MEMCAL .SCHOOL
LEIEMAl&lf

IN MEMORIAH
BERTRAM STONE, M.D.

A TEXT-BOOK

OF

PHYSIOLOGY

FOR

MEDICAL STUDENTS AND PHYSICIANS

BY

WILLIAM H. HOWELL, PH.D., M.D., LL.D.

PROFESSOR OF PHYSIOLOGY IN THE JOHNS HOPKINS UNIVERSITY, BALTIMORE

SeconD jemtion, Gborougblg

PHILADELPHIA AND LONDON

W. B. SAUNDERS COMPANY

1907

Set up, electrotyped, printed, and copyrighted. September, 1905. Reprinted,,

February, 1906, September, 1906, and January, 1907. Revised,

reprinted, and recopyrighted, August, 1907.

Copyright, 1907, by W. B. Saunders Company.

PRESS OF
W. B. 8AUNDERS COMPANY. PHILADA.

PREFACE TO THE SECOND EDITION.

IN the preparation of the second edition of this book the author
has made no fundamental change in its arrangement or scope.
Additions and changes havp been made freely throughout the
work, with the object of keeping the presentation of the subject
abreast of the times, but as far as possible the additions have been
counterbalanced by the elimination of such material as could be
spared. The book remains, therefore, of practically the same
size, an object which the author has purposely kept in view, since
he is convinced that in text-books there is a natural tendency to
overexpansion which should be guarded against with care. New
figures have been introduced whenever it seemed that an actual
improvement could be effected by this means.

The author has been gratified with the generous approval
accorded to the first edition and hopes that the present edition
may continue to find favor with teachers of physiology and medical
students, as well as among physicians who may feel the need of
keeping themselves in touch with the progress of physiology. There
are, in fact, many indications that the physiological side of medi-
cine is likely to receive a fuller recognition than has been given
to it in the recent past. Medical schools are providing courses in
experimental pathology and surgery, subjects in which physiological
methods and training are all important, and in clinical medicine
also it is becoming evident that the methods of physiological
experimentation and the application of physiological discoveries
are of practical value in diagnosis as well as in investigation. No
one doubts that anatomy, physiology, and pathology, using these
terms in a broad sense, constitute the basis upon which a rational
system of medicine must be constructed, but it would seem that,
in this country at least, the clinicians have failed to make full use
of the material offered to them by the subject of physiology.
Some explanation of this neglect is found in the fact -that the
physiologists themselves, not being practitioners, have no good

l

2 PREFACE TO THE SECOND EDITION.

opportunity to enforce the practical applications of their subject.
According to the division of labor existing in medicine to-day it is
the main duty of the physiologist to till his own field, and to the
clinician and practising physician belong the responsibility and
the opportunity of utilizing the results thus obtained by giving
them their practical application to diagnosis and treatment. It
is gratifying to find that tlje attention of the clinicians is being
directed more to this side of the subject. Without doubt this
tendency will serve to emphasize to the student the importance
of a sound training in the physiological sciences.

PREFACE.

In the preparation of this book the author has endeavored to
keep in mind two guiding principles: first, the importance of
simplicity and lucidity in the presentation of facts and theories;
and, second, the need of a judicious limitation of the material
selected. In regard to the second point every specialist is aware
of the bewildering number of researches that have been and are
being published in physiology and the closely related sciences, and
the difficulty of justly estimating the value of conflicting results.
He who seeks for the truth in any matter under discussion is often-
times forced to be satisfied with a suspension of judgment, and
the writer who attempts to formulate our present knowledge
upon almost any part of the subject is in many instances obliged
to present the literature as it exists and let the reader make his
own deductions. This latter method is doubtless the most satis-
factory and the most suitable for large treatises prepared for the
use of the specialist or advanced student, but for beginners it is
absolutely necessary to follow a different plan. The amount of
material and the discussion of details of controversies must be
brought within reasonable limits. The author must assume the
responsibility of sifting the evidence and emphasizing those con-
clusions that seem to be most justified by experiment and obser-
vation. As far as material is concerned, it is evident that the
selection of what to give and what to omit is a matter of judg-
ment and experience upon the part of the writer, but the present
author is convinced that the necessary reduction in material
should be made by a process of elimination rather than by con-
densation. The latter method is suitable for the specialist with
his background of knowledge and experience, but it is entirely
unfitted for the elementary student. For the purposes of the
latter brief, comprehensive statements are oftentimes misleading,
or fail at least to make a clear impression. Those subjects that
are presented to him must be given with a certain degree of full-
ness if he is expected to obtain a serviceable conception of the
facts, and it follows that a treatment of the wide subject of physi-
ology is possible, when undertaken with this intention, only by
the adoption of a system of selection and elimination.

The fundamental facts of physiology, its principles and modes

3

4 PREFACE.

of reasoning are not difficult to understand. The obstacle that
is most frequently encountered by the student lies in the com-
plexity of the subject, — the large number of more or less dis-
connected facts and theories which must be considered in a dis-
cussion of the structure, physics, and chemistry of such an intri-
cate organism as the human body. But once a selection has been
made of those facts and principles which it is most desirable that
the student should know, there is no intrinsic difficulty to prevent
them from being stated so clearly that they may be comprehended
by anyone who possesses an elementary knowledge of anatomy,
physics, and chemistry. It is doubtless the art of presentation
that makes a text-book successful or unsuccessful. It must be
admitted, however, that certain parts of physiology, at this par-
ticular period in its development, offer peculiar difficulties to the
writers of text-books. During recent years chemical work in the
fields of digestion and nutrition has been very full, and as a result
theories hitherto generally accepted have been subjected to crit-
icism and alteration, particularly as the important advances
in theoretical chemistry and physics have greatly modified the
attitude and point of view of the investigators in physiology.
Some former views have been unsettled and much information
has been collected which at present it is difficult to formulate and
apply to the explanation of the normal processes of the animal
body. It would seem that in some of the fundamental problems
of metabolism physiological investigation has pushed its experi-
mental results to a point at which, for further progress, a deeper
knowledge of the chemistry of the body is especially needed. Cer-
tainly the amount of work of a chemical character that bears di-
rectly or indirectly on the problems of physiology has shown a re-
markable increase within the last decade. Amid the conflicting
results of this literature it is difficult or impossible to follow always
the true trend of development. The best that the text-book can
hope to accomplish in such cases is to give as clear a picture
as possible of the tendencies of the time.

Some critics have contended that only those facts or conclu-
sions about which there is no difference of opinion should be pre-
sented to medical students. Those who are acquainted with
the subject, however, understand that books written from this
standpoint contain much that represents the uncertain compromises
of past generations, and that the need of revision is felt as fre-
quently for such books as for those constructed on more liberal
principles. There does not seem to be any sound reason why a
text-book for medical students should aim to present only those
conclusions that have crystallized out of the controversies of other
times, and ignore entirely the live issues of the day which are

PREFACE. 5

of so much interest and importance not only to physiology, but
to all branches of medicine. With this idea in mind the author
has endeavored to make the student realize that physiology is a
growing subject, continually widening its knowledge and read-
justing its theories. It is important that the student should
grasp this conception, because, in the first place, it is true; and,
in the second place, it may save him later from disappointment
and distrust in science if he recognizes that many of our conclu-
sions are not the final truth, but provisional only, representing
the best that can be done 'with the knowledge at our command.
To emphasize this fact as well as to add somewhat to the interest
of the reader short historical resumes have been introduced from
time to time, although the question of space alone, not to men-
tion other considerations, has prevented any extensive use of such
material. It is a feature, however, that a teacher might develop
with profit. Some knowledge of the gradual evolution of our
present beliefs is useful in demonstrating "Mie enduring value of
experimental work as compared with mere theorizing, and also in
engendering a certain appreciation and respect for knowledge
that has been gained so slowly by the exertions of successive
generations of able investigators.

A word may be said regarding the references to literature
inserted in the book. It is perfectly obvious that a complete
or approximately complete bibliography is neither appropriate
nor useful, however agreeable it maybe to give every worker full
recognition of the results of his labors. But for the sake of those
who may for any reason wish to follow any particular subject
more in detail some references have been given, and these have
been selected usually with the idea of citing those works which
themselves contain a more or less extensive discussion and litera-
ture. Occasionally also references have been made to works of
historical importance or to separate papers that contain the experi-
mental evidence for some special view.

TABLE OF CONTENTS.

SECTION I.
THE PHYSIOLOGY 'OF MUSCLE AND NERVE.

PAGE

CHAPTER I. — THE PHENOMENON OF CONTRACTION 17

The Histological Structure of the Muscle Fiber, 18. — Its Appearance by
Polarized Light, 19. — The Extensibility and Elasticity of Muscular Tissue,
19. — The Independent Irritability of Muscle, 22. — Definition and Enumeration
of Artificial Stimuli, 23. — The Duration of the Simple Muscle Contraction, 25. —
The Curve of a Simple Muscle Contraction, 25. — The Latent Period, 26. — The
Phases of Shortening and Relaxation, 26. — Isotonic and Isometric Contrac-
tions, 27. — Maximal and Submaximal Contractions, 27. — Effect of Temperature
upon the Simple Contraction, 28. — Effect of Veratrin on the Simple Contraction,
30. — Contracture, 33. — Fatigue, the Treppe, and Effect of Rapidly Repeated
Stimulation, 33. — The Wave of Contraction and Means of Measuring, 34. —
Idiomuscular Contractions, 34. — The Energy Liberated During a Muscular
Contraction, 35. — The Proportional Amount of this Energy Utilized in Work,
36.— The Curve of Work and the Absolute Power of a Muscle, 38.— Definition
of Tetanus or Compound Contraction, 39. — The Summation of Contractions,
41. — Discontinuity of the Processes of Contraction in Tetanus, 42. — The
Muscle-tone, 41. — The Rate of Stimulation Necessary for Complete Tetanus,
42. — The Tetanic Nature of Voluntary Contractions, 43. — The Ergograph, 45. —
Results of Ergographic Experiments, 47. — Sense of Fatigue, 48. — Muscle
Tonus, 48. — Rigor Mortis and Rigor Caloris, 49. — The Occurrence and Struc-
ture of Plain Muscle Tissue, 52.— Distinctive Properties of Plain Muscle, 53.—
The General Properties of Cardiac Muscular Tissue, 54. — The Contractility of
Cilia and Their General Properties, 54.

CHAPTER II. — THE CHEMICAL COMPOSITION OF MUSCLE AND THE CHEM-
ICAL CHANGES OF CONTRACTION AND OF RIGOR MORTIS 57

The Composition of Muscle Plasma, 57.— The Proteins of Muscle, 58.— The
Carbohydrates of Muscle, 59. — Phosphocarnic Acid, 60. — Lactic Acid in Muscle,
60. — The Nitrogenous Extractives of Muscle, 61. — Pigments of Muscle, 61. —
Enzymes of Muscle, 61. — Inorganic Constituents of Muscle, 62. — The Chemi-
cal Changes in Muscle during Contraction, 62. — The Chemical Changes during
Rigor Mortis, 66. — The Relation of the Waste Products to Fatigue, the Chemical
Theory of Fatigue, 66. — Theories of the Mechanism of the Contraction of
Muscle, 68.

CHAPTER III. — THE PHENOMENON OF CONDUCTION. PROPERTIES OF

THE NERVE FIBER 72

General Statement Regarding Property of Conductivity, 72. — Structure of
the Nerve Fiber, 73. — Function of the Myelin Sheath, 73.— The Nerve Trunk
an Anatomical Unit Only, 74. — Definition of Afferent and Efferent Nerve
Fibers, 75. -^-Classification of Nerve Fibers, 75. — The Bell-Magendie Law of
the Composition of the Anterior and the Posterior Roots of the Spinal Nerves,
77. — Cells of Origin of the Anterior and Posterior Root Fibers, 78. — Origin
of the Afferent and Efferent Fibers in the Cranial Nerves, 79. — Independent
Irritability of Nerve Fibers, Artificial Nerve Stimuli, 80. — Du Bois-Reymond's
Law of Stimulation by the Galvanic Current, 82. — Electrotonus, 83. — Pfluger's
Law of Stimulation, 84.— The Opening and the Closing Tetanus, 86.— M9de
of Stimulating Nerves in Man, 86. — Motor Points of Muscles, 88. — Physical
and Physiological Poles, 89.

CHAPTER IV. — THE ELECTRICAL PHENOMENA SHOWN BY NERVE AND

MUSCLE 91

The Demarcation Current, 91. — Construction of the Galvanometer, 92. — Con-
struction of the Capillary Electrometer, 94. — Non-polarizable Electrodes, 95. —
Action Current or Negative Variation, 96. — Monophasic and Diphasic Action
Currents, 98. — The Rheoscopic Frog Preparation, 99. — Relation of Action
Current to the Contraction Wave and Nerve Impulse, 100. — The Electrotonic
Currents, 101.— The Core-model, 102.

7

8 TABLE OF CONTENTS.

PAGE

CHAPTER V. — THE NATURE OF THE NERVE IMPULSE AND THE NUTRI-
TIVE RELATIONS OF NERVE FIBER AND NERVE CELL 104

Historical, 104. — Velocity of the Nerve Impulse, 105. — Relation of the Nerve
Impulse to the Wave of Negativity, 107. — Direction of Conduction in the
Nerve, 107. — Effect of Various Influences on the Nerve Impulse, 109. — The
Fatigue of Nerve Fibers, 110. — The Metabolism of the Nerve Fiber during
Functional Activity, 112. — Theories of the Nerve Impulse, 113. — Qualitative
Differences in Nerve Impulses, 115. — Doctrine of Specific Nerve Energies,
116. — Nutritive Relations of Nerve Fibers and Nerve Cells, 117. — Nerve Degen-
eration and Regeneration, 118. — Degenerative Changes in the Central End
of the Neuron, 121.

SECTION II.

THE PHYSIOLOGY OF THE CENTRAL NERVOUS SYSTEM.

CHAPTER VI. — STRUCTURE AND GENERAL PROPERTIES OF THE NERVE

CELL 123

The Neuron Doctrine, 123. — The Varieties of Neurons, 125. — Internal Structure
of the Nerve Cell, 127. — General Physiology of the Nerve Cell, 129. — Sum-
mation of Stimuli in Nerve Cells, 131. — Response of the Nerve Cell to Varying
Rates of Stimulation, 132. — The Refractory Period of the Nerve Cell, 133.

CHAPTER VII.— REFLEX ACTIONS 134

Definition and Historical, 134.— The Reflex Arc, 134.— The Reflex Frog, 136.—
Spinal Reflex Movements, 136. — Theory of Co-ordinated Reflexes, 138. — Spinal
Reflexes in Mammals, 139. — Dependence of Co-ordinated Reflexes upon the
Excitation of the Sensory Endings, 139. — Reflex Time, 140. — Inhibition of
Reflexes, 140. — Influence of the Condition of the Cord on its Reflex Activities,
142.— Reflexes from Other Parts of the Nervous System, 143.— Reflexes
Through Peripheral Ganglia, Axon Reflexes, 144. — The Tonic Activity of the
Spinal Cord, 145. — Effects of the Removal of the Spinal Cord, 145. — Knee-jerk,
147. — Reinforcement of the Knee-jerk, 147. — Is the Knee-jerk a Reflex Act?
149. — Conditions Influencing the Extent of the Knee-jerk, 150. — The Knee-
jerk and Spinal Reflexes as Diagnostic Signs, 151. — Location of the Centers
for the Different Spinal Reflexes, 152.

CHAPTER VIII. — THE SPINAL CORD AS A PATH OF CONDUCTION 155

Arrangement and Classification of the Nerve Cells in the Cord, 155. — General
Relations of the Gray and White Matter in the Cord, 157. — Ihe Methods
of Determining the Tracts of the Cord, 157. — General Classification of the
Tracts of the Cord, 158. — The Names and Locations of the Long Tracts, 160. —
The Termination in the Cord of the Fibers of the Posterior Root, 161. — Ascend-
ing or Afferent Paths in the Posterior Columns, 162. — Ascending or Afferent
Paths in the Lateral Columns, 165. — The Spinal Paths for the Cutaneous
Senses (Touch, Pain, Temperature), 167.— The Homolateral or Contralateral
Conduction of the Cutaneous Impulses, 168. — The Descending or Efferent
Paths in the Anterolateral Columns (Pyramidal System), 168. — Less Well-
known Tracts in the Cord, 170.

CHAPTER IX. — THE GENERAL PHYSIOLOGY OF THE CEREBRUM AND ITS

MOTOR FUNCTIONS 173

The Histology of the Cortex, 174. — The Classification of the Systems of Fibers
in the Cerebrum (Projection, Association, and Commissural), 175. — Physio-
logical Deductions from the Histology of the Cortex, 177. — Extirpation of the
Cerebrum, 179. — Localization of Functions in the Cerebrum, Historical, 181. —
The Motor Areas of the Cortex, 184. — Differences in Paralysis from Injury
to the Spinal Neuron and the Pyramidal Neuron, 186. — Voluntary Motor
Paths Other than the Pyramidal Tract, 186.— The Crossed Control of the
Muscles and Bilateral Motor Representation in the Cortex, 187. — Are the
Motor Areas Exclusively Motor ? 188.

CHAPTER X. — THE SENSE AREAS AND THE ASSOCIATION AREAS IN THE

CORTEX 190

The Body-sense Area, 191. — The Course of the Fillet, 192. — The Center for
Vision, 194. — Histological Evidence of the Course of the Optic Fibers, 195. —
The Decussation in the Chiasma, 197. — The Projection of the Retina on the
Occipital Cortex, 197. — The Function of the Lower Visual Centers, 199. —
The Auditory Center, 200. — Course of the Cochlear Nerve, 202. — The Physio-
logical Significance of the Lower Auditory Centers, 203. — Motor Responses
from the Auditory Cortex, 203.— The Olfactory Center, 204.— The Olfactory
Bulb and its Connections, 204. — The Cortical Center for Smell, 205. — The
Cortical Center for Taste, 206.— Aphasia, 206.— Sensory Aphasia, 208.— The
Association Areas, 209. — Subdivision of the Association Areas, 211. — The
Development of the Cortical Areas, 212. — Histological Differentiation in Cor-
tical Structure, 215. — Physiology of the Coipus Callosum, 216. — Physiology
of the Corpora Striata and Optic Thalami, 216.

TABLK OK CONTENTS. 9

PAGE

CHAPTKR XL — THE FUNCTIONS OF THK CEREBELLUM, THE PONS, AND

THE MEDULLA 'J 1 s

Anatomical Structure and Relations of the Cerebellum, 218. — General State-
ment of Theories Regarding the Cerebellum, 222. — Experiments upon Ablation
of the Cerebellum, 223. — Interpretation of the Experimental and Clinical
Results, 224. — Conclusions as to the General Functions of the Cerebellum, 226. —
The Psychical Functions of the Cerebellum, 227. — Localization of Function
in the Cerebellum, 227. — The Functions of the Medulla Oblongata, 228.— The
Nuclei of Origin and the Functions of the Cranial Nerves, 229.

CHAPTER XII. — THE SYMPATHETIC OK AUTOXOMIC NERVOUS SYSTEM. . . . 'Jo 4

General Statements, 234. — Autonomic Nervous System, 235. — The Use of
the Nicotin Method, 236.— General Course of the Autonomic Fibers Arising
from the Cord, 236. — General Course of the Fibers Arising from the Brain,
237. — General Course of the Fibers Arising from the Sacral Cord, 239. — Normal
Mode of Stimulation of Autonomic Nerve Fibers, 239.

CHAPTER XIII. — THE PHYSIOLOGY OF SLEEP -'A

General Statements, 241. — Physiological Relations during Sleep, 241. — The
Intensity of Sleep, 242. — Changes in the Circulation during Sleep, 245. — Effect
of Sensory Stimulation, 246. — Theories of Sleep, 247. — Hypnotic Sleep, 251.

SECTION III.
THE SPECIAL SENSES.
CHAPTER XIV. — CLASSIFICATION OF THE SENSES AND GENERAL STATE-

252

Classification of the Senses, 252. — The Doctrine of Specific Nerve Energies,
254.— The Weber-Feehner Psychophysical Law, 2.'.0.

CHAPTER XV. — CUTANEOUS AND INTERNAL SENSATIONS 2">9

General Statements, 259. — The Punctiform Distribution of the Cutaneous
Senses, 260. — Specific Nerve Energies of the Cutaneous Nerves, 262. — The
Temperature Senses, 263.— The Sense of Pressure, 263.— The Threshold Stimu-
lus and the Localizing Power, 264. — The Pain Sense, 266. — Localization or
Projection of Pain Sensations, 267. — Reflected or Misreferred Pains, 267. — The
Muscle Sense, 268. — The Quality of the Muscle Sense, 269. — Sensations of
Hunger and Thirst, 270. — The Sense of Thirst, 272.

CHAPTER XVI. — SENSATIONS OF TASTE AND SMELL 274

The Nerves of Taste, 274.— The End-organ of the Taste Fibers. 276.— Classi-
fication of Taste Sensations, 276. — Distribution and Specific Energy of the
Fundamental Taste Sensations. 277. — Method of Sapid Stimulation, 278. —
The Threshold Stimulus for Taste, 279.— The Olfactory Organ, 279.— The
Mechanism of Smelling, 280. — Nature of the Olfactory Stimulus, 281. — The
Qualities of the Olfactory Sensations, 281. — Fatigue of the Olfactory Apparatus,
283. — Delicacy of the Olfactory Sense, 283. — Conflict of Olfactory Sensations,
285. — Olfactory Associations, 285.

CHAPTER XVII. — THE EYE AS AN OPTICAL INSTRUMENT. DIOPTRICS

OF THE EYE 280

Formation of an Image by a Biconvex Lens, 286. — Formation of an Image
in the Eye, 289. — The Inversion of the Image on the Retina, 291 . — The Size
of the Retinal Image, 292. — Accommodation of the Eye, 293. — Limit of the
Power of Accommodation and Near Point of Distinct Vision, 296.— Far Point
of Distinct Vision, 297. — The Refractive Power of the Surfaces in the Eye,
297.— Optical Defects of the Normal Eye, 298.— Spherical Aberration, 299.—
Abnormalities in the Refraction of the Eye, Myopia, 299. — Hypermetropia,
300. — Presbyopia, 301. — Astigmatism, 302. — Innervation and Control of
the Ciliary "Muscle and the Muscles of the Iris, 304. — The Accommodation
Reflex and the Light Reflex, 306. — Action of Drugs upon the Iris, 308. —
The Antagonism of the Sphincter and Dilator Muscles of the Iris, 309.— In-
traocular Pressure, 310. — The Ophthalmoscope, 311. — Retinoscope, 313. —
Ophtalmometer, 314.

CHAPTER XVIII. — THE PROPERTIES OF THE RETINA. VISUAL STIMULI

AND VISUAL SENSATIONS 316

The Portion of the Retina Stimulated by Light, 316. — The Action Current
Caused by Stimulation of the Retina, 317. — The Visual Purple, Rhodopsin,
318. — Extent of the Visual Field, Perimetry, 320. — Central and Peripheral
Fields of Vision, 321. — Visual Acuity, 323. — Relation Between Stimulus and
Sensation, Threshold Stimulus, 325. — The Light Adapted and the Dark Adapted

10 TABLE OF CONTENTS.

PAGE

Eye, 326. — Luminosity or Brightness, 327. — Qualities of "Visual Sensations,
328. — The Achromatic Series, 329. — The Chromatic Series, 329. — Color Satura-
tion and Color Fusion, 329. — The Fundamental Colors, 330. — The Comple-
mentary Colors, 331. — After Images, Positive and Negative, 331. — Color
Contrasts, 332. — Color Blindness, 333. — Dichromatic Vision, 334. — Tests for
Color Blindness, 335. — Monochromatic Vision, 336. — Distribution of Color
Sense in the Retina, 336. — Functions of the Rods and Cones, 337. — Theories
of Color Vision, 340. — Entoptic Phenomena, 344. — Shadows of Corpuscles
and Blood-vessels, 345. — Shadows from Lens and Vitreous Humor, 346.

CHAPTER XIX.— BINOCULAR VISION 347

Movements of the Eyeballs, 347. — Co-ordination of the Eye Muscles, Muscular
Insufficiency and Strabismus, 349. — The Binocular Field of Vision, 350. —
Corresponding or Identical Points, 350. — Physiological Diplopia, 351. — The
Horopter, 353. — Suppression of Visual Images, 353. — Struggle of the Visual
Fields, 353. — Judgments of Solidity, 354. — Monocular Perspective, 354. —
Binocular Perspective, 356. — Stereoscopic Vision, 356. — Explanation of Binoc-
ular Perspective, 358. — Judgments of Distance and Size, 359. — Optical Decep-
tions, 360.

CHAPTER XX. — THE EAR AS AN ORGAN FOR SOUND SENSATIONS 363

The Pinna or Auricle, 364.— The Tympanic Membrane, 364.— The Ear Bones,
365.— Mode of Action of the Ear Bones, 366.— Muscles of the Middle Ear,
368. — The Eustachian Tube, 369. — Projection of the Auditory Sensations,
370. — Sensory Epithelium of the Cochlea, 370.— Nature and Action of the
Sound Waves, 371. — Classification and Properties of Musical Sounds, 372. —
Upper Harmonics or Overtones, 374.— Sympathetic Vibrations and Resonance,
376. — Functions of the Cochlea, 376. — Sensations of Harmony and Discord,
379.— Limits of Hearing, 380.

CHAPTER XXI. — FUNCTIONS OF THE SEMICIRCULAR CANALS AND THE

VESTIBULE 382

Position and Structure of the Semicircular Canal s 382. — Flouren's Experi-
ments upon the Semicircular Canals, 383. — Temporary and Permanent Effects
of the Operations, 384. — Effect of Direct Stimulation of the Canals, 384.—
Effect of Section of the Ampullary or the Acoustic Nerve, 385. — Is the Effect
of Section of the Canals Due to Stimulation? 385. — Theories of the Functions
of the Semicircular Canals, 385. — Summary of the Views upon the Function
of the Semicircular Canals, 388. — Functions of the Utriculus and Sacculus, 389.

SECTION IV.
BLOOD AND LYMPHi

CHAPTER XXII. — GENERAL PROPERTIES OF BLOOD. PHYSIOLOGY OF

THE CORPUSCLES 392

Histological Structure of Blood, 392. — Reaction of the Blood, 393. — Specific
Gravity of the Blood, 394.— The Red Corpuscles, 395.— Condition of the
Hemoglobin in the Corpuscles, 396. — Hemolysis, 397. — Hemolysis Due to
Variations in Osmotic Pressure, 397. — Hemolysis Due to Action of Hemoly-
sins, 398. — Nature and Amount of Hemoglobin, 401. — Compounds of Hemo-
globin with Oxygen and Other Gases, 403. — The Iron in the Hemoglobin, 404. —
Crystals of Hemoglobin, 405. — Absorption Spectra of Hemoglobin and Oxy-
hemoglobin, 406. — Derivative Compounds of Hemoglobin,. 410. — Origin and
Fate of the Red Corpuscles, 412. — Variations in the Number of Red Corpuscles,
414. — Physiology of the Blood Leucocytes, 416. — Variations in Number
of the Leucocytes, 417. — Functions of the Leucocytes, 417. — Physiology of
the Blood Plates, 418.

CHAPTER XXIII. — CHEMICAL COMPOSITION OF THE BLOOD PLASMA;
COAGULATION; QUANTITY OF BLOOD; REGENERATION AFTER
HEMORRHAGE 420

Composition of the Plasma and Corpuscles, 420. — Proteins of the Blood Plasma,
422. — Serum Albumin, 422. — Paraglpbulin (Serum Globulin), 423. — Fibrin-
ogen, 424. — Less Well-known Proteins of the Blood, 426. — Coagulation of
Blood, 426. — Theories of Clotting, 427. — Why Blood Does Not Clot Within
the Vessels, 432. — Intravascular Clotting, 433. — Means of Hastening or of
Retarding Coagulation, 434.— Total Quantity of Blood in the Body, 436.—
Regeneration of the Blood after Hemorrhage, 437. — Blood Transfusion, 439.

CHAPTER XXIV. — COMPOSITION AND FORMATION OF LYMPH 440

General Statements, 440. — Formation of Lymph, 441. — Lymphagogues of the
First Class, 443. — Lymphagogues of the Second Class, 444. — Summary of
the Factors Controlling the Flow of Lymph, 445.

TABLE OF CONTEXTS. 11

SECTION V.

PHYSIOLOGY OF THE ORGANS OF CIRCULATION OF THE
BLOOD AND LYMPH.

PAGE

CHAPTER XXV. — THE VELOCITY AND PRESSURE OF THE BLOOD FLOW. . . 447

The Circulation as Seen under the Microscope, 447. — The Velocity of the
Blood Flow, 448. — Mean Velocity in the Arteries, Veins, and Capillaries, 451. —
Cause of the Variations in Velocity, 452. — Variations of Velocity with the
Heart Beat or Changes in the Blood-vessels, 453. — Time Necessary for a Com-
plete Circulation of the Blood, 454. — The Pressure Relations in the Vascular
System, 455. — Methods of Recording Blood-pressure, 455. — Systolic, Dias-
tolic, and Mean Arterial Pressure, 459. — Method of Measuring Systolic and
Diastolic Pressure in Animals, 461. — Data as to the Mean Pressure in Arteries,
Veins, and Capillaries, 463. — Methods of Determining Blood-pressure in the
Large Arteries of Man, 466. — Normal Pressure in Man and Its Variations, 471.

CHAPTER XXVI. — THE PHYSICAL FACTORS CONCERNED IN THE PRODUC-
TION OF BLOOD-PRESSURE AND BLOOD-VELOCITY 473

Side Pressure and Velocity Pressure, 473. — The Factors Concerned in Pro-
ducing Normal Pressure and Velocity, 476. — General Conditions Influencing
Blood-pressure and Blood-velocity, 477. — The Hydrostatic Effect, 478. — Venous
Pressures, 479. — Accessory Factors Aiding the Circulation, 480. — The Con-
ditions of Pressure and Velocity in the Pulmonary Circulation, 480. — Variations
of Pressure in the Pulmonary Circuit, 481.

CHAPTER XXVII.— THE PULSE 483

General Statement, 483.— Velocity of the Pulse Wave, 484.— Form of the
Pulse Wave, Sphygmography, 486. — Explanation of the Catacrotic Waves,
488. — Anacrotic Waves, 489. — The Kinds of Pulse in Health and Disease, 490. —
Venous Pulse, 491.

CHAPTER XXVIIL— THE HEART BEAT 494

General Statement, 494. — Musculature of the Auricles and Ventricles, 495. —
Contraction Wave of the Heart, 496.— The Electrical Variation, 497.— Change
of Form during Systole, 499. — The Apex Beat, 500. — Cardiogram, 500. —
Intraventricular Pressure during Systole. 502. — The Heart Sounds, 503. —
Events Occurring during a Cardiac Cycle, 506. — Time Relations of Systole and
Diastole, 507. — Normal Capacity of Ventricle and Work Done by the Heart,
507. — Coronary Circulation during the Heart-beat, 509. — Suction-pump Action
of the Heart, 510. — Occlusion of the Coronary Vessels, 512. — Fibrillar Con-
tractions of Heart Muscle, 513.

CHAPTER XXIX. — THE CAUSE AND THE SEQUENCE OF THE HEART BEAT.

PROPERTIES OF THE HEART MUSCLE 514

General Statement, 514. — The Neurogenic Theory of the Heart Beat, 516. —
Myogenic Theory, 517. — Automaticity of the Heart, 519. — Action of Calcium,
Potassium, and Sodium Ions on the Heart, 520. — Connection of Inorganic
Salts with the Causation of the Beat, 521. — Maximal Contractions of the Heart,
523. — Refractory Period of the Heart Beat, 523. — The Compensatory Pause,
525. — Normal Sequence of the Heart Beat, 525. — Tonicity of the Heart
Muscle, 529.

CHAPTER XXX. — THE CARDIAC NERVES AND THEIR PHYSIOLOGICAL

ACTION 531

Course of the Cardiac Nerves, 531. — Action of the Inhibitory Fibers, 531. —
Analysis of the Inhibitory Action, 533. — Effect of Vagus on the Auricle and
the Ventricle, 535. — Escape from Inhibition, 536. — Reflex Inhibition of the
Heart Beat, the Cardio-inhibitory Center, 536. — The Tonic Activity of the
Cardio-inhibitory Center, 537. — The Action of Drugs on the Inhibitory Appara-
tus, 539. — The Nature of Inhibition, 539. — Course of the Accelerator Fibers,
541. — Action of the Accelerator Fibers, 543. — Tonicity of the Accelerators
and Reflex Acceleration, 543. — The Accelerator Center, 545.

CHAPTER XXXI. — THE RATE OF THE HEART BEAT AND ITS VARIATIONS

UNDER NORMAL CONDITIONS 546

Variations in Rate with Sex, Size, and Age, 546. — Variations through the
Extrinsic Cardiac Nerves, 547. — Variations with Blood-pressure, 547. — With
Muscular Exercise, 548. — With the Gases of the Blood, 549. — With Tempera-
ture of the Blood, 549.

12 TABLE OP CONTENTS.

CHAPTER XXXII. — THE VASOMOTOR NERVES AND THEIR PHYSIOLOGICAL

ACTIVITY 551

Historical, 551. — Methods Used to Determine Vasomotor Action, 552. — The
Plethysmograph, 553. — General Distribution and Course of the Vasoconstrictor
Nerve Fibers, 555. — Tonic Activity of the Vasoconstrictors, 558. — The Vaso-
constrictor Center, 558. — Vasoconstrictor Reflexes, Pressor and Depressor
Fibers, 560. — Depressor Nerve of the Heart, 583. — Vasoconstrictor Centers in
the Spinal Cord. 564. — Rhythmical Activity of the Vasoconstrictor Center,
564.— Course and Distribution of the Dilator Fibers, 565. — General Properties
of Vasodilator Fibers, 565.— Vasodilator Center and Reflexes, 566.— Vasodila-
tation Due to Antidromic Impulses, 568. — Regulation of the Blood-supply
by Chemical and Mechanical Stimuli, 569.

CHAPTER XXXIII. — THE VASOMOTOR SUPPLY OF THE DIFFERENT

ORGANS 570

Vasomotors of the Heart, 570. — Vasomotors of the Pulmonary Arteries, 571. —
Circulation in the Brain and Its Regulation, 572. — Arterial Supply, 572. —
Venous Supply, 573. — The Meningeal Spaces, 574. — Intracranial Pressure,
576. — Effect of Changes in Arterial Pressure upon the Blood-flow through
the Brain, 577. — The Regulation of the Brain Circulation, 579. — Vasomotor
Nerves of the Head Region, 581. — Of the Trunk and the Limbs, 582. — Of the
Abdominal Organs, 582. — Of the Genital Organs, 583. — Of the Skeletal Muscles,
583.— The Vasomotor Nerves to the Veins, 584.— The Circulation of the
Lymph, 585.

SECTION VI.

PHYSIOLOGY OF RESPIRATION.

CHAPTER XXXIV. — HISTORICAL STATEMENT. THE ORGANS OF EXTER-
NAL RESPIRATION AND THE RESPIRATORY MOVEMENTS 587

Historical, 587. — Anatomy of Organs of Respiration, 591. — Thorax as a Closed
Cavity, 592. — Normal Position of the Thorax, 592. — Inspiration by Contraction
of the Diaphragm, 593. — Inspiration by Elevation of the Ribs, 594. — The
Muscles of Inspiration, 595. — Muscles of Expiration, 595. — Quiet and Forced
Respiratory Movements, Eupnea and Dyspnea, 596. — Costal and Abdominal
Types of Respiration, 597. — Accessory Respiratory Movements, 598. — Registra-
tion of the Respiratory Movements, 598. — Volumes of Air Respired, Vital
Capacity, Tidal Air, Complemental Air, Supplemental Air, Residual Air,
Minimal Air, 600. — Size of the Bronchial Tree, 602. — Artificial Respiration, 602.

CHAPTER XXXV. — THE PRESSURE CONDITIONS IN THE LUNGS AND

THORAX AND THEIR INFLUENCE UPON THE CIRCULATION 604

The Intrapulmonic Pressure and Its Variations, 604. — Intrathoracic Pressure,
605. — Variations of, with Forced and Unusual Respirations, 606. — Origin of
the Negative Pressure in the Thorax, 607. — Pneumothorax, 608. — Aspiratory
Action of the Thorax, 608. — Respiratory Waves of Blood-pressure, 609.

CHAPTER XXXVI. — THE CHEMICAL AND PHYSICAL CHANGES IN THE AIR

AND THE BLOOD CAUSED BY RESPIRATION 613

The Inspired and Expired Air, 613. — Physical Changes in the Expired Air,
613. — Injurious Action of Expired Air, 614. — Ventilation, 616. — The Gases
of the Blood, 617. — The Pressure of Gases, 620. — Absorption of Gases in
Liquids, 620.— The Tension of Gases in Solution, 622.— The Condition of
Nitrogen in the Blood, 623. — Condition of Oxygen in the Blood, 624. — Con-
dition of Carbon Dioxid in the Blood, 625. — The Physical Theory of Respira-
tion, 627.— Gaseous Exchanges in the Lungs, 627. — Exchange of Gases in the
Tissues, 629.— Secretory Activity of Lungs, 630.

