, it is desirable to prevent the distortion 
of the object from the pressure of contact with the glass container. 
This is accomplished by suspending the object by means of a thread, or 
by resting the tissue upon a thin layer of cotton placed in the bottom of 
the jar. 
DECALCIFICATION 
Tissues containing bone or other calcareous material require decalci- 
fication before they can be sectioned for examination. If the calcareous 
deposit is limited in amount, as in early fetal tissues, this can be ac- 
complished and the tissue fixed at the same time by the use of Kleinen- 
berg's fluid, a saturated aqueous solution of picric acid, or a 5 to 10 
per cent, aqueous solution of sulphurous acid, the tissues being per- 
mitted to remain in the decalcifying fluid until a needle or slender scal- 
pel can be readily pushed to the most central portions without producing- 
great resistance or any grating sensation. 
For well developed and mature bones the above methods are in- 
sufficient, and stronger acids must be relied upon. Nitric acid is the 
one most generally used for this purpose. The tissue should have been 
previously fixed, Muller-formol, Zenker's fluid, or mercuric chlorid being 
the preferable fixatives. The fixed and washed tissues are placed in 2 
to 5 per cent, nitric acid, and the fluid changed daily until decalcifi- 
cation is complete. They are then thoroughly washed in running water 
for twelve to twenty-four hours and hardened in graded alcohol. 732 
HISTOLOGIC TECHNIC 
INJECTION 
Injection is used either for the rapid dissemination of fixing fluids 
through whole organs, embryos, etc., or for the demonstration of blood 
or lymphatic vessels. For the former purpose mercuric chlorid is the 
most useful fixative, since it may be immediately followed by the in- 
jection of a hardening fluid, alcohol, by which the remaining mercury 
is dissolved out of the tissue before overfixation occurs. For the latter 
purpose a colored fluid, either aqueous or gelatinous, is forced into the 
blood or lymphatic vessels. Berlin blue, carmin, vermilion, and lamp- 
black are the coloring matters most frequently used. The last two 
merely require suspension in a gelatinous or an aqueous menstruum; 
the preparation of Berlin blue and carmin is somewhat more com- 
plicated. 
Berlin Blue Gelatin Mass: 
Saturated aqueous solution (1 to 20) of 
Berlin blue (Griibler's) 100 c.c. 
Pure French gelatin (in sheets) 5 to 10 grm. 
The gelatin should be quickly washed to remove dust, etc., and then 
placed for several hours in a very little distilled water until it becomes 
swollen and soft. The superfluous water is then poured off, and the 
gelatin melted over a water bath. The warmed solution of Berlin blue 
may now be added, a little at a time, and continuously stirred. Finally, 
the mixture is filtered through cotton flannel (or flannel) which has 
been previously wrung out of hot water. If the mass is not to be used 
at once, a few crystals of thymol may be added as a preservative, or, 
after cooling, a little methylic alcohol may be floated upon the surface of 
the solidified mass. It is better to use it at once. 
Carmin Gelatin Mass: 
Carmin (Griibler's) 3 grm. 
Ammonium hydrate, strong 6 c.c. 
Pure French gelatin 7 grm. 
Distilled water 80 c.c. 
The gelatin is prepared and melted as above, 50 c.c. of the water being 
used, and the evaporation replaced. The carmin is rubbed up in a 
mortar with the remaining 30 c.c. of the water, and the ammonia is 
added to render the carmin soluble. The mixture is now permitted to HARDENING 
733 
stand for two hours, after which it is neutralized by the gradual addi- 
tion of 4 to 6 c.c. of glacial acetic acid, the mixture being constantly 
stirred, and the latter portions of the acid diluted with four volumes 
of distilled water, and added drop by drop. The acid soon changes the 
color of the mixture from a purplish carmin to a bright crimson. Care 
should be taken not to add too much acid. When properly prepared, 
the sense of smell should detect both ammonia and acetic acid, and the 
fluid should have a dark crimson color (the addition of too much acid 
produces a brighter crimson). Should the mixture be slightly over- 
acidified a few drops of diluted ammonia will restore the proper con- 
dition. The carmin solution is now added to the gelatin mass, a little 
at a time and with constant stirring, and the whole is filtered through 
cotton flannel wrung out of hot water. 
The gelatin mass may be kept for a short time by being covered 
with methylic alcohol, but is better used at once. 
The pressure required for injection may be obtained by the gentle 
use of a hand syringe; by the displacement of the confined air in a 
large bottle or carboy by tap -water; or much better by the use of a 
water blast, of which the small glass type is relatively inexpensive and 
will furnish a pressure for injection about equal to 180 mm. of mercury. 
The air outflow of the water blast is connected by rubber tubing with 
a glass canula of proper size to fit the vessel injected, a Wolff bottle 
containing the warm injection mass being interposed. If a manometer 
is connected, by means of a T -canula, on the proximal side of the 
Wolff bottle, a relatively even and accurately measured pressure is 
assured. The amount of pressure should be at first low (20 to 40 
mm. of mercury), and should be gradually increased up to, but not 
much beyond, the normal blood pressure in the vessel injected. 
The injected organ is cooled rapidly in a refrigerator, or by being 
packed in ice or immersed in ice water. After solidification small pieces 
are immediately placed in 95 per cent, alcohol for fixation, dehydration, 
and hardening. 
HARDENING 
After proper fixation nearly all tissues require to be further hardened 
before satisfactory sections can be cut. This is accomplished by im- 
mersion in alcohol until dehydration is complete. The process requires 
from a day to a week, according to the size of the tissue and the volume 
and strength of the fluid. Various strengths of alcohol are advised. For 734 
HISTOLOGIC TECHNIC 
general use the procedure recommended by Gage ("The Microscope") 
is found to be very satisfactory. The tissues after fixation are suc- 
cessively placed for one or two days in each of the following strengths 
of alcohol-70, 80 and 95 per cent. They are then returned to 80 per 
cent, alcohol, where they may remain indefinitely, but it is generally 
safer to embed for sectioning without great delay; this is especially 
true of tissue which has been fixed with Zenker's solution. Most fixing 
fluids also harden; the terms 'fixing' and 'hardening' are consequently 
often used synonymously. 
EMBEDDING 
Thick sections may be obtained from the firmer tissues by freehand 
sectioning with a razor, but for the satisfactory preparation of thin sec- 
tions a microtome is a necessity and the tissues must have been pre- 
viously embedded to render them sufficiently firm. This is accomplished 
by infiltrating the tissue with celloidin or paraffin, either of which yields 
a firm, waxy consistence. 
Embedding in Celloidin.-Make a saturated solution of a little cel- 
loidin (Schering's) in a mixture of equal parts of alcohol and ether. 
The alcohol should contain no trace of copper sulphate. This solution 
is for convenience known as number III and should have a very thick, 
syrupy consistence. 
A small portion of number III is mixed with three to five times its 
volume of the alcohol and ether mixture, to obtain number II, which 
should have a somewhat viscid consistence. 
A second small portion of number III is diluted with ten to fifteen 
times its volume of the alcohol and ether, to produce celloidin number 
I, which should have a thin, watery consistence. 
Small pieces of tissue which have been thoroughly hardened in 95 
per cent, alcohol are treated as follows: 
1. Dehydrate in absolute alcohol, six to twenty-four hours. 
2. Place in the absolute alcohol and ether mixture, twelve to twenty- 
four hours. 
3. Place in celloidin number I, twelve to twenty-four hours. 
4. Place in celloidin number II, twelve to twenty-four hours. 
5. Place in celloidin number III, twenty-four to forty-eight hours, 
or longer. 
Pieces of tissue of considerable size may be satisfactorily embedded EMBEDDING 
735 
in celloidin, but should be passed through the successive solutions in 
a much more leisurely manner. Thus an eye requires two to three 
weeks, a large piece of the central nervous system three to four weeks 
for proper embedding. The tissue should now be fastened to a wooden 
block and the celloidin hardened. Ordinary wood yields its resins to 
the alcohol in which the blocks are to be kept; the white pine blocks 
which are commercially knowm as 'deck plugs' contain very little resin 
and are admirably adapted for the purpose. Vulcanized fiber blocks are 
still better, and glass blocks are also serviceable. The piece of tissue 
should be so oriented upon the block that the future sections may be 
cut nearly parallel to the block surface. Thick celloidin is then poured 
over the tissue; a few moments' exposure to the air cements it firmly 
to the block. After the celloidin has become firm by partial drying in 
air, the block may be stored indefinitely in 70 per cent, alcohol {stronger 
alcohol is apt to soften the celloidin), where the hardening is completed. 
If it is desired to harden the celloidin rapidly for early cutting, the 
block may be floated in a jar of chloroform, tissue down, for two or 
three hours. 
The final step in the embedding process may be accomplished ad- 
vantageously by allowing the tissue to remain in the slowly hardening 
thick celloidin in a shallow dish. Care must be taken to begin this 
step with sufficient celloidin to keep the tissue covered until the harden- 
ing is completed. The tissue may then be cut from the firm celloidin 
and blocked. 
Embedding in Paraffin.-If sections thinner than 15 p. are de- 
sired, paraffin embedding must be used; it is impossible to cut celloidin 
sections with any great degree of certainty thinner than 10 p to 15 /z. 
Paraffin sections are readily cut at 5, and may be cut as thin as 2 /z. 
The paraffin method is also to be selected for the rapid preparation 
of tissues for sectioning, but it is only applicable to small pieces of 
tissue. For large pieces better results will be obtained with celloidin. 
Many methods for the employment of paraffin have been extolled; the 
following can be recommended. The tissue, after fixation, should have 
been hardened in alcohol. 
1. Dehydrate in absolute alcohol twenty-four to forty-eight hours; 
very small pieces of tissue (1 to 2 mm.) may be completely dehydrated 
in three to six hours. 
2. Place in equal parts of absolute alcohol and xylol (xylene), one 
to three hours. 
3. Place in pure xylol until clear and translucent, one-half to two 736 
HISTOLOGIC TECHNIC 
hours. (For relatively large pieces of tissue cedar-wood oil or pure 
anilin oil may be substituted for the xylol). 
4. Place in melted paraffin containing a little xylol (or cedar oil) ; 
that which has been previously used for embedding does very well. 
5. Transfer to pure melted paraffin. 
6. Transfer to a second dish of pure melted paraffin (with melting 
point of about 54°). The object of these changes is to replace the 
xylol (or oil) with pure paraffin. If the xylol is not completely re- 
moved the tissue will contain bubbles and satisfactory sections cannot 
be made. 
7. Embed in a paper box or a watch glass. If glass is used the 
surface should be smeared with the least trace of glycerin to prevent 
adhesion. The box should be filled with pure melted paraffin, the tissue 
handled with warmed forceps, and placed with proper orientation so 
that it is completely covered with the melted paraffin. The paraffin is 
now rapidly cooled by immersion in cold water; in summer months 
ice water must be used. If a paper box is used it can be left to float 
on the water until the paraffin is thoroughly congealed. The manner 
of preparing these boxes is shown in Fig. 594. 
Considerable depends upon the choice of a proper grade of paraffin. 
That which melts at 58° to 65° is most desirable for use in temperate 
climates during the warmer months; during the winter months paraffin 
of 54° to 56° is preferable. If too hard, the paraffin cracks; if too soft, 
it fails to retain its form during sectioning. The former condition may 
be improved, if necessary, by the proximity of a small flame during the 
sectioning process, or by breathing upon the knife blade and tissue block; 
the latter fault may be remedied by placing the tissue for a short time 
in the refrigerator, just prior to cutting. 
SECTIONING 
The cutting of free-hand sections is so simple an operation as to 
scarcely require description. A small, inexpensive hand microtome and 
a sharp razor whose surfaces are ground flat, not concave, are all that is 
necessary. 
For more precise sectioning a stationary microtome is a necessity. 
Many types of these instruments are on the market. The Thoma type 
of instrument is specially adapted for celloidin work, but may also be 
used for paraffin sections. The Schanze instrument is very useful for SECTIONING 
737 
celloidin sections and may also be used for small paraffin sections. The 
Minot and the new Spencer rotary microtomes are specially adapted for 
the production of serial sections in paraffin. These instruments of them- 
selves suggest the manner in which they are to be used, and the technic 
is easily acquired. Like all delicate instruments, they must be kept well 
cleaned and properly oiled, to do good service. 
Much depends upon the choice and care of the knife. The micro- 
Fig. 594.-A Method of Preparing a Paper Box for Paraffin Embedding. 
I. A slip of paper, A, B, D, C, is folded, both ways, on the lines a-a', b-b', c-c', 
and d-d'. Then being folded into the form shown in II, it is laid flat, the section 
a, a', b', b, shown in I, being uppermost, and the paper is creased on the fines e-e' 
and/-/'. It is then opened, folded in the shape of a box, /, e, /', e', forming the bot- 
tom, and is secured by folding down the ends after creasing the paper on the lines 
e-f and f-e'. 
tome knives of Jung are of excellent quality and should be kept in good 
condition by the frequent use of the hone and strop. 
The hone should be of fine Belgian stone. It should be well moist- 
ened with water, the addition of a little fine soap being a distinct ad- 
vantage. The edge of the knife, carefully applied to the hone, should 
first be drawn obliquely from heel to toe and toward the operator, being 
held at a constant angle and drawn the whole length of the stone. The 
knife is then turned over and the motion is reversed, the knife being 
held obliquely at an angle equal to the previous one, the edge directed 738 
HISTOLOGIC TECHNIC 
away from the operator, and the knife pushed from heel to toe, 
the whole length of the stone. The motion being repeated, a sharp 
edge is gradually acquired, which can be finished by the use of the 
strop. 
In the use of the strop the motions are the reverse of those with 
the hone, the back of the knife in this case preceding its edge as it is 
drawn along the leather, and the draw should be from the toe to heel 
of the knife. The angle, however, between the knife and the hone and 
the knife and the strop should always be a constant one, and should 
be such that the microscopical Teeth' which are thus formed on the edge 
of the knife should be directed obliquely toward its heel. 
In sectioning, the knife should be so placed in the microtome that 
its edge crosses the paraffin-embedded object at right angles, and for 
ribbon sectioning the paraffin block should be so trimmed that it forms 
a perfect rectangle. In sectioning celloidin-embedded objects, the knife 
should cross the object at as acute an angle as possible. With paraffin, 
also, the stroke should be sharp and quick; with celloidin, somewhat 
slower and rhythmic. The knife should remain dry when used with 
paraffin; with celloidin both the knife and the object should be at all 
times well moistened with 70 per cent, alcohol. 
STAINING 
The sections, having been cut, are at once ready for staining, pro- 
vided they were embedded in celloidin. If paraffin was used for em- 
bedding, the sections have first to be fastened to the slide. This is 
accomplished in the following manner. 
The paraffin sections are properly arranged upon the surface of a 
clean slide, a few drops of water from a pipette are allowed to flow 
between the slide and the sections, so that the latter float upon the 
surface of the water; and the slide is gently heated over a small flame. 
Thus the paraffin sections are straightened; care should be used not 
to melt them. The excess of water is now carefully drained off and the 
slide placed in an oven and heated to about 40° C. for several hours, 
until thoroughly dried. Most tissues will now adhere firmly to the 
slide. If, however, the tissue was fixed with solutions containing bi- 
chromate of potassium the sections are Hable to come off the slide, a 
misfortune which may be avoided by the use of a celloidin adhesive, 
with or without the previous use of Mayer's albumin. As a precautionary STAINING 
739 
measure against the loss of sections, the routine use of albumin ad- 
hesive is recommended. 
Mayer's Albumin: 
White of egg, chopped with scalpel or scissors 
and filtered 10 c.c. 
Glycerin 10 c.c. 
Thymol a small crystal 
A drop of this fluid is rubbed evenly upon the surface of a clean 
slide. Distilled water is added with a pipette and the paraffin sections 
arranged upon the slide by the method detailed above. In the process 
of drying the albumin is coagulated and the tissue becomes firmly at- 
tached to the slide. The drying may be accomplished without special 
heating, but requires at least twelve hours at ordinary room tempera- 
tures. 
Celloidin Adhesive.-The sections having been fastened to the slide 
and dried, the paraffin is removed by dipping the slide into one or two 
changes of pure xylol, the xylol removed by washing with absolute al- 
cohol, and a few drops of very thin solution of celloidin (made by 
diluting thin celloidin, number I (see page 734) with eight or ten vol- 
umes of the alcohol and ether solvent) are poured over the sections. 
The solution of celloidin should be so thin as to scarcely leave an appreci- 
able film on the slide. The excess of celloidin is drained off and the 
film hardened by first flooding the slide with 70 per cent, alcohol, and 
after a few minutes transferring it to water. The sections will not now 
be removed from the slide except by mechanical violence. In handling 
serial sections of embryos, time may be saved, and the same end ac- 
complished, by simply spreading by means of a soft brush a thin film 
of the very thin celloidin solution over the dried paraffin sections. The 
sections may then be manipulated for staining in the usual way. 
Celloidin sections do not need to be fastened to the slide before 
being stained; they are sufficiently firm to be gently handled with a 
needle. 
Staining in Bulk.-It is occasionally desirable to stain tissue in bulk 
so that sections once cut can be immediately mounted. This is best 
accomplished by the use of a single stain applied to small blocks of 
tissue immediately after fixation and hardening, and is usually done in 
aqueous media. Borax carmin is the most useful dye for the purpose, 
and is used as described below, except that it will require two or three 740 
HISTOLOGIC TECHNIC 
days to penetrate the tissue. Delafield's hematoxylin also gives brilliant 
results in bulk staining. 
Regressive Staining.-Staining in bulk is necessarily a regressive 
process, viz., the tissue is first overstained and then partially decolorized. 
With borax carmin the decolorization is accomplished by acid alcohol 
(hydrochloric acid 1 c.c., 70 per cent, alcohol 100 c.c.). Since the 
stain is removed more rapidly from the cytoplasm than from the nucleus, 
a differentiation is thus produced. 
Progressive Staining.-In progressive staining the dye, having been 
once taken up by the tissue, is not removed, the differentiation of 
nucleus and cytoplasm being accomplished by the selective affinity of 
the dye. Thus, certain dyes are nuclear (basic), others are cytoplasmic 
(acid). The former possess a special affinity for the nucleus, the latter 
stain both nucleus and cytoplasm. 
Certain dyes may be used either progressively or regressively; in 
the former case care must be exercised that the section be not over- 
stained; in the latter case overstaining is impossible, but decolorization 
must be watched with care. 
Classification of Dyes.-Dyes may be classified according to their 
affinity for certain granules or other portions of the cytoplasmic struc- 
ture. A classification of this kind was advanced by Ehrlich through 
his pupil, G. Schwartze (Inaug. Dissert., 1880), and has been greatly 
elaborated by Pappenheim (Grundriss der Farbechemie, 1901). Such 
a classification is very incomplete and unsatisfactory, but in a very 
general way serves a useful purpose. The following is sufficient for our 
present needs: 
1. Basic dyes, those which color the chromatin of the nucleus 
(largely nucleic acid) and the so-called basophil granules. Hematein, 
methylene blue, methyl green, safranin, and basic fuchsin are examples. 
2. Acid dyes, those which are usually cytoplasmic dyes, and have 
an affinity for the acidophil (i.e., basic) granules. Such are eosin, 
Congo red, orange G, methyl blue, and acid fuchsin. 
3. Neutral dyes, which result from a due admixture of acid and 
basic colors, and which gives a specific tint to the so-called neutrophil 
or azure granules. Such dyes are Ehrlich's triacid mixture, eosinated 
methylene blue, etc. 
4. Specific dyes, which result from the due admixture of dyes with 
certain reagents, other dyes or chemicals, and which have a selective 
affinity for particular tissues. This is an indefinite class which includes 
Weigert's elastic tissue stain, Mallory's connective tissue stain, Sudan III STAINING 
741 
for fat, the intra vitam staining of nerve tissues with methylene blue, etc. 
Mordants.-The successful application of a dye requires that the 
tissue shall have a chemical affinity for the stain. This affinity may be 
either natural or artificial, e.g., eosin will color nearly all tissues under 
any ordinary conditions without the aid of any other reagent; the colora- 
tion is, however, largely a physical phenomenon, due to inhibition 
of the dye; hematoxylin, on the other hand, stains ordinary tissue but 
slightly, but its action is much enhanced by first acting upon the tissue 
with alum or a similar reagent. The alum, in this case, serves as a 
mordant. . 
A mordant should have a strong affinity for both the stain and the 
tissue. Hence it is that, after a tissue has been once stained by the 
aid of a mordant, it may be decolorized, partially or completely, by the 
second application of the same or another mordant of equal strength. 
Single Stains with Nuclear Dyes 
Hematein.-Hematein is the active principle of the dye, hema- 
toxylin, obtained by extracting logwood. Hematein is derived from the 
solutions of hematoxylin by oxidation, either by chemical reagents or by 
prolonged exposure to the air. As a dye it must be combined with a 
mordant, which, most frequently, is some form of alum. The following 
formulas are recommended: 
Alum Hematein (Mayer) : 
Alum hematein (Griibler's) 0.2 grm. 
95 per cent, alcohol 5 c.c. 
Saturated aqueous solution of ammonium 
alum 100 c.c. 
About 10 grm. of alum are required for this solution. The hematein 
should be first dissolved in the alcohol, with gentle heat if necessary, 
and afterward added to the warm solution of alum. The fluid is ready 
for use in two or three days, but will increase in strength for several 
weeks; it then requires dilution. 
Bohmer's Hematoxylin: 
Hematoxylin 0.5 grm. 
Absolute alcohol 5 c.c. 
Saturated aqueous solution of potassium alum 100 c.c. 742 
HISTOLOGIC TECHNIC 
The ingredients should be mixed as above and allowed to stand for 
eight to ten days in an open bottle and exposed to sunlight. Filter. 
Ripening will continue for some weeks, and the dye will require dilution 
from time to time with a saturated solution of potassium alum. 
Delafield's Hematoxylin: 
Hematoxylin ... 4 grm. 
95 per cent, alcohol 25 c.c. 
Saturated aqueous solution of ammonium alum 400 c.c. 
Mix as above and permit the fluid to stand in an open vessel ex- 
posed to the air and sunlight for three or four days. Add: 
Glycerin 100 c.c. 
Methylic alcohol 100 c.c. 
Expose to light in a cotton-plugged bottle. After two days filter. 
After several days filter again, and keep in tightly stoppered bottle. 
The fluid will ripen for several weeks and may require dilution with 
a saturated aqueous solution of alum, containing glycerin and methylic 
alcohol in the above proportions. 
This is a very deep nuclear stain, in fact it is so deep that, while 
the nuclei are sharply differentiated, the intranuclear structure is nearly 
obliterated. The stain is somewhat improved in this particular by the 
slight regressive action of very weak acids-e.g., hydrochloric, picric, or 
dilute acetic acid. This is a very useful dye for the toto staining of 
small embryos. 
Mann's Acid Hematein {Ehrlich's Hematoxylin) : 
Hematein (Griibler's) or hematoxylin crystals 2 grm. 
Absolute alcohol 100 c.c. 
Glycerin 100 c.c. 
Distilled water 100 c.c. 
Potassium alum 10 grm. 
Glacial acetic acid 10 c.c. 
The hematein (or hematoxylin) is dissolved in the acetic acid, with 
25 c.c. of the alcohol; the glycerin and the remainder of the aloohol 
are then added. The alum is dissolved in water by the aid of heat, 
and the warm solution is poured slowly while stirring into the solution 
of hematein. The fluid keeps indefinitely and is an excellent hematein 
stain for general use. Hematoxylin solutions may be ripened immedi- 
ately by the addition of small amounts of hydrogen peroxide (about 1 
c.c. to 200 c.c. of stain, neutralized by a few grains of sodium chlorid). STAINING 
743 
Application of the Hematein Stains.-All of the above solutions 
are used in a similar manner. Sections, either free or attached to the 
slide, are taken from water and immersed in the dye for three to five 
minutes; they are then thoroughly washed in water. The stained sec- 
tions are at first of a reddish-purple color, but soon become a deep 
blue from the slight alkalinity of the tap water used for washing. If 
necessary this alkalinity may be increased by the addition of one or two 
drops of ammonia to 500 c.c. of the water used for washing. 
Hematoxylin solutions require air and sunlight for ripening. After 
ripening is complete the solution should be kept tightly stoppered. The 
solutions should be filtered before using. Ehrlich's hematoxylin is prob- 
ably the best nuclear dye for general routine work. Better differentia- 
tion is usually obtained if the sections are over-stained (5 to 10 minutes) 
and then, after thorough washing, partially decolorized in a 1 per cent, 
solution of hydrochloric acid in 70 per cent, alcohol (a few seconds 
is usually sufficient), washed, and the color restored in an ammoniacal 
solution (1 per cent, aqueous solution of ammonium hydroxid). The 
sections must again be thoroughly washed, and the best differentiation 
is secured if the sections are now placed in very dilute watery eosin for 
ten to twelve hours. 
Methylene Blue.-This dye is a derivative of thionin, and may be 
similarly used. For staining fresh tissues the dye is used in 2 per cent, 
aqueous solution. Its preparations are not very permanent. The chief 
uses of this dye are in combination with eosin as a stain for blood; as 
a stain for nerve cells according to the method of Nissl; and as applied 
to living organs as a specific stain for nerve tissues after the method of 
Ehrlich. These methods will be described below. 
Methyl Green.-This dye is preferable to methylene blue as a stain 
for fresh tissues. It is used in 2 per cent, aqueous solution and applied 
as a progressive stain. It also enters into the composition of Ehrlich's 
triacid mixture. It is strongly basic. 
Garmin.-This valuable dye is derived from the cochineal bug, and 
is used either as a progressive or a regressive stain. For the former, 
picro-carmin or alum carmin are recommended; for the latter, borax 
carmin is preferable. 
Borax Carmin: 
Borax 4 grm. 
Distilled water (boiling) 100 c.c.; cool, filter, and add 
Carmin 3 grm.; when dissolved, add 
70 per cent, alcohol 100 c.c. 744 
HISTOLOGIC TECHNIC 
Mix the ingredients in the above order, and after twenty-four hours 
filter. It may be necessary to use a drop or two of ammonia to complete 
the solution of the carmin. This is again removed by evaporation. 
Tissues are to be overstained in the carmin solution, and differen- 
tiated in acid alcohol (70 per cent, alcohol containing 0.5 to 1 per cent, 
of hydrochloric acid) until the red color is no longer removed in clouds. 
The sections are then well washed with several changes of 95 per cent, 
alcohol, cleared and mounted. This is a most excellent dye for staining 
embryos in toto. 
Alum Carmin: 
Potassium alum 5 grm. 
Distilled water (hot) 100 c.c. 
Carmin 1 grm. 
Mix in the order given, boil for twenty minutes, and when cold filter. 
Piero-Carmin: 
Ammonium hydrate 5 c.c. 
Distilled water 50 c.c. 
Carmin 1 grm.; when dissolved, add 
Saturated aqueous solution of 
picric acid 50 c.c. 
Expose to light and air for two days; filter. 
Picro-carmin is used as a progressive stain. Since the picric acid is 
soluble in alcohol, dehydration should be rapid, or a crystal of picric 
acid should be added to the alchohol used for dehydration. 
Aceto-Carmin.-This is an invaluable fluid for certain purposes, 
especially where it is desired to study nuclear structure, chromosomes 
and spindles in fresh and uncut (teased) tissue. The tissue is simul- 
taneously fixed and stained in this mixture, and remains preserved in the 
fluid in a condition favorable for study for a considerable time. The 
stained tissue, e.g., insect testes, etc., is teased out on a slide in the fluid, 
covered with cover glass, and may then be studied under an oil immer- 
sion lens. The mitotic figures are almost as clear as in sectioned ma- 
terial. The solution is made by dissolving to saturation carmin in boil- 
ing acetic acid of 45 per cent, strength, and filtering. 
Safranin.-This dye is a coal-tar derivative; it is an excellent 
nuclear stain. Like carmin, safranin yields a deep red color. 
Safranin O (Griibler's) 1 grm. 
Distilled water 100 c.c. STAINING 
745 
1. Tissues taken from water are stained five minutes. 
2. Wash in water. 
3. Dehydrate rapidly in absolute alcohol. The alcohol removes some 
of the safranin, giving a regressive effect. 
Single Stains with Cytoplasmic Dyes 
Eosin.-This dye is a coal-tar derivative. There are no less than 
seventeen varieties of the dye on the market, of which five are in general 
use. These are: (1) yellowish alcoholic; (2) bluish alcoholic; (3) 
yellowish watery; (4) bluish watery; (5) pure French eosin. The most 
reliable of these dyes are manufactured by Griibler. The first and fifth 
varieties are to be recommended as blood stains, the first and fourth 
are the best for general use. Two distinct methods are based upon 
this choice of dyes. 
Method I: 
Yellowish alcoholic eosin 1 grm. 
70 per cent, alcohol 100 c.c. 
This stock solution is usually diluted with four to ten volumes of 
70 to 95 per cent, alcohol just before using. The stain is preferably 
preceded by the use of a nuclear dye, after which the sections should 
be dehydrated in 95 per cent, alcohol. 
1. Stain in the diluted eosin, one to five minutes, or until the sec- 
tions become a bright red color. 
2. Wash quickly in absolute alcohol, clear, and mount. The color 
is dissolved out during this process, producing some differentiation by 
regression. 
Method II: 
Bluish watery eosin 1 grm. 
Distilled water 100 c.c. 
The stock solution should be diluted with one to four volumes of 
distilled water before using. 
1. Tissues are taken from water and placed in the dilute eosin, one 
to five minutes. 
2. Wash quickly in water to remove the excess of the dye. 
3. Pass radially through graded alcohol, clear, and mount. 
Slight differentiation may be obtained by prolonging the washing 
in water, otherwise the stain is progressive. Much greater differenti- 746 
HISTOLOGIC TECHNIC 
ation is possible with either eosin method by making the stain very 
dilute and staining for twenty-four to forty-eight hours. 
Congo Red: 
Congo red 1 grm. 
Distilled water 100 c.c. 
A few drops of dilute acetic acid should usually be added to the 
above; the bright red color is then exchanged for a dull bluish red, and 
in this neutralized condition the stain usually gives the highest differen- 
tiation. The dye should be used in the same manner as watery eosin 
(see Method II, above). Congo red gives especially good results when 
applied to fetal and young tissues. 
Orange G.-There are many varieties of orange. The orange G 
and the aurantia of Griibler will be found satisfactory. As a cytoplasmic 
stain the former is preferable. It should be used in the same manner 
as alcoholic eosin (see Method I, above). 
Fuchsin.-Two distinct dyes, the one of acid, the other of basic, 
properties, pass under this name. Acid fuchsin is a cytoplasmic dye, 
but when used in acid solution has a slight selective affinity for the 
nuclei. Basic fuchsin is chiefly useful in bacteriology. It is also used 
in preparing Weigert's elastic tissue stain. 
It is recommended that eiiparal be used as a mounting medium 
with this group of stains. The tissue may be mounted directly from 90 
per cent, alcohol. 
Double Staining 
Hematein and Eosin: 
1. Stain with one of the hem- 
atein solutions, preferably Mann's 
or Ehrlich's for general use, five 
minutes. 
2. Wash well in water. 
3. Stain in watery eosin,'one 
to ten minutes. Or- 3. Dehydrate in 95 per cent, 
alcohol. 
4. Wash quickly in water. 4. Stain in alcoholic eosin, 
one to five minutes. 
5. Dehydrate in absolute al- 5. Dehydrate quickly (one to 
cohol. five minutes) in absolute alcohol. 
6. Clear and mount. 6. Clear and mount. STAINING 
747 
Methyl Blue and Safranin. --Methyl blue is a very different dye 
from methylene blue but is practically identical with water blue (Wasser 
blau). It is an acid or cytoplasmic stain. 
1. Stain with a 2 per cent, aqueous solution of methyl blue, three 
minutes. 
2. Rinse in water. 
3. Stain in a 1 per cent, aqueous solution of safranin, five minutes. 
4. Wash in water. 
5. Differentiate and dehydrate quickly in absolute alcohol, till the 
sections become again blue. 
6. Clear and mount. 
This method gives a permanent stain which yields excellent results 
with certain tissues-e.g., the skin. 
Other nuclear and cytoplasmic dyes may be combined in a similar 
manner to the above methods. 
Special Staining Methods 
Iron Hematoxylin (Heidenhain) : 
I. Mordant: 
Ferric alum (iron ammonium sulphate-violet 
crystals) 2 grm. 
Distilled water 100 c.c. 
II. Stain: 
Hematoxylin 1 grm. 
95 per cent, alcohol 10 c.c. 
Distilled water 100 c.c. 
1. Mordant the sections four to twelve hours in I. 
2. Rinse in water. 
3. Stain twelve to twenty hours in II. 
4. Wash well in water. The sections should become very black; 
a drop or two of ammonia to one-half liter of water often improves 
the color. 
5. Decolorize in the mordant, watching each section under the 
microscope, and stopping the decolorization at the proper time by- 
6. Wash thoroughly in slowly running water, or in several changes 
of still water. 
7. Counter-stain if desired, dehydrate, clear, and mount. 748 
HISTOLOGIC TECHNIC 
This method gives an excellent stain for the finer nuclear structure, 
mitosis, etc. 
Muchematein (Mayer) : 
Hematein (Griibler's) 0.2 grm. 
Glycerin 40 c.c. 
Aluminium chlorid 0.1 grm. 
Distilled water 60 c.c. 
Mix the ingredients in the order given, rubbing the hematein with 
the glycerin in a mortar. One or two drops of nitric acid added to the 
final mixture will sharpen its properties as a nuclear stain. 
This dye is used as a specific stain for mucinous tissues. It is used 
in the same manner as hematein, and stains rapidly (three to ten 
minutes). 
Mucicarmin (Mayer) : 
Garmin 1 grm. 
Aluminium chlorid 0.5 grm. 
Distilled water 2 c.c. 
50 per cent, alcohol 100 c.c. 
Mix in the order given; heat over a small flame till the fluid darkens 
(two minutes) ; after twenty-four hours, filter. For use, dilute with 
five to ten volumes of 50 per cent, alcohol. Like muchematein, mucicar- 
min' is a specific stain for mucus-containing cells. It also stains 
rapidly. 
Weigert-Pal Stain for Medullated Nerve Fibers.-The tissues 
must have been previously fixed in Muller s fluid or in 10 per cent, 
formalin, washed in water, hardened in alcohol, and sectioned. 
I. Stain: 
Hematoxylin 1 grm. 
Absolute alcohol 10 c.c. 
Distilled water 90 c.c. 
Saturated aqueous solution of lithium carbonate 
(1 to 80) 1 c.c. 
II. Differentiating Solution: 
Potassium permanganate 0.25 grm. 
Distilled water 100 c.c. STAINING 
749 
III. Decolorizing Solution: 
1 per cent, aqueous solution of oxalic acid 50 c.c. 
1 per cent, aqueous solution of potassium sulphate 50 c.c. 
This last solution should be freshly prepared by mixing the two 
stock solutions just prior to use. 
1. Stain sections (six to twenty-four hours) until black. 
2. Wash well in water. A few drops of lithium carbonate solution 
added to the water may improve the color, which should become a 
deep blue-black. 
3. Differentiate until the gray matter becomes brown (one-quarter 
to two minutes). 
4. Rinse in water. 
5. Decolorize until the white matter becomes a steel blue, the gray 
matter a light brown (one-quarter to one minute), watching each 
section with care. 
6. Wash thoroughly in several changes of water, or in running water. 
7. If desired, counter-stain with alum carmin, and wash in water. 
8. Dehydrate, clear, and mount. 
Methylene Blue, for non-medullated nerve fibers (Intravitam 
Method): 
I. Stain: 
Methylene blue (Griibler's 'rectif. nach 
Ehrlich') 0.1 grm. 
Distilled water 100 c.c. 
Dissolve with heat, cool, and filter. 
II. Fixing Solution (Bethels') : 
Ammonium molybdate 1 grm. 
Distilled water 20 c.c. 
Hydrochloric acid, C. P 1 drop. 
The solution should be freshly made and kept at or near 0° C. 
1. The method is only applicable to living tissues, by injecting the 
blood-vessels with the stain, or by partially immersing in the staining 
fluid small pieces of tissue, freshly removed from the living animal. 
2. After ten to thirty minutes, rinse in normal saline solution, and 
place in the cold fixing solution for two to six hours, according to the 
size of the pieces. The tissue should be kept cold. 
3. Wash well in distilled water. 750 
HISTOLOGIC TECHNIC 
4. Dehydrate quickly in 95 per cent, and absolute alcohol, kept at 
or near 0° C. 
5. Embed in paraffin. At a convenient time, cut and mount. 
The stain is rather unstable, but may be kept fairly well if mounted 
in glycerin or in neutral balsam. 
This technic is invaluable for the demonstration of the terminal 
nerve supply of tissues. 
Methylene Blue, for chromophilic (tigroid) granules in cyton and 
dendron (Nissl's Method): 
I. Stain: 
Methylene blue (Griibler's 'B pat.') 3.75 grm. 
Venetian soap (white Castile) 1.75 grm. 
Distilled water 1000 c.c. 
II. Differentiating Solution: 
Anilin oil (pure) 10 c.c. 
95 per cent, alcohol 90 c.c. 
This method is only applicable to tissue which has been fixed in 95 
per cent., or in absolute alcohol. Thionin may be substituted for the 
methylene blue in the stain. 
1. Warm the stain till steam begins to rise; then immerse the 
sections for four to six minutes. They acquire a deep blue color. 
2. Rinse in distilled water. 
3. Differentiate in the anilin alcohol till the sections become a light 
blue, carefully observing each section (twenty to sixty seconds). 
4. Wash in 95 per cent, alcohol. 
5. Clear in equal parts of origanum and cajuput oils, and mount 
in neutral balsam or in colophonium dissolved in xylol. 
Cajal's Method for Demonstrating Neurofihrils: 
1. Fix small pieces of tissue in 10 per cent, formalin for six hours. 
2. Wash in water for four hours. 
3. Transfer to 40 per cent, alcohol for six hours. 
4. Place in 50 c.c. of 40 per cent, alcohol, adding 5 drops of am- 
monia, for twenty-four hours. 
5. Transfer to 1.5 per cent, silver nitrate solution at incubator tem- 
perature (38° C.) for five days. 
6. Rinse, and place in a solution of 1 gram pyrogallic acid or hydro- 
chinon, 100 c.c. water, and 15 c.c. formalin for twenty-four hours. 
7. Pass through graded alcohols, and embed in paraffin or celloidin. STAINING 
751 
For other more complicated Cajal technics for demonstrating neuro- 
fibrils, also for the Bielschowsky, Bethe and Apathy methods for the 
same purpose, reference must be made to the special works on technic. 
Golgi's Stain for Nerve Cells (cyton, axis cylinder, and dendrons, 
and neuroglia): 
I. Mordant: 
1 per cent, aqueous solution of osmium tetroxid 10 c.c. 
3| per cent, aqueous solution of potassium bi- 
chromate 40 c.c. 
II. Silver Solution: 
Silver nitrate (crystals) 0.75 grm. 
Distilled water 100 c.c. 
This method is only applicable to fresh tissues, and the best results 
are obtained when the tissue is taken from a fetus or from an animal 
not over three days old. Thin slices or small fragments of tissue must 
be used. 
1. Fix in the mordant for ten days, frequently changing the fluid, 
which should not become turbid, nor should its odor of osmium tetroxid 
entirely disappear. 
2. Rinse quickly in water. 
3. Place tissues in the silver solution, diluted with two volumes of 
distilled water, for fifteen minutes. 