CHAPTER XXXVII. — INNERVATION OF THE RESPIRATORY MOVEMENTS . . 631

The Respiratory Center, 631. — Spinal Respiratory Centers, 632. — Automatic
Activity of the Respiratory Center, 633. — Reflex Stimulation of the Center,
633. — Afferent Relations of the Vagus to the Center, 635. — The Inspiratory
and Inhibitory Fibers of the Vagus, 637. — Respiratory Reflexes from the
Larynx, Pharynx, and Nose, 638. — Voluntary Control of the Respiratory
Movements, 639. — Nature of the Respiratory Center, 639. — Respiratory Cen-
ters in the Midbrain, 640. — Automatic Stimulus to the Respiratory Center,
640. — Cause of the First Respiratory Movements, 643. — Dyspnea, Hyperpnea,
and Apnea, 643. — Innervation of the Bronchial Musculature, 646.

TABLE OF CONTEXTS. 13

PAGE

CHAPTER XXXVIII. — THE INFLUENCE OF VARIOUS CONDITIONS UPON

THE RESPIRATION 648

Effect of Muscular Work on the Respiratory Movements, 048. — Effect of
Variations in the Composition of the Air, 648. — High and Low Barometric
Pressures, Mountain Sickness, Caisson Disease, 650. — The Respiratory Quotient
and Its Variations, 652. — Modified Respiratory Movements, 653.

SECTION VII.

PHYSIOLOGY OF DIGESTION AND SECRETION.
CHAPTER XXXIX. — MOVEMENTS O-F THE ALIMENTARY CANAL 655

Mastication, 655. — Deglutition, 655. — Nervous Control of Deglutition, 659. —
Anatomy of the Stomach, 660. — Musculature of the Stomach, 661. — Move-
ments of the Stomach, 661. — Effect of the Nerves on the Movements of the
Stomach, 664. — Movements of the Intestines, 666. — Peristaltic and Pendular
Movements of the Intestines, 666. — Nervous Control of the Intestinal Move-
ments, 669. — Effect of Various Conditions on the Intestinal Movements, 669. —
Movements of the Large Intestines, 670.— Defecation, 671. — Vomiting, 672. —
Nervous Mechanism of Vomiting, 674.

CHAPTER XL. — GENERAL CONSIDERATION OF THE COMPOSITION OF THE

FOOD AND THE ACTION OF ENZYMES 675

Foods and Foodstuffs, 675. — Accessory Articles of Diet, 677. — Enzymes,
Historical, 678. — Reversible Reactions, 680.— Specificity of Enzymes, 682. —
Definition and Classification of Enzymes, 682. — General Properties of Enzymes,
684. — Partial List of Enzymes, 685. — Chemical Composition of the Enzymes,
685.

CHAPTER XLL— THE SALIVARY GLANDS AND THEIR DIGESTIVE ACTION . 687

Anatomy of the Salivary Glands, 687. — Histological Structure, 689,-^Com-
position of the Secretion, 690. — The Secretory Nerves, 691. — Trophic and
Secretory Nerve Fibers, 693. — Histological Changes during Activity, 694. —
Action o*f Drugs upon the Secretory Nerves, 697. — Paralytic Secretion, 698. —
Normal Mechanism of Salivary Secretion, 698. — Electrical Changes in Glands,
700. — Digestive Action of Saliva; Ptyalin, 700. — Conditions Influencing the
Action of Ptyalin, 701. — Functions of the Saliva, 702.

CHAPTER XLII. — DIGESTION AND ABSORPTION IN THE STOMACH 703

Structure of the Gastric Glands, 703. — Histological Changes during Secretion,
704. — Method of Obtaining the Gastric Secretion and Its Normal Composition,
705.— The Acid of Gastric Juice, 707.— Origin cf the HC1, 707.— Secretory
Nerves of the Gastric Glands, 708. — Normal Mechanism of the Secretion of
the Gastric Juice, 709. — Nature and Properties ct Pepsin, 711. — Artificial
Gastric Juice, 713.— Pepsin-hydrochloric Digestion, 713. — The Rennin En-
zyme, 715. — Digestive Changes in the Stomach, 717. — Absorption in the
Stomach, 718.

CHAPTER XLIII. — DIGESTION AND ABSORPTION IN THE INTESTINES 721

Structure of the Pancreas, 721. — Composition of the Secretion, 722. — Secre-
tory Nerve Fibers to the Pancreas, 722. — The Curve of Secretion, 723. — Nor-
mal Mechanism of Pancreatic Secretion, 724. — Secretin. 725.— Enterokinase,
725. — Digestive Action of Pancreatic Juice, 725. — Significanceof Tryptic Diges-
tion, 728. — Action of the Diastatic Enzyme (Amylopsin), 729. — Action of the
Lipolytic Enzyme (Lipase, Steapsin), 730. — The Intestinal Secretion (Succus
Entericus), 731. — Absorption in the Small Intestine, 733. — Absorption of
Carbohydrates, 734. — Absorption of Fats, 735. — Absorption of Proteins, 737. —
Digestion and Absorption in the Large Intestine, 738. — Bacterial Action in
the Small Intestine, 739.— Bacterial Action in the Large Intestine, 740. —
Physiological Importance of Intestinal Putrefaction, 740. — Composition of
the Feces, 741.

CHAPTER XLIV. — PHYSIOLOGY OF THE LIVER AND SPLEEN 743

Structure of the Liver, 743. — Composition of Bile, 744.— The Bile Pigments,
745.— The Bile Acids, 746.— Cholesterin, 747.— Lecithin, Fats, and Nucleo-
albumins, 748. — Secretion of the Bile. 748. — Ejection of the Bile — Function of
the Gall-bladder, 749. — Occlusion of the Bile-ducts, 751. — Physiological Im-
portance of Bile, 751 . — Occurrence of Glycogen, 752. — Origin of Glycogen. 753. —
Function of Glycogen. Glyrogenic Theory, 756. — Glycogen in the Muscles and
Other Tissues, 757. — Conditions Affecting the Supply of Glycogen, 757. — For-
mation of Urea in the Liver, 758. — Physiology of the Spleen, 759.

14 TABLE OF CONTENTS.

PAGE

CHAPTER XLV. — THE KIDNEY AND SKIN AS EXCRETORY ORGANS 762

Structure of the Kidney, 762. — The Secretion of Urine, 763. — Function of
the Glomeralus, 765. — Function of the Convoluted Tubule, 767. — Action of
Diuretics, 769. — The Blood-flow Through the Kidneys, 769. — The Composi-
tion of Urine, 772. — The Nitrogenous Excreta in the Urine, 773. — Origin and
Significance of Urea, 774. — Origin and Significance of the Purin Bodies (Uric
Acid, Xanthin, Hypoxanthin), 777.— ^-Origin and Significance of the Creatinin,
780. — Hippuric Acid, 781. — The Conjugated Sulphates and the Sulphur Excre-
tion, 781. — Secretion of the Water and Inorganic Salts, 782. — Micturition,
783. — Contractions of the Bladder, 784. — Nervous Mechanism of Micturition,
787. — Excretory Functions of the Skin, 788. — Composition of Sweat, 788. —
Secretory Fibers of Sweat Glands, 789. — Sweat Centers, 791. — Sebaceous
Secretion, 791. — Excretion of Carbon Dioxid through the Skin, 792.

CHAPTER XLVI. — SECRETION OF THE DUCTLESS GLANDS — INTERNAL

SECRETION 793

Internal Secretion of Liver, 794. — Internal Secretion of the Thyroid Tissues,
794. — Extirpation of Thyroids and Parathyroids, 795.— Function of the Para-
thyroids, 795. — Theories of General Functions of Thyroid and Parathyroids,
797. — Cyon's View of Function of Thyroid, 797. — Function of Thymus, 798. —
Structure and Properties of Adrenal Bodies, 798. — General Function of Adre-
nals, 801.— Pituitary Body, 801.— Internal Secretion of Testis and Ovary,
802. — Internal Secretion of Pancreas, 804. — Internal Secretion of Kidney, 806.

SECTION VIII.
NUTRITION AND HEAT PRODUCTION AND REGULATION.

CHAPTER XLVII. — GENERAL METHODS. HISTORY OF THE PROTEIN

FOOD 808

General Statement, 808. — Nitrogen Equilibrium, 808. — Carbon Equilibrium
and Body Equilibrium, 810. — Balance Experiments, 810. — Respiration Cham-
ber, 811. — Effect of Non-protein Food on Nitrogen Equilibrium, 811. — Nutri-
tive History of the Protein Food, 811. — Tissue Protein and Circulating Protein,
812. — Amount of Protein Necessary in Normal Nutrition, Question of Luxus
Consumption, 813. — Specific Character of Protein Metabolism, 815. — Specific
Dynamic Action of Proteins, 818. — Nutritive Value of Albuminoids, 818.

CHAPTER XLVIII. — NUTRITIVE HISTORY OF CARBOHYDRATES AND FATS 821

The Carbohydrate Supply of the Body, 821. — Regulation of the Sugar Supply
of the Body, 821. — Fate of the Carbohydrates in the Body, 824. — Functions of
the Carbohydrate Food, 825. — Nutritive Value of Fats, 826. — Fate of Fats in
the Tissues, 826.— Origin of Body Fat, 827.— Origin of Body Fat from Carbohy-
drates, 829. — Origin of Body Fat from Food Fat, 828. — Source of Fat in
Ordinary Diets, 829.— Cause of the Formation of Fat, Obesity, 829.— General
Functions of Fat, 830.

CHAPTER XLIX. — NUTRITIVE VALUE OF THE INORGANIC SALTS AND THE

ACCESSORY ARTICLES OF DIET 832

The Inorganic Salts of the Body, 831. — Effect of Ash-free and Ash-poor Diets,
833. — Special Importance of Sodium Chlorid, Calcium, and Iron Salts, 833. —
The Condiments, Flavors, and Stimulants, 835. — Physiological Effects of
Alcohol, 836.

CHAPTER L. — EFFECT OF MUSCULAR WORK AND TEMPERATURE ON BODY

METABOLISM; HEAT ENERGY OF FOODS; DIETETICS 840

The Effect of Muscular Work, 840. — Effect of Sleep, 842. — Effect of Variations
in Temperature, 842. — Effect of Starvation, 843. — The Potential Energy of
Food, 845.— Dietetics, 848.

CHAPTER LI. — THE PRODUCTION OF HEAT IN THE BODY; ITS MEASURE-
MENT AND REGULATION; BODY TEMPERATURE; CALORIMETRY;
PHYSIOLOGICAL OXIDATIONS 852

Historical Account of Theories of Animal Heat, 852. — Body Temperature in
Man, 853. — Calorimetry, 855. — Heat Regulation, 860. — Regulation of Heat
Loss, 860. — Regulation of Heat Production, 863. — Existence of Heat Centers
and Heat Nerves, 864. — Theories of Physiological Oxidations, 866.

TABLE OF CONTENTS. 15

SECTION IX.
PHYSIOLOGY OF REPRODUCTION.

PAGE

CHAPTER LII. — PHYSIOLOGY OF THE FEMALE REPRODUCTIVE ORGANS . . 872

The Relation of the Ovaries to Menstruation, 876. — Physiological Significance
of Menstruation, 878. — Effect of the Menstrual Cycle on Other Functions,
879. — Passage of the Ovum into the Uterus, 879. — Maturation of the Ovum,
880. — Fertilization of the Ovum, 883. — Implantation of the Ovum, 884. —
Nutrition of the Ovum — Physiology of the Placenta, 885. — Changes in the
Maternal Organism during Pregnancy, 887. — Parturition, 888. — The Mammary
Glands, 889. — Connection between the Uterus and the Mammary Glands,
889.— Composition of Milk, 891.

CHAPTER LIII. — PHYSIOLOGY OF THE MALE REPRODUCTIVE ORGANS .... 893

Sexual Life of Male, 893. — Properties of the Spermatozoa, 893. — Chemistry
of the Spermatozoa, 895. — The Act of Erection, 896. — Reflex Apparatus of
Erection and Ejaculation, 897.

CHAPTER LIV. — HEREDITY; DETERMINATION OF SEX; GROWTH AND

SENESCENCE 899

Definition of Heredity, 899. — Evolution and Epigenesis, 899. — Determination
of Sex, 901. — Growth and Senescence, 904.

APPENDIX.
I. — PROTEINS AND THEIR CLASSIFICATION 907

Definition and General Structure of Proteins, 907. — Reactions of Proteins, 908.
— Classification of Proteins, 910. — The Albumins, 911. — The Globulins, 911. —
The Albuminates, 911. — Nucleo-albumins or Phosphoproteins, 911. — Pro-
teoses and Peptones, 912. — Protamins and Histons, 912. — The Compound
Proteins, 913.— The Albuminoids, 913.

II. — DIFFUSION AND OSMOSIS 914

Diffusion, Dialysis, and Osmosis, 914. — Osmotic Pressure, 914. — Electrolytes,
915.— Gram-molecular Solutions, 916. — Calculation of Osmotic Pressure in
Solutions, 916. — Determination of Osmotic Pressure by the Freezing Point,
917.— Application to Physiological Processes, 917. — Osmotic Pressure of
Proteins, 917. — Isotonic, Hypertonic, and Hypotonic Solutions, 918. — Diffu-
sion or Dialysis of Soluble Constituents, 918. — Diffusion of Proteins, 919.

INDEX.. , 921

A TEXT-BOOK

OF

PHYSIOLOGY.

SECTION I.
THE PHYSIOLOGY OF MUSCLE AND NERVE.

CHAPTER I.
THE PHENOMENON OF CONTRACTION.

The tissues in the mammalian body in which the property of
contractility has been developed to a notable extent are the mus-
cular and the ciliated epithelial cells. The functional value of the
muscles and the cilia to the body as an organism depends, in fact,
upon the special development of this property. The muscular
tissues of the body fall into three large groups, considered from
either a histologicalor a functional standpoint, — namely, the striated
skeletal muscle, the striated cardiac muscle, and the plain 'muscle.
These tissues exhibit certain marked differences in properties which
are described farther on. In each group, moreover, there are
certain minor differences in structure which are associated with
differences in properties; thus, skeletal muscle from different re-
gions of the same animal may show variations in properties, — for
instance, in the rapidity of contraction; and similar, perhaps more
marked differences are observed in the plain muscular tissue of
various organs. The muscular tissues from animals belonging to
different classes exhibit naturally even wider variations in proper-
ties, and these differences in some cases are not associated with
visible variations in structure.

2 17

18

THE PHYSIOLOGY OF MUSCLE AND NERVE.

THE PHYSIOLOGY OF SKELETAL MUSCLE TISSUE.

This tissue makes up the essential part of the skeletal muscles by
means of which our voluntary movements are effected. Each muscle
fiber arises from a single cell and in its fully developed condition
may be regarded as a multinuclear giant cell. It is inclosed entirely
in a thin, structureless, elastic membrane, the sarcolemma. The
material of the fiber is supposed to be semifluid or viscous when
in the living condition; it is designated in general as the muscle

There is on record an interesting observation by Kiihne* which seems
to demonstrate the fluid nature of the living muscle substance. He hap-
pened, on one occasion, to find a frog's muscle fiber containing a nematode
worm within the sarcolemma. The animal swam readily from one end of
the fiber to the other, pushing aside the cross bands, which fell into place

Fig. 1. — A cross-section of muscle
fiber of rabbit. The bundles of fibrils are
dark; the intervening small amount of
sarcoplasm is represented by the clear
spaces. — (Kolliker.')

Fig. 2. — Cross-section of two muscle
fibers of the fly: Ms, The columns of
fibrils; Sp, the sarcoplasm. — (Schieffer-
decker.)

again after the animal had passed. At one end, where the fiber had been
injured, the worm was unable to force its way. The muscle substance at
this point was dead and apparently had passed into a solid condition. The
fact that the cross bands were displaced only temporarily by the movement
and fell back into their normal position would indicate that they may have
a more solid structure.

Disregarding the nuclei, the muscle plasma consists of two
different structures: the fibrils, which are long and thread-like and
run the length of the fiber, and the intervening sarcoplasm. The
fibrils consist of alternating dim and light discs or segments, which,
falling together in the different fibrils, give the cross-striation
that is characteristic. In mammalian muscles the fibrils are grouped
more or less distinctly into bundles or columns, between which lies
the scanty sarcoplasm. The relative amount of sarcoplasm to
fibrillar substance varies greatly in the striped muscles of different
* Kiihne, 'Archiv fur pathologische Anatomic," 26, 222, 1863.

THE PHENOMENON OF CONTRACTION.

19

animals, as is indicated in the accompanying illustrations. The

evidence from comparative physiology indicates that the fibrils

are the contractile element of the fiber, while the sarcoplasm, it

may be assumed, possesses a general nutritive function. Com-

parative histology suggests that in the

fibrils we possess, so to speak, a mechanism

adapted to rapid contraction, and that the

perfection of the mechanism — -that is, the

rapidity of the contraction — ;3 proportional

to the clearness of the cross-striation. The

fibril, moreover, shows two kinds of sub-

stance, the alternating dim and light sub-

stance, and these two materials are obviously

different in physical structure as seen by

ordinary light. When examined by polarized

light this difference becomes more evident,

for the dim substance possesses the property

of double refraction. When the muscle fiber

is placed between crossed Nicol prisms

the dim bands appear bright, while the

light bands remain dark, as is shown in

Fig. 3. From this standpoint the material

of the light bands in the normal fibrils is

spoken of as isotropous, while the dim bands

are anisotropous. The anisotropic material

of the dim bands is composed Of doubly

refracting positive uniaxial particles, and

Engelmann has shown that such particles

may be discovered in all contractile tissues.

The inference made by him is that this

anisotropic substance is the contractile p

material in the protoplasm, the machinery, Fig. 3.— TO show the

so to speak, through which its shortening ?aTsot?SpCfc)ofandhe HgS

is accomplished. In the striated fiber this £3t£SSt£StonfaJL Sen

Conclusion is Supported by the fact, repre- by ordinary and by polar-

J . ized light. The figure rep-

sented in Fig. 3, that during contraction resents a muscle fiber

-.. . , ,, ,, /T i j_\ i i (beetle) in which the lower

liquid passes from the ISOtrOpOUS (light) band portion has been fixed in a

<

into the anisotropous (dim) band.*

The Extensibility and Elasticity of

Muscular Tissue. — The muscular tissue when acted upon by
a weight extends quite readily, and when the weight is removed
it regains its original form by virtue of its elasticity. In our
bodies the muscles stretched from bone to bone are, in fact, in

* Biedermann, "Electro-physiology," vol. i, translated by Welby, and
Engelmann, "Archiv fiir die gesammte Physiologic," 18, 1.

20 THE PHYSIOLOGY OF MUSCLE AND NERVE.

a state of elastic tension. If a muscle is severed by an incision
across its belly the ends retract. The extensibility and elasticity
of the muscles add to the effectiveness of the muscular-skeletal
machinery. A muscle that is in a state of elastic tension con-
tracts more promptly and more effectively for a given stimu-
lus than one which is entirely relaxed. Moreover, in our joints
the arrangement of antagonists — flexors and extensors — is such
that the contraction of one moves the bone against the pull of
the extensible and elastic antagonist. It would seem that the
movements of the skeleton must gain much in smoothness and
delicacy by this arrangement. The physical advantages of the
extensibility and elasticity of muscular tissue are evident not

Ffc. 4.— a, Curve of extension of a rubber band, to show the equal extensions for equal
increments of weight. The band had an initial load of 17 gms., and this was increased
by increments of 3 gms. in each of the nine extensions, the final load being 44 gms. The
line joining the ends of the ordinates is a straight line, b. Curve of extension of a frog s
muscle (gastrocnemius). The initial load and the increment of weight were the same as with
the rubber. The curve shows a decreasing extension for equal increments. The line join-
ing the ends of the ordinates is curved.

only in the contractions of our voluntary muscles, but, as we shall
see, in a striking way also in the circulation, in which the force of the
heart beat is stored and economically distributed, as it were, by
the elastic tension of the distended arteries. The extensibility of
muscular tissue has been studied in comparison with the extensi-
bility of dead elastic bodies. With regard to the latter it is known
that the strain that the body undergoes is proportional, within the
limits of elasticity, to the stress put upon it. If, for instance,
weights are attached to a rubber band suspended at one end
the amount of extension of the band will be directly proportional
to the weights used. If the extensions are measured the relation-
ship may be represented as shown in the accompanying figure,
the equal increments in weight being indicated by laying off equal

THE PHENOMENON OF CONTRACTION.

21

distances on the abscissa, and the resulting extensions by the
height of the ordinates dropped from each point. If the ends of
the ordinates are joined the result is a straight line. When a
similar experiment is made with a living muscle it is found that
the extension is not proportional to the weight used. The amount
of extension is greatest in the beginning and decreases propor-
tionately with new increments of weight. If the results of such
an experiment are plotted, as above, representing the equal incre-
ments of weight by equal ^distances
along the abscissa and the resulting
extensions by ordinates dropped from
these points, then upon joining the
ends of the ordinates we obtain a curve
concave to the abscissa. At first the
muscle shows a relatively large exten-
sion, but the effect becomes less and
less with each new increment of weight,
the curve at the end approaching slowly
to a horizontal. If the weight is in-
creased until it is sufficient to overcome
the elasticity of the muscle the curve
is altered — it becomes convex to the
abscissa, or, in other words, the amount
of extension increases with increasing
increments of weight up to the point
of rupture, as is shown in the accom-
panying curve* (Fig. 5). Haycraftf
calls attention to the fact that under
normal conditions the physiological
extension of the frog's muscles in the
body is equal to that produced by a
weight of 10 to 15 gms., and that
when the excised muscle is extended
by weights below this limit it follows
the law of dead elastic bodies, giving
equal extensions for equal increments
of weight. It is only after passing this limit that the law stated
above holds good. It should be added also that the amount of
extension exhibited by a muscle or other living tissue placed
under a stress varies with the time that the stress is allowed
to act. The muscle is composed of viscous material, and yields
slowly to the force acting upon it. In experiments of this kind,
therefore, the weights should be allowed to act for equal intervals

* See Marey, "Du mouvement dans les fonctions de la vie," 1868, p. 284.
t Haycraft, "Journal of Physiology," 31, 392, 1904.

JC

Fig. 5. — Curve given by
Marey to show the effect upon
the extension of muscle caused
by increasing the load regularly
to the point of rupture : From
o to a the extension of the
muscle decreases as the weight
increases, giving a curve concave
to the abscissa, ox; at a the
limit of elasticity is passed and
the muscle lengthens by in-
creasing extensions for equal
increments ; at x rupture (,750
gms. for frog's gastrocnemius).

22 THE PHYSIOLOGY OF MUSCLE AND NERVE.

of time. It has been shown that the extensibility of a muscle is
greater in the contracted than in the resting state.

The curve of extension described above for skeletal muscle
holds also for so-called plain muscle. This latter tissue forms a
portion of the walls of the various viscera, the stomach, bladder,
uterus, blood-vessels, etc., and the facts shown by the.above curve
enter frequently into the explanation of the physical phenomena
exhibited by the viscera. For instance, it follows from this curve
that the force of the heart beat will cause less expansion in an
artery already distended by a high blood-pressure than in one in
which the blood-pressure is lower.

The Irritability and Contractility of Muscle. — Under normal
conditions in the body a muscle is made to contract by a stimulus
received from the central nervous system through its motor nerve.
If the latter is severed the muscle is paralyzed. We owe to Haller,
the great physiologist of the eighteenth century, the proof that
a muscle thus isolated can still be made to contract by an artificial
stimulus — e. g., an electrical shock — applied directly to it. This
significant discovery removed from physiology the old and harmful
idea of animal spirits, which were supposed to be generated in the
central nervous system and to cause the swelling of a muscle during
contraction by flowing to it along the connecting nerve. But to
remove a muscle from the body and make it contract by an artificial
stimulus does not prove that the muscle substance itself is capable
of being acted upon by the stimulus, since in such an experiment
the endings of the nerve in the muscle are still intact, and it may
be that the stimulus acts only on them and thus affects the muscle
indirectly. In a number of ways, however, physiologists have
found that the muscle substance can be made to contract by a
stimulus applied directly to it, and therefore exhibits what is
known as independent irritability. The term irritability, according
to modern usage, means that a tissue can be made to exhibit its
peculiar form of functional activity when stimulated, — e. g., a
muscle cell will contract, a gland cell will secrete, etc., — and inde-
pendent irritability in the case under consideration means simply
that the muscle gives its reaction of contraction when artificial
stimuli are applied directly to its substance. This conception
of irritability was first introduced by Francis Glisson (1597-1677),
a celebrated English physician.* Subsequent writers frequently
used the term as synonymous with contractility and as applicable
only to the muscle. But it is now used for all living tissues in
the sense here indicated. A simple proof of the independent
irritability of a striated muscle is obtained by cutting the motor
nerve going to it and stimulating the muscle after several days.
*See Foster's " History of Physiology," p. 287.

THE PHENOMENON OF CONTRACTION. 23

We know now that in the course of several days the severed nerve
fibers degenerate completely down to their terminations in the
muscle fibers, and the muscle, thus freed from its nerve fibers by
the process of degeneration, can still be made to contract by an
artificial stimulus. The classical proof of the independent irri-
tability of muscle fibers was given by Claude Bernard, the great
French physiologist of the nineteenth century. He made use
of the so-called arrow poison of the South American Indians.
This substance or mixture o£. substances is known generally under
the name curare; it is prepared from the juices of several plants
(strychnos) (Thorpe). The poisonous part of the material is soluble
in water, and Bernard showed that when such an extract is injected
into the blood or hypodermically it paralyzes the motor nerves
at their peripheral end, so that direct stimulation of these nerves

Fig. 6. — The induction coil as used for physiological purposes (du Bois-Reymond
pattern): A, The primary coil; B, the secondary coil; P', binding posts to which are at-
tached the wires from the battery, they connect with the ends of coil A : P", binding posts
connecting with ends of coil B, through which the induction current is led off; S, the slide,
with scale, in which coil B is moved to alter its distance from A.

is ineffective. Direct stimulation of the muscle substance, on the
contrary, causes a contraction.*

Artificial Stimuli. — If we designate the stimulus that the
muscle receives normally from its nerve as its normal stimulus,
all other forms of energy which may be used to start its contraction
may be grouped under the designation artificial stimuli. Experi-
ments have shown that a contraction may be aroused by mechanical
stimuli, — for instance, by a sharp blow applied to the muscle; by
thermal stimuli, — that is, by a sudden change in temperature; by
chemical stimuli, — for example, by the action of concentrated solu-
tions of salts, and finally by electrical stimuli. In practice, however,
only the last form of stimulus is found to be convenient. The
mechanical and thermal stimuli cannot be well applied without at
the same time injuring the muscle substance, and the same is prob-
ably true of chemical stimuli, which possess the disadvantage, more-
over, of not exciting simultaneously the different fibers of which the

* 'Lecons sur les effets des substances toxiques et medicamenteuses/'
1857, pp. 238 et seq.

24 THE PHYSIOLOGY OF MUSCLE AND NERVE.

muscle is composed. Electrical stimuli, on the contrary, are
applied easily, are readily controlled as regards their intensity, and
affect all the fibers simultaneously, thus giving a co-ordinated
contraction of the entire bundle, as is the case with the normal
stimulus. For electrical stimulation we may use the galvanic
current taken directly from the battery, or the induced or so-called
faradic current obtained from an induction coil. Under most
conditions the latter is more convenient, since it gives brief shocks,
the strength and number of which can be controlled readily. The
form in which this instrument is used in experimental work in
physiology we owe to du Bois-Reymond (1849-); hence it is
frequently known as the du Bois-Revmond induction coil. Experi-

A B

Fig. 7.— Schema of induction apparatus. — (Lombard.) b represents the galvanic
battery connected by wires to the primary coil, A. On the course of one of these wires
is a key (k) to make and break the current. B shows the principle of the secondary
coil, and the connection of its two ends with the nerve of a nerve-muscle preparation.
When the battery current is closed or made in A, a brief current of high intensity is
induced in B. This is known as the making or closing shock. When the battery current
is broken in A, a second brief induction current is aroused in B. This is known as the
breaking or opening shock.

mental physiology owes a great deal to this simple and serviceable
instrument. A figure and brief description of the apparatus is
appended (Figs. 6 and 7).

SIMPLE CONTRACTION OF MUSCLE.

Experiments may be made upon the muscles of various animals,
but ordinarily in physiological laboratories one of the muscles
(gastrocnemius) of the hind leg of the frog is employed. If such
a muscle is isolated and connected with the terminals from an
induction coil it may be stimulated by a single shock or by a series
of rapidly repeated shocks. The contraction that results from a
single stimulus is designated as a simple contraction. In the frog's
muscle it is very brief, lasting for 0.1 second or less; but in this,
as in other respects, cross-striated muscular tissue varies in different
animals,* as is shown by the accompanying table, which gives an
idea of the range of rapidity of contraction.

* Cash, "Archiv f. Anat. u. Physiol.," 1880, suppl. volume, p. 147.

THE PHENOMENON OF CONTRACTION. 25

DURATION OF A SIMPLE MUSCULAR CONTRACTION.

Insect 0.003 sec.

Rabbit (Marey) 0.070 "

Frog 0.100 "

Terrapin. 1.000 "

The series may be continued by the figures obtained from the
plain muscle, thus:

The involuntary muscle (mammal) 10.00

Foot muscle of slug* (Ariolimax) 20.00

There is reason to believe that the rapidity of contraction is re-
lated to the distinctness of the cross-striation. This is indicated
by the properties of the so-called red and pale muscles that occur
in some animals — the rabbit, for instance. The pale muscles con-
tract much more rapidly than the red ones, and corresponding with

Fig. 8. — Curve of simple muscular contraction.

this fact it is found that the cross-striation is more distinct in the
former. As was explained above, the active agent in contraction
is contained in the dim bands of the fibers, and the more highly
differentiated this structure becomes the more perfect apparently
is its work as a mechanism for shortening. According to Cash, the
duration of contraction of the soleus muscle (red) in rabbits is one
second, while that of the gastrocnemius medialis (white) is only
0.25 second.

The Curve of Contraction. — When a contracting muscle is
attached to a lever this lever may be made to write upon a smoked
surface and thus record the movement, more or less magnified
according to the leverage chosen. If the recording surface is sta-
tionary the record obtained is a straight line and indicates only the
extent of the shortening. If, however, the recording surface is in
movement during the contraction the record will be in the form of a
curve, which, making use of the system of right-angled co-ordinates,
* Carlson, " American Journal of Physiology," 10, 418, 1904.

26 THE PHYSIOLOGY OF MUSCLE AND NERVE.

will indicate not only the full extent of the shortening, but also
the amount of shortening or subsequent relaxation at any moment
during the entire period. To obtain such records from the rapidly
contracting frog's muscle it is evident that the recording surface
must move with considerable rapidity and with a uniform velocity.
A curve of this kind is represented in Fig. 8, on page 25. C rep-
resents the axis of abscissas and gives the factor of time. A vertical
ordinate erected at any point on C gives the extent of shortening
at that moment. Below the jcurve of the muscle is the record
of the vibrations of a tuning fork giving 100 double vibrations
per second; that is, the distance from crest to crest represents an
interval of T-J-7 of a second. Three principal facts are brought out
by an analysis of the curve: I. The latent period. By this is
meant that the muscle does not begin to shorten until a certain
time after the stimulus is applied. On the curve the stimulus
enters the muscle at S, and the distance between this point and the
beginning of the rise of the curve, interpreted in time, is the latent
period. II. The phase of shortening, which has a definite course
and at its end immediately passes into III., the phase of relaxation.

The Latent Period. — In the contraction of the isolated frog's
muscles as usually recorded the latent period amounts to 0.01 sec.,
but it is generally assumed that this period is exaggerated by the
method of recording used, since the elasticity of the muscle itself
prevents the immediate registration of the movement. By improve-
ments in methods of technique the latent period for a fresh muscle
may be reduced to as little as 0.005 or even 0.004 sec. Under the
conditions in the body, however, the muscle contracts against a
load, as when lifting a lever; hence, we may assume that normally
there is a lost time of at least 0.01 sec. after the stimulus enters the '
muscle. In addition to the latent period due to the elasticity
of the muscle it is certain that a brief amount of time actually
elapses after the stimulus enters the muscle before the act of
shortening begins ; some time is taken up in the chemical changes
and the effect of these changes in putting the mechanism of con-
traction into play (see below on the Theory of Muscle Contractions).
The latent period varies greatly in muscles of different kinds, and in
the same muscle varies with its conditions as regards temperature,
fatigue, load to be raised, etc.

The Phases of Shortening and of Relaxation. — In the normal
frog's muscle the phase of shortening for a simple contraction occu-
pies about 0.04 second, while the relaxation may be a trifle longer,
0.05 sec. In muscles whose duration of contraction differs from
that of the frog the time values for the shortening and the relaxation
exhibit corresponding differences. As we have seen, the appearance
of the muscle fiber when viewed by polarized light indicates that
during the phase of shortening some of the material in the light

THE PHENOMENON OF CONTRACTION. 27

bands is imbibed into the substance composing the dim bands.
The process is evidently a reversible one; during the phase of
relaxation the absorbed or imbibed material passes back to the
light band. Many conditions, some of which will be described
below, alter the time necessary for these processes, that is, the
duration of the simple contraction. It is noteworthy that it is
the phase of relaxation which may be most easily prolonged or
shortened by varying conditions.

?

Isotonic and Isometric Contractions. — In the method of recording the
shortening of the muscle that is described above the muscle is supposed to con-
tract against a constant load which it can lift. Such a contraction is spoken
of as an isotonic contraction. If the muscle is allowed to contract against
a tension too great for it to overcome — a stiff spring, for instance — it is prac-
tically prevented from shortening, and a contraction of this kind, in which
the length of the muscle remains unchanged, is spoken of as an isometric-
contraction. A curve of such a contraction may be obtained by magnifying
greatly, by means of levers, the slight change in the stiff spring against which
the muscle is contracting. Such a curve gives a picture of the liberation of
energy within the muscle during contraction.

The usual oval form of dynamometer employed to record the grip of the
flexors of the fingers gives an isometric record of the energy of contraction
of these muscles.

Fig. 9. — Effect of varying the strength of stimulus. The figure shows the effect upon
the gastrocnemius muscle of a frog of gradually increasing the stimulus (breaking induction
shock) until maximum contractions were obtained. The stimuli were then decreased in
strength and the contractions fell off through a series of gradually decreasing submaximal
•contractions. The series up and down is not absolutely regular owing to the difficulty of
obtaining a regular increase or decrease in the stimulus. (The prolongations of the
curves below the base line are due to the elastic extension of the muscle by the weight dur-
ing relaxation.)

Effect of Strength of Stimulus upon the Simple Contraction.

—The strength of electrical stimuli can be varied conveniently and

28 THE PHYSIOLOGY OP MUSCLE AND NERVE.

with great accuracy. When the stimulus is of such a strength as
to produce a just visible contraction it is spoken of as a minimal
stimulus and the resulting contraction as a minimal contraction.
Stimuli of less strength than the minimal are designated as sub-
minimal. If one increases gradually the intensity of the electrical
current used as a stimulus without altering its duration, beginning
with a stimulus sufficient to cause a minimal contraction, the result-
ing contractions increase proportionally up to a certain maximum
beyond which further increase of stimulus, other conditions remain-
ing the same, causes no greater extent of shortening. Contrac-
tions between the minimal and the maximal are designated as-
submaximal.* (See Fig. 9.)

Effect of Temperature upon the Simple Contraction. — Varia-
tions in temperature affect both the extent and the duration of the
contraction. The relationship is, however, not a simple one in the
case of the frog's muscle upon which it has been studied most fre-
quently. If we pay attention to the extent of the contraction alone
it will be found that at a certain temperature, 0° C., or slightly below,

Fig. 10. — Curve showing the effect of temperature. The temperatures at which the
contractions were obtained are indicated on the figure. In this experiment a large resis-
tance was introduced into the secondary circuit so that changes in the resistance of the
muscle itself due to heating could not affect the strength of the stimulus.

the muscle loses its irritability entirely. As its temperature is
raised a given stimulus, chosen of such a strength as to be maximal
for the muscle at room temperatures, causes greater and greater •
contractions up to a certain maximum, which is reached at about
5° to 9° C. As the temperature rises beyond this point the con-
tractions decrease somewhat to a minimum that is reached at about
15° to 18° C. Beyond this the contractions again increase in

* Fick, " Untersuchungen iiber elektrische Nervenreizung," Braun-
schweig, 1864.

THE PHENOMENON OF CONTRACTION.