4. Place in the undiluted silver solution twenty-four to forty- 
eight hours. If several pieces of tissue are prepared they should be 
removed at intervals, as the duration of the impregnation by silver is 
always an experiment. 
5. Dehydrate in absolute alcohol, one hour. 
6. Transfer to equal parts of absolute alcohol and ether, half an 
hour. 
7. Thin celloidin (number 1), thirty minutes. 
8. Thick celloidin (number 3), thirty to forty-five minutes. 
9. Transfer to a wooden block and fasten with celloidin. 
10. Harden the celloidin block in chloroform, one-half to one hour. 
11. Cut at once, the sections being 50 /x to 100 /x thick. While 
cutting, the knife should be well moistened with bergamot oil, not al- 
cohol, and the sections, if not mounted at once, may be preserved for 
a short time in the same oil. Oil of lavender, cajuput, or origanum 
may be used in a similar manner. < 752 
HISTOLOGIC TECHNIC 
Nitrate of Silver for Cement Substances.-This reagent is used 
to outline epithelial cells by blackening the intercellular substance, the 
silver, after impregnation, being reduced or blackened by exposure to 
light. 
1. The fresh tissue is immersed in a 0.25 per cent, to 0.5 per cent, 
aqueous solution of silver nitrate (crystals), and left in the dark for 
ten to twenty minutes. Protargol may be substituted for silver nitrate 
crystals. 
2. Wash in distilled water, and while still in water, expose to direct 
sunlight until the object becomes a dark reddish-brown color (ten to 
thirty minutes). 
3. Transfer to 70 per cent, alcohol, three to twelve hours. 
4. Preserve in 95 per cent, alcohol. The tissue may be mounted in 
the usual way. 
Since nitrate of silver will attack metal instruments, the tissues 
while in this solution should be handled with glass rods. In silvering 
serous membranes, it is well to slightly stretch the object by tying it 
over a cork with a thread tightly fastened around the edge. 
Gold Chlorid for Nerve Plexuses and Nerve Endings (Ranvier's 
Method).-1. Wash the fresh tissues in normal saline solution, and 
place them in pure lemon-juice until they appear clear (live to ten 
minutes). 
2. Wash quickly in distilled water. 
3. Place in the dark in a 1 per cent, aqueous solution of chlorid 
of gold for ten to forty-five minutes, according to the permeability of 
the tissue. 
4. Wash in distilled water. 
5. Place in a 25 per cent, aqueous solution of formic acid, and 
keep in the dark for twenty-four to forty-eight hours. 
6. Wash thoroughly in water. 
7. The tissue is now properly teased and mounted in glycerin, or 
sections may be dehydrated, cleared, and mounted in balsam. 
The gold method is used for the demonstration of nerve plex- 
uses and nerve terminations. It is applicable also for the demonstra- 
tion of certain connective tissue cells, e.g., corneal cells, and tendon 
cells. 
Picro-Fuchsin (Van Gieson)This method is used as a specific 
stain for connective tissue; it colors the collagenous fibers a bright red, 
all other tissues appearing yellow. Picric-acid-fuchsin may be used 
as an after stain with nuclear dyes, e.g., hematoxylin, though the tissue STAINING 
753 
must be greatly overstained with the nuclear dye, since the picric acid 
will decolorize hematein. 
Saturated aqueous solution of picric acid 100 c.c. 
1 per cent, aqueous solution of acid fuchsin.... 5 c.c. 
The acid fuchsin solution must be boiled well and filtered before 
adding to the picric acid solution, otherwise a precipitate will occur 
and the mixture be spoiled. 
1. Stain with Delafield's or Bohmer's hematoxylin, fifteen to thirty 
minutes. 
2. Wash well with water. The sections should be almost black. 
3. Stain with picro-fuchsin, three to five minutes. 
4. Rinse quickly in water (water removes the fuchsin). 
5. Dehydrate in absolute alcohol, clear, and mount. 
Weigert's Elastic Tissue Stain.-This method gives a specific stain 
for elastic fibers; it may be used alone, or in combination with hema- 
tein and picro-fuchsin. 
1 per cent, aqueous solution of basic fuchsin.. 100 c.c. 
2 per cent, aqueous solution of resorcin 100 c.c. 
Boil the mixture in a porcelain dish, and while hot, add liquor 
ferri sesquichlorati (Pharm. Ger., Ill), 25 c.c. 
Heat and stir for five minutes; a heavy precipitate is formed. Cool 
and filter. Dry the precipitate in a porcelain dish over a water bath 
or sand bath. Dissolve the dried precipitate in 200 c.c. of 95 per 
cent, alcohol, filter and replace the alcohol lost by evaporation. Add 
4 c.c. of pure hydrochloric acid. 
Tissues should be stained twenty to sixty minutes, then thoroughly 
washed in water, dehydrated, cleared, and mounted. 
The following method gives very beautiful results: 
1. Stain in Delafield's or Bohmer's hematoxylin, twenty to thirty 
minutes. 
2. Wash well with water. 
3. Stain in Weigert's elastic tissue stain, twenty minutes. 
4. Wash in water. 
5. Stain in picro-fuchsin, three to five minutes. 
6. Rinse quickly in water. 
7. Dehydrate in absolute alcohol, clear, and mount. 
Orcein may also be employed as a specific stain for elastic fibers. 
Mallory's Connective Tissue Stain.-This method is applicable 754 
HISTOLOGIC TECHNIC 
only to tissues which have been fixed in Zenker's solution and de- 
hydrated with alcohol. Somewhat inferior results are obtained after 
fixation with mercuric chlorid. 
It stains collagenous fibers and reticulum, blue; nuclei, neuroglia 
and cytoplasm, red; and hemoglobin (red blood corpuscles), yellow. 
Elastic fibers remain unstained. 
I. Stain: 
Acid fuchsin ■................. 0.1 grm. 
Distilled water 100 c.c. 
II. Fixative: 
Phosphomolybdic acid 1 grm. 
Distilled water 100 c.c. 
III. Count er-Stain: 
Anilin blue (soluble in water) 0.5 grm. 
Orange G (Griibler's) 2 grm. 
Oxalic acid 2 grm. 
Distilled water 100 c.c. 
1. Stain in the fuchsin solution, three to twenty minutes. The 
sections should become a bright red. 
2. Wash in water. 
3. Fix in the phosphomolybdic acid solution, one minute. This 
'fixes' the fuchsin and prevents decolorization. 
4. Wash well in water. 
5. Counter-stain in the anilin blue solution (No. Ill), five to 
twenty minutes. The section should become decidedly blue. 
6. Wash in water. 
7. Dehydrate, clear, and mount. 
Eosinate of Methylene Blue (Basting's Method for Blood).-For 
the somewhat complicated method of preparing the stain the reader is re- 
ferred to the original article, Johns Hop. Hosp. Bull., 1904, vol. xv, p. 
122. The stain is applicable to smears of blood, marrow, splenic cells, 
etc. When used with smears which contain traces of fat, a preparatory 
treatment with a 2 per cent, aqueous solution of sodium metaphosphate, 
which probably serves as a mordant, improves the staining properties. 
Otherwise the stain is applied without previous fixation. 
1. Stain for one minute. 
2. Dilute the stain with several volumes of distilled water, and STAINING 
755 
continue the stain for five minutes, or until satisfactorily differentiated. 
3. Wash with distilled water. 
4. Dry and mount. 
The Giemsa and the Wright blood stains (other modifications of the 
original Romanowsky stain) may be used for the same purposes, and 
are applied in a similar manner. 
Eosin and Methyl Blue Mixture (Mann): 
1 per cent, aqueous solution of methyl blue 35 c.c. 
1 per cent, aqueous solution of bluish watery eosin 45 c.c. 
Distilled water 100 c.c. 
1. Mordant the sections in water, leaving them till all alcohol has 
been replaced (five to thirty minutes). 
2. Stain in the above mixture, five to ten minutes. 
3. Wash well and differentiate in water; the effect may be varied 
by the duration of the washing (ten to forty minutes). 
4. Dehydrate in alcohol, clear, and mount. 
When a sharper nuclear dye is desired the stain may be used as a 
counter-stain after hematein. In this case the methyl blue solution 
should be allowed to act only three to five minutes. The methyl blue 
used in this method is a cytoplasmic dye and should not be confounded 
with methylene blue. This is a valuable stain for differentiating cyto- 
plasmic granules. 
Triacid Stain (Ehrlich): 
Saturated aqueous solution of orange G 13 c.c. 
Saturated aqueous solution of acid fuchsin. ... 7 c.c. 
Distilled water 15 c.c. 
95 per cent, alcohol 15 c.c. 
Saturated aqueous solution of methyl green. .. . 12.5 c.c. 
95 per cent, alcohol 10 c.c. 
Glycerin 10 c.c. 
Be certain that the solutions of the dyes are saturated, and mix in 
the order given. 
The following formula by Mayer may be substituted: 
Distilled water 45 c.c. 
Glycerin 10 c.c. 
95 per cent, alcohol 25 c.c. 
Acid fuchsin 3 grm. 756 
HISTOLOGIC TECHNIC 
Orange G 2 grm. 
Methyl green 1 grm. 
Mix the fluids and dissolve the dyes in the order given. 
When used for staining sections, either of these formulas should be 
diluted with five to ten volumes of the following mixture: 
Glycerin 10 c.c. 
Distilled water 15 c.c. 
95 per cent, alcohol 25 c.c. 
1. Stain five to ten minutes in the diluted solution. (Use full 
strength for blood smears.) 
2. Binse in water. 
3. Dehydrate in absolute alcohol. (Smears are dried in the air.) 
4. Clear and mount. 
The best results are obtained with tissues fixed in a sublimate mix- 
ture. It is a delicate cytologic stain, and is serviceable in differentiating 
between chromatin (chromosomes) and plastin (plasmosomes and linin) ; 
also in differentiating cytoplasmic granules. Sections should not be over 
3 /j. in thickness. The stain is more or less capricious. 
Auerbach's Fuchsin-Methyl-Green Stain.-This stain does well 
only after a sublimate fixative. It is serviceable in cytologic work for 
differentiating between 'active' and 'resting' chromatin. When suc- 
cessfully manipulated it stains the chromosomes green and the plasmo- 
somes and linin red. 
Keep in separate bottles the following stock solutions: 
I. Acid fuchsin 1 part, distilled water 1,000 parts. 
II. Methyl green 1 part, distilled water 1,000 parts. 
Mix when ready to use in the following proportions: 
2 parts of I, acidulating every 50 c.c. with 1 drop of a 10 per 
cent, solution of glacial acetic acid. 
3 or 4 parts of II. 
Fix tissues (e.g., insect testes, etc.) in the sublimate acetic mixture, 
transfer direct to 80 per cent, alcohol (removing the mercury with tinc- 
ture of iodin), dehydrate, and embed in paraffin. Sections should not 
be cut over 3 /* thick. 
Stain for fifteen minutes, and pass directly to 95 per cent, alcohol. 
When the green stain no longer leaves the sections in clouds, pass STAINING 
757 
rapidly through absolute alcohol and xylol, and mount in balsam. The 
sections may also be mounted directly from 95 per cent, alcohol in 
euparal. 
Mitochondria] Technics.-Mitochondria (chondriosomes, plasto- 
somes) are readily destroyed by acids, hence these must be eliminated 
from fixing solutions, or greatly reduced. 
I. Meves' Method.-This is the simplest method for demonstrating 
mitochondria, and in many instances it is quite satisfactory. 
Very small pieces of tissue are fixed for eight days in Flemming's 
strong solution in which the acetic acid has been reduced to 3 or 4 drops 
in the simplest formula (see page 728). The tissue is then embedded 
in paraffin in the usual way, and the sections cut at 3 to 6 p- are stained 
by the iron-hematoxylin method. The nuclei and cytoplasm are a uni- 
form pale gray; the mitochondria appear as deep black granules, rods 
or filaments. 
II. Benda's Method.-This is a more complicated technic, but 
gives excellent results. 
1. Fixation in strong Flemming's fluid (acetic acid reduced to 
3 drops) for eight days. 
2. Wash in water one hour. 
3. Place in a mixture of equal parts of pyroligneous acid and 1 
per cent, chromic acid for twenty-four hours. 
4. Transfer to a 2 per cent, solution of potassium bichromate for 
twenty-four hours. 
5. Wash, dehydrate and embed in paraflin and fix on slide in the 
usual way. 
6. Mordant sections on slide in 4 per cent, solution of ferric 
alum for twenty-four hours. 
7. Rinse with water, and place in an amber-yellow aqueous solu- 
tion of Kahlbaum's suphalizarinate of soda (prepared by 
dropping 1 c.c. saturated alcoholic solution in 100 c.c. of 
water) for twenty-four hours. 
8. Rinse with water, flood slides with a solution of crystal violet 
(1 vol. sat. sol. of dye in 70 per cent, ale.; 1 vol. 1 per cent. 
HC1 in 70 per cent. ale.; 2 vols. anilin water) and warm 
until vapor is given off. 
9. Rinse, differentiate one or two minutes in 30 per cent, acetic 
acid solution. 
10. Wash in running water five to ten minutes. 758 
HISTOLOGIC TECHNIC 
11. Dry with blotting paper, drop in absolute alcohol, pass 
through bergamot oil into xylol and mount in balsam. 
According to Wildman (Jour. Morph., 24, 3, 1913) the slides may 
be passed from the alizarin solution, after rinsing, 1, into a 3 per cent, 
solution of crystal violet (3 c.c. anilin stain in 100 c.c. distilled water) 
for ten minutes; 2, rinse and place in 80 per cent, alcohol for five sec- 
onds; 3, pass through 95 per cent, and 100 per cent, alcohol, where the 
differentiation is watched; 4, clear and mount in the usual way. 
Zimmermann's Technic, for demonstrating the intercalated disks 
of cardiac muscle. 
1. Small pieces of tissue are fixed for twenty-four hours in a solu- 
tion of 90 parts absolute alcohol and 10 parts 25 per cent, nitric acid. 
2. Wash in several changes of 95 per cent, alcohol, or until it re- 
mains neutral to litmus paper. 
3. Pass through graded alcohols to distilled water. 
4. Transfer to solution of 1 gram hemalum (Griibler's) to 10 c.c. 
water, where it remains for eight to ten days. 
5. Wash in distilled water, embed in paraffin, and section. 
The intercalated disks are conspicuously stained a dark blue, which 
contrasts sharply with the light-blue background. 
These disks can be well demonstrated also by fixation in Carnoy's 
fluid, followed by iron-hematoxylin stain. For the same purpose Heiden- 
hain employs vanadium hematoxylin after sublimate fixation (see Lee's 
Vade Mecum). * 
Gage's Method, for Demonstrating Glycogen.-Glycogen granules 
are readily soluble in aqueous media. Tissue which is to be tested for 
this substance should be fixed in 95 per cent, alcohol. 
1. Embed in paraffin in the usual way. 
2. Flatten sections on slide by use of the following iodin solution 
(Lugol's solution), which is subsequently used for staining: 
lodin 1.5 grm. 
Potassium iodid 3.0 grm. 
Sodium chlorid 1.5 grm. 
50 per cent, alcohol 300 c.c. 
3. Stain, dehydrate, dissolve paraffin with xylol, mount in melted 
vaselin, and seal cover glass with shellac. The glycogen grains 
are stained mahogany red. 
Osmic Acid Technic for Fat.-Free fats and lipoids are soluble in MOUNTING 
759 
ether, chloroform, absolute alcohol, xylol, benzene, and essential oils. 
Since these must be employed in both paraffin and celloidin embedding, 
fat cannot be very satisfactorily demonstrated by these technics. Frozen 
sections (made with a freezing microtome) of fresh or formalin-fixed 
tissues are therefore preferable (in some instances indispensable) ; these 
may be satisfactorily stained with Sudan III (red), Sharlach R (red), 
Nile blue (blue) ; they must be mounted in glycerin jelly. 
Osmic acid, however, renders certain fats resistant to solution in 
oils, and tissue so fixed may accordingly be treated by the paraffin tech- 
nic; but thick cedar oil must be substituted for xylol or chloroform, and 
absolute alcohol should be avoided: 
1. Fix small pieces of fatty tissue in Flemming's fluid for two days. 
2. (a) Embed in paraffin (use cedar oil), section, and mount in 
euparal; or 
(b) Embed in celloidin, the different solutions of which should 
be made up in 95 per cent, alcohol (see Kingsbury, Anat. Rec., 
5, 6, 1911). 
Technic for Demonstrating Chromaffin Granules-Chromaffin 
material ('pheochrome' granules; adrenin granules) is highly susceptible 
to solution by acids. When preserved the chromaffin granules react to 
chromium (acid and solutions of salts) and stain light brown. The 
best method for their preservation is Helly's fluid (see page 728), which 
coincidently stains the granules. Paraffin or celloidin sections may be 
stained with various nuclear dyes for the clear differentiation of the 
nuclei. 
MOUNTING 
After staining, the sections are opaque; they must be rendered 
transparent for microscopic examination. This is accomplished by per- 
meating the sections with oil; but since oil and water are not miscible, 
the tissue must first be thoroughly dehydrated with alcohol. Immers- 
ing thin sections in 95 per cent, alcohol for three to five minutes is 
usually sufficient for this purpose unless xylol is to be used as the clarify- 
ing oil or unless the stain is injured by so prolonged an immersion. 
In either of these cases absolute alcohol is to be used for dehydration, 
because of its more rapid and thorough action. 
Clarification.-Sections, either free or fastened to the slide, are 
immersed in oil until clear. Free sections will at first float on the oil, 
but when fully permeated will sink. Attached sections should lose all 760 
HISTOLOGIC TECHNIC 
traces of 'milky' appearance. The following oils are commonly used 
for clarification: Bergamot, origanum cretici, cajuput, clove, carbo- 
xylol. Xylol carbolic acid, melted, 25 to 33 c.c.; xylol, 75 to 67 c.c.), and 
xylol. Xylol (xylene) is the most desirable in that it is perfectly miscible 
with the balsam in which the section is usually mounted, and is finally 
lost by evaporation. It will not act in the presence of the least trace of 
water. Carbo-xylol has the advantage of a slight affinity for water; 
this is also true of the heavier oils. Complete dehydration is therefore 
not required. Bergamot is desirable for celloidin sections, but has £he 
disadvantage of rapid deterioration, after which it dissolves the celloidin. 
Either origanum or cajuput oil, or a mixture of the two, serves well for 
celloidin sections, but leaves them somewhat stiffer than does bergamot 
oil. The latter is therefore preferable for elastic tissues. On the whole, 
origanum serves best for routine work with celloidin sections, xylol or 
carbo-xylol for paraffin. 
After clarification celloidin sections must be transferred to a slide. 
This is accomplished by means of a metal lifter or by a strip of rice 
paper (ordinary cigarette paper does nicely). The section, lying on the 
paper, is inverted upon the surface of the slide, to which it remains 
adherent after the paper is gently lifted. The excess of oil is then 
removed with blotting paper or by gentle pressure with a folded towel, 
a drop of xylol-balsam applied, and the cover glass dropped into position. 
The preparation is permanent. 
Xylol-balsam is prepared by adding to Canada balsam sufficient 
xylol so that the mixture will have a thick, syrupy consistence, but will 
drop from a glass rod without stringing. 
Sections may also be permanently mounted in glycerin without pre- 
vious dehydration, the edge of the cover glass being, after some hours, 
covered with a ring of King's cement. 
Glycerin jelly is also serviceable, and does not require cementing of 
cover glass. 
Neutral Balsam.-Sections may frequently be rendered more per- 
manent by the use of neutral balsam, prepared as follows: 
Dilute Canada balsam with xylol until it acquires a very thin watery 
consistence. Add sodium bicarbonate in excess. Shake thoroughly, and 
allow to stand in a stoppered bottle for twelve hours or more. Filter; 
this is readily, though slowly, accomplished if the dilution is sufficient. 
Permit the solution to stand in an open vessel, protected from dust, 
until it evaporates to the proper consistence for use. 