29

extent to a second maximum at about 26° to 30° C., this maxi-
mum being in some cases greater, and in others less than the first
maximum. Beyond the second maximum the contractions again
decrease rather rapidly as the temperature rises until at a certain
temperature, 37° C., irritability is entirely lost (Fig. 10). If the tem-
perature is raised somewhat beyond this latter point heat rigor makes
its appearance, and the muscle may be considered as dead. The re-
lationship between temperature and extent of contraction, therefore,

38*

Fig. 11. — Curve to show the effect of a
rise of temperature from 0° C. to 38° C. upon
the height of contraction of frog's muscle.
The first maximum at 9° C, the second at
28° C. Beyond 38° C. the muscle lost its
irritability and went into rigor mortis.

Fig. 12. — Curve to show the effect
of a rise of temperature from 5° C. to
39° C. upon the duration of contraction
of frog's muscle. The relative dura-
tions at the different temperatures are
represented by the height of the cor-
responding ordinates.

may be expressed by a curve such as is represented in Fig. 11, in
which there are two maxima and two points at which irritability is
lost . The second maximum indicates a fact of general physiological in-
terest,— namely, that in all of the tissues of the body there is a certain
high temperature at which optimum activity is exhibited, and if the
temperature is raised beyond this point functional activity becomes
more and more depressed. The point of optimum effect is not identi-
cal for the different tissues of the same animal, much less so for those
of different animals, but the fact may be emphasized that in no
case do protoplasmic tissues withstand a very high temperature.

30 THE PHYSIOLOGY OF MUSCLE AND NERVE.

Functional activity is lost usually at 45° C. or below. The duration
of the contraction shows usually in frogs' muscles a simple relation-
ship to the changes of temperature. At low temperatures, 4 or 5° C.,
the contractions are enormously prolonged, particularly in the phase
of relaxation ; but as the temperature is raised the duration of the
contractions diminishes, at first rapidly, then more slowly, to a
certain point — about 18° to 20° C., beyond which it remains more or
less constant in spite of the changes in extent of shortening. The
relationship between duration of contraction and temperature may
therefore be expressed by such a curve as is shown in Fig. 12, in
which the heights of the ordinates represent the relative durations
of the contractions. Muscles from different frogs show considerable
minor variations in their reactions to changes in temperature, and
we may suppose that these variations depend upon differences in
nutritive condition. In this, as in many other respects, the reactions
obtained from so-called winter frogs after they have prepared for
hibernation are more regular and typical than those obtained in the
spring or summer.

Effect of Veratrin. — The alkaloid veratrin exhibits a peculiar
and interesting effect upon the contraction of muscle. A muscle
taken from an animal that has been veratrinized and stimulated
in the usual way by a single stimulus gives a contraction such as
is exhibited in the accompanying curve (Fig. 13). Two peculiarities
are shown by the curve : (1) The phase of shortening is not altered,
but the phase of relaxation is greatly prolonged. (2) The curve

Fig. 13. — Curve showing the effect of veratrin.

shows two summits, — that is, after the first shortening there is a
brief relaxation followed by a second, slower contraction. The
cause of this second shortening is not known. Biedemann has
suggested that it is due to the presence in the muscle of the
two kinds of fibers — red and pale — which were spoken of on p.
25, and that the veratrin dissociates their action, but this expla-
nation, according to Carvallo and Weiss,* is disproved by the
fact that muscles composed entirely of white or red fibers show
* "Journal de la physiol. et de la path, generate," 1899.

THE PHENOMENON OF CONTRACTION.

31

a similar result from the action of veratrin. Although the explana-
tion is not forthcoming, the fact that a single stimulus gives under

these conditions two processes of contractions is interesting as an
exception to the general rule. It may be added that a curarized
frog's muscle, when heated to the point of optimum activity (28° C.)

32 THE PHYSIOLOGY OF MUSCLE AND NERVE.

sometimes shows also a double contraction for a single stimulus.
The very prolonged relaxation is, however, the most peculiar effect

Fig. 15. — Effect of repeated stimulation; complete curve, showing late contracture.
The muscle was stimulated by induction shocks at the rate of 50 per minute. The separate
contractions are so close together that they can not be distinguished.

of the veratrin. A somewhat similar effect is produced by the
action of glycerin. We have in such substances reagents that affect
one phase of the contraction process without materially influencing
the other. As regards the veratrin effect, it becomes less and less

Fig. 16. — Effect of repeated stimulation, curve showing no contracture or very little.
"The muscle was stimulated by induction shocks at the rate of 50 per minute. A very
slight contracture is shown in the beginning, but subsequently the contractions show
only a diminished extent, the rate of relaxation remaining apparently unchanged.

marked if the muscle is made to give repeated contractions, but
reappears after a suitable period of rest. The peculiar action of
the veratrin is therefore antagonized seemingly by the chemical
products formed during contraction.

THE PHENOMENON OF CONTRACTION. 33

Contracture. — The prolonged relaxation that is so character-
istic of the veratrinized muscles may be observed in frog's muscle
under other circumstances, and is described usually as a condition
of contracture. By contracture, therefore, we mean a state of con-
tinuous contraction, or, looking at it from the other point of view,
a state of retarded relaxation. This condition is apparent in
muscles that have been cooled to a low temperature, and is shown
also as a result of repeated stimulations. In Fig. 14 the phe-
nomenon is exhibited very clearly in the form in which it was first
described by Kronecker and Tiegel,* while in the following figure
(Fig. 15) the phenomenon is shown as it usually appears, that is,
after many contractions, and at a time when fatigue is beginning
to make itself felt.

The Effect of Rapidly Repeated Contractions. — When a
muscle is stimulated repeatedly by stimuli of equal strength that
fall into the muscle at equal intervals the contractions show certain
features that, in a general way, are constant, although the precise
degree in which they are exhibited varies curiously in different
animals. Such curves are exhibited in Figs. 14, 15, and 16, and
the features worthy of note may be specified briefly as follows :

1. The Introductory Contractions. — The first three or four con-
tractions decrease slightly in extent, showing that the muscle at
first loses a little in irritability on account of previous contractions.
This phenomenon is frequently absent.

2. The Staircase or " Treppe."— After the first slight fall in
height has passed off the contractions increase in extent with great
regularity and often for a surprisingly large number of contractions.
This gradual increase in extent of shortening, with a constant
stimulus, was first noticed by Bowditch upon the heart muscle,
and was by him named the phenomenon of "treppe/' the
German word for staircase. It indicates that the effect of activity
is in the beginning beneficial to the muscle in that its irritability
steadily increases, and the fact that the same result has been ob-
tained from heart muscle, plain muscle, and nerve fibers indicates
that it may be a general physiological law that functional activity
leads at first to a heightened irritability.

3. Contracture. — This phenomenon of retarded relaxation has
been described above. In frog's muscles stimulated repeatedly it
makes its appearance, as a rule, sooner or later in the series of
contractions; but there is a curious amount of variation in the
muscles of different individuals in this respect.

4. Fatigue. — After the period of the " treppe " has passed the
contractions diminish steadily in height until at last the muscle

* Tiegel, "Pfliiger's Archiv fur die gesammte Physiologic/' etc., 13, 71,
1876.

3

34 THE PHYSIOLOGY OF MUSCLE AND NERVE.

fails entirely to respond to the stimulus. This progressive loss of
irritability in the muscle caused by repeated activity is designated
as fatigue. It will be considered more in detail under the head of
Compound Muscular Contractions and in Chapter II.

Lee has discovered the interesting fact that while in frog's muscle, as
a rule, fatigue is accompanied by a prolongation, especially of the phase of
relaxation, this does not hold for mammalian muscle. In the latter muscle
the successive contractions become smaller as fatigue sets in, but their
duration is not increased.

The Contraction Wave. — Under ordinary conditions the fibers
of a muscle when stimulated contract simultaneously or nearly so,
and the whole extent of the muscle is practically in the same phase
of contraction at a given instant. It is comparatively easy to
show, however, that the process of contraction spreads over the
fibers, from the point stimulated, in the form of a wave which moves
with a definite velocity. In a long muscle with parallel fibers one
may prove, by proper recording apparatus, that if the muscle is
stimulated at one end a point near this end enters into contraction
before a point farther off. Knowing the difference in time between
the appearance of the contraction at the two points and their
distance apart, we have the data for determining the velocity of its
propagation. In frog's muscles this velocity is found to be equal
to 3 to 4 meters per second, while in human muscle, at the body
temperature, it is estimated at 10 to 13 meters per second. Know-
ing the time it takes this wave to pass a given point (d) and its
velocity (v), its entire length is given by the formula 1= vd. In the
frog's muscle, therefore, with a velocity of 3000 mm. per second,
and a duration of, say, 0.1 second, the product 3000 X 0.1 = 300
mms. gives the length of the wave or the length of muscle which
is in some phase of contraction at any given instant. Under
normal conditions the muscle fibers are stimulated through their
motor plates, which are situated toward the middle of the fiber,
or perhaps one muscle fiber may have two or more motor plates,
giving two or more points of stimulation. It follows, therefore,
from this anatomical arrangement and the great velocity of the
wave, that all parts of the fibers are in contraction at the same
instant and, indeed, in nearly the same phase of contraction. Under
abnormal conditions muscles may exhibit fibrillar contractions ; that
is, separate fibrils or bundles of fibrils contract and relax at different
times, giving a flickering, trembling movement to the muscle.

Idipmuscular Contractions. — In a fatigued or moribund muscle mechan-
ical stimulation may give a localized contraction which does not spread or
spreads very slowly, showing that the abnormal changes in the muscle prevent
the excitation from traveling at its normal velocity. A localized contraction
of this kind was designated by Schiff as an idiomuscular contraction. It may

THE PHENOMENON OF CONTRACTION. 35

be produced in the muscle of a dying or recently dead animal by localized
mechanical stimulation, as by drawing a blunt instrument — e. g., the handle
of a scalpel — across the belly of the muscle. The point thus stimulated stands
out as a wheal, owing to the idiomuscular contraction.

The Energy Liberated in the Contraction. — When a muscle
contracts, energy is, as we say, liberated in several forms, and
can be measured quantitatively. First there is a production of
heat, which is indicated by a rise in temperature of the muscle.
According to Heiclenhain, the temperature of the frog's muscle
is increased in a single contraction by 0.001° C. to 0.005° C. Larger
muscles, such as those of the thigh of the dog, when repeatedly
stimulated may cause a rise of temperature of from 1° to 2° C.
The thermometer does not, of course, measure the amount of heat
produced, but only the temperature of the muscle. Heat is esti-
mated quantitatively in terms of calories. By a calorie is meant
the quantity of heat necessary to raise 1 gm. of water 1° C.
Knowing the specific heat and weight of muscle, we can readily
calculate the number of calories produced. Thus, if a frog's
muscle weighing 2 gms. shows a rise of temperature of 0.005° C.
from a single contraction the production of heat in calories is given
by multiplying the weight of the muscle by its specific heat,
0.83, to reduce it to an equivalent weight of water, and this
product by the rise in temperature: 2 X 0.83 X 0.005 = 0.0083
calorie. The fact that muscular exercise increases the produc-
tion of heat in the body is a matter of general observation. Second.
Some electrical energy is developed during the contraction. The
means of detecting and measuring this energy will be described
in a subsequent chapter. Considered quantitatively, the amount
is small. Third. Work is done if the muscle is allowed to shorten
during the contraction. By work is meant external or useful
work — that is, the muscle lifts a weight or overcomes an opposing
resistance. If a muscle contracts against a weight too heavy
to be lifted or a resistance too strong to be overcome it does no
external work, although, of course, much energy is liberated as
heat or, as it is sometimes called, internal work. The work done
by a muscle during contraction is measured in the usual mechanical
units, by the product of the load into the lift. That is, if a muscle
lifts a weight of 40 grams to a height of 10 millimeters, the work
done is 40 X 10 = 400 gram-millimeters, or 0.4 grammeter. We
can in calculations convert external work into heat or internal
work by making use of the ascertained mechanical equivalent of
heat, according to which 1 calorie -= 425 grammeters of work.
The work, 0.4 grammeter, supposed to be done in the above experi-
ment would be equivalent, therefore, to 0.4 ~ 425, or about 0.001
of a calorie.

36 THE PHYSIOLOGY OF MUSCLE AND NERVE.

The Proportion of the Total Energy Liberated that may
be Utilized in Work. — All of the energy liberated in the muscle
has its origin in the chemical changes that follow upon stimulation.
We assume that these changes are such that complex molecules
are broken down, with the formation of simpler ones, and that
some of the so-called chemical or internal energy that holds together
the atoms in the complex molecule is liberated and takes the three
forms described above. The chemical changes occurring in the
muscle during contraction are complex and not entirely understood,
but the significant ones from our present standpoint are oxidations
which destroy some of ^ the material in the muscle, with the forma-
tion of carbon dioxid and water and the liberation of heat. It is
a matter of interest to inquire as to the proportion of the total
heat energy which may be converted into useful work and the
conditions under which the optimum amount of work may be
realized. Regarded from this standpoint, the muscle may be
considered as a piece of machinery comparable, let us say, to a gas
engine. In the latter the heat generated by the explosive chemical
change is converted partially into external work by a properly
adapted mechanism— and in a well-constructed engine as much
as 15 to 25 per cent, of the total energy may be obtained as work.
In the muscle there is also a mechanism of some kind, not as yet
understood, by means of which a part of the energy liberated
may be converted into work. Experiments made by Fick with
frogs' muscles indicate that the proportion of the total energy
which under optimum conditions may be utilized as work is, in
round numbers, from 25 to 30 per cent. Chauveau,* in experiments
made upon the elevator of the upper lip in the horse, found a pro-
portion of only 12 to 15 per cent. The last observer points out
that this proportion must vary greatly for different muscles and
for muscles in different animals, while for the same muscle it will
vary with the extent and duration of the contractions and other
conditions. From experiments made upon dogs in which a meas-
ured amount of work was done and in which the energy changes
were estimated from the oxygen absorbed and carbon dioxid
eliminated, Zuntz f calculates that somewhat more than ^ of the
total chemical energy liberated in the muscles may be applied to
external work, the other § taking the form of heat. Similar ex-
periments made by the same observer J upon men have indicated
that the muscles work most economically in lifting the weight
of the body, as in mountain-climbing. In this form of muscular
work he estimates that from 35 to 40 per cent, of the heat energy

* Chauveau, "Le travail musculaire, etc.," Paris, 1891.

t Zuntz, "Archiv f. d. gesammte Physiologic," 68, 191, 1897.

J Zuntz and Schumberg, "Physiologic des Marsches," Berlin, 1901.

THE PHENOMENON OF CONTRACTION. 37

yielded by the material oxidized in the body may take the form

Fig. 17. — To show the decrease in extent of contraction of the gastrocnemius muscle
of a frog with increase in load. In the first contraction, to the right, the load was 14.2
gms. At each successive contraction the load was increased by 5.3 gms. With a load of
182 gms. the lever gave only the slightest indication of a shortening, and this may have
been due to some lateral movement.

Fig. 18. — The curve of work obtained by plotting the results shown in Fig. 17. The
initial contraction was made with a load of 14.2 gms., and the work done in gram-milli-
meters is represented by the ordinate erected at this point. The maximum work was done
with a load of 88.6 gms., and the absolute power of this particular muscle was found to be
equal to 182 gms.

of external work. When the muscular work performed was effected
by the muscles of the arms and upper part of the body, as in turning

38 THE PHYSIOLOGY OF MUSCLE AND NERVE.

a wheel, a smaller yield (25 per cent.) was obtained. It appears
from these figures that the muscular machine is an especially
efficient one as regards the amount of external work that can be
obtained from the oxidation of a given amount of material. Steam
engines are said to be capable of yielding only 10 to 15 per cent,
of the heat energy of the fuel in the form of mechanical or useful
work.

The Curve of Work and the Absolute Power of a Muscle.—
The statements in the preceding paragraph prove that the muscle,
judged from the standpoint of a machine to do work, compares most
favorably in its efficiency with machinery of human construction.
But it should be borne in mind that in this as in other respects the
properties of cross-striated muscular tissues vary greatly. In some
animals or individuals it is a much more efficient machine than in
others. This fact is indicated by our general experience regarding
variations in muscular strength in different individuals, and is proved
more precisely by direct experiments on single muscles. A frog's
muscle may be isolated and the extent of its contractions and the
work done may be estimated directly. Under such conditions it
will be found that, while the height of the successive contractions
diminishes as the load increases (see Fig. 17), the work done — that
is, the product of the load into the lift — first increases and then
decreases. For example :

Work Done in Gram-millimeters.
Load in Grams. Lift in Millimeters. Load X Lift.

5 27.6 138.0

15 25.1 376.5

25 11.45 286.25

35 6.3 220.5

A series of experiments of this kind furnishes data for construct-
ing a curve of work by plotting off along the abscissa at equal inter-
vals the equal increments in load and erecting over each load an
ordinate showing the proportional amount of work done. The
curve has the general form indicated in Fig. 18. Three facts are
expressed by this curve: First, that if the muscle lifts no weight
no work will be done; this follows theoretically from the formula
W = L H, in which W represents the work done, L the load, and
H the lift. If either L or H is equal to zero the product, of course,
is zero; that is, no external work is done; the chemical energy
liberated in the contraction takes the form of heat. Under such
circumstances the amount of heat given off from the muscle should
be greater than when a load is lifted. In accordance with this
fact it is found that a muscle lifting a light load gives off more heat
during the contraction than when lifting a heavier load. Second,
There is an optimum load for each muscle with which the greatest

THE PHENOMENON OF CONTRACTION. 39

proportion of work can be obtained. Third. When the load is just
sufficient to counteract the contraction of the muscle no work i?
done, H in the above formula being zero. This amount of load
measures what Weber called the absolute power of the muscle.
As will be seen from the above curve, it is measured by the
weight which the muscle cannot lift and which, on the other
hand, cannot cause any extension of the muscle while contracting.
Or, in more general terms (Hermann), the absolute power of a
muscle is the maximum of tension which it can reach without
alteration of its natural length. This absolute power can be
measured for the muscles of different animals and for convenience
of comparison can then be expressed in terms of the cross-area
of the muscle given in square centimeters. Weber has shown
that the absolute power of a muscle varies with the cross-area, since
this depends upon the number of constituent fibers whose united
contraction makes the contraction of the muscle. Expressed in
this way, it is found that the absolute power of human muscle is,
size for size, much greater than that of frog's muscle. For in-
stance, the absolute power of a frog's muscle of 1 square centimeter
cross-area is estimated at from 0.7 kilogram to 3 kilograms, while
that of a human muscle of the same size is estimated by Hermann
at 6.24 kilograms. Taken as a whole, the human muscle is a better
machine for work, but it seems possible, although exact figures are
lacking, that the absolute power of the muscles of some insects
reckoned for the same unit of cross-area would be much greater
than in human muscle.

COMPOUND OR TETANIC CONTRACTIONS.

Definition of Tetanus — When a muscle receives a series of
rapidly repeated stimuli it remains in a condition of contraction as
long as the stimuli are sent in or until it loses its irritability from
the effect of fatigue. A contraction of this character is described
as a compound contraction or tetanus. If the stimuli follow each
other with sufficient rapidity the muscle shows no external sign
of relaxation in the intervals between stimuli, and if its contractions
are recorded upon a kymographion by means of an attached lever
a curve is obtained such as is shown at 5 in Fig. 19. A con-
traction of this character is described as a complete tetanus. If,
however, the rate of stimulation is not sufficiently rapid the mus-
cle will relax more or less after each stimulus and its recorded
curve, therefore, will present the appearance shown in 1,2, 3, and
4 of Fig. 19. A tetanus of this character is described as an incom-
plete tetanus. It is obvious that according to the rate of stimu-
lation there may be numerous degrees of incomplete tetanus, as
shown in Fig. 19, extending from a series of separate single con-

40

THE PHYSIOLOGY OF MUSCLE AND NERVE.

Fig. 19. — Analysis of tetanus. Experiment made upon the gastrocnemius muscle of a
frog to show that by increasing the rate of stimulation the contractions, at first separate
( 1), fuse more and more through a series of incomplete tetani (2, 3, 4) into a complete tetanus
(5) in which there is no indication, so far as the record goes, of a separate effect for each
stimulus.

THE PHENOMENON OF CONTRACTION. 41

tractions, on the one hand, to a perfect fusion of the contractions,
a complete tetanus, on the other. Tetanic contractions present
two peculiarities in addition to the mere matter of duration,
which is governed, of course, by the duration of the stimu-
lation: First, the more or less complete fusion of the contrac-
tions due to the separate stimuli. This, as stated above, is the
distinctive sign of a tetanus. Second, the phenomenon of sum-
mation in consequence of which the total shortening of the muscle
in tetanus may be considerably greater than that caused by a maxi-
mal simple contraction.

Summation. — The facts of summation may be shown most read-
ily by employing a device to send into the muscle two successive
stimuli at varying intervals. If the second stimulus falls into the
muscle at the apex of the contraction caused by the first stimulus,
then, even if the first contraction is maximal, the muscle will shorten
still farther; the first and second contractions are summated, giv-
ing a total shortening greater than can be obtained by a single stim-
ulus (see Fig. 20). The extent of the summation in such cases
varies with a number of conditions, such as the intervals between the

Fig. 20. — Summation of two successive contractions. Curve 1 shows a simple con-
traction due to a single stimulus, the latent period being indicated at the beginning of the
contraction. Curve 2 shows the summation due to two succeeding stimuli.

stimuli, the relative strengths of the stimuli, the load carried by the
muscle, etc. Taking the simplest conditions of a moderately loaded
muscle and two maximal stimuli, it is found that the greatest sum-
mation occurs when the stimuli are so spaced that the second contrac-
tion begins at the apex of the first. If the stimuli are closer together,
so that, for instance, the second contraction follows shortly after
the first has begun, the total shortening is less, and the same is true

42 THE PHYSIOLOGY OF MUSCLE AND NERVE.

to an increasing^ extent as the second contraction falls later and
later in the period of relaxation after the first contraction.* If
instead of two we use three successive stimuli, falling into the muscle
at proper intervals, a still further summation occurs. In this way
the total extent of shortening in a muscle completely tetanized may
be several times as great as that of a single maximal contraction.

The Discontinuous Character of the Tetanic Contraction
—The Muscle-tone. — In complete tetanus the muscle seems to
be in a condition of continuous uniform contraction; the re-
corded curve shows no sign of relaxation between stimuli and no
external indication, in fact, that the separate stimuli do more than
maintain a state of uniform contraction. It can be shown, how-
ever, that in reality each stimulus has its own effect, and that the
chemical changes underlying the phenomenon of contraction are
probably not continuous, but form an interrupted series correspond-
ing, within limits, to the series of stimuli sent in. The clearest
proof for this belief is found in the electrical changes that result
from each stimulus, and the facts relating to this side of the question
will be stated subsequently in the chapter on The Electrical
Phenomena of Muscle and Nerve. Another proof is found in the
phenomenon of the muscle-tone. When a muscle is stimulated
directly or through its motor nerve a musical note may be heard
by applying the ear or a stethoscope to the muscle. -The note that
is heard corresponds in pitch, up to a certain point, with the num-
ber of stimuli sent in, — that is, the muscle vibrates, as it were, in
unison with the number of stimuli, and, although the vibrations
are not sufficient to affect the recording lever, they can be heard
as a musical note. This fact, therefore, may be taken as a proof
that during complete tetanus there is a discontinuous series of
changes in the muscle the rate of which corresponds with that of the
stimulation. The series of electrical changes corresponding with the
series of stimuli sent in may be made audible by applying a telephone
to the muscle. Making use of this method, Wedenskif has shown
that the ability of the muscle to respond isorhythmically to the
rate of stimulation is limited. In frog's muscle the pitch of the
musical tone may correspond with the rate of stimulation up to
about 200 stimuli per second. In the muscle of the warm-blooded
animal the correspondence may extend to about 1000 stimuli per
second. If the rate of stimulation is increased beyond these
limits the musical note heard does not correspond, but falls
to a lower pitch, indicating that some of the stimuli under these
conditions become ineffective. It should be added that the high

* Von Kries, "Archiv fur Physiologic," 1888, p. 537.

fWedenski, "Du rhythme musculaire dans la contraction normale,"
"Archives de physiologic," 1891, p. 58.

THE PHENOMENON OF CONTRACTION.

43

figures given above for the correspondence between the stimuli and
the muscle-tone hold good only for entirely fresh preparations.
The lability of the muscle quickly becomes less as it is fatigued ; so
that in the frog, for instance, the correspondence in long-continued
contractions is accurate only when the rate of stimulation does
not exceed 30 per second.

The Number of Stimuli Necessary for Complete Tetanus. —
The number of stimuli necessary to produce complete tetanus
varies, as we should expect, wath the kind of muscle used and in
accordance with the rapidity of the process of relaxation shown
by these muscles in simple contractions. The series that may be
arranged to demonstrate this variation is quite large, extending
from a supposed rate of 300 per second for insect muscle to a low
limit of one stimulus in 5 to 7 seconds for plain muscle. The frog's
muscle goes into complete tetanus with a rate of stimulation of
from 20 to 30 per second. Inasmuch as the rapidity of relaxation
of the muscle is much retarded by certain influences, such as a
low temperature or fatigue, it follows that these same influences
affect in a corresponding way the rate of stimulation necessary to
give complete tetanus. A frog's muscle stimulated at the rate of
10 stimuli per second may record an incomplete tetanus, but if the
stimulus is maintained for some time the tetanus finally becomes
complete in consequence of the slowing of the phase of relaxation.

Voluntary Contractions. — After ascertaining that muscles may
give either simple or tetanic contractions one asks naturally
whether in our voluntary movements we can also obtain both
sorts of contractions. In the first place, it is obvious that most
of our voluntary movements
are too long continued to be
simple contractions. The time
element alone would place
them in the group of tetanic
contractions, and this is the
usual conclusion regarding
them. In voluntary move-
ments a neuromuscular me-
chanism comes into play.
This mechanism consists, on
the motor side, of at least two
nerve units or neurons and the
muscle, as indicated in the
accompanying diagram (Fig.
21) . If in ordinary voluntary
movements the muscular con-
tractions are tetanic, we must suppose that the motor nerve
cells discharge a series of nerve impulses through the motor

ing. 21. — Schema to show the mnerva-
tion of the skeletal (voluntary) muscles: 1,
the inter-central (pyramidal) neuron; 2, the
spinal neuron; 3, the muscle.

44 THE PHYSIOLOGY OF MUSCLE AND NERVE.

nerve into the muscle. The contraction of voluntary muscle has
been investigated, therefore, in various ways to ascertain whether
there is any objective indication of the number of separate con-
tractions that are fused together to make this normal tetanus. In
the first place, the normal movements of the muscles have been re-
corded graphically by levers or tambours. The records thus obtained
show that our usual contractions are not entirely complete tetani, —
that is, there is an indication in some part of the curve of
the single contractions that are being fused. According to most
observers,* these records show that our normal contractions are
compounded of single contractions following at the rate of 10
per second, or, in other words, the motor neurons discharge
about 10 impulses per second into the muscle. The so-called
natural muscle-tone has been used for the same purpose. When
one places a stethoscope or lays his ear upon a contracting muscle a
low tone is heard the pitch of which corresponds with 40 vibrations
per second. It is assumed, however, that this note does not represent
the actual rate of stimulation of the muscle, since the number
is higher than that obtained by other methods. The ear cannot
perceive a musical note much lower than 40 vibrations per second,
and if the muscle were really vibrating 10 or 20 times per second
we could not perceive this fact directly by the ear. Vibrating
bodies, however, give out overtones of a higher pitch, and it is
supposed, therefore, that the normal muscle tone (40) represents
either the first octave of the muscle vibrations, 20 per second, or
the second octave, 10 per second. Helmholtz made use of a simple
and direct method to determine this point. He utilized the prin-
ciple of sympathetic vibrations, according to which a vibrating
body will be set into movement most easily by vibrations that
correspond in number to its own period. Helmholtz attached to
the muscle watch springs that had different periods of vibration
and found that when the muscle was contracted the spring that
vibrated 20 times per second was set into most active movement.
He concluded, therefore, that the muscle receives 20 stimuli per
second in ordinary contractions and that the tone that is heard,
40 vibrations per second, represents the first overtone. The agree-
ment among the results of those who have made graphic records
of voluntary contractions would lead us, however, to suppose that
10 stimuli per second is more probably the true rate of stimulation
and that the muscle-tone heard represents the overtone correspond-
ing to the second octave of this vibration. It is to be borne in mind,
however, that the motor nerve cells do not necessarily discharge
their impulses into the muscle at a perfectly uniform rate. The
rate is, in fact, liable to vary in different individuals or in the same
*Horsley and Schafer, "Journal of Physiology," 7, 96, 1886.

THE PHENOMENON OF CONTRACTION. 45

individual under different circumstances. Von Kries,* for instance,
states that the rate of stimulation in voluntary movements may
vary according to the character of the movement. In slow, sus-
tained movements the rate is from 8 to 12 per second, while in
short, sharp, rhythmical movements of the fingers the rate may be
as rapid as 40 per second. The fact that movements of this latter
character — the trilling movements of the fingers of the pianist,
for instance — may last for only T^ of a second or less, is considered
by some authors as a proof that they are not tetanic contractions,
.and that therefore we can voluntarily make either long-continued
tetanic contractions or quick, simple contractions. Von Kries
has shown, however, that when these quick, rhythmical movements
of the fingers are recorded the curves, even of such brief contractions,
show that they are short-lasting tetani. It is the usual belief,
therefore, that all voluntary movements are tetanic in character
and that it is not possible for us, by a so-called act of the will, to
cause a simple contraction, — that is, to cause the motor nerve cells
to discharge a single motor impulse. This general conclusion is sup-
ported by the results of artificial stimulation of the motor regions
of the brain. In experiments of this kind made by Horsley and
Schafer it was shown that, at whatever rate the stimulus might
be applied to the motor cells, they responded by motor discharges
of about 10 per second, so far as this could be determined from
the contractions of the muscle. The interesting conclusion from
the whole discussion, therefore, is that our motor centers, under
the stimulus of the will, discharge motor impulses at a certain low
rate, which, while somewhat variable, averages in ordinary move-
ments about 10 per second.

The Ergograph. — Voluntary contractions in man may be re-
corded in a great many ways, but Mosso has devised a special in-
strument for this purpose, known as the ergograph. It has been
much used in quantitative investigations upon muscular work
and the conditions influencing it. The apparatus is shown and
described in Fig. 22. The person experimented upon makes a
series of short contractions of the flexor muscle of the middle
finger, thereby lifting a known weight to a definite height
which is recorded upon a drum. In a set of experiments the
rate of the series of contractions — that is, the interval of rest
between the contractions — is kept constant, as also is the load lifted.
Under these conditions the contractions become less and less ex-
tensive as fatigue comes on, and finally, with the strongest voluntary
effort, the contraction of the muscles is insufficient to lift the weight.
In this way a record is obtained such as is shown in Fig. 23
In such a record we can easily calculate the total work done by
* Von Kries, " Archiv fur Physiologic/' suppl. volume, 1886, p. 1.

46 THE PHYSIOLOGY OF MUSCLE AND NERVE.

obtaining the product of the load into the lift for each contrac-

Fig. 22. — Mosso's ergograph: c is the carriage moving to and fro on runners by means
of the cord d, which passes Trom the carriage to a holder attached to the last two phalanges
of the middle finger (the adjoining fingers are held in place by clamps) ; p, the writing point
of the carriage, c, which makes the record of its movements on the kymographion ; w, the
weight to be lifted.

tion and adding these products together. By this means the-
capacity for work of the muscle used can be studied objectively

Fig. 23. — Normal fatigue curve of the flexors of the middle finger of right hand.
3 kilograms, contractions at intervals of two seconds. — (Maggiora.)

Weight?,

under varying conditions, and many suggestive results have beeni

THE PHENOMENON OF CONTRACTION. 47

obtained, some of which will be referred to specifically.* It should
be borne in mind, however, that the ergograph in this form does
not enable us to compute the total work that the muscle is capable
of performing. It is obvious that when the point of complete
fatigue is reached, as illustrated in the record, Fig. 23, the muscle is
still capable of doing work, that is external work, if we replace the
heavy load by a lighter one. For this reason some investigators
have substituted a spring in place of the load,f giving thus a
spring ergograph instead of a weight ergograph. Although with the
spring ergograph every muscular contraction is recorded and the
entire work done may be calculated, it also possesses certain theo-
retical and practical disadvantages, for a discussion of which refer-
ence must be made to the authors quoted.

The weight ergograph has, so far at least, given us the most sug-
gestive results. Among these the following may be mentioned:
(1) If a sufficient interval is allowed between contractions no fatigue
is apparent. With a load of 6 kilograms, for instance, the flexor
sublimis showed no fatigue when a rest of 10 seconds was given
between contractions. (2) After complete fatigue with a given
load a very long interval (two hours) is necessary for the muscle to
make a complete recovery and give a second record as extensive as
the first. (3) After complete fatigue efforts to still further contract
the muscle greatly prolong this period of complete recovery, — a
fact that demonstrates the injurious effect of straining a fatigued
muscle. (4) The power of a muscle to do work is diminished by
conditions that depress the general nutritive state of the body
or the local nutrition of the muscle used; for instance, by loss of
sleep, hunger, mental activity, anemia of the muscle, etc. (5)
On the contrary, improved circulation fh the muscle — produced
by massage, for example — increases the power to do work. Food
also has the same effect, and some particularly interesting experi-
ments show that sugar, as a soluble and easily absorbed foodstuff,
quickly increases the amount of muscular work that can be per-
formed. (6) Marked activity in one set of muscles — the use of
the leg muscles in long walks, for example — will diminish the
amount of work obtainable from other muscles, such as those of
the arm. It is very evident that the instrument may be used to
advantage in the investigation of many problems connected with
gymnastics, dietetics, stimulants, { medicines, etc.

A point of general physiological interest that has been brought out in
connection with the use of the ergograph calls for a few words of special
mention. Mosso found that if a muscle — e. g., the flexor sublimis — is stimu-

*Mosso, "Archives italiennes de biologic," 13, 187, 1890; also "Archiv f.
Physiologic," 1899, p. 191, 342. Lombard, a Journal of Physiology," 13, 1, 1892.

t Franz, " American Journal of Physiology," 4, 348, 1900; also Hough,
ibid., 5, 240, 1901.

JSchumberg, "Archiv f. Physiol.," 1899, suppl. volume, p. 289.

48 THE PHYSIOLOGY OF MUSCLE AND NERVE.

lated directly by the electrical current and its contractions are recorded by
the ergograph, it will give a curve similar to that figured above for the volun-
tary contractions, except that the contractions are not so extensive. Under
these conditions the muscle', when completely fatigued to electrical stimula-
tion, will respond to voluntary stimulation from the nerve centers. It
seems likely, as suggested by Hough, that this result is due mainly to the
fact that the electrical current cannot be applied to a muscle in its normal
position so as to excite uniformly all the constituent muscle fibers, although
it is also possible that what we call the normal or voluntary stimulus is more
effective or, to use a physiological term, more adequate to the muscle fibers
than the electrical shock. On the other hand, after fatigue from a series
of voluntary contractions it has been observed that the muscle will still
give contractions if stimulated directly by electricity. This fact has been
interpreted to mean that, in the neuromuscular complex involved in a mus-
cular contraction — namely, motor nerve cell, motor nerve fiber, and muscle
fiber — the first named fatigues most easily, and that the ordinary fatigue
curve obtained from the ergograph does not represent pure 'muscle fatigue,
but fatigue of the neuromuscular apparatus as a whole, the point of complete
fatigue being reached in the neural component of the mechanism before
the muscle itself loses its power of contraction. This interpretation, however,
is not entirely certain. Wedenski has called attention to the fact that in
the neuromuscular apparatus the motor end-plate is a sensitive link in the
chain, and that, when the nerve is stimulated strongly with artificial stimuli,
at least, this structure falls into a condition in which it fails to conduct the
nerve impulse to the muscle. It may be, therefore, that in sustained volun-
tary contractions the end-plate fails first, and thus is directly responsible
for the failure of the apparatus to perform further work. That the fatigue in
ordinary voluntary contractions affects the muscles before the motor nerve
centers is indicated by the experiments of Storey.* Making use of a weight
ergograph and experimenting upon the abductor indicis he found that after
fatiguing this muscle to voluntary contractions with a certain weight, re-
moval of the weight enabled the individual to make contractions as high and
as rapid as before the fatigue. On the other hand, if after removing the
weight the muscle was stimulated electrically the contractions were lower and
slower than before the fatigue. So far as our knowledge goes, therefore,
fatigue as it appears in sustained voluntary contractions is due probably
primarily to a loss of irritability in the muscle and in the motor end-plates.
The motor nerve fibers do not fatigue, and as regards the motor nerve centers
it is not possible as yet to say what may be their relative susceptibility to
fatigue.

Sense of Fatigue. — It should be noted in passing that in con-
tinued voluntary contractions we are conscious of a sense of fatigue,
which eventually leads us, if possible, to discontinue our efforts.
This sensation must arise from a stimulus of sensory nerve fibers
within the muscle or its tendons, and it may be regarded as an
important regulation whereby we are prevented from pushing our
muscular exertions to the point of " straining."