Gum-Damar.-This material, also dissolved in xylol, is in some re- MOUNTING 
761 
spects even a better mounting medium than balsam; it does not turn 
yellow with age. 
Euparal.-This new mounting medium is for most purposes the 
best. Sections are mounted direct from 95 per cent, alcohol. Delicate 
tissues may thus be spared the passage through absolute alcohol and 
oil. This curtailment of the technic is also a saving of expense.. 
Euparal has., moreover, a lower index of refraction than balsam or 
gum damar, and is thus more favorable for the demonstration of cyto- 
logic details (see Lee, "Vade Mecum," 8th ed., p. 247). 
For more detailed and extensive information on histologic technic, 
and microchemic methods, the following books should be consulted: 
1. Lee: "The Microscopist's Vade Mecum" (8th ed., 1913). Blakis- 
ton, Phila. 
2. Mann: "Physiological Histology-Methods and Theory." Clar- 
endon Press, Oxford, 1902. 
3. Guyer: "Animal Micrology." Univ, of Chicago Press, 1906. 
4. Hardesty: "Neurological Technique." Univ, of Chicago Press, 
1902. 
5. Kingsbury: "Laboratory Directions in Histology-Histological 
Technique." Ithaca, N. Y., 1910. 
6. Mallory and Wright: "Pathological Technique." Saunders, 
Phila. 
7. "Enzyklopaedie der mikroskopischen Technik" (2d ed., 1910). 
Urban und Schwarzenberg, Berlin. 
8. Gage: "The Microscope" (11th ed., 1911). Comstock Pub. Co., 
Ithaca, N. Y. INDEX 
Abiogenesis, 17 
Absorption, bone, 83 
Accessory suprarenal, 556 
Accessory thyroid, 562 
Acervulus, 584 
Aceto-carmin stain for tissues, 744 
Acid dyes, 740 
Acidophil cells, of small intestine, 371 
of pituitary body, 576 
Acoustic meatus, external, 683 
Acoustic nerve, 712 
cochlear branch of, 712 
spiral ganglion of, 712 
vestibular branch of, 712 
vestibular ganglion (of Scarpa),712 
Acromegaly, 573 
Adenoid tissue, 84 
Adipose tissue, 61 
Adrenal (suprarenal) gland, blood sup- 
ply of, 554-555 
cells of medulla, 553 
chromaffin granules in, 554 
lymphatics and nerves of, 556 
zona fasciculata of, 552 
zona glomerulosa of, 552 
zona reticularis of, 553 
Adrenalin (epinephrin), 549-554 
Adrenin, 549 
Agminate nodules of small intestine 
(Peyer's patches), 366 
Alcohol for fixation of tissues, 724 
Alimentary canal, fibroserous coat of, 
345 
glands of, (crypts of Lieberkuhn), 
366 
ileocecal valve of, 379 
intestinal villi in, 366 
intestine, large, 377 
appendices epiploicae of, 377 
Alimentary canal, intestine, large, 
lymphoid tissue and lymph nodes 
of, 378 
mucous membrane of, 377 
plicae semilunares of, 377 
rectum of, 379 
sacculations or haustra of, 377 
teniae (lineae) coli, 377 
vascular and nerve supply of, 379 
vermiform appendix of, 378 
intestine, small, 375 
absorption from, 375 
agminate nodules of (Peyer's 
patches), 366 
blood supply of, 373 
corium of, 366 
duodenal glands of (Brunner's 
glands), 365-372 
granules of Paneth in, 370 
intestinal glands of, 370 
intestinal villi in, 368 
lacteals of, 369-374 
lining epithelium of, 369 
lymphatics of, 374 
mucous membrane of, 366 
nerve supply of, 374 
Peyer's patches in, 366 
solitary nodules of, 366 
structure of, 363 
submucosa of, 364 
valvulae conniventes of, 364 
mucous membrane of, 347 
muscular coat of, 346 
submucous coat of, 346 
stomach, blood supply of, 360 
cardiac glands of, 360 
fundus glands of, 354 
lenticular glands of, 360 
lymphatics of, 362 
763 764 
INDEX 
Alimentary canal, stomach, mucous 
coat of, 353 
muscular coat of, 353 
nerve supply of, 362 
oxyntic or delomorphous cells of, 
356 
peptic or adelomorphous cells of, 
355 
parietal cells of, 356 
pyloric glands of, 357 
secretion of, 357 
serous coat of, 352 
submucous coat of, 353 
Alimentary tract, tabular statement of 
characteristics, 381 
Alum carmin for staining tissues, 744 
Alum hematein (Mayer) for staining 
tissues, 741 
Ameboid mobility, 16 
Ameloblasts (adamantoblasts), 333 
Amitosis, 19 
Anaphase, 25 
Anatomy, microscopic, 1 
Angioblast, 215 
Annulus tympanicus of ear, 685 
Anterior chamber of eye, 636 
Appendix epididymis, 502 
Appendix testis, 502 
Appendix vermiformis, 378 
Aqueductus Fallopii, relations of, to 
ear, 686 
Aqueous humor of eye, 665 
Arachnoid membrane, 620 
granulations, 621 
villi, 621 
Arciform veins of kidney, 443 
Areas of Cohnheim in muscle, 112 
Areolar connective tissue, 56 
Arterial wall, general characteristics 
of, 180 
Arteries, 176 
anterior ciliary, of eye, 673 
anterior spinal, 624 
arciform, of kidney, 440 
arteria centralis of retina, 664, 670 
arterias propriae renales, 440 
arteriae rectae of kidney, 441 
Arteries, atypical, structure of, 182 
auditory, 714 
bronchial, 317 
central, of retina, 664, 670 
circle of Willis, of brain, 624 
circle of Zinn, of eye, 672 
cortical, of cerebrum, 625 
external elastic membrane of, 179 
fissural, of brain, 625 
helicine, of corpus cavernosum penis. 
504 
hyaloid, of eye, 672 
interlobular, of kidney, 441 
of liver, 415 
internal elastic membrane of, 178 
large, structure of, 181 
large and small compared, 184 
long ciliary, of eye, 672 
medium-sized, coats of, 177 
medullary, of cerebrum, 625 
middle cerebral, 625 
pulmonary, 314 
structure of, 183 
precapillary, structure of, 182 
short-ciliary, of eye, 672 
small, structure of, 181 
tunica adventitia of, 177-178 
tunica intima of, 177 
tunica media of, 177-178 
umbilical, structure of, 182 
vasa vasorum of, 180 
Arterioles, structure of, 181 
Atrioventricular bundle of His, 102 
Auerbach's fuchsin methyl green stain, 
756 
Auditory area of cerebral cortex, cell 
layers of, 618 
Auditory canal, 683 
Auditory ossicles, 689 
Auditory tube of ear, 691 
Auerbach's stain for chromatin, 756 
Auricle or pinna of external ear, 682 
Axis cylinder, the, 132 
Axon, the, 128 
Balsam (Canada) for mounting sec- 
tions, 760 INDEX 
765 
Bartholin's glands of the vulva, 541 
Basic dyes, 740 
Basket cells of cerebellum, 608 
Basophilic cells of pituitary body, 576 
Bellini's ducts of kidney, 438 
Benda's technic for demonstrating 
mitochondria, 757 
Berlin blue gelatin mass for injection 
of tissues and organs, 732 
Betz cells of cerebral cortex, 613 
Bibliography of histologic technics, 761 
Bioplasm, 1 
Bladder, urinary, 448 
Blastomeres, 27 
Blood, 203 
angioblast, 215 
coagulation of, 214 
development of, 24 
fibrin of, 203 
hematin of, 212 
hematoidin, 214 
hemin, 212 
hemoglobin of, 203-211 
hemokonia of, 206 
hemolysis of, 206 
hemosiderin, 213 
hypertonic solution for, 206 
hypotonic solution for, 206 
isotonic solution for, 206 
leukoblasts in, 218 
mononuclear leukocytes in, 218 
oxyhemoglobin, 211 
prothrombin, 203 
Teichmann's crystals in, 212 
thrombin, 203 
Blood cells, basophils, 210 
crenation of, 206 
dyes for, 210 
eosinophils, 210 
erythroblasts, 217 
erythrocytes, 203-217 
erythroplastids, 203-217 
giant, 209-218 
granulocytes, 209 
hyaloplasm of, 206 
ichthyoid stage, 217 
leukocytes, 203 
Blood cells, lymphocytes, 207 
megaloblasts, 217 
megalocytes, 209 
neutrophils, 209 
non-granular leukocytes, 208 
normoblasts, 217 
plastids, 203 
plates (plaques), 209 
polykaryocytes, 209 
primitive, derivatives from, 219 
red, 203 
rouleaus, 206 
sauroid stage, 217 
spindle cells, 209 
spongioplasm of, 206 
thrombocytes, 209 
transitional leukocytes, 208 
white, 207 
Blood clot, 203 
Blood corpuscles, 203 
crenated corpuscles, 206 
Blood crystals, 212 
Blood plasma, 203 
Blood platelets, 203-209 
Blood serum, 203 
Blood shadows, 206 
Blood stain, eosinate of methylene 
blue, Hastings' method, 754 
Blood vascular system, 176 
Blood vessels, circulus major of iris, 
672 
circulus minor of iris, 673 
development of, 192 
essential structure of, 194 
fetal, 538 
of brain and spinal cord, 619-624- 
625 
of bronchi, 317 
of eye, 636-643-664-670-673 
of eyelids, 678 
of heart, 201 
of internal ear, 714 
of kidney, 440-444 
of large intestine, 379 
of liver, 415-417 
of lungs, 314 
of lymph nodes, 242 766 
INDEX 
Blood vessels, of mammary gland, 547 
of middle ear, 693 
of olfactory mucosa, 298 
of ovary, 522 
of oviduct, 527 
of pancreas, 403 
of parathyroid glands, 565 
of penis, 503-504 
of prostate gland, 500 
of renal pelvis and ureter, 448 
of salivary glands, 392 
of skin, 290 
of small intestine, 373 
of spleen, 246 
of stomach, 360 
of suprarenal gland, 554 
of thymus gland, 568 
of thyroid gland, 560 
of tongue, 343 
of urinary bladder, 452 
of uterus, 532 
Bbhmer's hematoxylin for staining tis- 
sues, 741 
Bone, 72 
absorption of, 83 
cancellous, 85 
canaliculi of, 75 
circumferential lamella? of, 76 
compact, 74 
development of, 79 
diploe of, 88 
endochondrial ossification, 85 
epiphyseal line, 85 
epiphyseal ossification, 85 
external circumferential lamellae of, 
84 
general considerations of, 72 
Haversian canals of, 85 
Haversian lamellae of, 75 
Haversian spaces of, 84 
Haversian systems of, 75-84 
internal circumferential lamellae of, 
85 
interstitial lamellae of, 76-85 
intramembranous ossification, 86 
lacunae of, 75 
lacunae of Howship, of, 84 
Bone, lymphatics of, 78 
nerves of, 78 
osteoblasts of, 83 
osteoclasts of, 77 
periosteum of, 74 
primary, 83 
red marrow of, 77 
tables of, 88 
Volkmann's canals of, 76 
Bone marrow, 77-220 
Bone marrow cells, basophil granulo- 
cytes, 223 
eosinophil granulocytes, 222 
erythrocytes, 224 
giant cells, 223 
hemoblasts, 221 
large mononuclear leukocytes, 222 
lymphocytes, 221-222 
mast cells, 223 
mesameboid cells, 221 
myeloblasts, 221 
myelocytes, 220 
myeloplaxes, 223 
polymorphonuclear neutrophil gran- 
ulocytes, 222 
premyelocytes, 221 
primitive blood cells, 221 
Bony labyrinth of the internal ear, 694 
Borax carmin stain for tissue, 743 
Bonin's fluid for fixation of tissues, 
729 
Bowman's elastic membrane of cornea, 
631 
Box for embedding in paraffin, 737 
Brain sand (acervulus), 584 
Bronchi, 304 
structures of, 304 
Bronchial arteries, 317 
Bronchioles, 307 
Brownian movement, 17 
Bursae, 117-233 
Cajal's method for demonstrating 
neurofibrils, 750 
Calcified cartilage, 80 
Canal of Stilling (canalis hyaloideus), 
672 INDEX 
767 
Cells, of cerebral cortex, Golgi's, types 
1 and 2, 613 
centro-acinal, of Langerhans, 396 
centriole of, 7 
centrosome of, 7 
centroplasm of, 7 
centrosphere of, 7 
chondrioconts of, 8 
chondriomites of, 8 
chromaffin of small intestine, 371 
chromaffin, of suprarenal gland, 548 
chromidia of, 8 
chromophobe, of pituitary body, 576 
chromosomes of, 24 
cilia of, 16 
close spireme, 24 
connective tissue, 51 
cytology of, 1 
cytoplasm of, 7 
decidual, of gravid uterus, 535 
deutoplasm of, 8 
diplosome of, 7-24 
division of, 18 
eosinophil granulocytes, 52 
ependyma, of nervous system, 589 
general statements in regard to, 5 
hepatic, 412 
pigment in, 414 
goblet, of small intestine, 370 
granular, of cerebellum, 609 
granule of Paneth in small intestine, 
370 
kinoplasm of, 7 
lamellar, 52 
of Langhans, of chorionic villi of 
gravid uterus, 537 
large stellate, of cerebellum, 609 
loose spireme of, 24 
lutein, of ovary, 519 
of Martinotti of cerebral cortex, 617 
mastoid, of ear, 686 
metaphase, of division, 25 
metaplasm of, 8 
microsome of, 8 
mitochondria of, 8 
mitosis of, 22 
nucleus of, 6 
Capillary plexuses, 187 
Capillary wall, stigmata of, 186 
Capillaries, structure of, 184 
Cardiac glands of the stomach, 360 
Cardiac muscle, 94, 99 
Cardiac muscle, intercalated discs of, 
Zimmerman's method of 
staining, 758 
Cardiac Purkinje fibers, 102 
Cardiac plexus, origin of, 591 
Carmin gelatin mass for injection of 
tissues and organs, 732 
Carmin stain for tissues, 743 
Carnoy's fluid No. 1 for fixation of 
lung tissue, 729-730 
Carotid gland, the, 569 
Cartilage, 67 
blastema of, 69 
calcified, 80 
cells, enlargement of, 80 
elastic, 71 
fibro-, 71 
hyaline, 68 
matrix of, 69 
origin of, 70 
primordial marrow cavities in, 82 
Cell, definition of, 1 
Cell layers of motor area of cerebral 
cortex, 615, 616 
Cell plate (midbody), 25 
Celloidin, adhesive for sections, 739 
embedding of tissues in, 734 
Cells, acidophil, of parathyroid, 564 
acidophilic, of pituitary body, 
576 
acidophil, of small intestine, 371 
amitosis of, 19 
anaphase of, division of, 25 
archoplasm of, 7 
astral rays of, 7 
astral system of, 7 
basophilic, of pituitary body, 576 
basket, of salivary glands, 385 
basophil granules of, 52 
Betz, of cerebral cortex, 613 
cartilage, enlargement of, 80 
cementum, of teeth, 337 768 
INDEX 
Cells, neuroglia, of nervous system, 
589 
osteoblasts, 77 
osteoclasts, 78 
parietal (oxyntic or delomorphous), 
of stomach, 356 
peptic or adelomorphous, of stom- 
ach, 355 
pheochrome, of suprarenal gland, 
548 
pigment, 52 
plasma of, 51 
plastosomes of, 8 
prickle, 44 
pseudochromosomes of, 8 
Purkinje, of cerebellum, 607 
pyramidal, of cerebral cortex, 613 
reproduction of, 17 
resting nucleus of, 24 
segmented spireme of, 24 
Sertoli, of seminiferous tubules, 481 
small cortical, of cerebellum, 608 
solitary, of Meynert of cerebral cor- 
tex, 613-618 
spindle, 51 
telophase of, division of, 25 
tendon, 117 
interstitial, of Leydig of testis, 487 
trophospongium of, 8 
varieties of, 32 
vital properties of, 14 
Cement substance, intercellular, 30 
nitrate of silver stain for, 752 
terminal bars of, 34 
Cementoblasts, 337 
Cementum, development of, 336 
Centers of ossification, 79 
Central artery of retina, 664 
Central nervous system, blood supply 
of, 624 
veins of, 625 
Central spindle, 25 
Cerebellum, 603 
basket cells of, 608 
climbing fibers of medulla of, 609 
cortex of, 606 
granule cells of, 609 
Cerebellum, large stellate cells of, 609 
medulla of, 609 
Purkinje cells of, 607 
resume of structures of, 611 
small cortical cells of, 608 
Cerebral cortex, 611 
auditory area, cell layers of, 618 
cell layers of motor area, 615, 616 
cells (solitary) of Meynert, 613-618 
fiber tracts of, 618 
Golgi's types of cells of, 613 
motor area of, 615 
motor area, cells of Martinotti of, 617 
nerve cells of, 612 
olfactory area, cell layers of, 618 
stripes of Baillarger, 619 
stripe of Bechterew, 619 
visual area, cell layers of, 617 
Cerebrum, cortical arteries of, 625 
lobes of, 611 
medullary arteries of, 625 
meninges and blood supply of, 619- 
620-621 
middle cerebral artery of, 625 
Cervical glands of uterus, 532 
Ceruminous glands of ear, 684 
Chondrioconts, 50 
Chondroclasts, 82 
Chordae tendineae of heart, 197 
Chorionic villi, 537 
Choroid coat of eye, 636 
lamina basalis of, 637 
lamina capillaris of, 636 
membrane of Bruch, 637 
suprachoroid layer of, 636 
tapetum cellulosum of, 638 
tapetum fibrosum of, 637 
tunica Ruyschiana of, 637 
vascular layer of, 636 
Choroidal fissure of the eye, 645 
Chromaffin cells of small intestine, 371 
of suprarenal gland, 548 
Chromaffin granules, technic for dem- 
onstrating, 759 
Chromaffin system, 571 
Chromatin, Auerbach's fuchsin methyl- 
green stain for, 756 INDEX 
769 
Chromidia, in spermatogenesis, 474 
Chromo-acetic formalin mixture for 
fixation of tissues, 727 
Chromophobe cells of pituitary body, 
576 
Chromosomes, 24-476 
sex, in spermatogenesis, 475 
in spermatogenesis, 464 
Chyle, 226 
in small intestine, 374 
Cilia, 16 
Ciliary body of eye, 638 
fibrous layer of, 640 
Ciliary epithelium of eye, 640 
Ciliary glands of eye, 640 
Ciliary motility, 16 
Ciliary processes of eye, 638 
Ciliary muscle of eye, 638 
Circle of Willis, 604 
Circle of Zinn, 672 
Circulus venosus of Haller, 547 
Ciliated epithelium, 40 
Clarification of sections, 759 
Classification of dyes, 740 
Clitoris, 541 
Coagulation of blood, 214 
Coccygeal gland, 570 
Cochlea of internal ear, accessory tec- 
torial membrane of, 706 
basilar membrane of, 706 
cochlear artery of, 714 
function of, 716 
hamulus of, 701 
Hensen's stripe of tectorial mem- 
brane in, 706 
limbus spiralis of, 705 
membrana tectoria (membrane of 
Corti), 705 
membranous wall of scala tympani 
and scala vestibuli, 704 
organ of Corti, 708 
varieties of cells of, 708-709 
prominentia spiralis of, 705 
spiral ligament of, 704 
stria vascularis of, 705 
structure of, 701 
sulcus spiralis externus of, 705 
Cochlea of internal ear, sulcus spiralis 
internus of, 706 
vestibular membrane of Reissner, 704 
Collagen, 57 
Colloid in thyroid gland, 557 
Coloboma, eye, 646 
Colostrum, 546 
Columnae carnae, 198 
Comparison of artery with vein of cor- 
responding size, 79 
Concentric corpuscles (Hassall) of 
thymus, 567 
Congo red for tissue stain, 746 
Conjunctiva, ocular, 674 
palpebral, 674 
Conarium (pineal body), 579 
Connective tissue, Mallory's stain for, 
753 
Conus medullaris, 600 
Corium of skin, 268 
Cornea of eye, 630 
anterior homogeneous membrane in, 
631 
Bowman's elastic membrane of, 631 
endothelium of, 633 
epithelium of, 631-633-674 
layers of, 631 
membrane of Descemet, 632 
posterior epithelial layer of, 633 
posterior homogeneous membrane of, 
632 
vascular and nerve supply of, 633 
Corneal corpuscles, 631 
Corneal epithelium, 631-674 
Corneal substance, 631 
Corpora albicantia, of ovary, 510 
Corpora lutea spuria, 521 
Corpora lutea vera of pregnancy, 
521 
Corpus cavernosum penis, 503 
helicine arteries of, 504 
pectiniform septum of, 504 
tunica albuginea of, 504 
Corpus hemorrhagicum of ovary, 519 
Corpus Highmori testis, 480 
Corpus luteum of ovary, 519 
Corpus spongiosum penis, 503-506 770 
INDEX 
Corpuscles, Pacinian, 174 
Cover glass, how to apply, 722 
Cowper's glands of urethra, 501 
Cretinism, 561 
Crusta petrosa of teeth, 329 
Crystalline lens of eye, 666 
capsule of, 666 
lenticular epithelium of, 666 
nuclear zone of, 667 
nucleus of, 667 
substantia lentis, 666 
suspensory ligament of, 669 
Cutaneous appendages, 271 
Cutis vera, 268 
Cytogenesis, 1 
Cytologic stain, Ehrlich triacid, 755 
Cytology, 1 
Cytolymph, 8 
Cytomorphosis, 29 
Cytoplasm, 7 
Cytoplasmic dyes, 745 
Cytoplasmic granules, eosin and methyl 
blue mixture (Mann), stain 
for, 755 
Cytoreticulum, 8 
Dartos of scrotum, 481 
Decalcification of tissues, 731 
Decidua reflexa of the gravid uterus, 
537 
Decidua vera of the gravid uterus, 537 
Delafield's hematoxylin for staining 
tissues, 742 
Dendrons (dendrites), 128 
Dental cement, 329 
Dental cuticular membrane, 
Dental enamel, layers of, 335 
Dental groove, 330 
Dental lamina, 330 
Dental papilla, 330-336 
Dental pulp, 323 
odontoblasts in, 324 
Dentin, 325 
contour lines of Owen in, 327 
globules in, 326 
granular layer of Tomes in, 327 
incremental lines of Schreger in, 327 
Dentin, interglobular spaces of, 326 
sheaths of Neumann in, 327 
tubules in, 326 
Derma, 268 
Descemet's membrane of cornea, 632 
Determiners, chromosomal in sex hered- 
ity, 477 
Digestive system, 320 
alimentary canal, character of wall 
in, 344 
fibroserous coat of, 345 
mucous membrane of, 347 
muscular coat of, 346 
submucous coat of, 346 
esophagus, coats of, 348 
glands of, 351 
mucous coat of, 350 
muscular coat of, 350 
ileocecal (colic) valve, 379 
intestinal glands (crypts of Lieber- 
kuhn), 366 
intestine, large, 377 
appendices epiploic® of, 377 
lymphoid tissue and lymph nodes 
of, 378 
mucous membrane of, 377 
plic® semilunares of, 377 
rectum, 379 
sacculations or haustra of, 377 
teni® (line®) coli, 377 
vascular and nerve supply of, 
379 
vermiform appendix, lymphoid tis- 
sues in, 378 
intestine, small, absorption from, 
375 
agminate nodules of (Peyer's' 
patches), 366 
blood supply of, 373 
corium of, 366 
duodenal glands (Brunner's), 365- 
372 
granule cells of Paneth in, 370- 
371 
intestinal glands of, 370 
intestinal villi in, 368 
lacteals of, 369-374 INDEX 
771 
Digestive system, intestine, small, lin- 
ing epithelium of, 369 
lymphatics of, 374 
mucous membrane of, 366 
nerve supply of, 374 
Peyer's patches, 366 
solitary nodules of, 366 
structure of, 363 
submueosa of, 364 
valvulae conniventes of, 364 
liver, bile capillaries of, 411 
blood supply of, 417 
capsule of Glisson of, 408 
cells of, 412 
. course of blood through, 419 
gall-bladder, 420 
hepatic connective tissue in, 408 
hepatic lobule, 409 
interlobular arteries and veins of, 
415 
interlobular bile ducts, 415 
lymphatics of, 419 
nerves of, 420 
pigment cells in, 414 
portal canals, 408-415 
structure of, 405 
mouth, 320 
lymphoid tissues in mucous mem- 
brane of, 321 
mucous membrane of, 320 
secreting glands in mucous mem- 
brane of, 321 
pancreas, 394 
acini of, 396 
blood supply of, 403 
nerve supply of, 404 
resume, 404 
pharynx, 347 
portal vein, 417 
salivary glands, 382 
blood supply of, 392 
general considerations of, 382 
mucous acini of, 386 
nerve supply of, 393 
parotid gland, 390 
serous acini, 385 
sublingual gland, 392 
Digestive system, salivary glands, sub- 
maxillary gland, 391 
stomach, 360 
blood supply of, 360 
cardiac glands of, 360 
fundus glands of, 354 
lenticular glands of, 360 
lymphatics of, 362 
mucous coat of, 353 
muscular coat of, 353 
nerve supply of, 362 
peptic or adelomorphous cells of, 
355 
parietal cells (oxyntic or delomor- 
phous cells) of, 356 
pyloric glands of, 357 
serous coat of, 352 
secretion of, 357 
submucous coat of, 353 
teeth, 337 
ameloblasts (adamantoblasts) of, 
333 
eementoblasts of, 337 
cementum, 329 
development of, 336 
deciduous, 331 
papilla of, 336 
pulp of, 323 
dentin of, 325 
development of, 330 
enamel of, 328 
enamel germ of, 330-331 
enamel layers of, 335 
enamel organ of, 330 
layers of, 331 
Tome's processes in, 333 
odontoblasts, 324 
odontoclasts, 337 
permanent, 331 
structure of, 323 
tongue, 337 
blood vessels of, 343 
foramen cecum of, 343 
lymphatics of, 344 
mucous membrane of, 337 
muscle fibers of, 337 
nerve supply of, 344 772 
INDEX 
Digestive system, tongue, papillae of, 
339, 340, 341 
taste buds of, 341 
tonsil of, 343 
Diploe, of bone, 88 
Diploid number of chromosomes, 363 
Diplosome, 24 
Double staining of tissues, 746 
Ductless glands, 260-548 
hormones of, 586 
Ductuli aberrentes, mesonephric, 502 
Duodenal glands (Brunner's), 365- 
372 
Dura mater, 620 
Dyes, 740 
acid, 740 
basic, 740 
classification of, 740 
cytoplasmic, 745 
mordants for, 741 
neutral, 740 
specific, 740 
Dyspituitarism, 573 
Ear, 717 
development of, 717-719 
external, 682 
acoustic meatus of, 683 
auricle of, 682 
ceruminous glands of auditory ca- 
nal, 684 
pinna of, 682 
internal, 712 
acoustic nerve, 712 
cochlear branch of, 712 
vestibular ganglion of Scarpa, 
712 
aqueductus vestibuli of, 694 
auditory artery, 714 
blood supply of, 714 
bony labyrinth of, 694 
canalis communis of semicircular 
canals, 699 
cochlea, 706 
accessory tectorial membrane of, 
706 
basilar membrane of, 706 
Ear, internal, cochlea, cecum vestibu- 
lare of scala media, 703 
cochlear artery, 714 
cochlear nerve, spiral ganglion 
of, 712 
cupola of, 701 
development of, 719 
foramina nervosa of, 702 
function of, 716 
hamulus of, 701 
helieotrema of, 703 
Hensen's stripe of tectorial mem- 
brane in, 706 
lagena or cecum cupulare of 
scala media in, 703 
limbus spiralis of, 705 
membrana tectoria, membrane of 
Corti, 703-705 
membranous wall of scala tym- 
pani and scala vestibuli, 704 
organ of Corti, 708, 709-710 
organ of Corti, cells of, 708-709 
prominencia spiralis of, 705 
scala media, or cochlear duct, 
703 
scala tympani, 701 
secondary 'tympanic membrane 
of, 703 
scala vestibuli of, 701 
spiral ligament of, 704 
spiral ligament, stria vascularis 
of, 705 
spiral organ of Corti, 702 
structure of, 701 
sulcus spiralis externus, 705 
sulcus spiralis internus, 703-706 
vestibular membrane of Reissner, 
703-704 
vestibular artery, 714 
cupola of semicircular canals in, 
700 
ductus endolymphaticus, 694 
endolymph of, 695 
endolymphatic sac, 694 
fenestra vestibuli, 693 
general considerations of, 693 
internal auditory vein, 716 INDEX 
773 
Ear, internal, cochlea, lymphatics of, 
716 
macula acustica sacculi, 697 
macula acustica utriculi, 698 
membranous labyrinth, 694 
neuro-epithelium of saccule, 695 
neuro-epithelium, varieties of, 697 
organ of equilibration, 700 
otoliths in, 697 
otocyst, 699 
perilymph of, 695 
saccule of, 694 
sacculus of vestibule in, 694 
semicircular canals of, 699 
ampullae of, 699 
utricle of, 698 
utriculosaccular canal of vestibule, 
694 
utriculus of vestibule, 694 
veins of, 715-716 
vestibule of, 693 
middle, 686 
aqueductus Fallopii, relations of, 
686 
annulus tympanicus, 685-687 
auditory canal, 683 
auditory ossicles of, 689 
auditory tube (Eustachian tube), 
691 
blood vessels of, 693 
epitympanic cavity of, 685 
Eustachian tube, 691 
fenestra ovalis of tympanum, 686 
fenestra rotunda of tympanum, 685 
general considerations of, 685 
incus, 689 
orbicular process of, 689 
lymphatics of, 693 
malleus, 689 
ligaments of, 691 
mastoid cells, 686 
membrana flaccida of, 689 
Prussak's space, 691 
Shrapnell's membrane, 689 
stapedius muscles of, 690 
stapes, 689 
tensor tympani muscle, 690 
Ear, middle, tympanic membrane, 
687 
tympanic mucosa, 686 
tympanum, 685 
pelvis ovalis of, 686 
processus cochleariformis of, 690 
promontory of, 685 
tubal tonsil of, 692 
umbo of tympanic membrane in, 
687 
Ectoderm, 28 
Ehrlich's triacid stain, 755 
Ejaculatory ducts, 497 
Elastic fibers, 57 
Elastic tissue, Weigert's stain for, 753 
Elastin, 58 
Eleidin, 45 
Embedding, in paraffin, box for, 737 
of tissues, 734 
in celloidin, 734 
in paraffin, 735 
Embryonic connective tissue, 50-53 
Enamel, 328 
contour lines of Retzius in, 329 
prism, 328 
radial lines or prism stripe of 
Schreger in, 329 
Enchylema, 8 
Endocardium, 195-196 
Endocrin glands, 260-548 
hermones of, 586 
Endomysium, 195 
Endothelium, 37 
Enlargement of cartilage cells, 80 
Entoderm, 28 
Eosin, as a tissue stain, 745 
and methyl blue mixture (Mann), 
stain for cytoplasmic gran- 
ules, 755 
Eosinate of methylene blue stain 
(Easting's method) for 
blood, 754 
Ependyma cells, 141-589 
Epicardum, 195 
Epicritic sensibility, 164 
Epidermis, 262 
Epididymis, 492 774 
INDEX 
Epidural space, 620-623 
Epinephrin (adrenin), 549 
Epiphysis cerebri, 579 
blood supply of, 584 
development of, 580 
function of, 581 
habenular commissure of, 581 
histologic structure of, 582 
nerves of, 584 
posterior commissure of, 581 
Epithelia, classification of, 34 
Epithelial tissues, 30-33 
Epithelium, 40 
ciliated, 40 
endothelial, 37 
glandular, 40 
goblet cell, 41 
mesothelial, 37 
modified columnar, 40 
neuro-, 42 
non-stratified, 37 
pavement, 37 
plain, 39 
pseudo-stratified columnar, 46 
simple columnar, 39 
simple squamous, 37 
stratified, 43 
stratified squamous, 43 
transitional, 47 
varieties of, 33 
Epitympanic cavity of ear, 685 
Epoophoron (parovarium), of female 
genitalia, 539 
Equatorial plate, 25 
Eruptive tissue, of developing bone, 82 
Esophagus, 348 
coats of, 348 
glands of, 351 
mucous coat of, 350 
muscular coat of, 348 
submucous coat of, 348 
Euparal, for mounting sections, 74 
Eustachian tube, 691 
Exophthalmic goitre, 561 
External ear, 682 
External genitals, female, 540 
clitoris, 541 
External genitals, female, glandute 
vestibulares m a j o r e s 
(Glands of Bartholin), 541 
glandulae vestibulares minores, 541 
hymen, 541 
labia majora, 540 
labia minora, 540 
vestibule, 540 
External genitals, male, 503 
penis, 503 
corpora cavernosa of, 503-504 
corpus spongiosum urethrae of, 506 
helicine arteries of, 504 
lymphatics of, 506 
nerves of, 506 
nervi erigentes of, 506 
pectiniform septum of, 504 
preputial glands of, 506 
tunica albuginea of corpus caverno- 
sum, 504 
Tyson's glands of, 506 
Eye, anterior chamber of, 636-643 
appendages of, 674 
aqueous humor of, 665 
blood supply of sclerocorneal junc- 
tion, 636 
blood vessels of, 670 
canalis hyaloideus, or canal of Stil- 
ling, 672 
canal of Schlemm (sinus venosus 
sclera?), 635 
capsule of Tenon, 627 
choroid coat of, 636 
lamina basalis of, 637 
lamina capillaris of, 636 
membrane of Bruch, 637 
tapetum cellulosum of, 638 
tapetum fibrosum of, 637 
tunica Ruyschiana of, 637 
vascular layer of, 636 
ciliary arteries, anterior, 673 
long, 672 
short, 672 
ciliary body of, 638 
fibrous layer of, 640 
ciliary epithelium, 640 
ciliary glands, 640 775 
INDEX 
Eye, ciliary muscle, 638 
ciliary processes, 640 
circle of Zinn, 672 
coats of, 628 
conjunctiva, 674 
ocular, 674 
palpebral, 674 
contents of, 665 
cornea, 630 
anterior epithelium of, 674 
anterior homogeneous membrane 
of, 631 
Bowman's elastic membrane of, 631 
corpuscles of, 631 
endothelium of, 633 
epithelium of, 631 
layers of, 631 
membrane of Descemet, 632 
posterior epithelial layer of, 633 
posterior homogeneous membrane 
of, 632 
substance of (substantia propria), 
631 
vascular and nerve supply of, 633 
crystalline lens of, 666 
capsule of, 666 
lenticular epithelium of, 666 
nuclear zone of, 667 
nucleus of, 667 
substantia lentis, 666 
suspensory ligament of, 669 
development of, 645 
choroidal fissure, 645 
optic cup, 645 
optic stalk, 645 
optic vesicle, 645 
external or fibrous tunic of, 629 
general considerations of, 626 
gland of Harder, 681 
glaucoma, 635 
hyaloid artery of, 672 
hyaloid membrane of, 669 
iridocorneal angle, 643 
iris, 641 
circulus major of, 672 
cireulus minor of, 673 
coloboma of, 646 
Eye, iris, color of, 642 
dilator muscle of, 642 
endothelium of, 641 
fibrous stroma of, 642 
internal epithelium of, 643 
layers of, 641 
sphincter muscle of, 642 
lacrimal gland, 679 
lacrimal lake, 679 
ligamentum pectinatum of, 635-643 
lymphatic systems of, 673 
middle coat of, vascular tunic, 636 
muse® volitantes, 669 
nerves of, 674 
optic nerve, 664 
optical or visual axis, 628 
ora serrata, 665 
pineal, 580 
posterior chamber of, 636-643 
retina of, 644 
cell types of inner nuclear layer of, 
654-655-656 
central artery of, 664-670 
cones of, 651-652-653 
external limiting membrane of, 653 
fibers of Muller of, 658 
fiber layer of Henle, 654 
fovea centralis of, 660 
ganglion cell layer of, 657 
general considerations of, 644 
inner nuclear layer of, 654 
inner reticular layer of, 656 
inversion of, 663 
layers of, 646 
macula lutea of, 659 
nerve fiber layer of, 657 
optic papilla of, 665 
optic disk of, 665 
outer nuclear layer of, 654 
outer reticular layer of, 654 
pigment epithelium of, 646 
porus opticus of, 665 
rods of, 648-649-650 
rods and cones, development of, 
661-663 
layer of, 647 
supporting tissues of, 658 776 
INDEX 
Eye, retina of, visual purple of, 647- 
649 
yellow spot of, 659 
sclerocorneal junction of, 635 
sclerotic coat of, 634 
corpuscles of, 634 
lamina fusea of, 634 
lamina cribrosa of, 634 
pinguecula of, 634 
substantia propria of, 634 
spaces of Fontana of, 635-643 
spatia zonularis of (canals of Pe- 
tit), 670 
suprachoroid layer of, 636 
uvea of, 636 
uveal tract of, 636 
vascular tunic of, 636 
ven® vorticos® of, 672 
vitreous humor of, 669 
zonula ciliaris of Zinn, of, 670 
Eyelid, 674 
accessory lacrimal glands of Krause 
of, 677 
blood supply of, 678 
cutaneous portion of, 674 
conjunctival portion of, 676 
glands of Moll of, 676 
glands of Zeiss of, 676 
lymphatic and nerve supply of, 678 
palpebral muscle of Muller, 677 
posterior tarsal glands of Waldeyer, 
677 
tarsal (Meibomian) glands, 676 
tarsus of, 676 
Fallopian tube, 525 
blood supply of, 527 
mucosa of, 526 
lymphatics and nerves of, 528 
muscular wall of, 526 
serous coat of, 526 
structure of, 525 
Female reproductive organs, 507. See 
also Reproductive system. 
Fat, osmic acid test for, 758 
stains for, 62, 759 
Fat tissue, 61 
Fibers, collagenous, 49 
elastic, 49-57 
white, 49 
Fiber tracts of cerebral cortex, 618. 
See also Nervous system. 
Fibrocartillage, 71 
Filar mass, 8 
Filum terminale of spinal cord, 600. 
See Nervous system. 
Flagellate motion, 16 
Flagellum, 16 
Flemming's fluid for fixation of tis- 
sues, 728 
Fontana, spaces of, 635. See also Eye. 
Formalin, for fixation of tissues, 725 
Fovea centralis of retina, 660. See also 
Eye. 
Fresh tissues, examination of, 720 
Fuchsin for tissue stain, 746 
Gage's method for demonstrating 
glycogen, 750 
Gall-bladder, 420. See also Digestive 
system. 
Gametogenesis, 460. See also Repro- 
ductive system. 
Ganglia, 148. See also Nervous sys- 
tem. 
Gastric glands, 354. See also Digestive 
system. 