Muscle Tonus, — In addition to the conditions of contraction
and of relaxation the living muscle exhibits the phenomenon of
"tone." By muscle tone we mean a state of continuous shortening
or contraction which under normal conditions is slight in extent
and varies from time to time. This condition is dependent upon
the connection of the muscle with the nerve centers, and we may
assume that under normal circumstances the motor centers are
continually discharging subminimal nerve impulses into the muscles
* Story, 'American Journal of Physiology," 1903, viii., 355.

THE PHENOMENON OF CONTRACTION. • 49

which cause chemical changes similar in kind to those set up by
an ordinary voluntary effort, but less in degree; the result being
that the muscles enter into a state of contraction which, while
slight in extent, is more or less continuous. According to this view,
the whole neuromuscular apparatus is in a condition of tonic ac-
tivity, and this state may be referred in the long run to the con-
tinual inflow of sensory impulses into the central nervous system.
The tone of any particular muscle or group of muscles may be
destroyed, therefore, by cutting its motor nerve, or less completely
by severing the sensory paths from the same region. If, for in-
stance, one severs in a dog the posterior roots of the spinal nerves
innervating the leg there will be a distinct loss of muscular tone,
although the motor nerves remain intact. While we speak of this
muscle tone as a state of continuous contraction, it may be
that the apparently uniform condition is only superficial; that, in
fact, this phenomenon is substantially only a minimal tetanus, due
to a series of feeble but discontinuous stimuli received through
the motor nerve, each of which stimuli sets up its own chemical
change in the muscle. However this may be, the fact of muscle
tone is important in a number of ways. It is of value, without
doubt, for the normal nutrition of the muscle, and, as is explained
in the chapter on animal heat, it plays a very important part in
controlling the production of heat in the body. The extent of mus-
cle tone varies with many conditions, the most important of which,
perhaps, are external temperature and mental activity. With
regard to the first, it is known that, as the external temperature
falls and the skin becomes chilled, the sensory stimulation thus
produced acts upon the nerve centers and leads to an increased
discharge along the motor paths to the muscle. The tone of the
muscles increases and may pass into the visible movements of
shivering. By this means the production of heat within the body
is increased automatically. Similarly, an increase in mental
activity, so-called mental concentration, whether of an emotional
or an intellectual kind, leads, by its effect on the spinal motor
centers, to a state of greater muscle tonus, the increased muscular
tension being, indeed, visible to our eyes.

The Condition of Rigor. — When the muscle substance dies
it becomes rigid, or goes into a condition of rigor: it passes from
a viscous to a solid state. The rigor that appears in the muscles
after somatic death is designated usually as rigor mortis, since its oc-
currence explains the death stiffening in the cadaver. It is charac-
terized by several features: the muscles become rigid, they shorten,
they develop an acid reaction, and they lose their irritability to
stimuli. Whether all of these features are necessary parts of the
•condition of rigor mortis it is difficult to say; the matter will be

4

50 . THE PHYSIOLOGY OF MUSCLE AND NERVE.

discussed briefly below. Some of the facts which have been ob-
served regarding rigor mortis are as follows: After the death of an
individual the muscles enter into rigor mortis at different times.
Usually there is a certain sequence, the order given being the jaws,
neck, trunk, upper limbs, lower limbs, the rigor taking, therefore, a
descending course. The actual time of the appearance of the rigidity
varies greatly, however; it may come on within a few minutes or a
number of hours may elapse before it can be detected, the chief de-
termining factor in this respect being the condition of the muscle
itself. Death after great muscular exertion, as in the case of hunted
animals or soldiers killed in battle, is usually followed quickly by
muscle rigor; indeed, in extreme cases it may develop almost imme-
diately. Death after wasting diseases is also followed by an early

Fig. 24. — Curve of normal rigor mortis, gastrocnemius muscle of frog. The curve
was obtained upon a kymographion making one revolution in eight days. The marks on
the line below the curve indicate intervals of six hours. It will be seen that the shortening
required eighteen hours, the relaxation about seventy-two hours.

rigor, which in this case is of a more feeble character and shorter
duration. The development of rigor is very much hastened by many
drugs that bring about the rapid death of the muscle substance, such
as veratrin, hydrocyanic acid, caffein, and chloroform. A frog's mus-
cle exposed to chloroform vapor goes into rigor at once and shortens
to a remarkable extent. Rigor is said also to occur more rapidly
in a muscle still connected with the central nervous system than
in one whose motor nerve has been severed. After a certain
interval, which also varies greatly, — from one to six days in human
beings, — the rigidity passes off, the muscles again become soft and
flexible; this phenomenon is known as the release from rigor. In
the cold-blooded animals the development of rigor is very much
slower than in warm-blooded animals. Upon an isolated frog's
muscle the most striking fact regarding rigor mortis is the shortening
that the muscle undergoes. This shortening or contraction comes
on slowly, as is shown in the accompanying figure, but in extent

THE PHENOMENON OF CONTRACTION. 51

it exceeds the simple contraction obtainable from the living muscle
by means of a maximal stimulus. This part of the phenomenon
is, however, much less marked apparently in mammalian muscle,
and Folin* states that, if rigor be caused in frog's muscle by
lowering its temperature to — 15° C., the muscle becomes rigid
merely without undergoing any shortening or change in translu-
cency. The usual explanation that is given of rigor is that it is
due to a coagulation of the fluid substance, the muscle plasma, of
which the fibers are constituted. During life the proteins exist in
a liquid or viscous condition;' after death they coagulate into a
solid form. This view is referred to again in the chapter dealing
with the chemistry of muscle and nerve; it has received much
support from the investigations of Kiihne,f who proved that the
muscle plasma is really coagulable. After first freezing and mincing
the muscles he succeeded in squeezing out the plasma from the
living fibers and showed that it subsequently clotted. While the
coagulation theory of rigor explains the greater rigidity of the
muscle, it does not furnish in itself a satisfactory explanation of
the shortening, and the fact, as stated above, that the rigidity
may occur without the shortening indicates that this latter process
may possibly be due to changes that precede the appearance of
rigidity. In addition to the rigor mortis that occurs after death
at ordinary temperatures, a condition of rigor may be induced
rapidly by raising the temperature of the muscle to a certain point.
Rigor induced in this way is designated as heat rigor or rigor caloris.
Much uncertainty has prevailed as to whether heat rigor is different
essentially from death rigor. According to some physiologists, the
processes may be regarded as the same, the heat rigor being simply
a death rigor that is rapidly developed by the high temperature,
this latter condition accelerating the chemical changes leading to
rigor, as is the case, for instance, in the action of chloroform. This
view is supported by a study of the chemical changes that take place
under the two conditions, as will be described later, and by the fact
that some of the conditions that influence one phenomenon have a
parallel effect upon the other. For instance, death rigor is accel-
erated by previous use of the muscle, and the same is true for heat
rigor. While a resting frog's muscle begins to go into heat rigor,
as judged by the shortening, at 37° to 40° C.; a muscle that has
been greatly fatigued shows the same phenomenon at 25° to
27° C4 According to other observers, heat rigor is due to an
ordinary heat coagulation of the proteins present in the muscle

* " American Journal of Physiology," 9, 374, 1903.

fKiihne, " Archiv f. Physiologie," 1859, p. 788.

j JLatimer, " American Journal of Physiology/' 2, 29, 1899.

52 THE PHYSIOLOGY OF MUSCLE AND NERVE.

fiber. It has been pointed out,* for instance, that in frogs' muscles
three different proteins are known to be present, with three dif-
ferent temperatures of heat coagulation, — namely, myogen fibrin,
35° to 40° C. ; myosin, 47° to 50° C. ; and myogen, 58° to 65° Cv and
that when the living muscle is heated what is ordinarily designated
as the contraction of heat rigor comes on at the first temperature,
35° to 40° C., while small additional contractions occur at the
temperatures of coagulation of the other two proteins. This view,
however, does not make clear why the first of these coagulations,
that of myogen fibrin at 40°, should produce such a large contrac-
tion, 80 to 90 per cent, of the total shortening, although this protein
is present in smaller quantities than the other two. As long, how-
ever, as it remains uncertain whether or not the shortening and
the coagulation are necessary features of death stiffening, it seems
premature to speculate upon the identity or difference between
the coagulation and shortening caused by death and the similar
phenomenon caused by high temperatures.

PLAIN OR LONG STRIATED MUSCULAR TISSUE.

Occurrence and Innervation. — Plain or long striated muscular
tissue occurs in the walls of all the so-called hollow viscera of
the body, such as the arteries and veins, the alimentary canal,
the genital and urinary organs, the bronchi, etc., and in other
special localities, such as the intrinsic muscles of the eyeball, the
muscles attached to the hair follicles, etc. In structure it differs
fundamentally from cross-striated muscle, in that it occurs in the
form of relatively minute cells, each with a single nucleus, which
are united to form, in most cases, muscular membranes constituting
a part of the walls of the hollow viscera. These muscle cells, in
most cases at least, are supplied with nerve fibers which originate
directly from the so-called sympathetic nerve cells, and only in-
directly, therefore, from the central nervous system.

Speaking generally, the contractions of this tissue are removed
from the direct control of the will, being regulated by reflex and
usually unconscious stimulations from the central nervous system.
All the important movements of the internal organs, or, as they
are sometimes called, the organs of vegetative life, are effected
through the activity of this contractile tissue. From this stand-
point their function may be regarded as more important than that
of the mass of the voluntary musculature, since so far as the mere
maintenance of the life of the organism is concerned, the proper
action and co-ordination of the movements of the visceral organs
is at all times essential.

* Brodie and Richardson, 'Philosophical Trans., Roy. Spc.," London,
1899, 191, p. 127; also Inagaki, 'Zeitschrift f. Biol.," 1906, xlviii., 313.

THE PHENOMENON OF CONTRACTION. 53

Distinctive Properties. — The phenomena of contraction shown
by plain muscles are, in general, closely similar to those already
studied for striated muscle, the one great difference being the
much greater sluggishness of the changes. Plain muscles differ
among themselves, of course, as do the striated muscles, but, speak-
ing generally, the simple contractions of plain muscle have a very
long latent period that may be a hundred or five hundred times
as long as that of cross-striated muscle, and the phases of shortening
and of relaxation are also similarly prolonged; so that the whole
movement of contraction is relatively slow and gentle (see Fig.
25). Plain muscle responds to artificial stimuli, but the electrical
current is obviously a less adequate — that is, a less normal — stimulus
for this tissue than for the striped muscle. The amount of current

Fig. 25. — Curve of simple contraction of plain muscle. The middle line is the time
record, marking intervals of a second. The lowermost line indicates at the break the mo-
ment of stimulation (short-lasting, tetanizing current). It will be seen that the latent period
between beginning of stimulation and beginning of' contraction is equal to about three
seconds.

necessary to make it contract is far greater. The amount of con-
traction varies with the strength of stimulus, — that is, the tissue
gives submaximal and maximal contractions. Two successive
stimuli properly spaced will cause a larger or summated contraction,
and a series of stimuli will give a fused or tetanic contraction. The
rate of stimulation necessary to produce tetanus is, of course, much
slower than for cross-striped muscle. The stomach muscle of the
frog, for instance, requires only one stimulus at each five sec-
onds to cause tetanus.* A distinguishing and important charac-
teristic of the plain muscle is its power to remain in tone, — that
is, to remain for long periods in a condition of greater or less con-
traction. Doubtless this tonic contraction under normal relations
is usually dependent upon stimulation received through the ner-
vous system, but the muscle when completely isolated from the

* Schultz, "Zur Physiologie der langsgestreiften (glatten) Muskeln,"
" Archiv f. Physiologie," suppl. volume, 1903, p. 1. See also Stewart, "Amer-
ican Journal of Physiology," 4, 185, 1900.

54 THE PHYSIOLOGY OF MUSCLE AND NERVE.

central nervous system, whether in or out of the body, continues
to exhibit the phenomenon of tone to a remarkable degree. In
most of the organs in which plain muscle occurs there are present
also numerous nerve cells, and it is therefore still a question as to
whether the tonic changes shown by this tissue depend upon a
property of the muscle itself or upon their intrinsic nerve cells.
Most observers adopt the former view. The importance of this
property of tone in the plain muscle tissues will be made fully
apparent in the descriptions of the physiology of the organs of cir-
culation and digestion. Plain muscle may exhibit also the phenome-
non of rhythmical activity, — that is, under proper conditions it may
contract and relax rhythmically like heart tissue.* Such movements
have been observed and studied upon the plain muscle of the ureter,
the bladder, the esophagus, stomach, and other portions of the
alimentary canal, the spleen, the blood-vessels, etc. This property
seems to be very unequally distributed among the different kinds
of plain muscle found in the same or different animals, but this
fact serves only to illustrate the point already sufficiently empha-
sized, that grouping one kind of tissue — e. g., plain muscle — into
a common class does not signify that the properties of all the mem-
bers of the group are identical. The question as to how far the phe-
nomenon of rhythmical contraction is entirely muscular and how far
it depends upon intrinsic nerve cells is a complex one; the answer
will probably vary for different organs, and the subject will therefore
be considered in the organs as they are treated.

Cardiac Muscular Tissue. — As the muscle cells of cardiac
tissue are somewhat intermediate in structure between the striated
fibers of voluntary muscle and the cells of plain muscles, so their
physiological properties to some extent stand between these two
extremes. The rate of contraction, for instance, while slower than
that of the fibers of skeletal muscles, is more rapid than that of
plain muscle. The most striking peculiarity of heart muscle is,
however, its power of rhythmical contractility, and this, as well as
its other properties, is so directly concerned with its functions as
an organ of circulation that it may be discussed more profitably
in that connection.

Ciliated Cells. — In the mammalian body the phenomenon of
contractility is exhibited not only by the well-defined muscular
tissue, but also by the leucocytes and especially by the cilia of the
ciliated epithelium. Epithelium with motile cilia is found lining
the mucous membrane of the air-passages in the trachea, larynx,
bronchi, and nose, in the lacrimal duct and sac, in the genital pas-
sages, uterus and Fallopian tubes and the tubules of the epididymis,

*Engelmann, "Archiv f. d. ges. Physiologie," 2, 243, 1869. Stiles,
"Amer. Jour, of Physiology," 5, 338, 1901.

THE PHENOMENON OF CONTRACTION. 55

and in the Eustachian tube and part of the middle ear. Similar
cells are found lining the ventricles of the brain and the central
canal of the cord. The cilia in this latter position have been demon-
strated to be motile in the frog, but whether this is true for the mam-
mal has not been shown. So also in the neck of the uriniferous tubule
ciliated cells are said to occur, but whether they are motile or not has
not been demonstrated. In the internal ear and the olfactory mucous
membrane the so-called sense cells are also ciliated, but here at least
the cilia are probably not motile. Ordinarily each ciliated epithelial
cell carries a bunch of cilia, all of which contract together, but
motile protoplasmic prolongations of the cell may occur singly, as
is illustrated in the spermatozoa, for instance, and in many of the
protozoa and plant cells. In the lower forms of life cilia play
obviously a very important role in locomotion, the capture of food,
and respiration, and their form and manner of movement vary
greatly. The form of movement or manner of contraction was
formerly described under four heads, — the hook form, the pendular,
the undulatory or wave-like, and the funnel form or infundibulary.
With the exception of the spermatozoa, the cilia found in mam-
mals show the first form of contraction. The little processes are
contracted quickly in one direction, so as to take a hook shape,
and then relax more slowly, the relaxation taking several times
as long as the contraction. The whole movement is rhythmical and
very rapid. The cilia of the epithelium of the frog's pharynx and
esophagus, which have been the most frequently studied in the
higher animals, contract, according to Engelmann, at the rate
of 12 times per second. When a field of epithelium is observed
under the microscope the contractions pass over it in a definite
direction, but so rapidly that the eye is not able to analyze them;
one obtains the impression simply of a swiftly flowing current.
As the cilia begin to die, their movements become less rapid, and
the nature of the contractions and their progress from cell to cell
can be satisfactorily determined. In the mammalia the function
of the ciliated epithelium is supposed to be entirely mechanical, —
that is, they move along substances lying upon them. In the
oviducts they move or help to move the ovum toward the uterus,
and in this latter organ their motion is supposed to guide the
spermatozoa from the uterus toward the oviducts, — that is,
the resistance offered to the motile spermatozoa guides their move-
ments. So in the respiratory passages foreign particles of various
sorts, together with the secretion of the mucous glands, are moved
toward the mouth, the effect being to free the air-passages from
obstruction. The contraction and relaxation of the cilia are
assumed to be phenomena of essentially the same order as those
exhibited by the muscle tissue. A theory that will adequatelv

56 THE PHYSIOLOGY OF MUSCLE AND NERVE.

explain one will doubtless be applicable to the other. Many
interesting facts have been established regarding ciliary move-
ments. The contractions of the cilia in any given field — the
trachea, for instance — follow in a definite sequence and are co-
ordinated. The waves of contraction progress in a definite direction.
This fact increases greatly the effectiveness of the cilia in per-
forming work. Thus, in spite of their extremely minute size, it
is estimated that an area of a square centimeter is capable of
moving a load of 336 gms. The contractions are automatic,—
that is, the stimulus causing them is not dependent upon a con-
nection with the nervous system, but upon processes arising within
the cell itself; the cilia of a single completely isolated cell may
continue to contract vigorously. The movement may continue
for several days after the death of the individual, thus again showing
the physiological independence of the structure. The ciliated cells
may conduct a stimulus or impulse to other cells even after its
own cilia have lost their contractility. This fact is particularly
significant in general physiology, as it aids in showing that the
property of conductivity which is exhibited in such high degree
by nerve fibers is possessed to a lower degree by other tissues.
The ciliary movement is affected by variations in temperature, and
if the temperature passes beyond an optimum point the cilia fall
into a condition resembling heat rigor in the muscle. Their move-
ments are affected also by the reaction of the medium, being at
first accelerated and then slowed or destroyed by a slight degree
of acidity and favored by a very slight degree of alkalinity.*

* References for physiology of ciliary movement: Verworn, "General
Physiology," English translation by Lee; Putter, "Ergebnisse der Physiol-
ogic," 1902, vol. ii, part n; Engelmann, article, "Gils vibratils," in Richet's
" Dictionnaire de Physiologic," vol. iii, 1898.

CHAPTER II.

THE CHEMICAL COMPOSITION OF MUSCLE AND THE

CHEMICAL CHANGES OF CONTRACTION AND

OF RIGOR MORTIS,

Muscle Plasma. — The beginning of our present knowledge of
the chemical composition of muscle is found in some interesting ex-
periments made by Kiihne upon frog's muscle. Kiihne froze the
living muscle to a hard mass, cut it into fine shavings with cold
knives, and ground the pieces thoroughly in a cold mortar. The
fine muscle snow thus obtained was put under high pressure and
a liquid expressed which was assumed to represent the fluid living
substance in the normal fiber. This muscle plasma clotted on stand-
ing, much as blood does, the muscle clot shrinking and squeezing
out a muscle serum. Similar experiments have since been per-
formed by Halliburton* on mammalian muscle. This spontaneous
clotting of the living plasma has been held to be important in
showing the probable cause of death rigor.

Composition of the Muscle Plasma. — Using the term muscle
plasma to designate the entire contents of the muscle fiber within
the sarcolemma, it is obvious that it should contain all the con-
stituents that properly belong to the muscle, in contradistinction
to the substances found in the connective tissue binding the muscle
fibers together.

The constituents in addition to water that are known to occur
in muscle are very numerous indeed, and difficult to classify. They
may be grouped under the following heads: (1) Proteins. (2) Car-
bohydrates and fats. (3) Nitrogenous waste products. (4) Special
substances, such as lactic acid, inosite, inosinic acid, phosphocarnic
acid. (5) Pigments. (6) Ferments. (7) Inorganic salts. Very
little that is positive can be stated regarding the physiological role
of most of these constituents, the interest that attaches to them
at present being largely on the chemical side.

The Muscle Proteins.t — The proteins of the muscle have been
investigated by a number of observers, but unfortunately the

* Halliburton, "Journal of Physiology," 8, 133, 1888.

f Von Fiirth, "Archiv f. exper. Path. u. Pharmakol.," 36, 231, 1895. See
also Halliburton, "Journal of Physiology," 8, 133, 1888; and Stewart and
Sollman, ibid., 24, 427, 1899.

57

58 THE PHYSIOLOGY OF MUSCLE AND NERVE.

terminology employed has not been uniform, and the facts so far
as they are known to us seem to be obviously incomplete. Ac-
cording to von Fiirt h, two proteins may be obtained from mam-
malian muscle by extracting it with dilute saline solutions, — namely,
myosin and myogen, the latter existing to three or four times the
amount of the former. Myosin belongs to the globulin group of
proteins (see appendix); it is coagulated by heat at 44° to 50° C.,
it is precipitated by dialysis or by weak acids, it is easily precipi-
tated from its solutions by adding an excess of neutral salts, such
as sodium chlorid, magnesium or ammonium sulphate. With
the last salt it is completely precipitated when the salt is added
to one-half saturation or less. Its most interesting property, how-
ever, is that on standing at ordinary temperatures it passes over
into an insoluble modification which separates out as a sort of
clot. Following the terminology used for the blood, this insoluble
modification is called myosin fibrin. Myogen, the other protein,
seems to fall into the group of albumins rather than globulins.
It is not precipitated by dialysis and requires more than half
saturation with ammonium sulphate for its complete precipitation.
It is coagulated by heat at a temperature of 55° to 65° C. Solutions
of myogen on standing also undergo a species of clotting, the in-
soluble protein that is formed in this case being called myogen fibrin.
It appears, however, that in changing to myogen fibrin the myogen
passes through an intermediate stage, designated as soluble myogen
fibrin, in which its temperature of heat coagulation is as low as
30° to 40° C., — the lowest temperature recorded for any protein.
As was stated in the paragraph on muscle rigor, it is known that
frog's muscle goes into heat rigor at about 37° to 40° C., and in
accordance with this fact it is stated that this protein, soluble
myogen fibrin, which is not present in mammalian muscle, occurs
normally in the muscle of the frog and also of the fishes. On the
basis of these facts the rigidity of death rigor is explained by as-
suming that both of these proteins exist in the living muscle, and
that after death they undergo a partial or complete coagulation
according to the following schema:

Myosin. Myogen.

I I

Myosin fibrin. Soluble myogen fibrin.

T
Myogen fibrin.

In the dead muscle we should find, therefore, the insoluble
myosin fibrin and myogen fibrin, together with more or less of the
original myosin and myogen. Myogen is said not to occur in the

THE CHEMISTRY OF MUSCLE. 59

muscles of the invertebrates. It should be added that after the
most complete extraction with saline solutions the muscle fiber still
retains much protein material, and its structural appearance, so far
as cross-striation is concerned, remains unaltered. The portion of
protein material thus left in the muscle fiber as a sort of skeleton
framework is designated as the muscle stroma; it is not soluble
in solutions of neutral salts, but dissolves readily in solutions of
dilute alkalies. In striped muscle this so-called stroma forms
about 9 per cent, of the weight of the muscle; while in the heart
muscle it makes about 56 per cent., and in the smooth muscle,
72 per cent. It is at present uncertain whether the myosin and
myogen represent the protein constituents of the contractile ele-
ments of the muscle fibers or of the undifferentiated portion, the
sarcoplasm. The protein of plain muscle tissue and of cardiac
muscle have not received so much attention as those of voluntary
muscle. It is stated, however, that the proteins extracted from
these tissues by salt solutions are coagulable on standing, as in
the case of the extracts of voluntary muscle. In plain muscle
two proteins, in addition to some nucleoprotein, are described,
one belonging to the albumin and one to the globulin class, but
the identity or relationship of these proteins to those above de-
scribed has not been established. In heart muscle, myosin and
myogen occur in practically the same proportions as in voluntary
muscle, but the amount of stroma left undissolved after treatment
with saline solutions is, as stated above, much greater than in
skeletal muscle.*

The Carbohydrates of Muscle. — Muscle contains a certain
amount of sugar, dextrose or dextrose and isomaltose, and also
under normal conditions a considerable quantity of glycogen, or
so-called animal starch. The formation and the consumption of
glycogen in the body constitute one of the most interesting chapters
in the physiology of nutrition, and the relations of glycogen will
be treated more fully under that head. It may be stated here,
however, that the muscular tissue has the power of converting the
sugar brought to it by the blood into glycogen. This glycogenetic
action of the muscle is represented in principle by the reaction

C6H1208 — H20 = C?H1005.

Dextrose. Glycogen.

The glycogen thus formed is stored in the muscle and forms
a constant constituent of well-nourished muscle in the resting
condition, the amount varying between 0.5 and 0.9 per cent, of
the weight of the muscle. The glycogen thus stored in the muscle

* Vincent and Lewis, " Journal of Physiology," 26, 445, 1901 ; also " Zeit-
schrift f. physiolog. Chemie," 34, 417, 1901-2 ; Stewart and Sollman, loc. rit.;
Saxl, " Hofmeister's Beitriige," 1906, ix., 1.

60 THE PHYSIOLOGY OF MUSCLE AND NERVE.

is consumed by the tissue during its activity, and it is assumed
that before it is thus consumed it is converted back into sugar by
the action of an amylolytic enzyme contained in the muscle. The
glycogen, therefore, itself represents a local deposit of carbohydrate
nutritive material, resembling in this respect the fat. The sugar
and the glycogen must be considered as one from the standpoint
of the nutrition of the muscle. During muscular activity the
store of glycogen is used up, and if the activity is sufficiently pro-
longed it may be made to disappear entirely. Among the many
uncertain and contradictory statements regarding the chemical
changes in active muscle, this fact stands out in pleasant contrast
as one that is satisfactorily demonstrated.

Phosphocarnic Acid (Nucleon). — A peculiar substance containing phos-
phorus was discovered by Siegfried in the muscle extracts.* This substance
seems to resemble the proteins, but has a complex and peculiar structure, as
is shown by its split products when hydrolyzed by boiling with baryta water.
Under these conditions there are formed carbon dioxid, phosphoric acid,,
a carbohydrate body, succinic and lactic acids, and a crystallizable nitrogen-
ous acid body which is designated as carnic acid (C10H15N5O3). Siegfried
assumes that this latter substance is identical with one of the peptones
(antipeptone) formed during digestion, and conceives, therefore, that his
phosphocarnic acid is a complex substance built up from a peptone and a
phosphorus-containing compound. Compounds of simple proteins with
phosphorus-containing bodies (nucleic acids) are designated usually as
nucleins ; for this compound of a peptone with a phosphorus-containing com-
plex Siegfried suggests the name of nucleon. By the addition of ferric
chlorid the nucleon is precipitated readily from muscle extracts as an iron
compound, carniferrin, and under this name has come into the market as a
presumably efficient therapeutic preparation of iron. The discoverer of
nucleon has attributed to it a very great physiological importance, as a source
of energy to t>he muscle, and as an efficient means of transportation of iron,
calcium, potassium, and magnesium into the muscle substance, particularly
in such articles of diet as soups, bouillons, meat extracts, etc. It must be
stated, however, that there still remains doubt as to the chemical individuality
of the nucleon or the nucleons, their existence in normal muscle, and their
physiological role. The substance, whether a well-defined chemical individual
or not, is most interesting. Its properties are such as would aid in explaining
the occurrence of some of the known products of the chemical changes during
contraction; but obviously further investigation is still needed before such
an application can be made with confidence.

Lactic Acid (CHH6O3). — Lactic acid is found in varying amounts
in the extracts of muscle. The acid that is obtained is the so-called
ethidene lactic acid or «-hydroxypropionic acid (CH3CHOHOOOH),
and differs from the lactic acid found in sour milk in that it ro-
tates the plane of polarized light to the right. The lactic acid in
sour milk is produced by bacterial fermentation, and is inactive to-
polarized light, because it exists in racemic form ; that is, it con-
sists of equal amounts of the right-handed form which turns the
plane of polarization to the right and of the left-handed form
which turns it to the left. In the muscle the right-handed form

* Siegfried, " Zeitschrift f. physiol. Chemie," 21, 360, 1896 ; also 28, 524,
1899.

THE CHEMISTRY OF MUSCLE. 61

is found mainly or only, and this form therefore is frequently
designated as sarcolactic (or paralactic) acid.

The Nitrogenous Extractives (Nitrogenous Wastes).—-
Muscle extracts contain numerous crystallizable nitrogenous sub-
stances which are regarded as the end-products of the disassimila-
tion or catabolism of the living protein material of the muscle.
The number of these substances that have been found in traces or
weighable quantities is rather large. They have aroused great
interest because their structure throws some light on the nature
of protein catabolism. The one that occurs in largest amount is
creatin, C4H9N302, or methyl-guanidin-acetic acid, NHCNH2NCH3-
CH2COOH. Creatin may be present in amounts equal to 0.3 per
cent, of the weight of the muscle. It is supposed to be given off
to the blood and eventually excreted in the urine as creatinin
(C4H-N30), which is formed from creatin by the loss of a molecule
of water (seep. 780). The creatinin itself may occur in the muscle
in small quantities. In addition there is a group of bodies supposed
to represent the end-products of the breaking up of the nucleins
of the muscle, all of which belong to the so-called purin bases. These
are : Uric acid (C5H4N4O3), xanthin (C5H4N4O2), hypoxanthin
(C5H4N4O), guanin (C5H5N5O), adenin (C5H5N5), and carnin (C7H8-
N4O3). They will be referred to more fully in the section on Nutri-
tion. Still other bodies of similar physiological significance have
been described from time to time. These nitrogenous products are
found in the various meat extracts and meat juices used in dietetics.
While they possess no direct nutritive value, it seems probable (see
chapter on Gastric Digestion) that they may be very effective
indirectly by stimulating the secretion of the gastric glands.

Pigments. — The red color of many muscles is believed to be
due to the presence of a special pigment which resembles in its
structure and its properties the hemoglobin of the red blood
corpuscles, and perhaps is identical with it. This pigment is known
as myohematin or myochrome. It belongs presumably to the
group of so-called respiratory pigments, which have the property
of holding oxygen in loose combination, and by virtue of this
property it takes part in the absorption of oxygen by the muscular
tissue.

Enzymes. — A number of unorganized ferments or enzymes
have been described by one observer or another. In this tissue
as in others the processes of nutrition seem to be connected with
the development of special enzymes. A proteolytic enzyme capable
of digesting proteins has been described by Brucke and others;
an amylolytic enzyme capable of converting the glycogen to sugar
by Nasse ; a glycolytic enzyme capable of destroying the sugars
by Brunto'n, Cohnheim, and others ; a lipase capable of splitting

62 THE PHYSIOLOGY OF MUSCLE AND NERVE.

the fats by Kastle and Loevenhart; and, finally, a coagulating
enzyme responsible for the coagulation of the muscle plasma after
death by Halliburton.

The Inorganic Constituents. — Muscle tissue contains a number
of salts, chiefly in the form of the chlorids, sulphates, and phos-
phates of sodium, potassium, calcium, magnesium, and iron. As
in other tissues, the potassium salts predominate in the tissue itself.
These inorganic constituents are most important to the normal
activity of the muscle, and, indeed, in two ways: first, in that they
maintain a normal osmotic pressure within the substance of the
fibers and thus control the exchange of water with the sur-
rounding lymph and blood; second, in that they are necessary
to the normal structure and irritability of the living muscular
tissue. Serious variations in the relative amounts of these salts
cause marked changes in the properties of the tissues, as is ex-
plained in the section on nutrition, in which the general nutritive
importance of the salts is discussed, and also in connection with
the cause of the rhythmical activity of the heart.

Chemical Changes in the Muscle during Contraction and
Rigor. — Perhaps the most significant change in the muscle during
contraction is the production of carbon dicxid. After increased
muscular activity it may be shown that an animal gives off a
larger amount of carbon dioxid in its expired air. In such cases
the carbon dioxid produced in the muscles is given off to the
blood, carried to the lungs, and then exhaled in the expired air.
Pettenkofer and Voit, for instance, found that during a day in
which much muscular work was done a man expired nearly twice
as much CO2 as during a resting day. The same fact can be
shown directly upon an isolated muscle of a frog made to con-
tract by electrical stimulation. The carbon dioxid in this case
diffuses out of the muscle in part to the surrounding air, and
in part remains in solution, or in chemical combination as car-
bonates, in the liquids of the tissue. It has been shown by
Hermann* and others that a muscle that has been tetanized gives
off more carbon dioxid than a resting muscle when their contained
gases are extracted by a gas pump. This CO2 arises from the
oxidation of the carbon of some of the constituents of the muscle,
and its existence is an indication that in their final products the
changes in the muscle are equivalent in those of ordinary combus-
tion at high temperatures, the burning of wood or fats, for instance.
Moreover, the formation of the CO2 in the muscle is accompanied
by the production of heat, as in combustion; and for the same
amount of CO2 produced in the two cases the same amount of heat

* Hermann, " Untersuchungen iiber den Stoffwechsel der Muskeln, etc.,"
Berlin, 1867.

THE CHEMISTRY OF MUSCLE. 63

is liberated. It has been shown, however, in the frog's muscle
freshly removed from the body, that the CO2 is produced whether or
not any oxygen is supplied to the muscle, — that is, when the muscle
is made to contract in an atmosphere containing no oxygen, or
in a vacuum. In this respect the parallel between physiological
oxidation and ordinary combustion fails. Wood, oil, and other
combustible material cannot be burnt at high temperatures in
the absence of oxygen. We must believe, therefore, that in the
muscle there is a supply of stored oxygen, and that the muscle
will give off CO2 as long as 'this supply lasts. The oxidation,
instead of being direct, as in the case of combustions, is indirect.
The views regarding the nature of the oxidations in the body are
treated in the section on Nutrition.

The oxygen is absolutely necessary to the normal activity of
the muscular tissue, but the tissue, by storing the oxygen, can
function for some time when the supply is suspended. As Pfliiger
has expressed it, in a most interesting paper,* the oxygen is like
the spring to a clock : once wound up, the clock will go for a cer-
tain time without further winding. It must be borne in mind,
however, that different tissues show considerable variation in the
time during which they will function normally after suspension
of their oxygen supply. The cortex of the brain, for instance,
loses its activity, — that is, unconsciousness ensues almost imme-
diately upon cessation or serious diminution in the supply of blood,
and the same may be said of the functional activity of the kidney.
In the cold-blooded animals, with their slower chemical changes,
the supply of stored oxygen maintains irritability for a longer
time than in the warm-blooded animals.

Disappearance of the Gli/cogen. — An equally positive chemical
change in the muscle during contraction is the disappearance of its
contained glycogen. Satisfactory proof has been furnished that the
amount of glycogen in a muscle disappears more or less in proportion
to the extent and duration of the contractions, and that after pro-
longed muscular activity, especially in the starving animal, the
supply may be exhausted entirely. In what way the glycogen is
consumed is not completely known; the matter is discussed in the
section on Nutrition. The most probable view is that the glycogen
is first converted to sugar (dextrose) by the action of an amylolytic
enzyme, and the sugar in turn is destroyed by the serial action of
several enzymes. The first step, probably, is a conversion to lactic
acid (C6H12O. == 2C3H6O3), and the lactic acid then undergoes
oxidation, with the production of CO2 and H2O, under the influence
of an oxidizing enzyme, either directly or after conversion to still
lower members of the fatty acid series (acetic or formic acid).
*Pfliiger, "Archiv f. die gesammte Physiologic," 10, 251, 1875.

64 THE PHYSIOLOGY OF MUSCLE AND NERVE.

It is in the last step, that of oxidation, that the heat energy is given
off. The fact that the glycogen disappears as a result of the con-
tractions does not mean necessarily that this substance or the
sugar into which it is converted is absolutely necessary for the
chemical changes of contraction. It is stated that the muscle will
continue to contract after all its glycogen is used up * ; still it must
be borne in mind that the using up of the local store of glycogen
does not mean that all the sugar supply of the body is consumed.
After the most prolonged starvation the blood contains its normal
;supply of sugar, and we can only suppose that this sugar comes
from the material of the body itself, probably from its proteins,
and it remains quite possible that a constant supply of sugar from
some source is necessary to the chemical changes that occur in
normal contractions.