Gigantism, 573 
Gilson's fluid for fixation of tissues, 
730 
Glands, 253 
accessory lacrimal, of Krause, 677 
adrenal, 548 
lymphatics and nerves of, 556 
anterior lingual (of Nuhn), 342 
branched saccular, 260 
branched tubular, 258 
bulbo-urethral, 501 
cardiac, of stomach, 360 
carotid, 569 
ceruminous, of ear, 684 
ciliary, of eye, 640 
cervical, of uterus, 632 
classification of, 253 INDEX 
777 
Glands, coccygeal, 570 
compound saccular, 260 
compound tubular, 258 
compound tubulo-alveolar, 258 
convoluted tubular, 257 
Cowper's, of urethra, 501 
ductless, 260-548 
hormones of, 586 
duodenal (Brunner's), 365-372 
endocrin, 260-548 
hormones of, 586 
histologic types of, 254 
internal secretion of, 261 
intestinal (crypts of Lieberkuhn), 
366 
of small intestine, 370 
lacrimal, 679 
lenticular, of stomach, 360 
mammary, 541 
active, 543-545 
blood vessels of, 547 
milk, 547 
of Montgomery (areolar glands of 
Duval), 545 
Marchand's (Marchand's adrenal), 
557 
Meibomian (tarsal), of eyelid, 676 
mucous, 255 
mucus of, 256 
of Bartholin (Bartholin's glands of 
vulva), 541 
of esophagus, 351 
of eyelid (glands of Moll), 676 
of Harder, 681 
of tongue, 342 
of Tyson, of penis, 506 
of von Ebner, 343 
of Zeiss, of eyelid, 676 
parathyroid, acidophil cells of, 564 
blood supply of, 565 
structure of, 562 
parotid, 390 
physiologic types of, 254 
pineal, 579 
posterior tarsal, of Waldeyer, 677 
preputial, 506 
prostate, 497 
Glands, pyloric, 357 
racemose, 258 
secreting, of mouth, 321 
suprarenal, 548 
chromaffin granules in, 554-555 
development and function of, 
548 
lymphatics and nerves of, 556 
medulla, cells of, 553 
zona glomerulosa of, 552 
zona reticularis of, 553 
zona fasciculata of, 552 
salivary, 382 
serum-secreting cells of, 256 
simple saccular, 259 
simple tubular, 257 
submaxillary, 391 
thymus, 565-567 
thyroid, blood supply of, 560 
colloid in, 557 
development of, 561 
follicles of, 557 
follicular epithelium of, 559 
function of, 561 
lymphatics of, 560 
nerves of, 561 
structure of, 557 
urethral (Littre's), 454 
uterine, 531 
Glandulse vestibularis, majores (glands 
of Bartholin), 541 
minores of vulva, 541 
Glandular epithelium, 40 
Glaucoma, 635 
Glia cells, 141 
Glomus caroticum, 569 
Glomus coccygeum, 570 
Glycerin jelly, for mounting sections, 
760 
Glycogen, Gage's method for demon- 
strating, 758 
Goblet cell epithelium, 41 
Goitre, 561 
exophthalmic, 561 
Gold chlorid for demonstrating nerve 
plexuses and nerve endings 
(Ranvier's method), 752 778 
INDEX 
Golgi's cells of cerebral cortex, types 
1 and 2, 613 
Golgi's stain for nerve cells, 751 
Graafian follicle, 517 
Graafian follicle, Resume of structures, 
519 
Graves' disease, 561 
Guard cells, 38 
Gum-damar, for mounting sections, 760 
Hair, 277 
development of, 277 
regeneration of, 286 
root of, 281 
root sheaths of, 283 
shaft of, 281 
structure of, 277 
Haploid group of chromosomes in 
spermatogenesis, 464 
Hardening of tissues, 733 
Hasting's method for blood (eosinate 
of methylene blue stain), 754 
Haversian spaces in bone, 84 
Haversian systems of bone, 75-84 
Heart, 195 
annulus fibrosus of, 197 
atrioventricular bundle of, 199 
blood vessels of, 201 
chordae tendineae of, 197 
columnae carnae of, 198 
development of, 201 
endocardium of, 196 
endomysium of, 195 
epicardium of, 195 
moderator bands of, 199 
myocardium of, 195 
nerve supply of, 202 
valves of, 196 
venae minimae of, 201 
Heat, fixation of tissues by, 730 
Helly's fluid for fixation of tissues, 728 
Hemal nodes, 239 
Hemapoiesis, 214 
Hematein, for staining tissues, 741 
stains, application of, 743 
and eosin stains for tissues, 746 
Hemoglobin, 211 
Hemolymph nodes, 239 
Heterozygote, 478 
Histogenesis, 1-27 
Histologic technic, 720 
bibliography of, 761 
Histology, definition of, 1 
historical development of, 2 
relations of, to other biological sci- 
ences, 2 
Homozygote, 478 
Hone for microtome knife, 737 
Howship, lacuna; of, 84 
Hyaline cartilage, 68 
Hyaloid artery, of eye, 672 
Hyaloid membrane, of eye, 669 
Hyaloplasm, 8 
Hydatid of Morgagni, 539 
Hymen, 541 
Hypopituitarism, 573 
Hypophysis cerebri, 572-573-574-575 
function of, 573 
histologic structure of, 573-574-575 
pars buccalis seu glandularis, 575 
pars neuralis; infundibulum, 575 
parts of, 575 
Rathke's pouch, 572 
Ileocecal (colic) valve, 379 
Incus, of ear, 689 
Injection of tissues, 732 
pressure required for, how obtained, 
733 
with Berlin blue gelatin mass, 732 
with carmin gelatin mass, 732 
Intercalated discs of cardiac muscle, 99 
Internal ear, acoustic nerve, 702 
aqueductus vestibuli of, 694 
auditory artery of, 714 
blood supply of, 714 
bony labyrinth of, 694 
canalis communis of, 699 
cecum vestibulare of scala media, 703 
cochlea, accessory tectorial membrane 
of, 706 
basilar membrane of, 706 
function of, 716 
foramina nervosa of, 702 INDEX 
779 
Internal ear, cochlea, hamulus of, 
701 
helicotrema of, 703 
Hensen's stripe of tectorial mem- 
brane, 706 
limbus spiralis of, 705 
membrana tectoria (membrane of 
Corti) of, 703-705 
membranous wall of scala tympani 
and scala vestibuli, 704 
organ of Corti, cells of, 708-709 
prominentia spiralis of, 705 
spiral ligament of, 704 
structure of, 701 
sulcus spiralis externus of, 705 
sulcus spiralis internus of, 703 
vestibular membrane (of Reiss- 
ner), 704 
cochlear artery, 714 
cochlear nerve, spiral ganglion of, 
712 
ductus endolymphaticus of, 694 
endolymph of, 695 
endolymphatic sac of, 694 
fenestra vestibuli of, 693 
general considerations of, 693 
helicotrema, 703 
internal auditory vein, 716 
lagena or cecum cupulare of scala 
media, 703 
lymphatics of, 716 
macula acustica sacculi, 697 
macula acustica utriculi, 698 
membranous labyrinth of, 694 
neuro-epithelium, of saccule, 695 
varieties of, 697-708-709 
organ of equilibration, 700 
otocyst, 699 
otoliths in, 697 
perilymph of, 695 
saccule of, 695 
sacculus of vestibule, 694 
scala media or cochlear duct of, 703 
scala tympani of cochlea, 701 
scala vestibuli of cochlea, 701 
secondary tympanic membrane of 
cochlea, 703 
Internal ear, semicircular canals of, 
699 
ampull® of, 699 
spiral organ of Corti, 702 
utricle of, 698 
utriculosaccular canal of vestibule, 
694 
utriculus of vestibule, 694 
veins of, 715-716 
vestibular artery, 714 
vestibular ganglion (of Scarpa), 712 
vestibular membrane (of Reissner), 
702 
vestibule of, 693 
Internal genital organs, female, 507. 
See also Reproductive sys- 
tem. 
Interrenal bodies, 548 
Interstitial granules of Kolliker, 99 
Interfilar mass, 8 
Intestine, large, 377 
appendices epiploic® of, 377 
lymphoid tissue and lymph nodes of, 
378 
mucous membrane of, 377 
plic® semilunares of, 377 
rectum, 379 
sacculations or haustra of, 377 
t®ni® coli (line® coli), 377 
vascular and nerve supply of, 379 
vermiform appendix of, 378 
Intestine, small, absorption from, 
375 
acidophil cells of, 371 
agminate nodules of (Peyer's 
patches), 366 
blood supply of, 373 
chromaffin cells of, 371 
chyle in, 374 
corium of, 366 
duodenal glands (Brunner's), 365- 
372 
glands of, 370 
glands (crypts of Lieberkuhn) of, 
366 
granule cells of Paneth, 370-371 
lacteals of, 369 780 
INDEX 
Intestine, small, lining epithelium of, 
369 
lymphatics of, 374 
mucous membrane of, 366 
myenteric ganglionic plexus (Auer- 
bach's), 375 
nerve supply of, 374 
Peyer's patches of, 366 
solitary nodules of, 366 
structure of, 363 
submucosa of, 364 
submucous plexus (Meissner's), 375 
valvulas conniventes of, 364 
villi of, 366-368 
Intracartilaginous ossification, 79 
Intra vitam method of staining non- 
medullated nerve fibers with 
methylene blue, 749 
Iridocorneal angle, 643 
Iris, 641 
circulus major of, 672 
circulus minor of, 673 
color of, 642 
dilator muscle of, 642 
endothelium of, 641 
fibrous stroma of, 642 
internal epithelium of, 643 
layers of, 641 
sphincter muscle of, 642 
Iron hematoxylin, for staining tissues, 
747 
Joints, 88 
adaptation cartilages of, 89 
diarthroses, 88 
intra articular menisci, 88 
labra glenoidalia, 89 
sutura, 88 
synarthroses, 88 
synchondroses, 88 
syndesmoses, 88 
synovia, 89 
synovial membrane, 89 
Karyon, 18 
Keratin, 45 
Kidney, 423 
Kidney, arched collecting tubule of 
(junctional tubule), 437 
arciform arteries of, 440 
arciform veins of, 443 
arteries, interlobular, of, 441 
arteriolae rectae of, 441 
ascending limb of Henle's loop, 435 
Bellini's duct of, 438 
blood vessels, lymphatics and nerves 
of, 440 
capsule of Bowman, 429 
corpuscles in, 425 
cortex of, 424 
descending limb of Henle's tubule, 
434 
distal convoluted portion of tubule 
in, 436 
divisions of the renal tubule, 429 
glomerulus of, 429 
loop of Henle, 435 
lymphatics and nerves of, 444 
medulla of, 424 
neck of tubule of, 431 
papillary ducts of, 438 
proximal convoluted portion of tu- 
bule of, 431 
renal connective tissue, 426 
renal corpuscles (Malpighian body), 
425-429 
renal lobule, 426 
renal pelvis and ureter, 445 
blood supply, lymphatics and 
nerves of, 448 
mucosa of, 445 
muscular coat of, 448 
tunica propria of, 447 
straight collecting tubules of, 437 
table of divisions of renal tubule, 439 
table showing the course of the renal 
circulation, 443 
topography of, 423 
tubules, peculiarities of, 440 
uriniferous, or renal tubules of, 427 
venaa propriae renales, 443 
veins, stellate of, 443 
Kleinenburg's fluid, for fixation of tis- 
sues, 729 781 
INDEX 
Knife, microtome, hone for, 737 
Kolliker's muscle columns, 112 
venulae of, 443 
Labia ma j ora, of pudendum, 540 
Labia minora, of pudendum, 540 
Lacrimal gland, 679 
Lacrimal lake, 679 
Lacteals, of small intestine, 369-374 
Lactiferous duct, of mammary gland, 
542 
Lamellae, external circumferential, of 
bone, 84 
internal circumferential, of bone, 
85 
interstitial, of bone, 85 
Larynx, 300 
structures of, 300 
vocal cords of, 301 
Lenticular glands, of stomach, 360 
Ligamentum denticulatum, of spinal 
cord, 621-624 
Ligamentum pectinatum, of eye, 643 
Ligaments, 117 
circular dental, 329 
Lingual glands, anterior, 342 
Lingual tonsil, 244-343 
Littre's glands, urethral, 454 
Liver, 405 
bile capillaries of, 411 
blood supply of, 417 
capsule of Glisson, 408 
cells of, 412 
connective tissue of, 408 
course of blood through, 419 
interlobular arteries and veins in, 
415 
interlobular bile ducts of, 415 
lobule of, 409 
lymphatics of, 419 
nerves of, 420 
pigment in, 414 
portal canals of, 408-415 
portal vein of, 417 
structure of, 405 
Loose spireme, of cell nucleus, 24 
Lumbar region, of spinal cord, 600 
Lung, 304 
atria of, 310 
blood supply of, 314 
lobule of, 314 
lymphatics of, 318 
nerve supply of, 319 
pulmonary alveoli of, 311 
tissue fixation of, 730 
Lutein cells, of ovary, 519 
Lymphatic system, 225 
amygdala; (faucial tonsils), 242 
bursae, 233 
cisterna chyli, 230 
chyle, 226 
hemolymph, or hemal nodes, 239 
lymph, 225 
lymph cells, 235-238 
lymph corpuscles, 225 
lymph follicles, 233 
lymph glands, 235 
lymph nodes, 235 
blood vessels of, 239 
development of, 242 
structure of, 236 
lymph nodules, 233 
lymph sinus, 236 
lymph vessels, development of, 230 
lymphatic capillaries, 227 
lymphatic vessels, 226 
lymphatics, of adrenal gland, 556 
of bone, 78 
of eye, 673 
of eyelid, 678 
of internal ear, 716 
of kidney, 444 
of large intestine, 378 
of liver, 419 
of lung, 318 
of mammary gland, 547 
of middle ear, 693 
of penis, 506 
of salivary glands, 393 
of small intestine, 374 
of stomach, 362 
of thyroid gland, 560 
of tongue, 344 
lymphoid tissue, 64 782 
INDEX 
Lymphatic system, marrowlymph 
glands, 240 
spleen, 245 
blood vessels of, 246 
development of, 250 
differentiation of, from lymph 
node, 249 
functions of, 249 
pulp veins of, 248 
splenic cells, 249 
splenic nodule (Malpighian cor- 
puscle), 247 
splenolymph glands, 240 
thoracic duct, 230 
tonsils, faucial, 242 
lingual, 244 
palatine, 242 
pharyngeal, 244 
salivary corpuscles of, 243 
tubal tonsil (of Gerlach), 692 
Malleus, of ear, 689 
ligaments of, 691 
Mallory's connective tissue stain, 
753 
Mammary glands, 541 
active gland, 543 
blood vessels of, 547 
eirculus venosus of Haller, of, 547 
colostrum, 546 
lactiferous duct of, 542 
lymphatics and nerves of, 547 
milk, 547 
resting gland, 545 
Mann's acid hematein (Ehrlich's 
Hematoxylin) stain, for tis- 
sues, 742 
Marchand's glands (Marchand's adre- 
nal), 557 
Marginal velum, 590 
Marrow, of bone, 77 
blood supply of, 78 
cavities, primordial, in, 82 
primary osteogenic, 82 
red, 77 
Mastoid cells, of ear, 686 
Maturation, of germ cells, 460 
Mayer's albumin, for fastening sections 
to slide, 739 
Medullary sheath, 134 
Meibomian glands, of eyelid, 676 
Meissner's submucous plexus, 347 
Membrana propria, 34 
Membrane, mucous, of large intestine, 
377 
mucous, of small intestine, 366 
mucous, of mouth, 320 
synovial, 89 
Membranous labyrinth, of internal ear, 
694 
Meninges and blood supply of cere- 
brum, 619-620-621 
Mendelism, 477 
Mercuric chlorid, for fixation of tis- 
sues, 725 
Mercuro-nitric mixture, for fixation of 
tissues, 730 
Mesenchyma, 50 
Mesoderm, 28 
Mesothelium, 37 
Mesovarium, 507 
Metabolism, 14 
Metaphase, of mitotic eell division, 25 
Methyl blue and safranin stain, for 
tissues, 747 
Methyl green stain, for tissues, 743 
Methylene blue, for chromophilic 
(tigroid) granules in cyton 
and dendrons, 750 
stain for non-medullated nerve fibers 
(intra vitam method), 749 
tissue stain, 743 
Meves' method for staining mitochon- 
dria, 757 
Microtome, for sectioning tissues, 736 
Microtome knife, for sectioning tis- 
sues, 737 
hone for, 737 
use of strop for, 738 
Middle ear, 685 
blood vessels of, 693 
general considerations of, 685 
lymphatics of, 693 
Milk, 547 INDEX 
783 
Mitochondria, 8-50 
Mitochondrial technics, Meves' method, 
757 
Benda's method, 757 
Mitome, 8 
Mitosis, 22 
Montgomery's glands, of mammae, 545 
Molecular motility, 17 
Monaster stage of mitotic cell division, 
25 
Mordants, for dyes, 741 
Morphogenesis, 29 
Motor area, of cerebral cortex, 615 
Mounting sections, 759 
euparal for, 761 
glycerin jelly for, 760 
gum-damar for, 760 
neutral balsam for, 760 
xylo-balsam for, 760 
Mouth, 320 
lymphoid tissue of, 321 
mucous membrane of, 320 
secreting glands of, 321 
Muchematin stain, for tissues, 748 
Mucicarmin stain, for tissues, 748 
Mucous membranes, 251 
of alimentary canal, 347 
of mouth, 320 
structure of, 251 
Mucous tissue, 54 
Mucus, 256 
formation of, 41 
Muller's fibers, of retina, 658 
Muller's solution, for fixation of tis- 
sues, 726 
Mullerian ducts, 456 
Muscae volitantes, 669 
Muscle, striped, 112 
areas of Cohnheim, 112 
as a whole, 112 
blood supply of, 114 
cardiac (involuntary striped),90-94,99 
atrio-ventricular bundle of His, 102 
intercalated dises in, 99, 104 
intercalated discs (Zimmermann's 
technic for demonstrating), 
758 
Muscle, cardiac, nerve endings in, 
175 
Purkinje fibers of, 102 
contraction bands of, 93 
endomysium of, 112 
epimysium of, 112 
fasciculus of, 112 
histogenesis and structure of, 91 
inokonnnata of, 98-104 
interstitial granules of Kblliker, 99 
Kolliker's columns, 112 
mesophragina of, 98 
myoblasts, 90 
myofibrils, 90 
myochondria of, 92 
myofibrils of, 104 
myoglia of, 93 
myotomes, 106 
nerve endings in, 114-115, 171, 175 
of heart, 94-99 
perimysium of, 112 
red, 110 
sarcolemma of, 92 
sarcomeres of, 98-104 
sarcoplasm of, 90 
sarcosomes, of Retzius, 99 
sarcostyle of, 104 
skeletal, 90 
smooth (involuntary; unstriped), 90, 
91 
histogenesis, and structure of, 91 
myofibrils, 93 
nerve endings in, 175 
situation of, 94 « 
structure of border fibrils (myog- 
lia) in, 93 
telopragma of, 98 
types of, 90 
unstriped, 90 
voluntary striped, 104 
(skeletal), 90 
Muscle spindles, 172 
Muscular contraction, 111 
Myelospongium, of developing spinal 
cord, 509 
Myenteric plexus, and ganglion, 346 
Myoblasts, 90 784 
INDEX 
Myocardium, 195 
Myofibrils, 90 
Myxedema, 561 
Nabothian follicles, of uterus, 532 
Nails, 274 
structure of, 275 
Nasal cavity, 293 
blood vessels of, 298 
neuro-epithelium of, 297 
olfactory portion of, 296 
respiratory portion of, 294 
vestibule of, 293 
vomero nasal organ of Jacobson, 295 
Nasopharynx, 299 
Nerve cell, 121 
apyknomorphous condition of, 124 
association neurons, 131 
axis cylinder process of, 128 
axon, 125 
axon hillock, 129 
axoplasm, 129 
cellulifugal process of, 130 
chromophilic substance of, 123 
collaterals of, 129 
commissural neurons, 131 
cytochromatin of, 123 
cytoplasm of, 121 
dendrons (dendrites) of, 127-128 
end arborization of, 129 
ganglia, 148 
Golgi's cells, type 1 (Deiter's cells), 
131 
type 2, 131 
implantation cone of, 129 
mitochondria in, 125 
neuraxis, 128 
neuraxon, 128 
neurite, 128 
neuro-epithelium, 42 
neurons, 125 
Nissl's substance of, 123 
nucleus of, 121 
origin of, 131 
processes of, 127 
projection neurons, 131 
protoplasmic processes of, 128 
Nerve cell, pyknomorphous condition of, 
123 
size of, 131 
spinal ganglia, 150 
telodendrion of, 129 
tigroid substance of, 123 
Nerve endings, 159 
circumgemmal fibers in taste buds, 
163 
in connective tissue, 163 
corpuscles of Grandry, 169 
corpuscles of Herbst, 169 
end bulbs of Krause, 174 
end fibrils, 159 
epicritic sensibility of, 164 
epithelial cells in, 159 
genital corpuscle, 166 
Golgi end organs, 174 
Golgi-Mazzoni corpuscles, 169 
gustatory cells, 161 
gustatory organs, 160 
intergemmal fibers, 163 
intragemmal fibers, 163 
Key-Retzius corpuscles, 169 
lamellar (Pacinian) corpuscles, 167 
Merkel's corpuscles, 169 
motor end plates, 171 
muscular, 171 
muscle spindles, 172 
neuro-epithelium, 160 
neuromuscular end organs, 171 
neuromuscular spindles, 172 
neurotendinous end organs, 174 
Pacinian corpuscles, 167-174 
peripheral end organs, 159 
protopathic sensibility of, 164 
Ruffini's end organs, 165 
sole plate, 172 
sustentacular cells, 161 
tactile cells, 159 
tactile corpuscles, 163 
tactile meniscus, 160 
taste buds in, 160 
tendon in, 171 
tendon spindles, 174 
terminal cylinders, 165 
touch corpuscles of Meissner, 163 INDEX 
785 
Nerve endings, trefoil plates, 159 
Vater's corpuscles, 167 
Vater-Pacinian corpuscles, 167 
Nerve fibers, 132 
axis cylinder of, 132 
axolemma of Kiihne, 134 
axon fibrils, 134 
axoplasm of, 134 
endoneurium of, 132-147 
fiber bundles, 139 
funiculi of, 139 
glia fibers, 144 
incisures of Schmidt, 135 
internodal segments of, 135 
medullary segments of, 136 
medullary sheath of, 132-134 
medullated, 132 
with a neurolemma, 132 
without a neurolemma, 137 
myelin of, 135 
sheath of, 132-134 
neuroglia, occurrence of, in, 145 
neurolemma of, 136 
neurokeratin of, 135 
neuroplasm of, 134 
nodes of Banvier, 132 
non-medullated, 132 
with a neurolemma, 137 
without a neurolemma, 137 
nucleated sheath of Schwann of, 136 
Remak's fibers, 137 
Schmidt-Lantermann lines in, 135 
sheath cells of, 137 
sheath of Henle, 132-147 
sympathetic nerve fibers, 137 
telodendrions of, 140 
terminal arborizations of, 140 
tracts, 139 
trophic center of neuron, 137 
ultimate fibrillae of, 133 . 