The Formation of Lactic Acid. — The lactic acid that is present
in the muscle is believed to be increased in quantity by muscular
activity. Attention was first called to this point by du Bois-
Reymond, who showed that the reaction of the tetanized muscle
is distinctly, acid, while that of the resting muscle is neutral or
islightly alkaline. This fact can be demonstrated by the use of
litmus paper, but perhaps more strikingly by the use of acid fuchsin.|
If a solution of acid fuchsin is injected under the skin of a frog it
is gradually absorbed and distributed to the body without injuring
the tissues. In the normal media of the body this solution remains
colorless or nearly so. If now one of the legs is tetanized the
muscles take on a red color, showing that an acid is produced locally.
The supposition generally made is that the acidity during activity
is due to an increased production of sarcolactic acid. Experiments
have been made by a number of observers to determine quantita-
tively the amount of lactic acid in the resting and the worked
muscle respectively. Several have stated that the amount is act-
ually less in the worked muscle; others have found an increase. J
The balance of evidence seems to show that there is an increased
production, but that this increase may be obscured in the living
animal by the fact that the acid is removed by the circulating
blood. In accordance with this view we find that the so-called
titration-alkalinity of the blood may be decreased after muscular
activity, and some observers have shown that the lactates in the
blood are correspondingly increased. That lactic acid is produced
in the living muscle is shown by experiments § in which blood was
transfused for several hours through the legs of a freshly killed
;animal. In such cases the amount of lactic acid in the blood was

* Jensen, " Zeitschrift f. physiol. Chemie," 35, 525.

fDreser, " Centralblatt fur Physiologic," 1, 195, 1887.

JWerther, " Pfluger's Archiv," 46, 63, 1890.

% Berlinerblau, "Archiv. f. exp. Path. u. Pharm.," 23, 333, 1887.

THE CHEMISTRY OF MUSCLE. 65

distinctly increased. We must believe, therefore, that lactic acid
is a constant product of the chemical changes of nutrition going
on in the muscle, and that its production is increased by the greater
chemical activity which occurs during visible contraction. Normally
we must suppose that this lactic acid, as stated above, undergoes
oxidation with the production of heat, and this oxidation takes
place in the muscle itself. When the production is rapid or ex-
cessive some may be carried off by the blood and be oxidized else-
where or even be excreted in the urine as a lactate. The increased
acidity of the muscl^ during activity, especially when the circulation
is interrupted, is referable, in the long run, to this greater production
of lactic acid; but as the acid after its formation probably reacts
with the alkaline salts present it is frequently stated that the
actual acidity shown to litmus or other indicator is due to acid
salts produced by reaction with lactic acid, presumably the acid
phosphate of potassium (KH2PO4).

Much interest has been shown in the question of the origin of
the lactic acid. According to some observers, it arises from the
carbohydrates in the muscle, the glycogen or the sugar. In support
of this view it has been claimed that in contraction and especially
in rigor mortis the glycogen disappears as the lactic acid increases.
This relationship, however, is denied, as far as rigor mortis is con-
cerned, by competent observers*. Chemical studies, however,
upon the action of the enzymes contained in muscle tend strongly
to support the view that normally the glycogen after conversion
to sugar is split first into lactic acid before undergoing oxidation
(consult section on Nutrition, p. 824). Another suggestion is
that the lactic acid arises from the phosphocarnic acid described
above. This compound, when split by hydrolysis, yields lactic
acid; so that if we could obtain convincing proof that such
a compound exists in living muscle it would serve very well
to explain the production of lactic acid. From experiments
made upon general nutrition it has been shown that in birds
the uric acid in the urine is replaced largely by lactic acid
(ammomium lactate) when the liver is excised. Under these
conditions the quantity of lactic acid secreted varies with the
albumin destroyed in the body, and some physiologists are of the
opinion that the lactic acid produced in the muscle or in other
tissues is derived from the breaking down of the living protein
material. A decisive answer to this problem is not possible at
present, but it may be said perhaps that the trend of modern work
tends to support the view that lactic acid constitutes what is called
an intermediary product in the metabolism of the sugar (glycogen)
of the muscle.

*B6hm, "Pfliiger's Archiv f. d. gesammte Physiologic," 23, 44, 1880.
5

66 THE PHYSIOLOGY OF MUSCLE AND NERVE.

The Formation of Creatin. — Great in constitutes the chief nitrog-
enous waste product in the muscle, and we should expect that the
greater metabolism during activity would result in an increase in
the creatin. Some observers state positively that the creatin is
increased during contraction.

Chemical Changes during Rigor Mortis. — The chemical
changes during rigor have been referred to above, but may be
summarized here in brief form :

1. There is a coagulation of the protein material of the muscle
plasma, which at present may be explained by supposing that the
contained myosin and myogen, spontaneously, or under the action
of an enzyme, pass into their insoluble forms, — namely, myosin
fibrin and myogen fibrin.

2. There is an increased acidity, due doubtless to a production
of lactic acid.

3. There is a production of CO2. Hermann, in his original ex-
periments, asserts that in rigor there is, so to speak, a maximal
production of CO2, — that is, all of the material in the muscle capable
of yielding CO2 is broken down during rigor. The amount of CO2
given off, therefore, by a resting muscle when it goes into rigor
is greater than in the case of a worked muscle, since in the
latter some of the material capable of yielding CO2 has been used
up during contraction.

4. The consumption of glycogen. According to some observers,
glycogen disappears during rigor as it does during contraction;
but others find that the amount is not changed during this process,
As the glycogen after death is converted to sugar with some rapidity
it is possible that the disappearance noted by the former observers!
was not due to the rigor process, but to post-mortem fermentation-.*

The Relation of the Chemical Changes during Contraction
to Fatigue; Chemical Theory of Fatigue. — As we have seen, a
muscle kept in continuous contraction soon shows fatigue ; it
relaxes more and more until, in spite of constant stimulation, it
becomes completely unirritable. We may define fatigue, there-
fore, as a more or less complete loss of irritability and contractility
brought on by functional activity. But even when the fatigue is
complete and the muscle fails to respond at all to maximal
stimulation, a very short interval of rest is sufficient to bring about
some return of irritability. For a complete restoration to its
normal condition a long interval of time may be necessary. If
the muscle is isolated from the body and thus deprived of its cir-
culation, the recovery from fatigue is less rapid and less complete
than under normal conditions. In such an isolated muscle, more-

* Kisch, Hofmeister's "Beitrage zur chem. Physiol. u. Pathol./' viii.,
210, 1906.

THE CHEMISTRY OF MUSCLE. 67

over, if provision is made to irrigate its blood-vessels with a solution
of physiological saline (NaCl, 0.7 per cent.) the recovery from fatigue
is hastened. These facts seem to indicate clearly that fatigue is
not due to a complete consumption of the material in the muscle
that supplies the energy for the contractions. In other words,
fatigue as it usually presents itself to us in life or under experi-
mental conditions is a phenomenon different from exhaustion.
Ranke,* who made the first complete study of this subject, was
convinced that a muscle when ,tetanized to the point of complete
fatigue consumes only a fraction of the oxidizable or energy-yielding
material contained in its substance. He believed that there exists
in the fatigued muscle a something brought into existence by the
contraction itself, which retards or prevents further physiological
oxidation. In support of this view he found that if an extract
was made from the fatigued muscles of one frog and injected into
the circulation of a second frog, the muscles of this latter animal
gave evidence of fatigue, — that is, they showed diminished power
of contraction upon stimulation. A similar experiment made with
an extract from resting muscle gave no such effect. Investigation
of the separate products formed in a muscle during contraction
demonstrate that the sarcolactic acid, acid potassium phosphate,
and carbon dioxid are apparently responsible for this effect. |
According to these experiments, the accumulation of these products
is responsible for the appearance of fatigue; the muscle's own
metabolic products, therefore, serve to limit its responsiveness to
stimulation, and thus form a protective mechanism that saves it
from complete exhaustion. Under normal conditions these prod-
ucts are quickly removed by the blood or, in the case of the
lactic acid, destroyed by oxidation. It should be added that Lee
has published experiments which indicate that the first effect of
these so-called fatigue substances is to increase the irritability of
the muscle, while the later effect is to diminish the irritability or
to suppress it altogether. In this initial favoring influence Lee
finds an explanation of the phenomenon of Treppe (see p. 33).
This chemical theory of fatigue does not, however, explain all the
phenomena, particularly the after-results. As was stated in describ-
ing the experiments made with the ergograph, a very short rest
suffices to make the muscle again capable of lifting its load, but
a very long interval of rest, two hours, may be required before the
muscle is restored entirely to its normal condition. Such a long
interval is evidently not necessary for the removal of the metabolic
products, and we must recognize that a part of the fatigue is due to a

*Ranke, "Tetanus," Leipzig, 1865.

f For discussion and experiments, see Lee ; Harvey Lectures, 1905-06,
Philadelphia, 1906; also Journal of the American Medical Association, May
19, 1906, and American Journal of Physiology, xviii., 267, 1907.

68 THE PHYSIOLOGY OF MUSCLE AND NERVE.

using up of the material from which the energy is obtained. That
is, during contraction the processes of disassimilation or catabolism
are in excess of those of assimilation or anabolism, so that at the
end of prolonged muscular activity the muscle contains a diminished
supply of oxidizable or energy-yielding material. To supply this
deficiency new food material, including under this term also the
necessary oxygen,* must be assimilated by the muscle. We must
suppose, therefore, that two factors, accumulation of the products
of metabolism and exhaustion of energy-yielding material, co-
operate to produce the conditions actually observed; but the
former of these, the formation of metabolic products, seems to be the
protective mechanism that is especially adapted to save the muscle
from complete exhaustion. In what way these products depress
the irritability and contractility of the muscles is not known; their
presence may, as Ranke supposed, prevent the underlying chemical
changes, the so-called physiological oxidations, or their action
may be exerted on the contractile machinery alone, — that is, the
mechanism by means of which the shortening is effected.

Theories of Muscle Contraction. — It is universally admitted
that the ultimate cause of the muscle contraction is the chemical
change caused by the stimulus. While the nature of this chemical
reaction is not known, it is admitted also that it consists in a process
of splitting and oxidation whereby large and relatively unstable
molecules are reduced to smaller and more stable ones, such as
H2O and the CO2 and lactic acid which we recognize among the
products. This reaction is exothermic,— that is, some of the chemical
or internal energy of the complex compound is liberated as heat.
Both of these results are so frequently observed in other chemical
reactions that they call for no special comment in this case. The
particular problem regarding the muscle is how this chemical
reaction leads to the shortening of the muscle and thereby
makes it do mechanical work. We must assume that there is some
mechanism in the muscle by means of which the energy liberated
during the chemical change is utilized in causing movement, some-
what in the same way as the heat energy developed in a gas-engine
is converted by a mechanism into mechanical movement, or the
electrical energy in the coils of a motor is utilized by a device to
develop movement. Regarding the means used in the muscle to
transform the original chemical or internal energy to mechanical
movement we have no or very little positive knowledge. Numer-
ous theories of a more or less speculative character have been pro-
posed. It has been suggested (Weber) that the muscular force is
essentially due to the elasticity of the muscle. It is known that the
elasticity of substances may change with conditions, and it is
* Verworn, "Archiv f. Physiologie, " 1900, suppl. volume, p. 152.

THE CHEMISTRY OF MUSCLE.

69

assumed that after stimulation the physical condition of the muscle
is changed and that the increased elastic attraction between the
particles gives it the form of the contracted muscle. According
to others (Fick), the mechanical contraction is a direct result of
an increased chemical affinity, while others (Miiller) find an ex-
planation in supposed electrical charges upon the doubly refractive
particles of the muscle in consequence of which there are developed
electrical attractions and repulsions at the different poles. The
most specific and comprehensible hypothesis advanced is that
formulated by Engelmann.* This author has shown that all con-
tractile tissues contain doubly
refractive particles, that in the
striped muscle fiber these par-
ticles are arranged in discs, —
the dim bands, — with the
singly refracting material form-
ing the light bands on either
side. During contraction it has
been shown that the material
of this latter structure is ab-
sorbed by the doubly refractive
substance. Engelmann has
shown, moreover, that dead
substances, which contain
doubly refractive particles,
such as catgut, when soaked
with water will shorten upon
heating and relax again upon
cooling. His explanation of

f

I

Fig. 26. — Engelmann's artificial muscle.
The artificial muscle is represented by the
catgut string, m. This is surrounded by a
coil of platinum wire, w, through which an
electrical current may be sent. The catgut
is attached to a lever, h, whose fulcrum is at
c. The catgut is immersed in a beaker of
water at 50° to 55° C., and "stimulated"
by the sudden increase in temperature caused
by the passage of a current through the coil.
— (After Engelmann.)

the mechanics of contraction in
brief is that the chemical
change brought about in the
muscle liberates heat, and that
the effect of this heat upon the
adjacent doubly refractive par-
ticles is to make them imbibe
the surrounding water. If we

further suppose that these particles in the resting muscle are linear
or prismatic in shape, then upon imbibing water they will tend
to become spherical, causing thus a shortening in the long diameter
and an increase in the cross diameter. The muscle, in other words,
is an apparatus comparable, let us say, to a gas engine : each
stimulus, like a spark, causes the physiological oxidation of a portion

* Ens;elmann, "Ueber den Ursprung der Muskelkraft," Leipzig, 1893; see
also " Pfluger's Archiv," 7, 155, 1873.

70 THE PHYSIOLOGY OF MUSCLE AND NERVE.

of the usable material in the muscle, and the heat thus produced
acts upon the doubly refractive material as upon a piece of machin-
ery and causes it to shorten by imbibition. Contraction, in a word,
is a phenomenon of thermic imbibition. Engelmann has given an
appearance of verisimilitude to this hypothesis by constructing
an artificial muscle from a piece of violin string. The apparatus
used is illustrated in Fig. 26. A catgut string (ra) is surrounded
by a coil of platinum wire (w) through which an electrical current
may be sent. The object of this arrangement is to heat the catgut
suddenly. The platinum coil should not actually touch the catgut.
The catgut is attached to a lever, as shown in the figure. The

Fig. 27. — Curve of simple contraction obtained from an artificial muscle. The dura-
tion of the stimulus (heating effect caused by the current) is shown by the break in the
line beneath the curve.

catgut is thoroughly soaked by immersing it in a beaker of water
and the temperature is then raised to 50° to 55° C. If then a
current is turned into the coil the slight but somewhat rapid heating
of the catgut will cause it to shorten, owing to the imbibition of
more water. When the current is broken the catgut cools and
relaxes slowly. Records may be obtained in this way which are
altogether similar or identical with those given by a strip of plain
muscle when stimulated (see Figs. 27 and 28). The model may be
used to show the effect of temperature upon the extent and dur^
tion of the contractions, the effect of variations in strength of

THE CHEMISTRY OF MUSCLE. 71

stimulus as expressed in the amount of current used, the summation

Fig. 28. — Imitation of incomplete tetanus by the artificial muscle. The time and
duration of the successive heatings are indicated by the breaks in the lower line. Each
such heating causes a separate contraction, and these contractions are summated as in the
tetanic contraction of muscle.

of successive stimuli, etc. Under all of these conditions it imitates
closely the behavior of plain muscular tissue.

CHAPTER III.

THE PHENOMENON OF CONDUCTION— PROPERTIES
OF THE NERVE FIBER.

Conduction. — When living matter is excited or stimulated in
any way the excitation is not localized to the point acted upon,
but is or may be propagated throughout its substance. This prop-
erty of conducting a change that has been initiated by a stimulus
applied locally is a general property of protoplasm, and is exhib-
ited in a striking way by many of the simplest forms of life. A
light touch, for instance, applied to a vorticella will cause a retrac-
tion of its vibrating cilia and a shortening of its stalk. In the most
specialized animals, such as the mammalia, this property of con-
duction finds its greatest development in the nervous tissue, and
indeed, especially in the axis cylinder processes of the nerve cells,
the so-called nerve fibers. But the property is exhibited also to-
a greater or less extent by other tissues. When a muscular mass
is stimulated at one point the excitation set up may be propagated
not only through the substance of the cells or fibers directly affected,
but from cell to cell for a considerable distance. In the heart
tissue and in plain muscle it has been shown that a change of
this sort may be conducted independently of the phenomenon
of visible contraction. A stimulus applied to the venous end
of a frog's heart, for instance, may, under certain conditions,
be conducted through the auricular tissue without causing in it 'a
visible change, and yet arouse a contraction in the ventricular
muscle (Engelmann). The change thus conducted may be spoken
of as a muscle impulse. Under normal conditions a muscle fiber
is stimulated through its motor nerve fiber at some point near the
middle of its course, but the stimulus thus applied must be con-
ceived as arousing a muscle impulse that travels over the length of
the muscle fiber and precedes the change of contraction. Similarly
it can be shown that ciliary cells can convey an impulse from cell
to cell. A stimulus applied to one point of a field of ciliary epi-
thelium may set up a change that is conveyed as a ciliary impulse
to distant cells. The universality of this property of conduction
in the simpler, less differentiated forms of life, and its presence in
some form in many of the tissues of the higher forms would justify
the assumption that the underlying change is essentially the same
in all cases. But in nerve fibers this property has become special-

72

THE PHENOMENON OF CONDUCTION. 73

ized to the highest degree, and in this tissue it may be studied
therefore with the greatest success and profit.

Structure of the Nerve Fiber. — The peripheral nerve fiber,
as we find it in the nerve trunks and nerve plexuses of the body,
may be either medulla ted or non-medullated. All the nerve fibers
that arise histologically from the nerve cells of the central nervous
system proper — that is, the brain and cord and the outlying sensory
ganglia of the cranial nerves and the posterior spinal roots— are
medullated. These fibers contain a central core, the axis cylinder,
which is usually regarded as an enormously elongated process of
the nerve cell with which it is connected. The axis cylinder shows
a differentiation into fibrils (neurofibrils) and interfibrillar sub-
stance (neuroplasm). All of our evidence goes to show that the
axis cylinder is the essential part of the nerve fiber so far as its
property of conduction is concerned. It is further assumed that
the neurofibrils in the axis cylinder form the conducting mech-
anism rather than the interfibrillar substance. Surrounding the
axis cylinder we have the medullary or myelin sheath, varying
much in thickness in different fibers. This sheath is composed of
peculiar material and is interrupted or divided into segments at cer-
tain intervals, the so-called nodes of Ranvier. Outside the myelin
there is a delicate elastic sheath comparable to the sarcolemma of
the muscle fiber and designated as the neurilemma. Lying under
the neurilemma are found nuclei, one for each internodal segment
of the myelin, surrounded by a small amount of granular proto-
plasm. The non-medullated fibers have no myelin sheath. They
are to be considered as an axis cylinder process from a nerve cell,
surrounded by or inclosed in a neurilemmal sheath. These fibers
arise histologically from the nerve cells found in the outlying
ganglia of the body, the ganglia of the sympathetic system and
its appendages.

The Function of the Myelin Sheath. — The myelin sheath of
the cerebrospinal nerve fibers is a structure that is interesting and
peculiar, both as regards its origin and its composition. Much
speculation has been indulged in with regard to its function, but
practically nothing that is certain can be said upon this point. It
has been supposed by some to act as a sort of insulator, preventing
contact between neighboring axis cylinders and thus insuring
better conduction. But against this view it may be urged that
we have no proof that the non-medullated fibers do not conduct
equally as well. The view has some probability to it, however,
for we must remember that the non-medullated fibers do not run
in large nerve trunks that supply a number of different organs,
and therefore in them a provision for isolated conduction is not so
necessary. Moreover, in the medullated fibers the myelin sheath

74 THE PHYSIOLOGY OF MUSCLE AND NERVE.

is lost toward its peripheral end after the nerve has entered the
tissue to which it is to be distributed, indicating that its function
is then no longer necessary. According to the older conceptions
of the process of conduction in nerve fibers, not only anatomical
but also physiological continuity is necessary. Mere contact of
living axis cylinders would not enable the nerve impulse to pass
from one to the other. The newer views, included in the so-called
neuron theory, assume that mere contact of living, entirely normal
nerve substance does permit an excitatory change to pass from one
to the other. So that it is not impossible that the myelin sheath may
serve to prevent one axis cylinder from influencing the neighboring
axis cylinders in a nerve trunk. Others have supposed that the
myelin sheath serves as a source of nutrition to the inclosed axis
cylinder, or as a regulator in some way of its metabolism. No fact
is reported that would make this suggestion seem probable. In
general, it is found that the myelin sheath is larger in those fibers
that have the longest course; the size of the sheath, in fact, in-
creases with that of the axis cylinder. It is known also that the
medullated fibers in general are more irritable to artificial stimuli
than the non-medullated ones, and that when induction shocks
are employed the non-medullated fibers lose their irritability more
rapidly at the point stimulated. None of these facts are sufficient,
however, to indicate the probable function of the myelin. The
embryological development of the sheath also fails to throw light on
its physiological significance. For, while it is usually supposed that
the axis cylinder itself is simply an outgrowth from the nerve cell,
and the myelin sheath arises from separate mesoblastic cells which
surround the axis cylinder, this view, so far as the myelin is con-
cerned, is not beyond question, and the study of the process of
regeneration of nerve fibers indicates that the actual production
of myelin is controlled in some way by the functional axis cylinder.
The axis cylinder outgrowths from the sympathetic nerve cells
found in the ganglia of the sympathetic chain and in the peripheral
ganglia generally of the body are usually non-medullated, although
apparently this is not an invariable rule. In the birds all such
fibers, on the contrary, are medullated. (Langley.*) Nothing is
known as to the conditions that determine whether a nerve fiber
process shall or shall not be surrounded by a myelin sheath.

Union of Nerve Fibers into Nerves or Nerve Trunks. — The
assembling of nerve fibers into larger or smaller nerve trunks resem-
bles histoiogically the combination of muscle fibers to form a muscle.
Physiologically, however, there is no similarity. The various
fibers in a muscle act together in a co-ordinated way as a physio-
logical unit. On the other hand, the hundreds or thousands of
* Langley, "Journal of Physiology," 30, 221, 1903; 20, 55, 1890.

THE PHENOMENON OF CONDUCTION. 75

nerve fibers found in a nerve may form groups which are entirely
independent in their physiological activity. In the vagus nerve,
for instance, we have nerve fibers running side by side, some of
which supply the heart, some the muscles of the larynx, some the
muscles of the stomach or intestines, some the glands of the stom-
ach or pancreas, and so on. Nerves are, therefore, anatomical
units simply, containing groups of fibers which have very different
activities and which may function entirely independently of one
another. 9

Afferent and Efferent Nerve Fibers. — The older physiologists
believed that one and the same nerve or nerve fiber might conduct
sensory impulses toward the central nervous system or motor im-
pulses from the central nervous system to the periphery. Bell and
Magendie succeeded in establishing the great truth that a nerve
fiber cannot be both motor and sensory. Since their time it has
been recognized that we must divide the nerve fibers connected
with the central nervous system into two great groups : the efferent
fibers, which carry impulses outwardly from the nervous system
to the peripheral tissues, and the afferent fibers, which carry their
impulses inwardly, — that is, from the peripheral tissues to the
nerve centers. Under normal conditions the afferent fibers are
stimulated only at their endings in the peripheral tissues, in the
skin, the mucous membranes, the sense organs, etc., while the
efferent fibers are stimulated only at their central origin, — that
is, through the nerve cells from which they spring. The difference
in the direction of conduction depends, therefore, on the anatomical
fact that the efferent fibers have a stimulating mechanism at their
central ends only, while the afferent fibers are adapted only for
stimulation at their peripheral ends.

Classification of Nerve Fibers. — In addition to this funda-
mental separation we may subdivide peripheral nerve fibers into
smaller groups, making use of either anatomical or physiological
differences upon which to base a classification. For the purpose
here in view a classification that is physiological as far as possible
seems preferable. In the first place, experimental physiology has
shown that the effect of the impulse conveyed by nerve fibers may
be either exciting or inhibiting. That is, the tissue or the cell
to which the impulse is carried may be thereby stimulated to ac-
tivity, in which case the effect is excitatory, or, on the contrary,
it may, if already in activity, be reduced to a condition of rest or
lessened activity; the effect in this case is inhibitory. Many
physiologists believe that one and the same nerve fiber may carry
excitatory or inhibitory impulses, but in some cases at least we
have positive proof that these functions are discharged by separate
fibers. We may subdivide both the afferent and the efferent sys-
tems into excitatory and inhibitory fibers. Each of these sub-

76

THE PHYSIOLOGY OF MUSCLE AND NERVE.

groups again falls into smaller divisions according to the kind of
activity it excites or inhibits. In the efferent system, for instance,
the excitatory fibers may cause contraction or motion if they ter-
minate in muscular tissue, or secretion if they terminate in glandu-
lar tissue. For convenience of description each of the groups in
turn may be further classified according to the kind of muscle in
which it ends or the kind of glandular tissue. In the motor group
we speak of vasomotor fibers in reference to those that end in the
plain muscle of the walls of the blood-vessels; visceromotor fibers,
those ending in the muscular tissue of the abdominal and thoracic
viscera; pilomotor fibers, those ending in the muscles attached to
the hair follicles. The classification that is suggested in tabular
form below depends, therefore, on three principles: first, the direc-
tion in which the impulse travels normally; second, whether this
impulse excites or inhibits; third, the kind of action excited or
inhibited, which in turn depends upon the kind of tissue in which
the fibers end.

Efferent

Afferent

Excitatory

Inhibitory

Excitatory

Inhibitory j

Motor

Secretory

Inhibito-mo-
tor

In hibi to-se-
cretory

Sensory

Reflex

Inhibito-re-
flex

(Motor.
Vasomotor.
Cardioinotor.
Visceromotor.
Pilomotor.
( Salivary.
J Gastric.
) Pancreatic.
<• Sweat.

f Subdivisions corresponding to the varieties of mo-
( tor fibers above.

\ Subdivisions corresponding to the varieties of se-
1 cretory fibers above.
V Visual.
Auditory.
Olfactory.
Gustatory.
Pressu re.
Temperature.
Pain.
Hunger.
Thirst, etc.

According to the efferent fibers affected.
Inhibitory effects upon the conscious sensations are

not demonstrated.

The reflex fibers that cause unconscious reflexes
are known to be inhibited in some cases at least.

That the final action of a peripheral nerve fiber is determined
by the tissue in which it ends rather than by the nature of the
nerve fiber itself or the nature of the impulse that it carries is indi-
cated strongly by the regeneration experiments made by Langley.*
For instance, the chorda tympani nerve contains fibers which cause
a dilatation in the blood-vessels of the submaxillary gland, while
the cervical sympathetic contains fibers which cause a constriction
of the vessels in the same gland. If the lingual nerve (containing
the chorda tympani fibers) is divided and the central end sutured

* Langley, "Journal of Physiology," 23, 240, 1898; ibid., 30, 439, 1904;
"Proceedings Royal Society," 73, 1904.

THE PHENOMENON OF CONDUCTION. 77

to the peripheral end of the severed cervical sympathetic, the
chorda fibers will grow along the paths of the old constrictor fibers
of the sympathetic. If time is given for regeneration to take place,
stimulation of the chorda now causes a constriction in the vessels.
The experiment can also be reversed. That is, by suturing
the central end of the cervical sympathetic to the peripheral end
of the divided lingual the fibers of the former grow along the paths
of the old dilator fibers, and after regeneration has taken place
stimulation of the sympathetic causes dilatation of the blood-
vessels in the gland. These results are particularly instructive, as
vasoconstriction is an example of the excitatory effect of the nerve
impulse, being the result of a contraction of the circular muscles
in the vessels, while vasodilatation is an example of inhibitory
action, being due to an inhibition of the contraction of the same
muscles. Yet obviously these two opposite effects are determined
not by the nature of the nerve fibers, but by their place or mode
of ending in the gland.

Separation of the Afferent and Efferent Fibers in the Roots
of the Spinal Nerves. — According to the Bell-Magendie discovery,
the motor fibers to the voluntary muscles emerge from the spinal
cord in the anterior roots, while the fibers that give rise to sensa-
tions enter the cord through the posterior roots. These facts have
been demonstrated beyond all doubt. Magendie discovered an
apparent exception in the phenomenon of recurrent sensibility.
When the anterior root is severed and its peripheral end is stimu-
lated only motor effects should be obtained. Magendie observed,
however, upon dogs that in certain cases the animals showed signs
of pain. This apparent exception to the general rule was after-
ward explained satisfactorily. It was shown that the fibers in
question do not really belong to the anterior root, — that is, they do
not emerge from the cord with the root fibers; they are, in fact,
sensory fibers for the meningeal membranes of the cord which
are on their way to the posterior roots and which enter the cord
with the fibers of the latter. Since the work of Bell and Magendie
it has been a question whether their law applies to all afferent and
efferent fibers and not simply to the motor and sensory fibers proper.
The experimental evidence upon this point, as far as the mammals
are concerned, has accumulated slowly. Various authors have shown
that stimulation of the anterior roots of certain spinal nerves may
cause a constriction of the blood-vessels, an erection of the hairs
(stimulation of the pilomotor fibers), a secretion of sweat, and so
on, while stimulation of the posterior roots in the same regions is
without effect upon these peripheral tissues. One apparent excep-
tion, however, has been noted. A number of observers have found
that stimulation of the peripheral end of the divided posterior

78 THE PHYSIOLOGY OF MUSCLE AND NERVE.

roots (fifth lumbar to first sacral) causes a vascular dilatation in
the hind limb. The matter has been particularly investigated by
Bayliss,* who gives undoubted proof of the general fact. At the
same time he shows that the fibers in question are not efferent
fibers from the cord passing out by the posterior instead of the an-
terior roots. This is shown by the fact that they do not degenerate
when the root is cut between the ganglion and the cord, as they
should do if they originated from cells in the cord. Bayliss's own
explanation of this curious fact is that the fibers in question are
ordinary afferent fibers, but that they are capable of a double ac-
tion: they can convey sensory impulses from the blood-vessels to
the cord according to the usual type of sensory fibers, but they
can also convey efferent impulses, antidromic impulses as he desig-
nates them, to the muscles of the blood-vessels. In other words,
for this special set of fibers he attempts to re-establish the view
held by physiologists before the time of Bell, — namely, that one
and the same fiber transmits normally both afferent and efferent
impulses. An exception so peculiar as this to an otherwise general
rule cannot be accepted without hesitation. It is possible that
future work may give an explanation less opposed to current views
than that offered by Bayliss.

Cells of Origin of the Anterior and Posterior Root Fibers.—
The efferent fibers of the anterior root arise as axons or axis cylinder
processes from nerve cells in the gray matter of the cord at or near
the exit of the root. The motor fibers to the voluntary muscles
arise from the large cells of the anterior horn of gray matter; the
fibers to the plain muscle and glands, autonomic fibers according
to Langley's nomenclature, take their origin from spindle-shaped
nerve cells lying in the so-called lateral horn of the gray matter.f
According to the accepted belief regarding the nutrition of nerve
fibers, any section or lesion involving these portions of the gray mat-
ter or the anterior root will be followed by a complete degeneration
of the efferent fibers. In the case of the fibers to the voluntary
muscles this degeneration will extend to the muscles and include
the end-plates. In the case of the autonomic fibers the degenera-
tion will extend to the peripheral ganglia in which they terminate,
involving, therefore, the whole extent of what is called the pre-
ganglionic fiber (see the chapter on the autonomic nerves and the
sympathetic system). The posterior root fibers have their origin
in the nerve cells contained in the posterior root ganglia. These
cells are unipolar, the single process given off being an axis cylinder
process or axon. It divides into two branches, one passing into
the cord by way of the posterior root, the other toward the periph-

* Bayliss, "Journal of Physiology," 26, 173, 1901, and 28, 276, 1902.
t Herring, "Journal of Physiology," 29, 282, 1903.

THE PHENOMENON OF CONDUCTION. 791

eral tissues in the corresponding spinal nerve in which they form the
peripheral sensory nerve fibers. It follows that a section or lesion
of the posterior root will result in a degeneration of the branch
entering the cord, this branch having been cut off from its nutri-
tive relationship with its cells of origin. The degeneration will in-
volve the entire length of the branch and its collaterals to their
terminations among the dendrites of other spinal or bulbar- neurons
(see the chapter on the spinal cord). After a lesion of this sort
the stump of the posterior root that remains in connection with
the posterior root ganglion mairftains its normal structure. On the
other hand, a section or lesion involving the spinal nerve will be
followed by a degeneration of all the" fibers, efferent and afferent,
lying to the peripheral side of the lesion, since these fibers are cut
off from connection with their cells of origin, while the fibers in the
central stump of the divided nerve will retain their normal structure.
Afferent and Efferent Fibers in the Cranial Nerves.- — The
first and second cranial nerves, the olfactory and the optic, contain
only afferent fibers, which arise in the former nerve from the olfac-
tory epithelium in the nasal cavity, in the latter from the nerve
cells in the retina. The third, fourth, and sixth nerves contain
only efferent fibers which arise from the nerve cells constituting
their nuclei of origin in the midbrain and pons. The fifth nerve
resembles the spinal nerves in that it has two roots, one containing
afferent and the other efferent fibers. The efferent fibers, consti-
tuting the small root, arise from nerve cells in the pons and mid-
brain, the afferent fibers arise from the nerve cells in the Gasserian
ganglion. This ganglion, being a sensory ganglion, is constituted
like the posterior root ganglia. Its nerve cells give off a single
process which divides in T, one branch passing into the brain by way
of the large root, while the other passes to the peripheral tissues as a
sensory fiber of the fifth nerve. The seventh nerve may also be
homologized with a spinal nerve. The facial nerve proper consists
of only efferent fibers, which arise from nerve cells constituting
its nucleus of origin in the pons. £The geniculate ganglion, attached
to this nerve shortly after its emergence, is similar in structure to
the Gasserian or a posterior root ganglion. Its nerve cells send off
processes which divide in T and constitute afferent fibers in the
so-called nervus intermedius or nerve of Wrisberg. The eighth
nerve consists only of afferent fibers which arise from the nerve
cells in the spinal ganglion of the cochlea, cochlear branch, and from
there constituting the vestibular or Scarpa's ganglion, the vestibu-
lar branch. Both of these ganglia are sensory, resembling the
posterior root ganglia in structure. The ninth nerve is also mixed,
the efferent fibers arising from the motor nucleus in the medulla,
while the sensory fibers arise in the superior and petrosal ganglia

80 THE PHYSIOLOGY OF MUSCLE AND NERVE.

found on the nerve at its emergence from the skull. The tenth is a
mixed nerve, its efferent fibers arising in motor nuclei in the me-
dulla, the afferent fibers in the nerve cells of the ganglia lying upon
the trunk of the nerve at its exit from the skull (ganglion jugulare
and nodosum). The eleventh and twelfth cranial nerves contain
only efferent fibers that arise from motor nuclei in the medulla.

It will be seen from these brief statements that in all the nerve
trunks of the central nervous system — that is, the spinal and the
cranial nerves — the cells of origin of the efferent fibers lie within
the gray matter of the brain or cord, while the cells of origin of the
afferent fibers lie in sensory ganglia outside the central nervous
system, — namely, in the posterior root ganglia for the spinai
nerves, in the ganglion semilunare (Gasseri), the g. geniculi, the
g. spirale, the g. vestibulare, the g. superius, and g. petrosum of the
glossopharyngeal, and the g. jugulare and g. nodosum of the vagus.
These various sensory ganglia attached to the cranial nerves corre-
spond essentially in their structure and physiology with the posterior
root ganglia of the spinal nerves.

Independent Irritability of Nerve Fibers. — Although the
nerve fibers under normal conditions are stimulated only at their
ends, the efferent fibers at the central end, the afferent at the
peripheral end, yet any nerve fiber may be stimulated by artificial
means at any point in its course. Artificial stimuli capable of
affecting the nerve fiber — that is, capable of generating in it a nerve
impulse which then propagates itself along the fiber — may be divided
into the following groups :

1. Chemical stimuli. Various chemical reagents, when applied
directly to a nerve trunk, excite the nerve fibers. Such reagents
are concentrated solutions of the neutral salts of the alkalies, acids,
alkalies, glycerin, etc. This method of stimulation is not, however,
of much practical value in experimental work, since it is difficult or
impossible to control the reaction.

2. Mechanical stimuli. A blow or pressure or a mechanical in-
jury of any kind applied to a nerve trunk also excites the fibers.
This method of stimulating the fibers is also difficult to control
and has had, therefore, a limited application in experimental work.
The mechanical stimulus is essentially a pressure stimulus, and the
difficulty lies in controlling this pressure so that it shall not actually
destroy the nerve fiber by rupturing the delicate axis cylinder.
Various instruments have been devised by means of which light
blows may be given to the nerve, sufficient to arouse an impulse,
but insufficient to permanently injure the fibers. The results ob-
tained by this method have been very valuable in physiology as con-
trols for the experiments made by the usual method of electrical
stimulation. It may be mentioned also that under certain condi-

THE PHENOMENON OF CONDUCTION. 81

tions — for instance, at one stage in the regeneration of nerve fibers
mechanical stimuli may be more effective than electrical, that is,
may stimulate the nerve fiber when electrical stimuli totally fail
to do so.

3. Thermal stimuli. A sudden change in temperature may
stimulate the nerve fibers. This method of stimulation is very
ineffective for motor fibers, only very extreme and sudden changes,
such as may be obtained by applying a heated wire directly to
the nerve trunk, are capable of so stimulating them as to produce
a muscular contraction. On the other hand, the sensory nerve
fibers are quite sensitive to changes of temperature. If a nerve
trunk in a man or animal is suddenly cooled, or especially if it is
suddenly heated to 60° to 70° C., violent pain results from the
stimulation of the sensory fibers in the trunk, while the motor
fibers are apparently not acted upon. We have in this fact one
of several differences in reaction between motor and sensory fibers
which have been noted from time to time, and which seem to

Fig. 29. — Stimulating (catheter) electrodes for nerves: 6, Binding posts for attachment
of wires from the secondary coil; 8, insulating sheath of hard rubber; p, platinum points
laid upon the nerve.

indicate that there is some important difference in structure or
composition between them.

4. Electrical stimuli. Some form of the electrical current is be-
yond question the most effective and convenient means of stimulat-
ing nerve fibers. We may employ either the galvanic current — that
is, the current taken directly from a battery — or the induced current
from the secondary coil of an induction apparatus or the so-called
static electricity from a Ley den jar or other source. In most experi-
mental work the induced current is used. The terminal wires from
the secondary coil are connected usually with platinum wires im-
bedded in hard rubber, forming what is known as a stimulating elec-
trode. (See Fig. 29). By this means the platinum ends which now
form the electrodes, anode and cathode, can be placed close together
upon the nerve trunk, and the induced current passing from one to
the other through a short stretch of the nerve sets up at that point
nerve impulses which then propagate themselves along the nerve
fibers. The induction current is convenient because of its intensity,
which overcomes the great resistance offered by the moist tissue ; be-
cause of its very brief duration, in consequence of which it acts as a
sharp, quick, single stimulus or shock, and because of the great ease
6

82

THE PHYSIOLOGY OF MUSCLE AND NERVE.

with which it may be varied as to rate and as to intensity. Each
time that the battery current in the primary coil is made or broken
there is an induction current established in the secondary coil,
and if the nerve is on the electrode the current passes through it
and stimulates it. This induced current is, however, extremely
short, and alternates in direction, passing in one direction when the
primary current is made and in the opposite direction when it is
broken. The induced current set up by the making of the battery
current in the primary coil we designate as the making shock, that
set up by the breaking of the current in the primary as the breaking
shock. On account of the very brief duration of the induced cur-
rent it is difficult to distinguish between the effects of its opening
and closing.

The Stimulation of the Nerve by the Galvanic Current. — When

however, we employ the galvanic
current, taken directly from a bat-
tery, as a stimulus, we can, of
course, allow the current to pass
through the nerve as long as we
please and can thus study the effect
of the closing of the current as
distinguished from that of the open-
ing, or the effect of duration or
direction of the current, etc.

Du Bois-Reymond's Law of Stim-
ulation.— When a galvanic current
is led into a motor nerve it is
found, as a rule, that with all
moderate strengths of currents there
is a stimulus to the nerve at the
moment it is closed, the making or
closing stimulus, and another when
the current is broken, the breaking
or opening stimulus, while during
the passage of the current through the nerve no stimulation takes,
place: the muscle remains relaxed. We may express this fact
by saying that the motor nerve fibers are stimulated by the mak-
ing and the breaking of the current or by any sudden change
in its intensity, but remain unstimulated during the passage of cur-
rents whose intensity does not vary.

The Anodal and Cathodal Stimuli. — It has been shown quite con-
clusively that the nerve impulse started by the making of the current
arises at the cathode, while that at the breaking of the current
begins at the anode, or, in other words, the making shock or
stimulus is cathodal, while the breaking stimulus is anodal. This

Fig. 30. — Schema of the arrange-
ment of apparatus for stimulating the
nerve by a galvanic current: b, The
battery; k, the key for opening and
closing the circuit ; c, the commutator
for reversing the direction of the cur-
rent; + the anode or positive pole;
— the cathode or negative pole.

THE PHENOMENON OF CONDUCTION. 83

fact is true for muscle as well as nerve, and possibly for all irritable
tissues capable of stimulation by the galvanic current. This
important generalization may be demonstrated for motor nerves
by separating the anode and cathode as far as possible and re-
cording the latent period for the contractions caused respect-
ively by the making and the breaking of the current in the nerve.
If the cathode is nearer to the muscle the latent period of the mak-
ing contraction of the muscle will be shorter than that of the break- .
ing contraction by a time equal to that necessary for a nerve impulse
to travel the distance between anode and cathode. If the position
of the electrodes is reversed the latent period of the making con-
traction will be correspondingly longer than that of the breaking
contraction. It is very evident from these facts that when a
current is passed into a nerve or muscle the changes at the two
poles are different, as shown by the differences in reactions and
properties of the nerve at these points. Bethe has shown that a
difference may be demonstrated even by histological means. After
the passage of a current through a nerve for some time the axis
cylinders stain more deeply than normal at the cathode with
certain dyes (toluidin blue), while at the anode they stain less
deeply.

Electrotonus. — The altered physiological condition of the nerve
at the poles during the passage of the galvanic current is designated
as electrotonus, the condition round the anode being known as
anelectrotonus, that round the cathode as catelectrotonus. Elec-
trotonus expresses itself as a change in the electrical condition of
the nerve which gives rise to currents known as the electrotonic
currents, — a brief description of these currents will be given in
the next chapter, — and also by a change in irritability and con-
ductivity. The latter changes were first carefully investigated
by Pfliiger, who showed that when the galvanic current, or, as it is
usually called in this connection, the polarizing current, is not too
strong there is an increase in irritability and conductivity in the
neighborhood of the cathode, the so-called catelectrotonic increase
of irritability, while in the region of the anode there is an anelec-
trotonic decrease in irritability and conductivity. These opposite
variations in the state of the nerve are represented in the accom-
panying diagram. Between the two poles — that is. in the intrapolar
region — there is, of course, an indifferent point, on one side of which
the irritability of the nerve is above normal and on the other side
below normal. The position of this indifferent point shifts toward
the cathode as the strength of the polarizing current is increased.
In other words, as the current increases the anelectrotonus spreads
more rapidly and becomes more intense, and the conductivity in
this region soon becomes so depressed as to block entirely the

84 THE PHYSIOLOGY OF MUSCLE AND NERVE.

passage of a nerve impulse through it. The changes on the cathodal
side are not so constant nor so distinct. Later observers * have
shown, in fact, that if the polarizing current is continued for some
time the heightened irritability at the cathode soon diminishes
and sinks below normal, so that in fact at the cathode as well as
at the anode the irritability may be lost entirely. If the polarizing
current is very strong this depressed irritability at the cathode
comes on practically at once. Moreover, when a strong current
that has been passing through a nerve is broken the condition of
depressed irritability at the cathode persists for some time after
the opening of the current.

Pfliiger's Law of Stimulation. — It was said above that when
a galvanic current is passed into a nerve there is a stimulus (catho-
dal) at the making of the current and another stimulus (anodal)

Fig. 31. — Electrotonic alterations of irritability caused by weak, medium, and strong
battery currents: A and B indicate the points of application of the electrodes to the nerve, A
being the anode, B the cathode. The horizontal line represents the nerve at normal irri-
tability; the curved lines illustrate how the irritability is altered at different parts of the
nerve with currents of different strengths. Curve yl shows the effect of a weak current, the
part below the line indicating decreased, and that above the line increased irritability; at xl
the curve crosses the line, this being the indifferent point at which the catelectrotonic effects
are compensated for by anelectrotonic effects; y- gives the effect of a stronger current, and
y3, of a still stronger current. As the strength of the current is increased the effect becomes
greater and extends farther into the extrapolar regions. In the intrapolar region the in-
different point is seen to advance, with increasing strengths of current, from the anode
toward the cathode. — (Lombard.)

at the breaking of the current. This statement is true, however,
only for a certain range of currents. Of the two stimuli, the making
or cathodal stimulus is the stronger, and it follows, therefore,
that when the strength of the current is diminished there will come
a certain point at which the anodal stimulus will drop out. With
weak currents there is then a stimulus only at the make. On the
other hand, when very strong currents are used the stimuli that act
at the two poles set up nerve impulses whose passage to the muscle
may be blocked by the depressed conductivity caused by the electro-
tonic changes. Whether or not the stimulus will be effective in

*Werigo, "Pfliiger's Archiv," 84, 547, 1901. See Biedermann, " Elec-
trophysiology," translated by Welby, vol. ii, p. 140.

THE PHENOMENON OF CONDUCTION. 85

causing a contraction in the attached muscle will depend naturally
on the relative positions of the electrodes, — that is, on the direction
of the current in the nerve. In describing the effect of these strong
currents we must distinguish between what are called ascending
and descending currents. Ascending currents are those in which
the direction of the current in the nerve is away from the muscle,
a position of the poles, therefore, in which the anode is closer to
the muscle. In descending currents the positions are reversed.
Pfluger's law of contraction or of stimulation takes account of
the effect of extreme variations in the -strength of the current
and is usually expressed in tabular form as follows : The letter C
indicates that the nerve is stimulated and causes a contraction in
the attached muscle, and O indicates a failure in the stimulation
(weak currents) or a failure in the nerve impulse to reach the muscle
owing to blocking (strong currents) .

Fig. 32. — Schema to show the arrangement of apparatus for an ascending and a descending
current: A, ascending; £>, descending.

ASCENDING CURRENT. DESCENDING CURRENT.
Making. Breaking. Making. Breaking.

Very weak currents . . C O C O

Moderate " C C C C

Very strong " O C C O

The effects obtained with the strong currents are readily under-
stood if we bear in mind the facts stated above regarding electro-
tonus. When the current is ascending the stimulus on making
starts from the cathode, but cannot reach the muscle because it
is blocked by a region of anelectrotonus in which the conduc-
tivity is depressed. The stimulus on breaking takes place at
the anode and the impulse encounters no resistance in its passage
to the muscle. With the descending current the cathode lies next
to the muscle and the making or cathodal stimulus of course causes
a contraction. On breaking, however, the impulse that is started
from the anode is blocked by the depressed irritability in the

86 THE PHYSIOLOGY OF MUSCLE AND NERVE.

cathodal region, which, as has been said, comes on promptly with
strong currents and persists for a time after the current is broken.

The Opening and the Closing Tetanus. — While the du Bois-Reymond
law stated above expresses the facts as usually observed upon a nerve-muscle
preparation, there are a number of observations which indicate that the
excitation at the anode and the cathode during the passage of a current
may give rise to a series of stimuli instead of a single stimulus. Thus with
sensory nerves it is well known that the stimulation, as judged by the
sensations aroused, continues while the current is passing instead of being
limited to the moment of making or of breaking of the current. In this
respect, as in stimulation by high temperatures, the sensory fibers differ
apparently from the motor. . When a galvanic current is passed through the
ulnar nerve at the elbow sensations are felt during the entire time of passage
of the current.' But in an ordinary nerve-muscle preparation it is also fre-
quently observed that at the moment of opening the current a tetanic con-
traction, persisting for some time, is obtained instead of a single twitch. This
phenomenon is known as the opening tetanus or Hitter's tetanus, and Pfliiger
has shown that the continuous excitation proceeds from the anode, since
in the case of a descending current division of the nerve in the intrapolar
region brings the muscle to rest. In the same way it frequently happens
that upon closing the current through a nerve the muscle, instead of giving a
twitch, goes into a persistent tetanic contraction. The tetanus in this case
is designated as the closing or Pfliiger's tetanus. Both of these phenomena
are observed, especially when the irritability of the nerve is for any reason
greater than normal. It seems probable, therefore, to many observers that
the excitation at the cathode persists in reality during the passage of the
current even in motor fibers, although ordinarily the excitation makes itself
felt upon the muscles only at the moment of closure ; the excitations during
the passage of the current being either too weak to affect the muscle or the
condition of the nerve being such as to prevent their conduction to the muscle.
It should be added that the opening and the closing tetanus may be observed
also in a muscle when the galvanic current is passed through it.

Stimulation of the Nerves in Man. — For therapeutic as well
as diagnostic and experimental purposes it often becomes desirable
to stimulate the nerves, particularly the motor nerves, in man.
We may use for this purpose either the induced (faradic, alternat-
ing) current or the direct battery current (galvanic or continuous
current) . In such cases the electrodes cannot be applied, of course,
directly to the nerve; it becomes necessary to stimulate through
the skin, and the so-called unipolar method is employed. The
unipolar method consists in placing one electrode, the active or
stimulating electrode, over the nerve at the point which it is desired
to stimulate, while the other electrode, the inactive or indifferent
electrode, is applied to the skin at some more or less remote part,
usually at the back of the neck. The indifferent electrode is made
large enough to cover several square centimeters of the skin, and one
may conceive the threads of current passing from it into the moist
tissues of the body and thence to the active electrode. As the
threads of current condense to this latter electrode they pass through
the motor nerve which lies under it, and if sufficiently intense will
stimulate the nerve. The arrangement is represented in the accom-
panying schema (Fig. 33), showing the disposition of the electrodes

THE PHENOMENON OF CONDUCTION.

87

for stimulating the median nerve. At the indifferent electrode the
sensory nerves of the skin are of course stimulated, but no motor
response is obtained, as no motor nerve lies immediately under the
skin. Moreover the large size of this electrode tends to diffuse the
current and thus reduce its effectiveness in stimulating. The active
or stimulating electrode is small in size, particularly when induction
currents are employed, so that the current may be condensed and
thus gain in effectiveness. The dry surface of the skin is a poor
conductor of the electrical current, and to reduce the resistance at the
points at which the electrodes come in contact with the skin each is

t Fig. 33. — Schema to show the unipolar method of stimulation in man. The anode,
+, is represented as the stimulating pole, applied over the median nerve. The cathode,
— , is the indifferent pole.

covered with cotton or chamois skin kept moistened with a dilute
saline solution.

Motor Points. — By means of the unipolar method nearly every
voluntary muscle of the body may be stimulated separately. All
that is necessary, when the induced current is used, is to bring the
active electrode as nearly as possible over the spot where the
muscle receives its motor branch. A diagram showing these motor
points for the arm is given in Fig. 34. In the same way the nerves
of the brachial plexus and other nerve trunks may be stimulated very
readily through the skin. When the induction current is used no

88

THE PHYSIOLOGY OF MUSCLE AND NERVE.

distinction is made between the cathodic and anodic effects. When,
however, the battery current is employed one may make the
stimulating electrode either anode or cathode, and under these
circumstances a marked difference is observed in the strength of
the current that it is necessary to use to get a response. With the
battery or galvanic current, in fact, one may distinguish four
stimuli, the closing and the opening shock when the stimulating
electrode is cathode and the closing and the opening shock when

M. flexor carpi ulnaris

M. flex, digit, siibl
(digit, indicis el
minimi)

M. flexor digit, min.
M-Opponens digit.

M. abductor pollic. brer.
M. opponens pollicis

M. flex. poll. brcv.

M. adductor pollic. brflT-

Fig. 34. — Motor points in upper extremity.

it is anode. The contractions resulting from these four stimuli are
designated usually as follows : The cathodol closing contraction,
CCC; the cathodal opening contraction, C O C; the anodal clos-
ing contraction, A C C; and the anodal opening contraction,
A O C. Their relative efficiency as stimuli is given by the sequence
CCC > ACC > AOC> COC, although this sequence is subject
to some individual variation. Certain pathological or traumatic
lesions that cause the degeneration of the nerves may be revealed

THE PHENOMENON OF CONDUCTION. 89

by the use of these methods of stimulation. The nerve trunk
under such circumstances fails to respond to either form of stimulus,
induced or galvanic. The muscle, on the other hand, while it
fails to respond to induction shocks, is stimulated by the galvanic
current and, indeed, may show an increased irritability toward this
form of stimulus. Certain qualitative changes in the reaction of the
muscle to the galvanic current may also be noticed, for instance,
the A C C is sometimes obtained with less current than the C C 0,
and the contraction is more sluggish in character. This qualitative
and quantitative change in reaction to the galvanic current, and
the loss of irritability to the induced current, constitute what is
known as the reaction of degeneration.

n

Fig. 35. — Two schemata to show the relation between the physical and the physio-
logical electrodes or poles. Each schema represents the forearm with the median nerve,
M. In / the stimulating electrode is the cathode ; the threads of current which have started
from the anode (the indifferent electrode) placed elsewhere, converge to this pole. Where
these threads enter the nerve we have a series of physiological anodes, a; where they leave,
a series of physiological cathodes, c. In // the stimulating electrode is the anode. The
threads of current leave this pole to traverse the body toward the indifferent electrode
(cathode). Where they enter and leave the nerve we have, as in the first case, physio-
logical anodes and cathodes, now, however, on the opposite sides of the nerve.

Distinction between Physical and Physiological Poles. — The

facts stated above seem to show, at first sight, that by the
unipolar method we may obtain both an opening and a closing
shock at either the cathode or anode, — a result which is in
apparent contradiction to the general law that the making or
closing stimulus occurs only at the cathode and the breaking
or opening stimulus only at the anode. This apparent contra-
diction is readily explained when we remember that in the
unipolar method the active electrode rests upon the skin over the
nerve, and that the threads of current radiating from this point
enter the nerve at one point and leave it at another. Evidently,
therefore, so far as the nerve is concerned, there will be an anode
where the current is considered as entering the nerve and a cathode
where it leaves it, so that under the active electrode, whether this

90 THE PHYSIOLOGY OF MUSCLE AND NERVE.

is physically an anode or cathode, there will be, as regards the
nerve, a series of what may be called physiological cathodes and
anodes. The closing shock arises at these cathodes, the opening
shock at the anodes. The position of the series of anodes and
cathodes will vary according as the active electrode is an anode
or cathode, as is indicated in the accompanying diagram (Fig. 35).

CHAPTER IV.

THE ELECTRICAL PHENOMENA SHOWN BY NERVE
AND JVLUSCLE.

The Demarcation Current. — Our definite knowledge of the
-electrical properties of living tissue began with the celebrated in-
vestigations of du Bois-Reymond* (1843). When a muscle or
nerve is removed from the body, and, in the case of the muscle,
when one tendinous end is cut off, it is found that the cut end has
an electrical potential differing from that of the uninjured longi-
tudinal surface of the preparation. Following the usual nomen-
clature, the cut end is electronegative as regards the longitudinal
surface. If, therefore, the longitudinal surface is connected by
a conductor with the cut surface a current will flow from the former
to the latter, as is indicated in the accompanying diagram.

Fig. 36. — Schema showing the course of the demarcation current in an excised nerve,
when a point on the longitudinal and one on the cut surface are united by a conductor.

While the direction of the current through the conductor con-
necting the two points is from the longitudinal to the cut surface
the current may be considered as being completed in the opposite
-direction within the substance of the muscle or nerve, as shown
in the diagram. We may, in fact, consider an excised nerve or
muscle as a battery, the cut end representing the zinc plate and
the longitudinal surface the copper plate. Within the battery
the direction of the current is from zinc to copper, from cut end
to longitudinal surface; outside the battery the direction is from
-copper to zinc, from longitudinal to cut surface. If two wires
are connected with the muscle or nerve the end of the one attached
to the longitudinal surface will represent the positive pole or anode,
the end of the one attached to the cut end will represent the cathode

* "Untersuchungen iiber thierische Elektricitat," du Bois-Reymond,
1848-1860.

91

92

THE PHYSIOLOGY OF MUSCLE AND NERVE.

or negative pole. On joining the ends of the wires a current will
pass from positive to negative pole.

A current of this character from an excised nerve or muscle
is, of course, small in amount and to detect it one must make
use of a delicate electrometer of some sort (see below). Du Bois-
Reymond considered that the difference in electrical potential
which gives rise to this current exists normally in the muscle,
although masked by an opposite condition in the tendinous ends,
and he therefore spoke of the currents as the natural muscle or
natural nerve currents. It has since been shown by Hermann

that this view is incorrect; that the
perfectly normal uninjured muscle or
nerve has the same electrical potential
throughout and will therefore give no-
current when any two points are con-
nected by a conductor. Moreover, the
completely dead muscle or nerve shows-
no current. The difference in poten-
tial that is found in the excised
nerve or muscle is due, according to
Hermann, to the fact that at the cut
end the nerve or muscle is injured. The
chemical changes that take place as a
result of the injury make the tissue
electronegative as regards the un-

Fig. 37. — Schema showing ° . , ,

the principle of construction of changed living substance elsewhere.

For this reason Hermann described
the current as a demarcation current;
others have called it the current 'of
injury.

The nature of the changes at the injured end are not known. It is inter-
esting to note that Bernstein * has shown that the electromotive force of the
muscle current increases with the temperature, a fact which leads him to
conclude that the difference in potential between the longitudinal and cut
surface of the muscle depends upon a difference in concentration of the
electrolytes. The muscle, in fact, acts after the manner of a "concentration
cell." Such a difference in concentration may pre-exist in the normal mus-
cle, or, according to the view adopted above, is developed as the result of
injuring one end of the muscle. It may be supposed that the injury causes
changes which result in the formation of new organic or inorganic electro-
lytes and thus increases the concentration at that point.

Means of Demonstrating the Muscle Current. — The demarcation
current and other electrical conditions to be described require especial ap-
paratus for their study. To detect the existence of a current physiologists
use either a high-resistance galvanometer or a capillary electrometer. f The
galvanometers employed are usually of two types, the Kelvin reflecting
galvanometer or the d'Arsonval form. The principle of the galvanometer
lies in the fact that a magnetic needle is deflected when an electrical current

*"Pfluger's Archiv," 1902, xcii., 521.

the
ing off i
magnet.

ELECTRICAL PHENOMENA.

93

passes through a wire in its vicinity. If a magnetic needle is swung by a
delicate thread so as to move easily it will come to rest in the magnetic
meridian with its north pole pointing north. If now a wire is curved round it,
as shown in the accompanying diagram, and a battery current is sent through
this wire the needle will be deflected to the right if the current passes in one
direction and to the left if it passes in the opposite direction. The move-
ment of the needle is an indication of the presence and direction of the electrical
current in the wire. The extent of deflection of the needle may be used to
measure the strength of the current by ascertaining the amount of deflection
caused by a standard battery. The effect of the current upon the needle
increases with the number of turns of wire, so that delicate galvanometers
constructed upon this principle are spoken of as high resistance galvanom-
eters, the great length of wire used ^making, of course, a high resistance.
Instead of having the coil through which the current passes kept in a fixed
position and the magnet delicately swung or poised, the reverse arrangement
may be used, — that is, the coil may be swung between the poles of a fixed

Fig. 38. — D'Arsonval galvanometer as modified by Rowland.

magnet. Under these circumstances if a current is sent through the coil
this latter will move with reference to the magnet. A galvanometer con-
structed on this principle is designated as a d'Arsonval galvanometer, after
the physiologist who first employed this arrangement. The d'Arsonval form
of galvanometer possesses many practical advantages for physiological work,
and it may suffice to give the details of this form alone. In the d'Arsonval
form the magnet is fixed while the coil of wire through which the current
passes is swung by a very delicate thread of quartz, silk fiber, or phosphor-
bronze. The principle of the arrangement is shown in the accompanying
diagram (Fig. 39) and one form of a complete instrument in Fig. 38. A large
horseshoe magnet (n, s) is fixed permanently and between the poles is swung
a coil (c) of delicate wire, the two ends of the wire being connected with binding
posts in the frame of the instrument. The coil is held in place below by a
delicate spiral. In Fig. 39 it will be seen that the delicate thread suspending
the coil carries just above the coil a small mirror, m, and a plate of thin mica
or aluminum. The mirror is deflected with the coil, and when viewed through
the telescope pictured in Fig. 38 the image of the scale above the telescope is

94

THE PHYSIOLOGY OF MUSCLE AND NERVE.

reflected in this mirror. As the coil and mirror are twisted by the action
of the current passing through the former the reflection of the scale in the
mirror is displaced. By means of a cross hair in the telescope the angle of
deflection may be read upon the reflected scale. The aluminum vane back of
the mirror makes the system dead-beat so that when a deflection is obtained
the system comes quickly to rest with few or no oscillations. If the coil of wire
contains sufficient turns, enough to give a total resistance of two to three
thousand ohms, and the poles of the magnet are brought very close to the

Fig. 39.— Diagram of struc-
ture of the d'Arsonval galvanom-
eter, c is the coil of fine wire
through which the current is
passed. It is swung by a fine
thread of phosphor-bronze so as
to lie between and close to the
poles — (ri) north pole, and («)
south pole — of the magnet. Just
above the magnet the thread car-
ries a mica or aluminum vane to
which is attached a small mirror.
The scale of the instrument is re-
flected in this mirror and is
observed through the telescope
shown in Fig. 38.

Fig. 40. — Schema of capillary electrometer
arranged to show the demarcation current in
muscle (Lombard) : a, The glass tube containing
mercury and drawn to a fine capillary below; c,
the receptacle containing mercury by raising
which the mercury can be driven into the capil-
lary of a; /, a vessel with glass sides containing
mercury below, and above dilute sulphuric acid
into which the capillary of a dips; E, the micro-
cope for observing the mercury thread in the
capillary; m, the muscle; g and h, the wires
touching the longitudinal and cut surfaces of the
muscle. The current flows as indicated by the
small arrows; d, the capillary thread of mercury
as seen under the microscope.

coil, the instrument may be given a delicacy sufficient to study accurately
the muscle and nerve currents. In such an instrument the effect of the earth's
magnetism may be neglected and the galvanometer may be hung upon any
support without reference to the magnetic meridian.

The Capillary Electrometer. — The movable system of a galvanometer
possesses considerable weight, therefore inertia; so that it will not indicate
accurately the presence or extent of very brief electrical currents such as have
to be studied in physiology in some cases. For purposes of this kind a simple

ELECTRICAL PHENOMENA.

95

instrument known as the capillary electrometer is employed. The principle
of the construction of this instrument is illustrated in Fig. 40. A glass tube,
a, is drawn out at one end into a very fine capillary, the end of which dips
into some diluted sulphuric acid contained in the vessel (/) . At the bottom
of this vessel is a layer of mercury connecting with a wire, g, fused into the
glass vessel. The tube a is partially filled with redistilled mercury, which
penetrates for a short distance into the capillary. By means of pressure ap-
plied from above c, the mercury can be forced through the capillary. Then
by diminishing the pressure the mercury can be brought back into the capil-
lary a certain distance, drawing after it some of the dilute sulphuric acid.
The mercury in tube a is connected with the other pole of the battery by a
wire fused into its wall and dipping into the mercury By regulating the
pressure on the mercury the point o£ contact between the threacT of mercury
and the sulphuric acid in the capillary, d, can be brought to any desired posi-
tion. An equilibrium is then established which will remain constant as long
as the conditions are not changed. If now the circuit from a battery or
other source of electricity — for example, the excised nerve or muscle — is closed,
the current entering by wire g, if this represents the anode, traverses the sul-
phuric acid and mercury in the capillary and returns by the wire h. At the
moment of the establishment of the current the equilibrium of forces that holds
the mercury at a certain point in the capillary is disturbed, the end of the mer-
cury thread moves upward with the current for a cer-
tain distance, depending on the strength of the current
and the delicacy of the capillary. If the current be
passed in the opposite direction the mercury will move
downward a certain distance. The meniscus of contact
moves up or down with the direction of the current,
owing, it is supposed, to a change in the surface tension
at this point. The capillary tube as used for physiologi-
cal purposes is too small for the movements of the mer-
cury to be detected with the eye. It is necessary to
magnify it either with a microscope or a projection
lantern. Ordinarily the electrometer is so made that it
can be placed upon the stage of the microscope and
the capillary be brought into focus at the meniscus,
as shown in d, Fig. 40. By means of proper apparatus
the movement can be photographed and thus a per-
manent record be obtained of the direction and extent
of movement of the mercury.

Non-polarizable Electrodes. — In connecting a
muscle or nerve to an electrometer or galvanometer
it is necessary that the leading off electrodes — that is,
the points of contact between the wires and the
muscle or nerve — shall be iso-electrical and non-polar-
izable. By iso-electrical is meant that the two elec-
trodes shall have the same electrical potential, and it
is obvious that the leading off electrodes must fulfill
this condition approximately at least, since otherwise
the current obtained from the muscle or nerve could
not be attributed to differences in potential in the
tissue itself; it would be shown by any other moist
conductor connecting the two electrodes. Two clean
platinum electrodes would fulfill this condition. A
more serious difficulty is found in the polarization of
metallic electrodes. * Whenever a metal conductor
and a liquid conductor come into contact there is apt
to be polarization. What takes place may be represented by the following
diagram, in which a current is supposed to be passing

-2

Fig. 41.— To show
the structure of a non-
polarizable electrode :
1, The pad of kaolin or
filter paper moistened
with physiological sa-
line (NaCl, 0.7 per
cent.) (this is placed on
the tissue); 2, the sat-
urated solution of zinc
sulphate; (3) the. bar
of amalgamated zinc.

96

THE PHYSIOLOGY OF MUSCLE AND NERVE.

4-
Na

Cl

between the poles A and C through a solution of sodium chlorid. During
the passage of the current the cations, Na, with their positive charges
move toward the cathode; at the cathode the free sodium ion acts upon
the water, HHO, forming NaOH and liberating hydrogen, which gives
its charge to the cathode and accumulates upon it in the form of gas. The
anions, Cl, with their negative charges move toward the anode; there the
chlorin acts upon the water, forming HC1 and liberating oxygen. In conse-
quences of these chemical actions at the poles an electromotive force is de-
veloped at the cathode which diminishes the current passing from A to C.
It is obvious that in quantitative studies of the electrical currents of animal
tissues polarization will destroy the accuracy of the results; the demarcation
current will show a. diminution due not to changes in the nerve, but to physi-
cochemical changes at the leading off electrodes. To prevent polarization
du Bois-Reymond devised the non-polarizable electrodes consisting of zinc
terminals immersed in zinc sulphate. Theoretically any metal in a solution
of one of its salts may be used, but experience shows that the zinc-zinc sulphate
electrode is most nearly perfect. Each electrode where it comes into contact
with the tissue is made of one of these combinations. Various devices have
been used. For instance, the electrode may be constructed as shown in the
diagram (Fig. 41). A short glass tube of a bore of about 4 mms. is well
cleaned — one end, which is to come into contact with the nerve — is filled, as
shown, by a plug of kaolin made into a stiff putty with physiological saline
solution of NaCl (0.7 per cent.). The kaolin should have a neutral reaction
and unless good kaolin is obtainable it is better to use a plug made of clean
filter paper macerated in physiological saline and packed tightly into the end
of the tube. Above this plug the tube is filled in for a part of its length with
a saturated solution of zinc sulphate into which is immersed a bar of amal-
gamated zinc with a copper wire soldered to its end. With a pair of such
electrodes the conduction of the current through the nerve or muscle to the
metallic part of the circuit may be represented as follows:

Zn

S04 S04 Cl Cl Cl S04 S04

Zn

The liquid part of the circuit comes into contact with the metallic part
at the junction of Zn and ZnSO4. At the cathode it may be supposed that
the Zn cation instead of acting upon the water and liberating hydrogen,
deposits itself upon the zinc electrode; at the anode the sulphion (SO4)
attacks the zinc instead of the water, forming ZnSO4. In this way polarization
is prevented, and by the construction of the electrode the living tissue is
brought into contact only with the plug of kaolin moistened with physio-
logical saline. Such electrodes are indispensable in studying the electrical phe-
nomena of living tissues, and also in all investigations bearing upon the polar
effects during the passage of an electrical current from a battery. Ordinarily,
however, when it is only desired to stimulate a nerve or muscle, metal (plat-
inum) electrodes are employed.

The Action Current or Negative Variation. — Du Bois-Rey-
mond proved that when the excised muscle or nerve is stimulated

ELECTRICAL PHENOMENA. 97

its demarcation current suffers a diminution or negative variation.
If, for instance, the excised nerve gives a demarcation current suf-
ficient to cause a deflection in the galvanometer of 50 mms., then
if the nerve is stimulated by a series of induction shocks the galva-
nometer will show a lessened deflection, say, one of 40 mms. The
negative variation in this case is equal to 10 mms., on the scale of
the galvanometer used. It has been shown that this negative varia-
tion is due to a current in the opposite direction whose strength, in
the example given, relative to that of the demarcation current is
as 10 to 50. Frequently the phenomenon of the negative varia-
tion is known also as the action current. The explanation given
for this action current is that the nerve or muscle when excited
takes on an electrical condition which is negative as regards any
unexcited or less excited portion of the nerve. The effect upon the
demarcation current is illustrated in the accompanying diagram.

The demarcation current in a nerve is led off to a galvanometer
by electrodes placed at b and c. When the nerve is stimulated at
a the excitation set up passes along the nerve, and wherever it may
be that portion of the nerve is thrown into an electronegative condi-
tion. When this condition reaches a point at which it can influence
the galvanometer — that is, when it reaches 6, it will diminish the
difference in potential that exists between b and c, and therefore
reduce the current

flowing from b to c. _j_

Bernstein* has
shown that this neg-
ative condition
moves in the form of

a wave. That is, at ^-
any point the nega-
tivity grows to a Fig 42 _ Schema to indicate the method of detecting
mivirrmm flnrl tVlPn the action current in a stimulated excised nerve: b and c,
^ U the leading off electrodes, one 9n the longitudinal, one on

diminishes. More- tne cut surface; the demarcatipn current passes through

. the galvanometer, g, in the direction of the arrows; a, stimu-

OVer, it travels at a lating electrodes from induction coil; the stimulus causes a

•* r •> , ., negative condition, — which passes along the nerve; when

aennite Velocity this reaches b it causes a partial reversal of the demarca-

i • -i • •] tion current, giving the negative variation or action cur-

\vnicn is easii\ rent
measured. Accord-
ing to his experiments, the velocity of this wave in the frog's
motor nerve is from 25 to 28 meters per second, and the length
of the wave is about 18 mms. Hermann, on the contrary, be-
lieves that, in the excised nerve at least, the length of the wave
may be greater, reaching perhaps 140 mms.

These figures will vary naturally for the nerves of different ani-
mals or for different nerves in the same animal, for it must always

* Bernstein, '' Untersucliungen iiber den Erregungsvorgang im Nerven
und Muskelsysteme," Heidelberg 1871.
7

y& THE PHYSIOLOGY OF MUSCLE AND NERVE.

be remembered that nerve fibers, whose functions in general are so
similar, differ much in obvious microscopical structure and probably
more widely in their chemical composition. Using an analogy that
is familiar, we may say that when a stimulus acts upon a living
nerve a wave of electronegativity spreads from the stimulated
spot and travels in wave form with a definite velocity, just as water
waves radiate from the spot at which a stone is thrown into a quiet
pool. A similar phenomenon occurs in muscle fibers when stimu-
lated, but the negative condition travels over the muscle fiber at a
slower speed, 3 to 4 meters per second in frog's muscle, and with a
wave length, according to Bernstein, of only 10 mms. This wave
of negativity or of excitation in the muscle precedes the actual
wave of contraction.

This phenomenon of a negative electrical condition traveling
over the nerve or muscle and giving us an active current when led
off through a galvanometer is of the greatest physiological impor-
tance, particularly in the study of nerves. It has been shown
that in the nerve this wave of negativity marks the progress of the
wave of excitation, and, since we can study its progress by means
of the galvanometer or capillary electrometer, we can thus study the
excitability and conductivity in nerves when removed from con-
nection with their end-organs. That the negative wave, or the
action current that it gives rise to, is an invariable sign of the
passage of an excitation or nerve impulse is shown by the facts
that it is absent in the dead nerve, and that in the living nerve it is
produced by mechanical,* chemical, f and reflext stimulations, as
well as by the more usual method of electrical stimulation.

Herzen has claimed that under certain conditions of local narcosis the
nerve fibers when stimulated may give an action current, but no muscle con-
traction,— a fact which if true would seem to show that the excitation wave
or nerve impulse and the wave of negative potential are not associated
invariably. This result, however, has been denied by other competent
observers (Wedenski, Boruttau).

Monophasic and Diphasic Action Currents. — According to
the conception of the action current given above, it is evident that
it should be obtained upon stimulation when a living normal nerve
is connected at any two points of its course with a galvanometer or
capillary electrometer. The detection of the current under such
conditions offers more difficulties, because it is diphasic, as will
be seen from the accompanying diagram (Fig. 43). The figure rep-
resents a normal nerve led off to the galvanometer from two points,
b and c, of its longitudinal surface. As these points in the uninjured

* Steinach, " Pfliiger's Archiv," 55, 487, 1894.

t Griitzner, "Pfliiger's Archiv," 25, 255, 1881.

j Boruttau, "Pfliiger's Archiv/' 84 and 90, 1901-1902.

ELECTICAL PHENOMENA. 99

nerve have the same potential, no current is shown by the galvanom-
eter. If the nerve is stimulated at a by a single stimulus a neg-
ative condition or charge passes along the nerve. When it reaches
the point b there will be a momentary current through the gal-
vanometer from c to b; as the charge passes on to c this point in
turn will become negative to b} and there will be a momentary cur-
rent through the galvanometer in the other direction. The diphasic
current that occurs under these conditions cannot be detected by
a galvanometer, even when a series of stimuli is sent into the nerve
at a, since the movable system" in this instrument has too much
inertia to respond to such quick changes in opposite directions.
With the more mobile capillary electrometer the diphasic currents
have been demonstrated successfully. In laboratory investiga-
tions one of the leading off electrodes, c, is usually placed on the
cut end of the nerve. Under this condition the action current be-
comes monophasic and shows itself as a negative variation of the
demarcation current. This difference is due to the fact that a nega-
tive condition upon excitation depends upon a living condition
of the nerve, and it can not, therefore, affect the nerve at the
electrode c if this latter is placed upon the cut end where the nerve
is dead or dying. It will affect only the electrode 6, and give only
the monophasic current, which can now be shown by the galvanom-
eter provided a series of stimuli is thrown in at a.