Wallerian degeneration of, 140 
white substance of Schwann, 132- 
134 
Nerve trunks, funiculus of, 146 
lymphatic vessels of, 147 
nervi nervorum, 148 
nervi erigentes, of penis, 506 
Nerve trunks, perineurium of, 146 
structure of, 146 
vascular supply of, 147 
Nervous system, 587 
blood supply of, 624 
cerebellum, 603 
basket cells of, 608 
climbing fibers of medulla, 609 
cortex of, 606 
granule cells of, 609 
large stellate cells of, 609 
medulla of, 609 
Purkinje cells of, 607 
resume of structures of, 611 
small cortical cells of, 608 
cerebral cortex, 611 
arteries of, circle of Willis, 624 
cortical, 625 
fissural, 625 
medullary, 625 
middle cerebral, 625 
terminal, 625 
auditory area of, cells of, 618 
cell layers of, 612 
cells, Betz, of, 613-616 
giant pyramidal, 613 
Golgi's, types 1 and 2, 613 
solitary, of Meynert, 613 
frontal lobe of, 617 
granule cell layer of, 617 
inner large pyramidal cell layer of, 
617 
inner polymorphous cell layer of, 
617 
molecular layer of, 617 
occipital lobe of, 617 
outer large pyramidal cell layer of, 
617 
outer polymorphous cell layer of, 
617 
outer stripe of Baillarger, 619 
parietal lobe of, 617 
radial fibers of, 618 
small pyramidal cell layer of, 617 
temporal lobe of, 617 
thickness of, 612 
visual area of, 617 786 
INDEX 
Nervous system, cerebrum, 611 
and spinal eord, meninges and 
blood supply of, 619 
basal ganglia of, 611 
corpus callosum, 611 
gyri of, 611 
hemispheres of, 611 
insula of, 612, 617 
medulla of, 611 
occipital lobe of, 611 
pallium of, 611 
parietal lobe of, 611 
sulci of, 611 
Sylvian fissure of, 612 
temporal lobe of, 612 
veins of, 625 
development, 587-595 
of cardie plexus, 591 
of ependyma cells, 589 
of marginal velum, 590 
of myelospongium, 589 
of neural groove (medullary 
groove), 587 
of neural or ganglionic crest, 587 
of neural plate, 587 
of neural tube, 587 
derivatives of, 594 
of neuroblasts, 589 
of neuroglia cells, 589 
of neurons, 587 
of spongioblasts, 589 
of sympathetic plexus, 591 
meninges, 620 
arachnoid, 620 
granulations of, 621 
Pacchionian bodies of, 621 
subarachnoid space, 621 
villi of, 621 
dura mater, 620 
epidural space of, 620-623 
subdural space of, 620 
pia mater, 622 
choroid plexus of, 623 
tela? choroideae of, 623 
motor area of cerebral cortex, 
615 
cells of Martinotti, 617 
Nervous system, inner polymorphous 
eell layer of, 616 
layers of, 615 
marginal velum, 615 
molecular layer, 615 
outer polymorphous cell layer, 
615 
outer polymorphous cell layer of, 
618 
outer stripe of Baillarger of, 618 
pyramidal cell layer, 616 
small pyramidal cell layer, 615 
small pyramidal cell layer of, 
618 
solitary cells of Meynert of, 
618 
stratum zonale, 615 
stripe of Bechterew of, 619 
supraradial felt work, 619 
tangential fiber layer, 619 . 
spinal cord, 596 
anterior spinal artery of, 624 
basis cornu, 596 
caput cornu, 596 
cell column of Clarke, 600 
central canal of, 598 
central commissure, 596 
cervical region, lower half, 602 
upper half, 613 
cervix cornu, 596 
columns of, 598 
conus medullaris, 600 
filum terminale, 600 
gray matter of, 596 
intermediate zone of, 596 
ligamentum denticulatum, 621 
lumbar region of, 601 
nerve roots of, 596 
nucleus of Stilling, 602 
. regions of, 599 
sacral region of, 600 
segments of, 596 
septum posticum, 621 
structure of, 596 
thoracic region of, 607 
veins of, 625 
white matter of, 598 INDEX 
787 
Nervous system, sympathetic division 
of nervous system, 153 
cranial autonomic, 153 
sacral autonomic, 153 
sympathetic ganglia, 154 
sympathetic proper, 153 
tissues of nervous system, 119 
axon, 119 
cell body, 119-121 
cyton, 121 
dendrites, 119 
dendrons, 119 
epineurium of, 146 
ganglion, 121 
ganglion cell, 121 
glomerulus of, 152 
general considerations of, 119 
nerve fiber, 119 
neuroglia (glia tissue), 121 
astrocytes (neuroglia cells), 141 
long rayed or spider cells, 143 
short rayed or mossy cells, 143 
ependyma, 141 
neuron, 119 
neurone theory, 157 
perikaryon, 121 
stains of, 748 
Cajal's method for demonstrat- 
ing nerve fibrils, 750 
gold chlorid, Ranvier's method, 
for nerve plexuses and nerve 
endings, 752 
Golgi's, 751 
methylene blue, for non-medul- 
lated nerve fibers (intra 
vitam method), 749 
Nissl's method for staining 
chromophilic (tigroid) gran- 
ules in cyton and dendron 
with methylene blue, 750 
Weigert's, for medullated nerve 
fibers, 748 
Neurone theory, 157 
Neutral balsam, for mounting sections, 
760 
Neutral dyes, 740 
Normal salt solution, 720 
Nucleus, basic chromatin of, 6 
chromatin, 6 
chromatin nucleoli, 6 
chromioles, 6 
karyolymph, 6 
karyoplasm, 6 
karyosomes, 6 
linin, 6 
net knots in, 6 
nucleoplasm, 6 
nuclear sap, 6 
oxy chroma tin of, 6 
paralinin, 6 
plasmosomes, 6 
Ocular conjunctiva, 674 
Ocular contents, 665 
Odontoblasts, 324 
Odontoclasts, 337 
Olfactory area, of cerebral cortex, 618 
Oogenesis, 460-478 
oogonia, in ovary, 512 
ootid, or mature ovum, 479 
primary oocyte, 478 
polar body, 479 
secondary oocyte, 479 
Optic cup, 645 
Optic nerve, 664 
Optic stalk, 645 
Optic vesicle, 645 
Optical axis, of eye, 628 
Ora serrata of eye, 665 
Orange G. tissue stain, 746 
Organ, of Corti, of ear, 708-709 
of equilibration, 700 
of hearing, 716 
of Jacobson, 295 
of Rosenmuller, 539 
Orth's fluid, for fixation of tissues, 727 
Osmic acid stain, for fat, 758 
Ossification, centers of, 79 
endochondral, 85 
epiphyseal, 85 
intramembranous, 86 
intracartilaginous, 79 
periehondrial, 84 
Osteoblasts, 77-83 788 
INDEX 
Osteoclasts, 78 
Otoliths, 697 
Ovarian follicle, 518 
atresia of, 514 
corona radiata of, 518 
cumulus oophorus, 518 
development of, 513 
discus proligerus, 517 
liquor folliculi, 514 
Pfliiger's tubes, 513 
resume of structures, 519 
stigma of, 518 
stratum granulosum, 517 
vesicular, or Graafian follicle, 517 
Ovarian scars, 522 
Ovary, 507 
blood supply of, 522 
corpora albicantia, of, 510-521 
corpora lutea of, 509 
spuria, 521 
vera, of pregnancy, 521 
corpus hemorrhagicum, 519 
corpus luteum, 507-519 
cortex of, 508 
hilum of, 508 
lutein cells of, 519 
lymphatics of, 525 
medulla of, 508 
nerves of, 525 
ova, 510 
ovarian follicles, 509 
pampiniform plexus of, 523 
plexus venosus of, 523 
primitive follicles of (egg nests), 514 
tunica albuginea of, 510 
Oviduct, blood supply of, 527 
lymphatics and nerves of, 528 
mucosa of, 526 
muscular wall of, 526 
structure of, 525 
Ovum, the, 511 
accessory nucleus of, 511 
cytoplasm of, 511 
deutoplasm of, 511 
nuclear cap of, 511 
nucleus or germinal vesicle of, 511- 
512 
Ovum, the, oocytes, 512 
ootid, 512 
vitelline membrane of, 511 
vitellus, 511 
yolk nucleus of, 511 
zona pellucida of, 511 
Oxyhemoglobin, 211 
Pacchionian bodies, 621 
Pacinian corpuscles, 174 
Palpebral conjunctiva, 674 
Palpebral muscle, of Muller, 677 
Pampiniform plexus, of ovary, 523 
of spermatic cord, 494 
Pancreas, 394 
centro-acinal cells, of Langerhans, of, 
396 
general considerations of, 394 
islands of Langerhans, 399 
nerve supply of, 404 
pancreatic islets, 399 
resume of, 404 
Papillae, circumvallate, of tongue, 341 
conical, of tongue, 340 
filiform, 340 
foliate, of tongue, 341 
fungiform, of tongue, 340 
lenticular, of tongue, 342 
Paradidymis, organ of Giraldes, 502 
Paraffin, embedding of tissues in, 
735 
Paraganglia, 571 
Paraganglion caroticum, 570 
Parahypophysis, 578 
Paramitone, 8 
Paraplasm, 8 
Parasynapis, 463 
Parathyroid gland, 562 
acidophil cells of, 564 
blood supply of, 565 
structure of, 562 
Parietal lobe, of brain, 617 
Paroophoron, 540 
Parovarium, 539 
Parotid gland, 390 
Stenson's duct of, 390 
Pectinate ligament, of eye, 635 INDEX 
789 
Penis, 503 
corpus cavernosum, pectiniform sep- 
tum of, 504 
corpus spongiosum of, 503-506 
glands qf Tyson of, 506 
helicine arteries of, 504 
lymphatics of, 506 
nerves of, 506 
nervi erigentes of, 506 
preputial glands of, 506 
tunica albuginea of, 504 
Peptic glands, 354 
or adelomorphous glands, of stom- 
ach, 355 
Pericementum, of teeth, 329 
Perichondrial ossification, 84 
Perichondrium, 72 
Periodontium, 329 
Periosteum, 74 
Peyer's patches, 366 
Pharyngeal tonsil, 244 
Pharynx, 347 
Pheochrome cells, of adrenal, 548 
Pheocrome organs, 571 
Pia mater, 622 
Picrocarmin stain, for tissues, 744 
Picro-fuchsin (Van Gieson's) stain, for 
connective tissue, 752 
Pigment cells, 52 
Pineal body (conarium; epiphysis cere- 
bri), 579 
blood supply of, 584 
development of, 580 
function of, 581 
habenular commissure of, 581 
posterior commissure of, 584 
structure of, 582 
Pineal eye, 580 
Pineal recess, 580 
Pineal stalk, 580 
Pinna, 682 
Pituitrin, 573 
Pituitary body, 572 
pars buccalis of, 575 
pars neuralis of, 575 
Rathke's pouch, 572 
structure of, 573-575 
Placenta, 536 
Pleura, 312 
Pleural pores, 313 
Polarity, of cells, 39 
Portal vein, 417 
Posterior chamber of eye, 636-643 
Potassium bichromate, for fixation of 
tissues, 726 
Preputial glands, 506 
Prickle cells, 44 
Prophase, 24 
Prostate gland, 497 
blood supply of, 500 
concretions of, corpora amylacea, 499 
structure of, 497 
Protopathic sensibility, 164 
Protoplasm, 1 
alveolar, 13 
ameboid motility of, 16 
chemical constitution of, 2 
ciliary motility, 16 
circulatory movement of, 17 
colloidal biogens of, 10 
colloids, 4 
contractility of, 15 
crystalloids, 4 
emulsoid of, 14 
gel state of, 4 
granular, 13 
irritability of, 15 
metabolism of, 14 
molecular motility of, 17 
muscular movement, 17 
physical constitution of, 3 
sol state of, 4 
structure of, 10 
Prussak's space, of ear, 15 
Pseudopodium, 16 
Pseudo-stratified columnar epithelium, 49 
Pulmonary artery, 314 
Pulmonary veins, 317 
Pyloric glands, of stomach, 357 
Pyramidal cells, of brain, 613 
Racemose glands, 258 
Ranvier's method of staining nerve 
plexuses and endings, 752 790 
INDEX 
Rathke's pouch, of hypophysis cerebri, 
572 
Rectum, 379 
Renal pelvis and ureters, 445. See also 
Kidney. 
Reproductive system, 479 
development of, 456 
female organs of generation, 507 
external organs of, 540 
clitoris, 541 
hymen, 541 
glands of Bartholin, 541 
glandula* vestibulares minores, 541 
labia maj ora, 540 
labia minora, 540 
vestibule, 540 
mammary gland, 541 
active, 543 
blood vessels of, 547 
colostrum, 546 
glands of Montgomery, 545 
lactiferous duct of, 542 
lymphatics of, 547 
milk of, 547 
resting, 545 
internal organs of generation, 507 
Fallopian tube, 525 
lymphatics of, 528 
mucosa of, 526 
muscular wall of, 526 
serous coat of, 526 
structure of, 525 
Graafian follicle, resume, of 
structures, 519 
liquor folliculi of, 514 
stratum granulosum of, 518 
Pfliiger's tubes, 513 
primitive follicles (egg nests), 
514 
ovarian follicles, 509 
atresia of, 514 
corona radiata of, 518 
cumulus oophorus, 518 
development of, 513 
discus proligerus of, 517 
Graafian follicle, 517 
ovarian scars, 522 
Reproductive system, female organs of 
generation, internal organs 
of generation, ovary, 
507 
blood supply of, 523fc 
corpora lutea spuria, 521 
corpora lutea vera, of preg- 
nancy, 521 
corpus albicans of, 510-521 
corpus hemorrhagicum of, 519 
corpus luteum of, 507-519 
cortex of, 508 
hilum of, 508 
lutein cells of, 519 
lymphatics of, 525 
medulla of, 508 
mesovarium, 507 
nerves of, 525 
ova, 510 
pampiniform plexus of, 523 
tunica albuginea of, 510 
oviduct, 525 
blood supply of, 527 
lymphatics of, 528 
mucosa of, 526 
muscular coat of, 526 
structure of, 525 
ovum, 511 
accessory nucleus of, 511 
cytoplasm of, 511 
deutoplasm of, 511 
nucleus of (germinal spot, 
germinal vesicle), 511-512 
nuclear cap, 511 
oocyte, stage of, 512 
oogonial, stage of, 512 
ootid, stage of, 479-512 
vitelline membrane of, 511 
vitellus, 511 
yolk nucleus of, 511 
zona pellucida of, 511 
uterine cavity, 532 
uterine glands, 531 
uterus,' 528 
blood vessels of, 532 
cells of Langhans of chorionic 
villi, in, 537 INDEX 
791 
Reproductive system, female organs of 
generation, internal organs 
of generation, uterus, cer- 
vical glands of, 532 
chorionic villi of pregnant 
uterus, 537 
decidua menstrualis of, 534 
decidua reflexa of, 537 
decidua serotina of, 536 
decidua vera of, 537 
decidual cells of, 535 
fetal blood vessels in, 538 
gravid, the, 535 
lymphatics and nerves of, 
533 
menstruating, 533 
mucosa, or endometrium, of, 
529 
muscular coat of, or myo- 
metrium, 528 
Nabothian follicles of, 532 
placenta uterina, 536 
serous coat of, or perimetrium, 
528 
structure of, 528 
vagina, 538 
mucosa of, 538 
musculature, 538 
outer fibrous coat of, 539 
structure of, 538 
vestigial structures, 539 
epoophoron (parovarium, organ 
of Rosenmuller), 539 
hydatid of Morgagni (vesicu- 
lar appendage), 539 
paroophoron, 540 
fetal, derivatives of, 459 
gametogenesis, 460 
chromosomes in, 464 
determination of sex, 475 
chromosomes in, 476 
diploid number of chromosomes, 
463 
gonad, 460 
haploid chromosome group, 464 
heterotypic division, 460 
maturation, 460 
Reproductive system, gametogenesis, 
Mendelian inheritance, 478 
Mendelism, 477 
determiners in, 477 
homozygote, 478 
heterozygote, 478 
spermatocytes, primary, in, 463 
synapsis phenomena, in, 461 
synizesis in, 463 
telosynapsis in, 463 
tetrads, formation of, in, 460 
unit characters in heredity, 474 
zygote, 460 
general considerations of, 455 
gonads, or sex glands, 456 
male organs of generation, 501 
external organ, 503 
penis, 503 
corpora cavernosa of, 503 
corpus spongiosum of, 503-506 
erectile tissue of, 503-505 
glands of Tyson, 506 
helicine arteries of, 504 
pectiniform septum of, 504 
lymphatics of, 506 
nerves of, 506 
nervi erigentes of, 506 
preputial glands of, 506 
tunica albuginea of, 504 
internal organs, 479 
Cowper's glands, 501 
ejaculatory ducts, 497 
prostate gland, 497 
blood supply of, 500 
structure of, 497 
prostatic concretions, 499 
scrotum, dartos of, 481 
seminal vesicles, 495 
testis, 479 
corpus Highmori (mediasti- 
num) of, 480 
duct system of, 490 
ductuli efferentes of, 490 
epididymis of, 492 
functions of, 479 
histogenesis and structure of, 
485 792 
INDEX 
Reproductive system, male organs of 
generation, internal organs, 
testis, interstitial cells of 
Leydig, of, 487 
lipoid granules in, 488 
pampiniform plexus of, 494 
rete of, 490 
semen, 486 
spermatic cord, 494 
spermatid, 484 
spermatoblasts, 482 
spermatozoon, human, 486 
structure of, 479 
trophocytes (Sertoli cells) of, 
482 
tubules of, 487 
tubuli recti of, 490 
tunica albuginea of, 480 
tunica vaginalis of, 480 
tunica vasculosa of, 480 
vas (ductus) deferens of, 
493 
vestigial structures, associated 
with, 502 
appendix epididymis, 502 
appendix testis, 502 
ductuli aberrentes, 502 
paradidymis (organ of Gi- 
raldes), 502 
sinus pocularis (sinus prostati- 
cus), 502 
Mullerian duets, 456 
oogenesis, 460-478 
parasynapsis in, 463 
polar body in, 479 
primary oocyte in, 478 
secondary oocyte in, 479 
sex chromosome in, 475 
spermatogenesis, 460 
chromidia in, 474 
idiozome in, 475 
prespermatid in, 474 
spermatogonia in, 463 
spermatozoon in, 475 
Wolffian body, or mesonephros, 456 
Wolffian ducts, 456 
Resting nucleus, 24 
Respiratory system, 292 
development of, 293 
larynx, the, 300 
structures of, 300 
vocal cords of, 301 
lung, the, 304 
alveolar ducts of, 310 
alveoli of, 311 
atria of, 310 
blood supply of, 314-319 
bronchi of, 304 
bronchial arteries, 317 
bronchioles of, 307 
lobule of, 314 
lymphatics of, 318 
pleura of, 312 
pleural pores of, 313 
pulmonary artery, 314 
pulmonary veins, 317 
nasal cavity, 293 
blood vessels of, 298 
neuroepithelium of, 297 
olfactory portion of, 296 
organ of Jacobson, of, 295 
respiratory portion of, 294 
vestibule of, 293 
nasopharynx, 299 
trachea of, 302 
Retia mirabilia, of kidney, 187 
Reticulum, 49-55 
Retina, arteria centralis of, 664-670 
cell types of inner nuclear layer of. 
654 
cones of, 651 
external limiting membrane of, 653 
fiber layer of, 654 
fibers of Muller, 658 
fovea centralis of, 660 
ganglion cell layer of, 657 
general considerations of, 644 
inner nuclear layer of, 654 
inner reticular layer of, 656 
inversion of, 663 
layers of, 646 
macula lutea of, 659 
nerve fiber layer of, 657 
optic disc of, 665 INDEX 
793 
Retina, optic papilla of, 665 
outer nuclear layer of, 654 
outer reticular layer of, 654 
pigment epithelium of, 646 
porus opticus of, 665 
rod and cone layer of, 647 
rods of, 648-658 
and cones, development of, 661 
663 
supporting tissues of, 658 
visual purple of, 647-649 
yellow spot of, 659 
Ringer's solution, 720 
Safranin stain, for tissues, 744 
Salivary corpuscles, 243 
Salivary glands, 390 
blood supply of, 392 
lymphatics of, 393 
nerve supply of, 393 
parotid gland, 390 
sublingual gland, 392 
submaxillary gland, 391 
Santorini's duct, 394 
Sarcoplasm, 90 
Sarcosomes, of Retzius, 99 
Scala media, of cochlea, 703 
Scala tympani, 703 
Scleral corpuscles, 634 
Sclerotic coat of eye, 634 
Scrotum, 481 
Sectioning of tissues, 736 
microtome for, 736 
Sections, colloidin adhesive, for, 739 
clarification of, 759 
Mayer's albumin for, 739 
mounting, of, 759 
in euparal, 761 
in glycerin jelly, 760 
in gum damar, 760 
in neutral balsam, 760 
in xylol-balsam, 760 
Segmentation process, 27 
Segmented spireme, 24 
Semen, 486 
Semicircular canals, of ear, 699 
Seminal vesicles, 495 
50 
Septum posticum, 621 
Serous membranes, 232 
mesothelia of, 232 
stomata in, 232 
tunica propria of, 232 
Sertoli cells, 482 
Shrapnell's membrane, of ear, 689 
Sinus prostaticus, 502 
Sinusoids, vascular, 187 
Skin, 262 
blood supply of, 290 
capillary layer of, 268 
cylindrical cell layer of, 264 
derma, the, 268 
eleidin layer of (stratum lucidum), 
267 
epidermis, the, 262 
flattened eell layer and scaly layer 
(stratum corneum) of, 267 
granular layer or stratum granu- 
losum, of, 266 
growth and development of, 270 
hair, development of, 277 
mature, 279 
regeneration of, 286 
root of, 281 
shaft of, 281 
sheaths of, 283 
structure of, 277 
keratin of, 267 
layers of, 262 
nails, 274 
growth and development of, 276 
structure of, 275 
nerve supply of, 291 
prickle cell layer (stratum spinosum) 
of, 265 
reticular layer of, 269 
sebaceous glands of, 286 
stratum germinativum, 265 
sudoriparous glands of, 271 
Small intestine, 374. See Digestive 
system. 
Smears, method of making, 730 
Solution, Hogan's, 721 
normal saline, 720 
j Ringer's, 721 794 
INDEX 
Spaces, of Fontana, 643 
Specific dyes, 740 
Spermatic cord, 494 
Spermatid, and spermatozoon, 484 
Spermatocytes, primary, 463 
Spermatogenesis, 460 
idiozome in, 475 
prespermatid in, 470 
Spermatogonia, 463 
Spermatozoon, 475 
histogenesis,*and structure of, 485 
human, 486 
Spinal cord, 596 
basis cornu of, 596 
caput cornu of, 596 
cell column, of Clarke, 602 
central canal of, 598 
central commissure of, 596 
cervical region, lower half of, 602 
cervical region, upper half of, 603 
cervix cornu of, 596 
columns of, 598 
filurn terminale of, 600 
gray matter of, 596 
intermediate zone of, 596 
lumbar region of, 600 
nerve roots of, 596 
nucleus of Stilling, of, 602 
regions of, 599 
segments of, 596 
sacral region of, 600 
thoracic region of, 601 
white matter of, 598 
Spiral organ, of Corti, 702. See also 
Ear. 
Spireme, loose, 24 
Spleen, 245 
blood vessels of, 246 
development of, 250 
differentiation of, from lymph nodes, 
249 
functions of, 249 
pulp veins of, 248 
Splenic cells, 249 
Splenic nodules, 247 
Spongioblasts, 589 
Spongioplasm, 8 
Staining methods, special, 747 
Benda's mitrochondrial technic, 757 
blood, Hasting's eosinate of methy- 
lene blue, for, 754 
chromaffin granules, technic for, 759 
chromophilic (tigroid) granules in 
cyton and dendron, with 
methylene blue, 750 
connective tissue, Mallory's, 753 
with picro-fuchsin (Van Gieson's), 
752 
cytoplastie granules, eosin and 
methylene blue mixture, 
Mann's, 755 
Ehrlich's triacid, 755 
elastic tissue, Weigert's, 753 
fat, osmic acid for demonstrating, 758 
glycogen, Gage's method for demon- 
strating, 758 
medullate nerve fibers, Weigert-Pal 
method for demonstrating, 
748 
mitochondria, 757 
mucinous tissues, specific, 748 
nerve cells, Golgi's, 751 
nerve plexuses and endings, gold 
chlorid (Ranvier's) for, 752 
neurofibrils, Cajal's, 750 
nitrate of silver, for cement sub- 
stances, 752 
Staining of tissues, 738 
double, 746 
in bulk, 739 
progressive, 740 
regressive, 740 
Stains, aceto-carmin, 744 
alum car min, 744 
Auerbach's fuchsin-methyl-green, 756 
borax carmin, 743 
carmin, 743 
Congo red, 746 
Delafield's hematoxylin, 742 
eosin, 745 
fuchsin, 746 
hematein, 743 
and eosin, 746 
iron hematoxylin, 747 INDEX 
795 
Stains, Mann's acid hematein (Ehr- 
lich's hematoxylin), 742 
methylene blue, 743 
methyl blue and safranin, 747 
methyl green, 743 
muchematein, 748 
mueiearmin, 748 
orange G, 746 
picro-carmin, 744 
safranin, 744 
single, with cytoplasmic dyes, 745 
with nuclear dyes, 741 
Stapedius muscle, 690 
Stapes, 689 
Stenson's duct, 390 
Stigmata, 38 
Stomach, 353 
blood supply of, 360 
cardiac glands of, 360 
fundus glands of, 354 
lenticular glands of, 360 
lymphatics of, 362 
mucous coat of, 353 
muscular coat of, 353 
nerve supply of, 362 
parietal cells (oxyntic or delomor- 
phous cells) of, 356 
peptic, or adelomorphous cells, of, 355 
pyloric glands, 357 
secretion of, 357 
serous coat of, 352 
submucous coat of, 353 
Stomata, 38 
Stratified epithelium, 43 
Stratified squamous epithelium, 43 
Stripe of Bechterew, 619 
Stripes of Baillarger, 619 
Strop, use of, 738 
Subarachnoid space, 621-624 
Subcutaneous tissue, 269 
Subdural space, 620-623 
Sublingual gland, 392 
Submaxillary gland, 391 
Submucous plexus (Meissner's), of 
small intestine, 375 
Suprarenal glands, 548 
accessory, 556 
Suprarenal glands, chromaffin gran- 
ules in, 554 
blood supply of, 554-555 
. development and function of, 548 
lymphatics and nerves of, 556 
medulla, cells of, 553 
zona fasciculata, 552 
zona glomerulosa, 552 
zona reticularis, 553 
Sweat glands, 271 
Sympathetic plexus, 461-463 
Synapsis phenomena, 461-463 
Syncytia, 31 
Synizesis phase of gametogenesis, 463 
Synovia, 89 
Synovial membranes, 232 
Tapetum cellulosum, of eye, 638 
Tapetum fibrosum, of eye, 637 
Tarsus of eyelid, 676 
Technic, for demonstrating chromaffin 
granules, 759 
Teeth, 333 
ameloblasts (adamantoblasts), 333 
cementoblasts, 337 
cementum, 329 
development of, 336 
deciduous, 331 
dental enamel, layers of, 335 
dental papilla, 336 
dental pulp, 323 
dentin of, 325 
development of, 330 
enamel germ of, 330-331 
enamel organ, of, 330 
layers of, 331 
Tomes' processes, 333 
odontoclasts, 337 
permanent, 331 
root membranes of, 329 
root canals of, 336 
Sharpey's fibers in, 329 
structure of, 323 
Telae choroideae, 623 
Tellyesniczky's fluid, for fixation of 
tissues, 726 
Telophase of mitotic cell division, 25 796 
INDEX 
Telosynapsis, 463 
Tendon, 115 
nerve endings in, 171 
peritenoneum of, 115 
vagina fibrosa, 115 
vagina mucosa, 115 
Tendon cells, 117 
Tendon fasciculi, 115 
Tendon spindles, 174 
Testis, 479-480 
corpus Highmori of, 480 
duct system of, 490 
ductuli efferentes of, 490 
epididymis, 492 
human, 486 
interstitial cells, of Leydig, 487 
lipoid granules in, 488 
mediastinum of, 480 
rete of, 490 
semen, 486 
spermatic cord of, 494 
spermatid, and spermatozoon, 484 
spermatoblasts, 482 
spermatozoon, histogenesis and 
structure of, 485 
trophocytes of, 482 
tubules of, 487 
tubuli recti of, 490 
tunica albuginea of, 480 
tunica vaginalis of, 480 
tunica vasculosa of, 480 
vas (ductus) deferens of, 493 
Thoracic duct, 230 
Thrombin, 203 
Thymus gland, 565 
blood supply of, 568 
development and function of, 568 
lymphoid corpuscles of, 567 
Thyroid gland, 557 
accessory, 562 
blood supply of, 560 
colloid in, 557 
development of, 561 
follicles of, 557 
follicular epithelium of, 559 
function of, 561 
lymphatics of, 560 
Thyroid gland, nerves of, 561 
structure of, 557 
Thyroidin, 561 
Thyroglossal duct, 343 
Tissue 
adenoid, 64 
adipose, 61 
bone, 72 
compact, 74 
general consideration of, 72 
bone marrow, 77 
cartilage, 67 
blastema of, 69 
elastic, 71 
fibro-, 71 
hyaline, 68 
matrix of, 69 
origin of, 70 
connective, acidophil granulocytes, 
52 
areolar, 56 
basophil granule cells, in, 52 
blood and nerve supply of, 67 
cells of, 51 
dense elastic, 60 
dense fibrous, 59 
elastic fibers of, 57 
embryonal, 50-53 
eosinophil granulocytes of, 52 
fibrocartilage, 71 
general statements, 49 
lamellar cells of, 52 
loose fibro-elastic, 56 
marrow, blood supply, 78 
mucous, 54 
oxyphil granulocytes in, 52 
perichondrium, 72 
periosteum, 74 
plasma cells of, 51 
red marrow, 77 
reticular, 55 
spindle cells of, 51 
types of, 53 
yellow elastic, 61 
ectoderm, 28 
entoderm, 28 
epithelia, classification of, 34 INDEX 
797 
Tissue, epithelial tissue, 30-3 
epithelium, transitional, 47 
varieties of, 33 
eruptive, 82 
fat, 61 
stains for, 62 
intercellular cement substance, in, 30 
lymphatic corpuscles, 66 
lymphoid, 31-64 
mesoderm, 28 
mucous, 54 
muscular, 90 
Tissue fixation, by, 723 
alcohol, 724 
Bouin's fluid, 729 
Carnoy's fluid (lung), 729 
chromo-acetic-formalin mixture, 727 
Flemming's fluid, 728 
formalin, 725 
Gilson's fluid, 730 
heat, 730 
Belly's fluid, 728 
Kleinenberg's fluid, 729 
mercuric chlorid, 725 
mercuro-nitric mixture, 730 
Muller's solution, 726 
Orth's fluid, 727 
potassium bichromate, 726 
Tellyesniczky's fluid, 726 
vapors, 731 
van Gehuchten's fluid, 729 
Zenker's solution, 727 
Tissue fixation, of human embryos, 
726 
lung tissue, 730 
Tissue juice, 55 
Tissue staining, in bulk, 739 
progressive, 740 
regressive, 740 
Tissue stains, 744 
aceto-carmin, 744 
alum carmin, 744 
alum hematein (Mayer), 741 
Bohmer's hematoxylin, 741 
borax carmin, 743 
carmin, 743 
double staining, 746 
Tissue stains, Congo red, 746 
Delafield's hematoxylin, 742 
eosin, 745 
fuchsin, 746 
hematin, 741-743 
and eosin, 746 
iron-hematoxylin, 747 
Mallory's, for connective tissue, 
753 
Mann's hematein (Ehrlich's hema- 
toxylin), 742 
methyl green, 743 
methyl blue, and safranin, 747 
methylene blue, 743 
muchematein, 748 
mucicarmin, 748 
mucinous, specific stain, 748 
orange G, 746 
picro-carmin, 744 
picro-fuchsin, for connective tissue 
(Van Gieson), 752 
safranin, 744 
single, with nuclear dyes, 741 
Weigert's, for elastic tissue, 731 
Tissues, 30 
box for embedding for sectioning of, 
737 
decalcification of, 731 
dissociation of, 721 
chemical, 722 
embedding of, 734 
in celloidin, 734 
in paraffin, 735 
hardening of, 733 
injection of, 732 
maceration of, 721 
sectioning of, 736 
staining of, 738 
teasing of, 721 
Tongue, 337 
blood vessels of, 343 
foramen cecum of, 343 
glands of, 342 
lymphatics of, 344 
mucous membrane of, 337 
nerve supply of, 344 
papillae of, 339 798 
INDEX 
Tongue, serous glands of, 343 
taste buds of, 341 
Tonsil, faucial (palatine), 242 
lingual, 244, 343 
pharyngeal, 244 
tubal, 692 
Trachea, 302 
structures of, 302 
Tunica propria, corium of skin, 34 
Tympanic membrane, 687 
Tympanum of ear, 685. See also 
ear 
Tyson's glands, in penis, 506 
Umbo, of tympanic membrane, 687 
Unit characters, in Mendelian inheri- 
tance, 477 
Urinary system, 423 
kidney, 423 
arciform veins of, 443 
arteries, arterise proprise renales, 
440 
arciform, 440 
arterise recto*, 441 
interlobular, 441 
Bellini's ducts of, 438 
capsule of Bowman, of, 429 
corpuscles (renal) of, 425 
cortex of, 424 
glomerulus of, 429 
lymphatics and nerves of, 444 
medulla of, 424 
papillary ducts of, 438 
pelvis and ureter of, 445 
blood supply of, 448 
mucosa of, 445 
muscular coat of, 448 
tunica propria of, 447 
renal circulation, table showing 
course of, 443 
renal connective tissue, 426 
renal corpuscles (Malpighian bod- 
ies), 425-429 
renal lobule, 426 
topography of, 423 
tubules of, arched connecting 
(junctional tubule), 437 
Urinary system, kidney, tubules of, 
ascending limb of Henle's 
loop, 435 
descending limb of Henle's loop, 
434 
distal convoluted portion of, 436 
divisions of renal tubule, 429 
loop of Henle, 435 
neck of, 431 
peculiarities of, 440 
proximal convoluted portion of, 
431 
straight collecting, 437 
table of divisions of renal tu- 
bule, 439 
uriniferous, or renal, 427 
urethra, female, 452 
structure of, 452 
urethra, male, structure of, 454. 
urinary bladder, 448 
mucous membrane of, 4,48 
muscular coat of, 451 
vascular and nerve supply of, 
452 
veins of, stellate, 443 
venae propriae renales, 443 
venulae rectae of, 443 
Uterus, the, 532 
blood vessels of, 532 
cells of Langhans of chorionic villi 
of, 537 
cervical glands of, 532 
chorionic villi of pregnant uterus, 537 
decidua menstrualis of, 534 
decidua reflexa of, 537 
decidua serotina of, 536 
decidua vera of, 537 
decidual cells of, 535 
fetal blood vessels, 538 
glands of, 531 
gravid, 535 
lymphatics and nerves of, 533 
menstruating, 533 
mucosa, or endometrium, of, 529 
muscular coat, or myometrium, of, 
528 INDEX 
799 
Uterus, Nabothian follicles of, 532 
placenta uterina, 536 
serous coat, or perimetrium, of, 528 
structure of, 528 
Utricle, of ear, 698 
Vagina, mucosa of, 538 
musculature of, 538 
outer fibrous coat of, 539 
structure of, 538 
Valves, of heart, 196 
Valvulas conniventes, 364 
Vas (ductus) deferens, 493 
Vascular sinusoids, 187 
Vascular tissue, 176 
Veins, 187 
arciform, of kidney, 443 
atypical, 189 
auditory, 716 
circulus venosus, of Haller, 547 
cranial, 190 
larger, structure of, 188 
of central nervous system, 625 
of ear, 715 
of kidney, 443 
of liver, 415 
of ovary, 523 
of sclera, 635 
of spermatic cord, 494 
portal, 417 
pulmonary, 190-317 
small, 188 
smaller and larger, comparison of, 
190 
Veins, valves in, 191 
vena cava, 190 
vena conies, 191 
venae vorticosae, of eye, 672 
Velum, marginal, 590 
Venous spaces, 190 
Venules, precapillary, 187 
Vermiform appendix, 379 
Vesicular appendages, 539 
Vestibule, of pudendum, 540 
Vestigial structures, associated with 
reproductive organs, 539- 
540 
Visual area, 617 
Visual axis, 628 
Vitreous humor, 669 
Vocal cords, 301 
Weigert-Pal stain, for medullated 
nerve fibers, 748 
Weigert's elastic tissue stain, 753 
Wirsung's duct, 394 
Wolffian body, or mesonephros, 456 
Xylo-balsam, for mounting sections, 
760 
Zenker's solution, 727 
Zimmermann's technic, for intercalated 
discs of cardiac muscle, 758 
Zonula eiliaris, of eye, 670 
Zygote, 27-460