Fig. 43. — Schema to show the arrangement for obtaining a diphasic action current.
The arrangement differs from that in Fig. 42 only in that both leading off electrodes, b and
c, are placed on the longitudinal surface. No demarcation current is indicated. When
the nerve is stimulated at a the negative charge reaches b first, causing a current through
the galvanometer from c to b. Subsequently it reaches c and causes a second current
in the opposite direction from 6 to c.

The Positive Variation. — It happens not infrequently that when one
electrode is placed upon the cut end, the nerve upon stimulation with a series
of induction shocks gives a positive instead of a negative variation of the
demarcation current. This result is usually explained as being due to a pre-
dominance of the anelectrotonic currents (see below), but Wedenski has con-
tended recently that it is due to a peculiar condition of excitation in the nerve
at the cut end, a condition to which he gives the name of parabiosis. When
this phenomenon occurs it can usually be removed by making a fresh section
at the end of the nerve.

Detection of the Action Currents by the Rheoscopic Frog
Preparation or by the Telephone. — The motor nerve of a nerve-
muscle preparation from a frog is so extremely irritable to electrical

100 THE PHYSIOLOGY OF MUSCLE AND NERVE.

currents that it may be used instead of a galvanometer to detect
the action currents in a stimulated muscle. A nerve-muscle prep-
aration used for this purpose is known as a rheoscopic preparation.
The way in which it is used is indicated in the accompanying
diagram, b represents the rheoscopic preparation, its nerve being
laid upon the muscle whose currents are being investigated, a, so as
to touch the cut end (x) and the longitudinal surface (g) . When a is
stimulated, either directly or through its nerve, as represented in the
diagram, the negative charges that pass along the muscle fibers of
a with each stimulus cause action currents that will be led off
through the nerve of b from x to g. If the nerve is in a sensitive con-
dition it will be stimulated by the action currents and thus a series of
excitations will be sent into b corresponding exactly in rate with
the artificial stimuli given to the nerve of a. The rheoscopic
preparation may be used very . beautifully to demonstrate the
action current in the contracting heart muscle. If the nerve of
b is laid upon the exposed beating heart of an animal, the muscle
of b will give a single twitch for each beat of the ventricle. An-
other interesting method of detecting the action currents, particu-
larly in nerves, is by means of the telephone. Wedenski has made
especial use of this method, the telephone being connected with

Fig. 44. — Schema to show the arrangement of a rheoscopic muscle-nerve preparation:
6, The rheoscopic muscle-nerve preparation, the nerve being arranged to touch the cut sur-
face and the longitudinal surface of the muscle, a, whose action currents are to be detected.
When the nerve of a is stimulated each contraction of this muscle is followed by a contrac-
tion of 6, since each contraction of a is accompanied by an action current which passes
through the nerve of b and stimulates it.

the nerve in place of the galvanometer. The method has obvious
advantages in the fact that it may be used with a nerve to which
the muscle is also attached, so that the excitation processes in
the nerve and their effect upon the muscle may be studied simul-
taneously. In matters of rate the telephone method, appealing
to the ear, as it does, is more delicate than the galvanometer or
electrometer.

Relation of the Action Current to the Contraction Wave
in Muscle and to the Excitation Wave (Nerve Impulse) in
Nerve. — The action current, or, to be more accurate, the moving
negative charge which gives rise to an action current when two

ELECTRICAL PHENOMENA. 101

points of the muscle are led off to a galvanometer, has been shown
by Bernstein to precede the wave of contraction in muscle, that
is, in a stimulated muscle fiber the electrical change at any point
precedes the mechanical process of shortening. The electrical change
passes over the fiber from the point stimulated in the form of a
wave of definite velocity, but at any one point the electrical change
reaches its maximum before the process of contraction is visible.
We may suppose, therefore, that the electrical change is an indication
of the excitation or possibly constitutes the excitation that sets
up the chemical change of contraction, or else that the change IP
electrical potential is caused by the chemical change of contraction
and precedes the mechanical result of shortening, since the latter
process will have a certain latent period. It has been shown,
indeed, by Demoor that a completely fatigued muscle may still
conduct an excitation (muscle impulse), although unable to con-
tract, and the same fact has been demonstrated by Engelmann
for the heart muscle. In the nerve the action current, or the
negative change causing it, has been considered as simultaneous
with or possibly identical with the nerve impulse. The velocity
of the two is identical; the action current is given whenever the
nerve is stimulated, and, so far as experiments have gone, the
nerve cannot enter into activity without showing an action
current, — that is, without showing a moving electrical charge.
Whether this electrical charge constitutes the nerve impulse or
is simply an accompanying phenomenon will be discussed briefly
in the paragraph upon the nature of the nerve impulse in the
following chapter.

The Electrotonic Currents. — In speaking of the effect of
passing a galvanic current through a nerve attention was called
to the fact that the

condition of the / - — - — -- - - A
nerve is altered at
each pole. At the
anode there is a con-
dition of decreased
irritability and con-
ductivity known as

a t Fig- 45.— Schema to show the direction of the elec-

a I trotonic currents in an excised nerve: P, The battery for

thp Pflthnrlp in thp the polarizing current sent into the nerve at +, the an-

1G> 1] ode, and emerging at — , the cathode; g', galvanometer

beginning at least, arranged with leading off electrodes to detect the anelec-
trotonic current, the direction of which is indicated by

a Condition Ol in- the arrows (in the nerve it is the same as that of the po-

i • -j. I_'TJ. larizing current) ; gr, galvanometer similarly arranged to de-

creased irritability tect the catelectrotonic current. The anelectrotonic and

i M i catelectrotonic currents continue as long as the polarizing

known as CaieieC- current is maintained.

trot onus. In addi-

tion to these changes in the physiological properties of the nerve

there is a change also in its electrical condition at each pole, of

102

THE PHYSIOLOGY OF MUSCLE AND NERVE.

such a character that if the nerve- is led off from two points on
the anode side a current will be indicated. The current can be
obtained at a considerable distance from the anode, and is known
as the anelectrotonic current, while the electrical condition in the
nerve that makes it possible is designated as anelectrotonus. A
similar current can be led off from the nerve on the cathode side
for a considerable distance beyond the cathode; this is known as
the catelectrotonic current, and the electrical condition leading
to its production as catelectrotonus. Within the nerve these
electrotonic currents have the same direction as the battery or
polarizing current, as is shown in the diagram (Fig. 45). The
terms anelectrotonus and catelectrotonus are used, therefore,
in physiology to designate both the physiological and the elec-
trical changes around the poles when a battery current is led
into a nerve. Whether the physiological and the electrical changes
have a causal connection or are two independent phenomena is
at present undecided.

Bethe* has recently shown that during the passage of the polarizing cur-
rent the neurofibrils in the axis cylinder lose at the anode their power of stain-
ing with certain basic dyes (e. g., methylene blue), while at the cathode the
affinity for these dyes is increased. He assumes, that in the neurofibrils there
is an acid substance — fibril acid — and that at the anode the combination
with this body and the neurofibrils is loosened ; hence the loss of staining
power. At the cathode the reverse change takes place. He assumes further-

Fig. 46. — To show the action of the core-model: p, The polarizing current; g' and
g, the galvanometers with leading off electrodes to detect the anelectrotonic and catelec-
trotonic currents, respectively.

more, that when the affinity between neurofibril and fibril acid is increased
at the cathode an electronegative ion is liberated (anion), while at the
anode at the time that the combination between fibril and fibril acid is dis-
sociated an electropositive ion (cation) is liberated. In this way he constructs
an hypothesis of a complex of neurofibril, fibril acid, and electrolyte which
is capable of accounting for the electrotonus, both as regards the electrical and
the physiological phenomena, and which refers both phenomena to a single
reaction in the nerve.

Another explanation of the electrotonic currents which has been much
discussed is that first developed by Hermann. t This author constructed
a model consisting of a conductor surrounded by a less conductive liquid
sheath, and showed that such a model is capable of giving the electrotonic
currents. This model may be made as represented in the accompanying

* Bethe, " Allgemeine Anatomic u. Physiol. des Nervensystems," Leipzig,
1903.

tHermann, " Handbuch der Physiologic," vol. ii, p. 174.

ELECTRICAL PHENOMENA. 103

diagram, of a glass tube A-B, through the middle of which is stretched a
platinum wire, P, the rest of the tube being filled with a saturated solution
of zinc sulphate. The glass tube is provided with vertical branches by means
of which a polarizing current, p, can be sent into the solution of zinc sulphate
and the electrotonic currents be led off to galvanometers, g'. g, on
each side. Under these conditions a current similar to the anelectrotonic
current can be detected on the side of the anode (g'} and one equivalent to
the catelectrotonic current on the side of the cathode (g). The explanation
given to these currents is that as the threads of current pass into the platinum
core there is a polarization at the surface between the core and the zinc sul-
phate solution which extends to a considerable distance on each side of the
electrodes and causes diffusion currents from sheath to core. It is these
threads of current that may be led off as electrotonic currents. Hermann
suggested that in the nerve we have a structure essentially similar to that
of the core model. He thought that the axis cylinder might be considered
as representing the core and the myelin the less condu tive sheath as corres-
ponding to the zinc sulphate solution. Others (Boruttau) have suggested that
the neurofibrils in the axis cylinder may represent the core or cores and the sur-
rounding neuroplasm the sheath, thus providing for the possibility of electro-
tonic currents in non-medullated fibers. As a matter of fact, the non-medul-
lated fibers in mammals give very slight electrotonic currents compared with
the medullated fibers.*

According to the "core-model" explanation, the electrotonic currents
represent a purely physical phenomenon, which is dependent, however, upon
a certain structure of the nerve. That is, a completely dead nerve will not
show these currents, although an anesthetized nerve, in the mammal (Waller)
at least, continues to show them, and, according to Sosnowsky, excised rab-
bits' nerves kept in a moist atmosphere may show them for several days.
While the core-model hypothesis has led to much investigation in physiology
and has been made the" basis for a purely physical explanation of the nerve
impulse, it is still very uncertain whether it furnishes any positive informa-
tion concerning the processes that actually take place in the living nerve when
submitted to the action of electrical currents or other artificial stimuli.
*Alcock, " Proceedings Royal Society," 1904, 73, p. 166.

CHAPTER V.

THE NATURE OF THE NERVE IMPULSE AND THE

NUTRITIVE RELATIONS OF NERVE FIBER

AND NERVE CELL.

The question of the nature of the nerve impulse has always
aroused the deepest interest among physiologists. It has consti-
tuted, indeed, a central question around which have revolved vari-
ous hypotheses concerning the nature of living matter. The impor-
tance of the nerves as conductors of motion and sensation was
apparent to the old physiologists, and the nature of the conduction
or the thing conducted was the subject of many hypotheses and
many different names. For many years the prevalent view was
that the nerves are essentially tubes through which flows an ex-
ceedingly fine matter, of the nature of air or gas, known as the
animal spirits. Others conceived this fluid to be of a grosser struc-
ture like water and described it as the nerve juice. With Galvani's
discovery of electricity the nerve principle, as it was called, became
identified with electricity, and, indeed, this view, as will be ex-
plained, prevails in modified form to-day. Du Bois-Reymond,
after discovering the demarcation current and action current in
muscle and nerve, formulated an hypothesis according to which the
nerve fibers contain a series of electromotive particles, and by
this hypothesis and the facts upon which it was based he thought
that he had established that "hundred-year-old dream" of phys-
icists and physiologists of the identity of the nerve principle
and electricity. His theory to-day has fallen into disrepute, but
the facts upon which it was based remain, as before, of the deepest
importance. In the middle of the nineteenth century those who
were not convinced of the identity of the nerve principle with
electricity believed, nevertheless, that the process of conduction
in the nerve is a phenomenon of an order comparable to the trans-
mission of light or electricity, with a velocity so great as to defy
measurement. But in this same period a simple but complete
experiment by Helmholtz demonstrated that its velocity is, as
compared with light or with electrical conduction through the air
or through metals, exceedingly slow, — 27 meters per second.
Modern views have taken divergent directions; the movement
or excitation that is conducted along the fiber has been named

104

NATURE OF THE NERVE IMPULSE, 105

the nerve principle, the nerve energy, the nerve force, the nerve
impulse. As the latter term is less specific regarding the nature
of the movement, and emphasizes the fact of the conduction of an
isolated disturbance or pulse, it seems preferable to employ it
until a more satisfactory solution of its nature has been reached.
The Velocity of the Nerve Impulse. — The determination of
the velocity of the nerve impulse was first made by Helmholtz*
upon the motor nerves of frogs. His experiment consisted in
stimulating the sciatic nerve, first, near its ending in the muscle

Fig. 47. — Record to show the method of estimating the velocity of the nerve impulse
in a motor nerve. The experiment was made upon a nerve-muscle preparation from the
frog, the contractions bring recorded upon the rapidly moving plate of a pendulum myo-
graph. Two contractions were obtained, the first (a) when the nerve was stimulated
near the muscle, the second (b) when the nerve was stimulated as far as possible from the
muscle. The latent period of the second contraction was longer, as shown by the distance
between the curves measured on the line x. The value of this distance in time is obtained
by reference to the record of a tuning fork vibrating 100 times per second, which is given
on the lower line. In the experiment the length of a tuning fork wave (0.01 sec.) was 21
rams., the distance between the two muscular contractions was 3.35 mms., and the dis-
tance between the points stimulated upon the nerve was 49 mms. Hence the velocity of the
nerve impulse in this experiment was 49 divided by (^Wff * Ttta) or 30716 mms. (30.716m.)
per second.

and, second, near its origin from the cord, and measuring the time
that elapsed in each case between the moment of stimulation and
the moment of the muscular response. It was found that when
the nerve was stimulated at its far end this time interval was
longer, and since all other conditions remained the same this dif-
ference in time could only be due to the interval required for the
nerve impulse to travel the longer stretch of nerve. In the accom-

* Helmholtz, "Muller's Archiv f. Anat. u. Physiol.," 1852, p. 199.

106 THE PHYSIOLOGY OF MUSCLE AND NERVE.

panying figure the record of a laboratory experiment of this kind
is reproduced. Knowing the difference in time and also the length
of nerve between the points stimulated, the data are at hand to
calculate the velocity of the impulse. The velocity varies with the
temperature. According to Helmholtz, this variation lies between
24.6 and 38.4m. per second fora range of temperature between 11°
and 21° C. For average room temperatures we may say that in
the motor nerves of the frog the impulse travels with a velocity
of 28 to 30 meters per second. Similar experiments upon man and
other mammals indicate that the velocity in the medullated motor
nerves does not vary greatly in different animals. Helmholtz's
average figure for man was 34 meters per second.

It is interesting to recall that only six years before Helmholtz's first pub-
lication Johannes Miiller had stated that we should never find a means of
determining the velocity of the nerve impulse, since it would be impossible
to compare points at great distances apart, as in the case of the movement
of light. " The time," said he, " required for the transmission of a sensation
from the periphery to the brain and the return reflex movements of the mus-
cles is infinitely small and unmeasurable." The mode of reasoning by which
Helmholtz was led to doubt the validity of this assertion is interesting. He
says (" Muller's Archiv," 1852, 330) : " As long as physiologists thought it
necessary to refer nerve actions to the movement of an imponderable or
psychical principle, it must have appeared incredible that the velocity of this
movement could be measured within the short distances of the animal body.
At present we know from the researches of du Bois-Reymond upon the electro-
motive properties of nerves that those activities by means of which the con-
duction of an excitation is accomplished are in reality actually conditioned
by, or at least closely connected with an altered arrangement of their material
particles. Therefore conduction in nerves must belong to the series of self-
propagating reactions of ponderable bodies, such, for example, as the con-
duction of sound in the air or elastic structures, or the combustions in a tube
filled with an explosive mixture." One of the first fruits, therefore, of the
scientific investigation of the electrical properties of the nerve fiber was the
discovery of the important fact of the velocity of the nerve impulse.

Numerous efforts have been made to determine the velocity
of the nerve impulse in medullated sensory fibers. The results
have not been entirely satisfactory. The end-organ in this case is
the cortex of the cerebrum, and its reaction consists in arousing a
sensation, or a reflex action. Neither end-reaction can be meas-
ured directly. Attempts have been made to determine it indi-
rectly by noting the time of a voluntary muscle response for sensory
stimuli applied to the skin at different distances from the spinal
axis. In such cases the sensory impulse travels to the cord, thence
to the brain, and the return motor impulse travels from brain to
cord and then by the motor nerves to the muscle used for the re-
sponse. The results of this method have been discordant, owing
probably to the fact that the central paths from two different points
on the skin are not identical. It is usually assumed — without,
however, very convincing proof — that the velocity of the impulse

NATURE OF THE NERVE IMPULSE. 107

in the medullated afferent nerve fibers is the same as in the efferent
fibers. A large number of observations are on record which show
that the velocity varies greatly in the non-medullated nerves of
different animals. In the mammal, according to Chauveau, the
velocity for the non-medullated fibers is only 8 meters per second;
in the lobster it is 6 meters per second; in the octopus, 2 meters;
in the olfactory (sensory) nerve of the pike ^ meter, and in the
anodon only y^-g- meter per second.

Relation of the Nerve Impulse to the Wave of Negativity. —
A fact of great significance is that the velocity of the impulse in the
motor nerves of the frog corresponds exactly to the velocity of the
wave of negativity as measured by Bernstein. Evidently the two
phenomena are coincident in their progress along the fiber, and
physiologists generally have accepted the existence of an action cur-
rent as a proof of the passage of a nerve impulse. This belief is
strengthened by the fact that, as stated above, the negative wave ac-
companies the nerve impulse not only when the nerve is stimulated
by electrical currents, but also after mechanical, chemical, or reflex
stimulation. The question has been raised as to whether this elec-
trical phenomenon accompanies the normal nerve impulse, — that is,
the nerve impulse that originates in the nerve centers, in the case
of motor nerves, or in the peripheral sense organs in the case of sen-
sory nerves. In regard to the latter relation we have positive evi-
dence that when light falls upon the living retina an electrical distur-
bance is produced by the visible rays of the spectrum,* and there
is every reason to believe that the passage of visual impulses along
the optic nerve is accompanied by an electrical change. With
regard to normal motor impulses, the evidence is also positive that
motor discharges from the central nervous system are accompanied
by a wave of electrical potential. This fact may be shown by
stimulating the motor areas in the cerebral cortex and testing the
efferent nerves, such as the sciatic, for an action current; or by
stimulating a posterior root on one side in the lumbar region and
testing the sciatic nerve on the other side with a galvanometer.!
Moreover, all influences that alter the velocity or strength of the
nerve impulse affect the intensity of the action current in the same
manner. It is believed generally, therefore, that the electrical
charge is an invariable accompaniment of the excitatory wave,
and the demonstration of an action current in a nerve is tantamount
to a proof of the passage of a nerve impulse.

Direction of Conduction in the Nerve. — The fact that under
normal conditions the motor fibers conduct impulses only in one

* Consult Gotch, "Journal of Physiology," 31, 1, 1904.
fGotch and Horsley, "Phil. Trans., Royal Soc.," London, 1891, vol.
182 (B), and Boruttau, "Pfliiger's Archiv," 1901.

108 THE PHYSIOLOGY OF MUSCLE AND NERVE.

direction — i. e., toward the periphery — and the sensory fibers in
the opposite direction — that is, toward the nerve center — suggests,
of course, the question as to whether the direction of conduction is
conditioned by a fundamental difference in structure in the two
kinds of fibers. No such difference in structure has been revealed
by the microscope, although in two respects at least it will be re-
membered that the sensory nerve fibers react differently from the
motor fibers — namely, in the fact that they are readily stimulated
by high temperatures and that during the passage of a galvanic
current of constant strength they are stimulated continuously in-
stead of only at the opening or closing of the current. These latter
differences, however, may rest simply upon a difference in irrita-
bility and have no bearing upon the question in hand. It is the
accepted belief in physiology that any nerve fiber may conduct an
impulse in both directions, and does so conduct its impulses when the
fiber is stimulated in the middle of its course. An entirely satisfactory
proof for this belief is difficult to furnish unless the conclusion in

the preceding para-
graph is admitted,
— the conclusion,
namely, that the
electrical change is
a necessary and in-
variable accompani-

Fig. 48. — Schema to show the arrangement for proving ment of the nerve
the propagation of the negative charge in both directions: i -r, • x

a. The stimulating electrodes; g and gf, galvanometers impulse,

with leading off electrodes arranged to show the negative Hiffirmlf tn «Vinw V»v

variation on each side. OimCUlt IO snow Dy

means of a galva-:

nometer that when a nerve trunk is stimulated the negative
charge spreads in both directions from the point stimulated and
gives an active current on either side, as indicated in the accom-
panying diagram. This fact holds true for motor or for sensory
fibers. The older physiologists attempted to settle this question
in a more direct way, but by methods which later experiments
have proved to be insufficient. They attempted, for instance, to
unite a motor and sensory trunk directly, to cut the hypoglossal
(motor) and the lingual (sensory) and suture, say, the central stump
of the lingual to the peripheral stump of the hypoglossal. If stimu-
lation of this latter trunk, after union had been established, gave
signs of sensation it was considered as proof that the efferent hypo-
glossal fibers were now conducting afferent ly . We now know that in
such a case the old hypoglossal fibers degenerate completely, and
the new ones that are eventually formed in their place are out-
growths from the lingual stump, or at least are not the old efferent
fibers, and hence experiments of this kind are not so conclusive'

NATURE OF THE NERVE IMPULSE. 109

as they seemed to be at the time when it was supposed that severed
nerve fibers can unite immediately, by first intention, without
previous degeneration. A similar objection applies to Paul Bert's
often quoted experiment. Bert implanted the tip of a rat's tail
into the skin of its back. After union had taken place the tail
was severed at the base, and the stump now attached to the back
was tested from time to time as to its sensibility. Sensation
returned slowly. At first it was indefinite, but by the end of a
year was apparently normal.

Modification of the Nerve Impulse by Various Influences —
Narcosis. — The strength of the impulse and its velocity may be
modified in various ways: by the action of temperature, narcotics,
pressure, etc. Variations of temperature, as stated before, change
the velocity of propagation of the impulse, the velocity increasing
with a rise of temperature up to a certain point. So also the irri-
tability and the conductivity of the nerve fiber are influenced
markedly by temperature. If a small area of a nerve trunk be
cooled or heated the nerve impulse as it passes through this area
may be increased or decreased in strength or may be blocked
entirely. Different fibers show somewhat different reactions in
this respect; but, speaking generally, the limits of conductivity
in relation to temperature lie between 0° C. and 50° C. Cooling
a nerve to 0° C. will in most cases suspend the conductivity, but
this function returns promptly upon warming.* This fact fur-
nishes a convenient means of blocking the nerve impulses in a
nerve trunk for any desired length of time. In the same way
anesthetics and narcotics, f such as ether, chloroform, cocain,
chloral, phenol, alcohol, etc., may be applied locally to a nerve
trunk and if the application is made with care the conductivity
and irritability may be lessened or suspended entirely at that point,
to be restored again when the narcotic is removed. It is an inter-
esting fact that the conductivity of the nerve may be suspended
also by deprivation of oxygen,! — that is, by local suffocation or
asphyxia. A nerve fiber surrounded by an oxygen-free atmosphere
will slowly lose its conductivity, and this property will be restored
promptly upon the admission of oxygen. Compression of a nerve
will also suspend its conductivity without permanently injuring
the fibers provided the pressure is properly graduated. Lastly, as
was explained in a preceding chapter, the conductivity of the nerve
may be increased or decreased or suspended entirely by the action
of a galvanic (polarizing) current. This method of suspending
conductivity temporarily has been frequently employed for ex-

* Howell, Budgett, and Leonard, "Journal of Physiology," 16, 298, 1894.
t Frohlich, " Zeitschrift f . allgemeine Physiol.," 3, 75, 1903.
j Baeyers, ibid., 2, 169, 1903.

110

THE PHYSIOLOGY OF MUSCLE AND NERVE.

perimental purposes, the arrangement being as represented in
Fig. 49.

When the conductivity of the nerve is interrupted by any of the methods
described above, certain peculiar reactions may be obtained in the inter-
mediate stages before conduction is entirely abolished. The most interest-
ing of the stages is the paradoxical condition. In this stage a weak stimulus
applied at a will cause a contraction of the muscle, while a stronger stimulus
will prove ineffective. Wedenski,* who has studied these reactions with
great care, believes that the nerve in the narcotized area is thrown into a
peculiar condition of continued excitation to which he gives the name of
parabiosis. The condition is supposed to be characterized physiologically
by a loss of lability of the living material. It seems possible, however, that
the reactions which are taken as characteristic of the parabiotic condition
may be explained upon the assumption that the narcotics and other reagents
mentioned so alter the nerve as to make it more susceptible to fatigue (see
following paragraph).

The Question of Fatigue of Nerve Fibers. — An important
question in connection with the nature of the nerve impulse has

been that of the suscep-
tibility of the nerve fibers
to fatigue. The obvious
fatigue of muscles and
of nerve centers has been
referred to the accumula-
tion of the products of
metabolism of their tis-
sues or to the actual

Fig. 49.— Schema to show the method of block- consumption of the en-
ing the nerve impulse by means of a polarizing cur- • i *• • i •

rent: a, The stimulating electrodes; b, the battery, ergy-yielding material in

the current of which is led into the nerve. The de- ,1 -r-, , • , . .

pressed irritability at both anode, +, and cathode, — , them. Jb UnctlOnal actlV-

* ityin these tissues im-
plies the breaking down

of complex organic material (catabolism) and the setting free
of the so-called chemical energy. The potential, chemical, or internal
energy of the compound is liberated as kinetic energy of heat, etc.
It has been accepted, therefore, that, if the nerve fiber could be
demonstrated to show fatigue as a result of functional activity,
this fact would be probable proof that the conduction of the im-
pulse is associated with a chemical change of a catabolic nature in
the substance of the fiber. Experimental wrork, however, has
shown that under normal conditions the nerve fiber shows no
fatigue. The experiments made upon this point have been nu-
merous and varied. The general idea underlying all of them has
been to stimulate the nerve continuously, but to interpose a block
somewhere along the course of the nerve so that the impulses should
not reach the end-organ. This precaution is necessary because
* Wedenski, "Pfliiger's Archiv," 100, 1, 1904.

NATURE OF THE NERVE IMPULSE. Ill

the end-organ — muscle, gland, etc. — is subject to fatigue, and
must therefore be protected from constant activity. From time
to time or at the end of a long period of stimulation the block is
removed and it is noted whether or not the end-organ — for in-
stance, the muscle — gives signs of a stimulation. The removable
block has been obtained by the action of a polarizing current, by
cold, by narcotics, by curare, etc. Using curare, for instance,
Bowditch* found that the sciatic nerve might be stimulated continu-
ously by induction shocks for several (four to five) hours without
complete fatigue, since as the curare effect wore off the muscle
whose contractions were being recorded (M. tibialis ant.) began
to respond, at first with single and finally with tetanic contractions.
The curare in this case may be supposed to have blocked the nerve
impulse at the motor end-plate and thus protected the muscle
from responding until the lapse of several hours, although the
nerve during this entire time was conducting tetanic stimuli. This
experiment has since been repeated by Durig7f who has made use
of the fact that the effects of curare can be removed within a few
minutes by the salicylate of physostigmin. Durig stimulated the
nerve for as much as ten hours and then upon removing the curare
block found from the contraction of the muscle that the nerve
was still conducting. Edesf and others have shown that the
same result is obtained when the nerve is tested by a capillary
electrometer instead of by the response of an end-organ. Under
such conditions the nerve exhibits an undiminished action cur-
rent, although constantly stimulated by tetanizing shocks from an
induction apparatus. Brodie and Halliburton § have found that
the non-medullated fibers in the splenic nerve can also be stimulated
for many hours without losing their power of conduction, — that
is, without showing fatigue. Many other observers have obtained
similar results, which have confirmed physiologists in the belief
that the nerve fibers may conduct impulses indefinitely, or, in
other words, that their normal functional activity may be carried
on continuously without fatigue. If this belief is entirely correct
it would place the nerve fibers in a class by themselves, since all
other tissues that have been studied show evidence of fatigue when
kept in continuous functional activity. Moreover, if this belief is
entirely correct it would imply that the conduction of an impulse
in the nerve fiber is not associated with a consumption of material,
a metabolism, and in this respect also the functional activity of
the nerve would be placed in contrast with that of other organs.

* Bowditch, "Journal of Physidlogy," 6, 133, 1885.

t Durig, " Centralblatt f. Physiol.," 15, 751, 1902.

j Edes, "Journal of Physiology," 13, 431, 1892.

§ Brodie and Halliburton, "Journal of Physiology," 28, 181, 1902.

112 THE PHYSIOLOGY OF MUSCLE AND NERVE.

It must be remembered, however, that, although the above experi-
ments demonstrate the practical " unf atigueableness " of nerve
fibers under ordinary conditions of stimulation, there are some
reasons to make us hesitate in supposing that these structures
function absolutely without fatigue. In all the experiments re-
ferred to the nerve was stimulated by induction shock, and although
these stimuli followed very rapidly there was a short period of
rest after each stimulus, and possibly this interval of rest is
quite sufficient in the normal nerve for recovery from the effect
of the previous stimulus. It has been shown,* for instance, that, if
two stimuli be applied to a nerve with a very brief interval between
(0.006 sec. or less, according to the temperature), the second stimu-
lus is ineffective so far as can be determined by the response of an
attached muscle or by means of a capillary electrometer. And it
may very well be that in this case the lack of response to the second
stimulus is due to a short-lasting fatigue from the first stimulus.
This point of view is strengthened by the fact that, when the irrita-
bility of the nerve is greatly depressed by narcotics, f this critical
interval is much lengthened; two stimuli with a rate of more than
10 per second may give an effect only for the first stimulus.
Garten has shown also that one nerve, the olfactory of the pike,
when stimulated by induction shocks, with an interval between
the stimuli of as much as 0.27 sec., gives evidence of fatigue, since
its action current as measured by the capillary electrometer dimin-
ishes in extent quite rapidly, and recovers after a short rest.t

Does the Nerve Fiber Show any Evidence of Metabolism
during Functional Activity? — The functional part of a nerve
fiber in conduction is the axis cylinder, and, indeed, probably the
neurofibrils in the axis cylinder. The mass of this material even
in a large nerve trunk is small, and its chemistry is but little known.
The efforts that have been made to prove a metabolism in the
nerve fiber during activity have been directed along the lines
indicated by what is known of muscle metabolism. In a muscle
during contraction heat is produced, the substance of the muscle
shows an acid reaction, and among the products formed carbon
dioxid gas is perhaps the most prominent. Efforts to show similar
reactions in stimulated nerves have been unsuccessful. Rolleston§
investigated the question of heat production with the aid of a
delicate bolometer capable of indicating a difference of temperature
of -5-jnnj-°C. The frog's sciatic was used, but no increase in tem-
perature during stimulation could be demonstrated. No change

* Gotch and Burch, "Journal of Physiology," 24, 410, 1899.
t Frohlich, " Zeitschrift f. allgemeine Physiol.," 3, 468, 1904.
j Quoted from Biedermann, " Ergebnisse der Physiologic," vol. ii, part n,
p. 129.

§ Rolleston, "Journal of Physiology," 11, 208, 1890.

NATURE OF THE NERVE IMPULSE. 113

in reaction can be obtained by means of the usual indicators for
acidity. Waller has given some experiments to show that carbon
dioxid is produced during activity, but they are far from being con-
clusive. His line of argument is as follows: He has found that the
action current of a nerve that is being stimulated is increased by the
presence of very slight amounts of carbon dioxid, higher percentages
causing again naturally a decrease. This reaction for the presence
of carbon dioxid is apparently a very delicate one. When now a
normal nerve is stimulated its action current after some minutes
of tetanic stimulation is increased in the same way as would
happen if a little carbon dioxid was passed over it. He con-
siders that this temporary increase in the action current is due
to the formation of carbon dioxid from a functional metabolism.
The only significant evidence that we have of a chemical change in
the fiber during activity is found in two facts already mentioned:
one is the discovery that oxygen is requisite for normal conduction.
A nerve placed in an atmosphere free from oxygen loses its irrita-
bility, and regains it again quickly upon the admission of oxygen.
The other is found in the statement of Bethe, that when a nerve is
stimulated a definite change in the staining property of the neuro-
fibrils may be noted (see p. 102). At present we must admit,
therefore, that so far as the nerve fiber is concerned, we have no
positive proof of a functional metabolism. This negative state
of our knowledge, considering the difficulties involved in obtaining
proofs, hardly warrants a positive denial of the existence of such
a metabolism. All tissues whose chemistry can be studied show
a metabolism during functional activity, and, reasoning from
analogy, it seems probable that the same fact will eventually be
demonstrated for the axis cylinder.

Views as to the Nature of the Nerve Impulse. — The older con-
ceptions of the nerve principle, while they varied in detail, were
based upon the general idea that the nervous system contains a
matter of a finer sort than that visible to our senses. This matter
was pictured at first as a spirit (animal spirits), and later as a ma-
terial comparable to the luminiferous ether or to electricity. Since
the discovery that the nerve impulse travels with a relatively slow
velocity and is accompanied by a demonstrable change in the electrical
condition of the nerve, two main views regarding its nature have been
entertained. Many physiologists conceive the nerve impulse
as a progressive wave of chemical change which is started at one
end by the stimulus and is then self-propagated along the fiber.
The conception in general is represented by the transmission of a
spark along a line of gunpowder. The flame applied at one end
causes an explosive chemical change, which is then propagated
from point to point. The analogy is obviously very incomplete,
8

114 THE PHYSIOLOGY OF MUSCLE AND NERVE.

since in the train of gunpowder the material is entirely consumed,
whereas in the nerve an indefinite series of impulses may be trans-
mitted and with a strength varying with the intensity of the origina-
ting stimulus. This general view implies that a disassimilation or
catabolism occurs in the nerve, a breaking down of complex material
with the liberation of the potential chemical energy; it assumes,
in other words, that the wave of chemical change that sweeps
along a nerve fiber is similar to the wave of chemical change,
contraction wave, that passes over a muscle fiber. As was stated
in preceding paragraphs, there is no evidence for this view. It
has not been shown that in the conducting nerve there are any
detectible metabolic products formed. There is no rise in tempera-
ture, no change in reaction, no formation of carbon dioxid. The
view rests entirely upon analogy with what is known to occur in
other tissues, especially muscle, during functional activity. The
electrical change that accompanies the nerve impulse is considered
as a by-action, so to speak, due probably to the liberation of electro-
negative ions (anions) in the reaction that constitutes the nerve
impulse. The second general view of the nature of the nerve
impulse assumes that it is a physical or physico-chemical process
transmitted along the fiber without involving a metabolism of the
living nerve substance. One may find an analogy for such a process
in the wave of pressure transmitted through a tube filled with
liquid or the electrical current conveyed through a metallic con-
ductor. This view rests upon the fact that no consumption of
material can be demonstrated in the acting nerve fiber, and that
apparently the fiber can conduct indefinitely without showing
fatigue. Various suggestions have been offered as to the character
of this physical change, but the one that is perhaps most worthy
of consideration identifies the nerve impulse with the negative
electrical charge that is known to pass along the fiber. It is as-
sumed that this electrical charge constitutes the nerve impulse.
To explain the physics of the conduction it is supposed that the
nerve fiber has a structure essentially similar to the "core con-
ductor" (see p. 102) in that it contains a central thread surrounded
by a liquid sheath of less conductive material. The central thread
may be supposed to be the axis cylinder and the less conductive
sheath the surrounding myelin, or perhaps, to follow another
suggestion that fits the non-medullated as well as the medullated
fibers, the central threads are represented by the neurofibrils
within the axis cylinder and the surrounding sheath by the perifi-
brillar substance. That the axis cylinder is a better conductor
than the myelin sheath has been demonstrated by the micro-
chemical researches of Macallum. This observer has shown that
in the axis cylinder the chlorids exist in greater concentration

NATURE OF THE NERVE IMPULSE. 115

than in the surrounding sheath.* The point of importance is that,
with a core model (see Fig. 46) consisting of a glass tube with a
core of platinum wire and a sheath of solution of sodium chlorid,
0.6 per cent., electrical phenomena can be obtained similar to those
shown by the stimulated nerve. If an induction shock is sent into
such a model at one end and two leading off electrodes are connected
at another point, an action current may be detected for each stimu-
lus. It is evident, therefore, that in such a model, as in an ocean
cable, an electrical charge maybe transmitted in a wave-like form
when a current is applied at one end. And, as such a moving
electrical disturbance is the only objective phenomenon known
to occur in the stimulated nerve, it is assumed that it constitutes
the nerve impulse. When this electrical disturbance reaches the
end-organ, — the muscle, for instance, — it initiates the chemical
changes that characterize the activity of the organ. This kind
of theory makes the nerve impulse an electrical phenomenon, and
assumes that the nerve fibers have become differentiated to form
a specific kind of conductor, the efficiency of which depends upon
its having a structure similar to that of a "core conductor." It
should be added that this and, indeed, all specific theories of the
nature of the nerve impulse are, at present, matters for discussion
and experiment among specialists. We are far from having an
explanation of the nerve impulse resting upon such an experimental
basis as to command general acceptance, f

Bethe has proposed a theory of the production and conduction of the
nerve impulse which varies somewhat from the types given above. It is
founded upon an observed histological fact already referred to (p. 102). The
nerve impulse is defined in his hypothesis as a wave of chemical affinity be-
tween the fibrils and fibril acid which, starting at the point stimulated, is
transmitted along the nerve. There is thus conceived a kind of chemical
reaction which involves no liberation of internal energy. To account for
the electrical changes, it is assumed that, when the fibril and fibril acid com-
bine, electronegative ions — anions — are liberated, so that as the wave of
affinity progresses it is accompanied by an electronegative condition. J

Other somewhat similar theories have been proposed which attempt to
account for the negative electrical charge (nerve impulse) on the theory
of an electrolytic dissociation and an unequal velocity of migration in the
resulting ions. Thus Macdonald shows by microchemical reactions that the
axis cylinder contains potassium salts in combination with colloidal material.
On injury or stimulation the compound is dissociated and the colloid passes
possibly into a gel condition. The more rapid diffusion of the cations (K)
leaves an excess of anions which accounts for the negative change. The
process is reversible, so that an electrically neutral molecule is re-formed
after the passage of the impulse. §

* Macallum, "Proceedings of the Royal Society," 1906, B, Ixxvii., 165.

t For a summary of the literature upon the nature of the nerve impulse
consult Boruttau, "Zeit. f. allg. Physiologic," 1, 1, Sammelreferate, 1902;
Biedermann, " Ergebnisse der Physiologic," vol. ii, part n, 1903; Hering,
" Zur Theorie der Nerventhiitigkeit," 1899; Gotch, Schiifer's "Text-book of
Physiology," vol. ii, 1900.

J Bethe, " Allegemeine Ahatomie u. Physiologic des Nervensy stems." p.
301, 1903.

§ Macdonald, 'Proceedings of the Royal Society," B. Ixxvi., 322.

116 THE PHYSIOLOGY OF MUSCLE AND NERVE.

Qualitative Differences in Nerve Impulses and Doctrine of Spe-
cific Nerve Energies. — Whether or not the nerve impulses in vari-
ous nerve fibers differ in kind is a question of great interest in physi-
ology. The usually accepted view is that they are identical in
character in all fibers and vary only in intensity. According to
this view, a sensory nerve — the auditory nerve, for instance — car-
ries impulses similar in character to those passing along a motor
nerve, and the reason that in one case we get a sensation of hearing
and in the other a contraction of a muscle is found in the manner
of ending of the nerve, one terminating in a special part of the cortex
of the cerebrum, the other in a muscle. From this standpoint
the nerve fibers may be compared to electrical wires. The current
conducted by the wires is similar in all cases, but may give rise to
very different effects according to the way in which the wires ter-
minate, whether in an explosive mixture, an arc light, or solutions
of electrolytes of various kinds. We have in physiology what is
known as the doctrine of specific nerve energies, first formulated
by Johannes Miiller. This doctrine expresses the fact that nerve
fibers when stimulated give only one kind of reaction, whether
motor or sensory, no matter in what way they may be stimulated.
The optic nerve, for instance, gives us a sensation of light, usually
because light waves fall on the retina and thus stimulate the optic
nerve. But if we apply other forms of stimulation to the nerve
they will also, if effective, give a sensation of light. Cutting the
optic nerve or stimulating it with electrical currents gives visual
sensations. On the identity theory of the nerve impulses the
specific energies of the various nerves — that is, the fact that each
gives only one kind of response — is referred entirely to the charac-
teristics of the tissue in which the fibers end. If, as has been said,
one could successfully attach the optic nerve to the ear and the
auditory nerve to the retina then we should see the thunder and
hear the lightning.

The alternative theory supposes that nerve impulses are not
identical in different fibers, but vary in quality as well as intensity,
and that the specific energies of the various fibers depend in part at
least on the character of the impulses that they transmit. On
this theory one might speak of visual impulses in the optic nerves
as something different in kind from the auditory impulses in the
auditory fibers. With our present methods of investigation the
question is one that can not be definitely decided by experimental
investigation; most of the discussion turns upon the applicability
of the doctrine to the explanation of various conscious reactions
of the sensory nerves.

So far as experimental work has been carried out on efferent
nerves, it is undoubtedly in favor of the identity theory. The

NATURE OF THE NERVE IMPULSE.

117

action current is similar in all nerves examined; the reactions to
artificial stimuli are essentially similar. Moreover, nerves of,
one kind may be sutured to nerves of another kind, and, after re-
generation has taken place, the reactions are found to be deter-
mined solely by the place of ending (see p. 76) . i
The Nutritive Relations of the Nerve Fiber and Nerve Cell.
—In recent times in accordance with the so-called neuron doctrine
(see p. 123) every axis cylinder has been considered as a process of;
a nerve cell, and therefore as a part, morphologically speaking, of
that cell. However this may be, there is excellent experimental
evidence to show that the physiological integrity of the axis cylinder
depends upon its connection with its corresponding nerve cell. This
view dates from the interesting work of Waller,* who showed that
if a nerve be severed the peripheral stump, containing the axis cyl-
inders that are cut off from the cells, will degenerate in a few days.
The process of degeneration brought about in this way is known
as secondary or Wallerian degeneration. The central stump, on.
the contrary, remains intact, except for a short region immediately
contiguous to the wound, for a relatively long period, extending
perhaps over years. Waller, therefore, spoke of the nerve cells as
forming the nutritive centers for the nerve fibers, and this belief
is generally accepted* In what way the cell regulates the nutrition
of the nerve fiber throughout its whole length is unknown. Some of
the cells in the lumbar spinal cord, for instance, give rise to fibers of
the sciatic nerve which may extend as far as the foot, and yet

Fig. 50. — Diagram to show the direction of degeneration on section of the anterior
and the posterior root, respectively. The degenerated portion is represented in black.

throughout their whole length the nutritive processes in these fibers
are dependent on influences of an unknown kind, emanating from
the nerve cells to which they are joined. These influences may
consist simply in the effect of constant activity; that is, in the

* Waller, " Muller's Archiv," 1852, p. 392; and " Comptes rendus de
1'Acad. de la Science," vol. xxxiv., 1852.

118 THE PHYSIOLOGY OF MUSCLE AND NERVE.

conduction of nerve impulses, or there may be some kind of an
actual transferal of material. This latter idea is supported by the
interesting fact, which we owe to Meyer, that tetanus and diph-
theria toxins may be transmitted to the central nervous system
by way of the axis cylinders of the nerve fibers. By means of his
method Waller investigated the location of the nutritive centers
for the motor and sensory fibers of the spinal nerves. If an anterior
root is cut the peripheral ends of the motor fibers degenerate
throughout the length of the nerve, while the fibers in the stump
attached to the cord remain intact; hence the nutritive centers
for the motor fibers must lie in the cord itself. Subsequent histo-
logical work has corroborated this conclusion and shown that the
motor fibers of the spinal nerves take their origin from nerve cells
lying in the anterior horn of gray matter in the cord, the so-called
motor or anterior root cells. If the posterior root is cut between
the ganglion and the cord, the stump attached to the cord degener-
ates; that attached to the ganglion remains intact, and there is no
degeneration in the nerve peripheral to the ganglion (Fig. 50). If,
however, this root is severed peripherally to the ganglion degenera-
tion takes place only in the spinal nerve beyond the ganglion. The
nutritive center, therefore, for the sensory fibers must lie in the pos-
terior root ganglion, and not in the cord. This conclusion has also
been abundantly corroborated by histological work. It is known
that the sensory fibers arise from the nerve cells in these ganglia.
By the same means it has been shown that the motor fibers in the
cranial nerves arise from nerve cells (nuclei of origin) situated
in the brain, while the sensory fibers of the same nerves, with the
exception of the olfactory and optic nerves which form special
cases, arise from sensory ganglia lying outside the nervous axis,
such, for instance, as the spiral ganglia of the cochlear nerve, or
the ganglion semilunare (Gasserian ganglion) of the fifth cranial
nerve.

Nerve Degeneration and Regeneration. — When a nerve
trunk is cut or is killed at any point by crushing, heating, or other
means all the fibers peripheral to the point of injury undergo de-
generation. This is an incontestable fact, and it is important to
bear in mind the fact that the definite changes of degeneration are
exhibited only by living fibers. A dead nerve or the nerves in a
dead animal show no such changes.* The older physiologists
thought that if the several ends of the nerves were brought together
by sutures they might unite by first intention without degeneration
in the peripheral end. We know now that this degeneration is
inevitable once the living continuity of the fibers has been inter-
rupted in any way. Any functional union that may occur is a slow
* See Van Gehuchten, "Le Nevraxe," 1905, vii., 203,

Fig. 51. — Histology of a degenerating nerve fiber.

Fig. 52. — Embryonic fibers in a regenerating nerve.

Fig. 53. — A newly developed fiber in a regenerating nerve fiber.

NATURE OF THE NERVE IMPULSE. 119

process involving an act of regeneration of the fibers in the peripheral
stump. The time required for the degeneration differs somewhat
for the different kinds of fibers found in the animal body. In the
dog and in other mammalia the degeneration begins in a few (four)
days; in the frog it may require from thirty to one hundred and
forty days, depending upon the season of the year, although if the
frog is kept at a high temperature (30° C.) degeneration may
proceed as rapidly as in the mammal. In the dog it proceeds so
quickly that the process seems to be simultaneous throughout the
whole peripheral stump, while in the frog, and, according to Bethe,
in the rabbit, it can be seen clearly that the degenerative changes
begin at the wound and progress peripherally. The fibers break
up into ellipsoidal segments of myelin, each containing a piece of
the axis cylinder, and these segments in turn fragment very irregu-
larly into smaller pieces which eventually are absorbed* (Fig. 51).
The central stump whose fibers are still connected with the nerve
cells undergoes a similar degeneration in the area immediately
contiguous to the wound, but the degenerative processes extend
for only a short distance over an area covering a few internodal
segments. Although the central ends of the fibers remain sub-
stantially intact, it is interesting to find that the nerve cells from
which they originate undergo distinct changes, which show that
they are profoundly affected by the interruption of their normal
connections (see p. 121). In the peripheral end the process of
regeneration begins almost simultaneously with the degenerative
changes, the two proceeding, as it were, hand in hand. The regen-
eration is due to the activity of the nuclei of the neurilemmal sheath.
These nuclei begin to multiply and to form around them a layer of
protoplasm, so that as the fragments of the old fiber disappear
their place is taken by numerous nuclei and their surrounding
cytoplasm. Eventually there is formed in this way a continuous
strand of protoplasm with many nuclei, and the fiber thus produced,
which has no resemblance in structure to a normal nerve fiber,
is described by some authors as an "embryonic fiber"; by others
as a "band fiber" (Fig. 52). In the adult animal the process of
regeneration stops at this point unless an anatomical connection
is established with the central stump, and, indeed, such a connection
is usually established unless special means are taken to prevent it.
The central and peripheral stumps find each other in a way that
is often remarkable, the union being guided doubtless by intervening
connective tissue.

Forsmanns f has emphasized this peculiar attraction, as it were, be-
tween the peripheral and the central ends, giving some reason to believe that

*See Howell and Huber, "Journal of Physiology," 13, 335, 1892; also
Mott and Halliburton, "Proceedings Royal Society," 1906, B. Ixxviii., 259.
f Forsmanns, " Zeigler's Beitrage," 27, 216, 1902.

120 THE PHYSIOLOGY OF MUSCLE AND NERVE.

it is a case of chemotaxis or chemotropism. When the ends of the nerves
were given very unusual positions by means of collodium tubes into which
they were inserted they managed to " find " each other. Moreover, he states
that a central stump, if given an equal opportunity to grow into two collo-
dium tubes, one containing liver and the other brain tissue, will chose the
latter, a fact which would indicate some underlying chemical attraction or
affinity in nerve tissue for nerve tissue. A directive influence of this kind
depending upon some property connected with chemical relationship is desig-
nated as "" chemotaxis."

, If the central and peripheral stumps are brought together by
suture or grow together in any way, then, under the influence of the
central end, the " band fiber " gradually becomes transformed into
a normal nerve fiber, with myelin sheath and axis cylinder (Fig. 53).
It is usually believed that the axis cylinders are formed as out-
growths from those of the fibers of the central stump. These latter
penetrate the " band fibers" and grow throughout their length.

From a practical standpoint it is interesting to note that this influence
of the central stump may be exerted months or even years after the injury
to the nerve. The peripheral stump after reaching the stage of " band fibers "
is ready, as it were, for the influence of the central end, and cases are on record
in which a secondary suture was made a long time after the original injury,
with the result that functional activity was restored to the nerve.

Bethef has thrown some doubt upon this view, for he has
shown apparently that in young mammals (eight days to eight
weeks) the regeneration of the fibers in the peripheral stump does
not stop at the stage of "band .fibers/' but progresses until per-
fectly normal nerve fibers are produced, even though no connection
is made with the central stump. It should be added, however,
that the fibers so formed do not persist indefinitely unless they
become connected with the central stump. If this connection fails
to take place the newly formed fibers will degenerate after an
interval of some months. Still, the fact, if true, that in the young
fiber the regeneration is complete seems to indicate definitely that
the axis cylinder may arise independently of the fibers in the central
stump.

Whether or not Bethe's observations upon the autoregeneration of the
axis cylinders in the severed nerves of young animals can be accepted is at
present uncertain. Some authors have confirmed his results, others deny
their accuracy. (For discussion with references, see Barker, The Neurons in
the Harvey Lectures, 1905-06, Philadelphia, 1906 ; also Journal of the
American Medical Assoc., 1906, and the Neuron Theory, Stefanowska,
Journal de Neurologic, 1906, Nos. 16-19.)

The power of regeneration in the older animals is more limited
and carries the fiber only to the stage of the " band fiber." If under
the influence of the central stump an axis cylinder and myelin sheath
are now formed in this band fiber it is possible that this result
is due to local processes in the band fiber stimulated by nutritive
influences of some kind from the central stump, or more probably
there is an actual downgrowth of the axis cylinders from the central
ends.

*Bethe, " Allgemeine Anat. u. Physiologic des Nervensystems," 1903.

NATURE OF THE NERVE IMPULSE. 121

Degenerative Changes in the Neuron on the Central Side
of the Lesion. — According to the Wallerian law of degeneration,
as originally stated, the nerve fiber on the central side of the injury
and the nerve cell itself do not undergo any change. As a matter
of fact, the central stump immediately contiguous to the lesion
undergoes typical degeneration and regeneration similar to that
described for the fibers of the peripheral stump. The immediate
degenerative changes in the fibers in the central stump were supposed
to extend back only to the first node of Ranvier, — to affect, there-
fore, only the internodal segment actually injured. Later it was
found that the degeneration may extend back over a distance of
several internodal segments. This limited degeneration on the
central side must be considered as traumatic —that is, it involves
only those portions directly injured by the lesion. The central
end of the fiber in general was supposed to remain intact as long
as its cell of origin was normal. It was thought at first that after
simple section of a nerve trunk, in amputation, for instance, the
nerve cells and central stumps remain normal throughout the life
of the individual. Dickinson, however, in 1869 * showed that in
amputations of long standing the motor cells in the anterior horn
of the cord decrease in number and the fibers in the central stump
become atrophied. This observation has been corroborated by
other observers, and it is now believed that after section of a nerve
chronic degenerative changes ensue in the course of time in the
central fibers and their cells, resulting in their permanent atrophy.
We have, in such cases, what has been called an atrophy from
disuse. A fact that has been discovered more recently and that
is perhaps of more importance is that the nerve cells do undergo
certain definite although usually temporary changes immediately
after the section of the nerve fibers arising from them. It has been
shown that when a nerve is cut the corresponding cells of origin
may show distinct histological changes within the first twenty-four
hours. These changes consist in a circumscribed destruction of
the chromatin material in the cells (chromatolysis), which in a
short time extends over the whole cell, so that the primary staining
power of the cell is lost (condition of achromatosis) (see Fig. 58).
The cell also becomes swollen and the nucleus may assume an
excentric position. These retrogressive changes continue for a
certain period (about eighteen days). After reaching their maxi-
mum of intensity the cells usually undergo a process of restitution
and regain their normal appearance, although in some cases the
degeneration is permanent. According to other observers a number
of the cells in the spinal cord and spinal ganglia undergo simple
atrophy after section of their corresponding nerves, and some of
* " Journal of Anatomy and Physiology/' 3, 176, 1869.

122 THE PHYSIOLOGY OF MUSCLE AND NERVE.

the nerve fibers in the central stumps may also show atrophy,
while others undergo a genuine degeneration, which, however,
comes on much later than in the peripheral stumps. It seems
evident that the behavior of the cells and fibers on the central side
of the section is not uniform; atrophy rather than degeneration is
the change that is prominent, and this atrophy in some neurons
occurs early, while in others it is apparent only after a long interval
of time. An explanation of this variation in the reaction of the
nerve cells and their disconnected central stumps cannot yet be
given. On the peripheral side of the section, as stated above, the de-
generative changes are complete and affect all of the fibers.*

*Nissl, "Allgemeine Zeitschrift f. Psychiatric, " 48, 197, 1892. Also
Bethe, loc. tit., and Ranson, "Retrograde Degeneration in the Spinal Nerves,"
The Journal of Comparative Neurology and Psychology, 1906, xvi., 265.

SECTION II.

THE PHYSIOLOGY OF THE CENTRAL
NERVOUS SYSTEM.

CHAPTER VI.

STRUCTURE AND GENERAL PROPERTIES OF THE
NERVE CELL.

The Neuron Doctrine. — Since the last decade of the nineteenth
century the physiology of the nervous system has been treated
from the standpoint of the neuron. According to this point of
view, the entire nervous system is made up of a series of units,
the neurons, which are not anatomically continuous with each
other, but communicate by contact only. It has been taught also
that each neuron represents from an anatomical and physiological
standpoint a single nerve cell. The typical neuron consists of
a cell body with short, branching processes, the dendrites, and a
single axis cylinder process, the axon or axite, which becomes a
nerve fiber, acquiring its myelin sheath at some distance from the
cell. According to this view, the peripheral nerve fibers are simply
long processes from nerve cells. Within the central nervous system
each neuron connects with others according to a certain schema.
The axon of each neuron ends in a more or less branched " terminal
arborization/' forming a sort of end-plate which lies in contact
with the dendrites of another neuron, or in some cases with the
body of the cell itself, the essentially modern point of view being
that where the terminal arborization of the axon meets the dendrites
or body of another neuron the communication is by contact, the
neurons being anatomically independent units. It is usually ac-
cepted also as a part of the neuron doctrine that the conduction
of a nerve impulse through a neuron is always in one direction,
that the dendrites are receiving organs, so to speak, receiving a
stimulus or impulse from the axon of another unit and conveying
this impulse toward the cell body, while the axon is a discharging
process through which an impulse is sent out from the cell to reach
another neuron or a cell of some other tissue. The neuron, so

123

124

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

far as conduction is concerned, shows a definite polarity, the con-
duction in the dendrites being cellulipetal, in the axons, cellulifugal.

The neuron doctrine, so far as the name at least is concerned, dates from
a general paper by Waldeyer,* in which the newer work up to that time was
summarized. The main facts upon which the conception rests were furnished
by His (1886), to whom we owe the generally accepted belief that the nerve
fiber (axis cylinder) is an outgrowth from the cell, and secondly by Golgi,
Cajal, and a host of other workers, who, by means of the new method of Golgi,
demonstrated the wealth of branches of the nerve cells, particularly of the
dendrites, and the mode of connection of one nerve unit with another. The
view that these units are anatomically independent and on the embryological

Fig. 54. — Motor cell, anterior horn of gray matter of cord. From human fetus (Lenhoa-
sek): * marks the axon; the other branches are dendrites.

side are derived each from a single epiblastic cell (neuroblast) has proved
acceptable and most helpful; but the validity of this hypothesis has been
called into question. As was stated on p. 120. Bethe has claimed that in
young animals the nuclei of the neurilemmal sneath may regenerate a new
nerve fiber containing axis cylinder and myelin sheath, and this fact, if true,
at once brings into question the hitherto accepted belief that the axis cylin-
der can be formed only as an outgrowth from a nerve cell. Some histologists—
Apathy, Bethe, Nissl — have also attacked the most fundamental feature of
the neuron doctrine, — the view, namely, that each neuron represents an inde-
pendent anatomical element. These authors contend that the neurofibrils of
the axis cylinder pass through the nerve cells and enter by way of a network
into direct connection with the neurofibrils of other neurons (see Fig. 59).
*"Deut. med. Wochenschrift," 1891, p. 50.

PROPERTIES OF THE NERVE CELL. 125

The neurofibrils form a continuum through which nerve impulses pass without
a, break from neuron to neuron. According to this conception, the ganglion
cells plav no direct part hi the conduction of the impulse from one part of the
nervous' system to another; the neurofibrils alone, and the mtracellular
and pericellular networks with which they connect, form the conducting
paths that are everywhere in continuity. In the explanation given below
of the activities of the nervous system the author, following the usual cus-
tom, makes use of the neuron doctrine, since it is at present impossible to
say whether or not the newer views of the continuum of neurofibrils will be
-corroborated. While the physiological facts remain the same whichever view
prevails, there can be no doubt that the point of view of the physiologist
would be greatly changed if the present simple conception of a series of neu-
rons of a definite polarity as regards conduction were replaced by the more
•complex schema of independent neurofibrils and a central reticulum in which
a basis for polarity and definite paths of conduction is lacking.

The Varieties of Neurons. — The neurons differ greatly in
size, shape, and internal structure, and it is impossible to classify
them with entire success from either a physiological or an anatomical
standpoint. Neglecting the unusual forms whose occurrence is
limited and whose structure is perhaps incompletely known, there
are three distinct types whose form and structure throw some
light on their functional significance:

I. The bipolar cells. This cell is found in the dorsal root gan-
glia of the spinal nerves and in the ganglia attached to the sensory
fibers of the cranial nerves, the ganglion semilunare (Gasserian)
for the fifth cranial, the g. geniculi for the seventh, the g. vestibu-
lare and g. spirale for the eighth, the g. superius and g. petrosum
for the ninth, the g. jugulare and g. nodosum for the tenth.

The typical cell of this group is found in the dorsal root ganglia.
In the adult the two processes arise as one, so that the cell seems to
be unipolar, but at some distance from the cell this process divides
in T, one branch passing into the spinal cord via the posterior
root, the other entering the spinal nerve as a sensory nerve fiber
to be distributed to some sensory surface. Both processes become
medullated and form typical nerve fibers. That these apparently
unipolar cells are really bipolar is shown not only by this division
into two distinct fibers, but also by a study of their development
in the embryo. In early embryonic life the two processes arise
from different poles of the cell, and later become fused into an ap-
parently simple process (Fig. 55). The striking characteristics of
this cell, therefore, are that it gives rise to two nerve fibers, and that
it possesses no dendritic processes. On the physiological side these
cells might be designated as sensory cells, since they appear to be
associated always with sensory nerve fibers. So far as the sensory
fibers of the spinal and cranial nerves are concerned, it is worth
noting also that all of them arise from cells lying outside the main

* For discussion, see Barker, "Journal of the American Medical Associa-
tion," 1906, and Stefanowska, "Journal de Neurologic, " 1906, Nos. 16-19.

126 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

axis of the central nervous system. The sensory impulses brought
to the cell by the process arising in the peripheral tissue doubtless
pass into the body of the cell before entering the process that
leads to the cord or brain, — that is, it is not probable that the im-
pulse passes from one process to the other at the T junction, since
the really conducting elements in the axis cylinder, the neurofibrils,
are not in connection at this point, but end in the network or retic-
ulum of the cell itself.

II. The multipolar cells. The processes of these cells fall into
two groups: the short and branching dendrites with an inner
structure resembling that of the cell body, and the axon or axis
cylinder process (Fig. 54). According to the structure of this last
process, this type may be classified under two heads: Golgi cells of

Fig. 55. — Bipolar cells in the posterior root ganglion. Section through spinal gan-
glion of newborn mouse (Lenhossek): a, The spinal ganglion; b, the spinal cord; c, the
posterior, d, the anterior root.

the first and the. second type. The cells of the first type are charac-
terized by the fact that the axon leaves the central gray matter and
becomes a nerve fiber. This nerve fiber within the central nervous
system may give off numerous collaterals, each of which ends in a
terminal arborization. By this means the neurons of this type may
be brought into physiological connection with a number of other neu-
rons. This kind of nerve cell is frequently described as the typical
nerve cell. Golgi supposed that it represents the motor type of cell,
and this view is, in a measure, borne out by subsequent investiga-
tion. The distinctly motor cells of the central nervous system—
such, for instance, as the pyramidal cells of the cerebral cortex, the
anterior hern cells of the spinal cord, the Purkinje cells of the
cerebellum — all belong to this type. But within the nerve axis

PROPERTIES OF THE NERVE CELL. 127

most of the conduction from neuron to neuron, along sensory as
well as motor paths, is made with the aid of such structures, the
dendrites being the receptive or sensory organ and the axon the
motor apparatus.

The Golgi cells of the second type (Fig. 56) are relatively less
numerous and important. They are characterized by the fact that
the axon process instead of
forming a nerve fiber splits
into a great number of ' ^C\

branches within the gray W^,

matter. Assuming that in 1%;* $•

such cells the distinction be- w^ >/;??&

tween the axon and the den-
drites is well made and that
as in the other type the ^^^.'^^
dendrites form the receiving /i^fl
and the axon the discharging =
apparatus, these cells would
seem to have a distributive
function. The impulse that jfr'r,

they receive may be trans- ')

7,

V

Fig. 56. — Golgi cell (second type). Fig. 57. —Normal anterior horn ceti

The axon, a, divides into a number of (Warrington) , showing the Nissl granules in the

fine branches. — (From Obersteiner, after cell and dendrites: a, The axon.
Andriezen.)

mitted to one or many neurons. They are sometimes spoken of as
intermediate or association cells.

Internal Structure of the Nerve Cell.— Within the body of
the nerve cell itself the striking features of physiological signifi-
cance are, first, the arrangement of the neurofibrils, and, second, the

128 . PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

presence of a material in the form of granules, rods, or masses
which stains readily with the basic anilin dyes, such as methylene
blue, thionin, or toluidin blue. This latter substance is spoken of
as the " chromophile substance," tigroid, or more frequently as
Nissl's granules, after the histologist who first studied it success-
fully. These masses or granules are found in the dendrites as well
as in the cell, but are absent from the axon (see Fig. 57). Little is
known of their composition or significance, but their presence or ab-
sence is in many cases characteristic of the physiological condition
of the cell. After lesions or injuries of the neuron the material may
become dissolved and diffused through the cell or may decrease in
amount or disappear, and it seems probable, therefore, that it repre-
sents a store of nutritive material (Fig. 58). The non-staining
material of the cell, according to most recent observers, contains
neurofibrils which are continued out into the processes, dendrites as

Fig. 58. — Anterior horn cell fourteen days after section of the anterior root (Warring-
tori) : To show the change in the nucleus and the Nissl granules, beginning chromatolysis.

well as axons. These fibrils may be regarded as the conducting
structure along which passes the nerve impulse. The arrangement
of these fibrils within the cell is not completely known, the results
obtained varying with the methods employed. A matter of far-
reaching importance on the physiological side is the question of
the existence of an extracellular nervous network. Most recent
histologists agree in the belief that there is a delicate network
surrounding the cells and their protoplasmic processes. This
pericellular net or Golgi's net is claimed by some to be a ner-
vous structure connecting with the neurofibrils inside the cell
and forming not only a bond of union between the neurons, but
possibly also an important intercellular nervous structure that
may play an important role in the functions of the nerve centers.
This view is represented schematically in Fig. 59. According to
others, this network around and outside the cells is a supporting
tissue simply that takes no part in the activity of the nerve units.

PROPERTIES OF THE NERVE CELL. 129

General Physiology of the Nerve Cell. — Modern physiologists
have considered the cell body of the neuron, including the den-
drites, as the source of the energy displayed by the nervous system,
and it has been assumed that this energy arises from chemical
changes in the nerve cell, as the energy liberated by the muscle
arises from the chemical changes in its substance. It would follow
from this standpoint that evidences of chemical activity should be
obtained from the cells and that these elements should exhibit the
phenomenon of fatigue. Regarding this latter point, it is believed
in physiology that the nerve cells fatigue readily. The nerve
centers show fatigue as the result of continuous activity, as is evident
from our personal experience in prolonged intellectual or emo-
tional activity and as is implied in the necessity of sleep for re-

Fig. 59. — Bethe's schema to indicate the connections of the pericellular network:
Rz, A sensory cell in the posterior root ganglion; the fibrils in the branch that runs to the
cord are indicated as connecting directly with the pericellular network of the motor cells,
Gz.

cuperation and the rapidity with which functional activity is lost
on withdrawal of the blood supply. Objectively, also, it has been
shown in the ergographic experiments (see p. 45) that the well-
known fatigue of the neuromuscular apparatus possibly affects
the nerve centers as well as the muscle. Assuming that the nerve
cells are the effective agent in the nerve centers, such facts indicate
that they are susceptible to fatigue. But we have no very direct
proof that this property is possessed universally by the nerve cells
nor any indication of the probable differences in this regard shown
by nerve cells in different parts of the central nervous system.
It seems probable that under normal conditions — that is, under
the influence of what we may call minimal stimuli — some portions
of the nerve centers remain in more or less constant activity during

9

130 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

the day without showing a marked degree of fatigue, just as our
muscles remain in a more or less continuous state of tonic con-
traction throughout the waking period at least. Doubtless when
the stimulation is stronger the fatigue is more marked, because the
processes of repair in the nerve centers can not then keep pace
with the processes of consumption of material. Evidence of a
probable chemical change in the nerve cells during activity is found
also in the readiness with which the gray matter of the nervous
system takes on an acid reaction.* In the fresh resting state it
is probably alkaline or neutral, but after death it quickly shows an
acid reaction, due, it is said, to the production of lactic acid. Its
resemblance to the muscle in this respect leads to the inference
that in functional activity acid is also produced. Mosso states
that in the brain increased mental activity is accompanied by a
rise in the temperature of the brain, f His experiments were made
upon individuals with an opening in the skull through which a
delicate thermometer could be inserted so as to lie hi contact with
brain. So also the facts briefly mentioned in regard to the Nissl
granules give some corroborative evidence that the activity of
the nervous system is accompanied by and probably caused by
a chemical change within the cells, since the excessive activity of
the nerve cells seems to be accompanied by some change in these
granules, and in abnormal conditions associated with loss of func-
tional activity the granules undergo chromatolysis, — that is, they
are disintegrated and dissolved. Obvious histological changes which
imply, of course, a change in chemical structure, have been observed
by a number of investigators.:]: All seem to agree that activity of
the tissue, whether normal or induced by artificial stimulation,
may cause visible changes in the appearance of the cell and its
nucleus. Activity within normal limits may cause an increase in
the size of the cell together with a diminution in the stainable
(Nissl) substance, and excessive activity a diminution in size of the
cell and the nucleus, the formation of vacuoles in the cell body,
and a marked effect upon the stainable material. Hodge has
shown that in birds, for instance, the spinal ganglion cells of a
swallow killed at nightfall after a day of activity exhibit a marked
loss of substance as compared with similar cells from an animal
killed in the early morning (Fig. 60).

It must be remembered, however, that our knowledge of the
nature of the chemical changes that occur in the cell during activity
is very meager. Presumably carbon dioxid and lactic acid are

* Lan^endorff, "Centralbl. f. d. med. Wiss.," 1886. See also Halliburton,
"The Croonian Lectures on The Chemical Side of Nervous Activity, " 1901.

f Mosso, " Die Temperatur des Gehirns," 1894.

} See especially Hodge, "Journal of Morphology," 7, 95, 1892, and
9, 1, 1894.

PROPERTIES OF THE NERVE CELL.

131

formed as in muscle, and we know that oxygen is consumed.
Enough is known perhaps to justify the general view that the energy
exhibited by the nervous system is derived, in the long run, from
a metabolism of material in the nerve cells, a metabolism which
consists essentially in the splitting and oxidation of the complex
substances in the protoplasm of the cell.

Summation of the Effects of Stimuli. — In a muscle a series
of stimuli will cause a greater amount of shortening than can be
obtained from a single stimulus of the same strength. In this case
the effects of the stimuli are' summated, one contraction taking
place on top of another, or to put it in another way, the muscle
while in a condition of contraction from one stimulus is made to

Fig. 60. — Spinal ganglion cells from English sparrows, to show the daily variation in
the appearance of the cells due to normal activity: A, Appearance of cells at the end of
an active day; B, appearance of cells in the morning after a night's rest. The cytoplasm
is filled with clear, lenticular masses, which are much more evident in the rested cells than
in those fatigued.— (Hodge.)

contract still more by the following stimulus. In the nerve fiber
such a phenomenon has not been demonstrated. The strength of
the nerve impulse can be determined only by means of the effect
on the end-organ, — e. gr.,the muscle, — in which case the properties
of the end-organ must be taken into account, or by the aid of the
electrical response. Now, when a nerve is stimulated so rapidly
that the second stimulus falls into the nerve before the electrical
change due to the first stimulus has passed off, the second stimulus,
instead of adding its effect to that of the first, simply has no effect
at all; it finds the nerve unirritable.* According to this result,
we should expert that a summation of the effeets of rapidly
* Gotch and Burch, " Journal of Physiology," 24, 410, 1899.

132 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

following stimuli is not possible in the case of the nerve fiber.
In the nerve cell, on the contrary, it is usually taught that the
power of summation is a characteristic property, although it
may be said that the proofs for this belief are not very direct.
It is pointed out that, while a single stimulus applied to a sensory
nerve may be ineffective in producing a reflex response from the
central nervous system, a series of such stimuli will call forth a
reaction. In this case it is assumed that the effects of the suc-
ceeding stimuli are summated within the nerve cells through which
the reflex takes place, and, generally speaking, it is assumed in
physiology that the nerve centers are adapted by their power of
summation to respond to a series of stimuli or to continuous stimu-
lation. The best examples of this kind of action are obtained
perhaps from sensory nerves, in which case we judge of the intensity
of the cell activity by the concomitant sensation, or by a reflex
response.

Response of the Nerve Cell to Varying Rates of Stimula-
tion.— The various parts of the neuromuscular apparatus —
namely, the nerve cell, the nerve fiber, and the muscle fiber — have
different degrees of responsiveness to repeated stimuli, and this
responsiveness varies, moreover, for the different kinds of mus-
cles and of nerve fibers, and, probably for the different kinds
of nerve cells. The motor cells of the brain discharge their
motor impulses normally at a rate probably of about 10 per second
(see p. 44), and it is very interesting to find that, if these cells
are stimulated artificially, their rate of motor discharge does not
keep pace with that of the stimulation employed, but occurs at
about the same rate as the normal, — namely, at about 10 per
second. Thus, Horsley and Schafer* found that in monkeys, dogs,
cats, and rabbits, stimulation of the motor regions of the cortex
or the motor cells in the cord gave tetanic muscular contractions,
which from their graphic records were evidently composed of
simple contractions following at an average rate of 10 per second,
although the stimuli applied to the center might vary in rate from
10 to 50 per second. Similar results by a somewhat different
method were obtained by Broca and Richet.f These authors point
out, moreover, that no mental act can be repeated more rapidly
(on the average) than 10 times per second. If one, for instance,
attempts to think a series of syllables or words in a given phrase
the maximum of rapidity with which each syllable can be clearly
thought is at the rate named. The authors last named believe,
therefore, that the minimal duration for an intellectual act is
probably approximately about y-g- of a second. These facts, so

* Horsley and Schafer, " Journal of Physiology," 7, 96, 1886.

t Broca and Richet, "Journal de physiol. norm, et pathol," 1897, p. 864.

PROPERTIES OF THE NERVE CELL. 133

far as they go, would indicate that in the cerebrum and the cord
the nerve cells react with a certain rhythm.

The Refractory Period of the Nerve Cell. — The peculiar
rhythm of the active nerve cell just referred to in the para-
graph above is explained most satisfactorily by an assumption
first used in connection with the rhythmical beat of the heart. As
will be explained more fully in the section on the physiology of
the heart, it has been found that after the contraction of the
heart begins it is unirritable *to artificial stimuli, and that its
irritability is recovered during the period of rest, — the diastole.
The heart has, therefore, alternate periods of irritability and
unirritability. The latter phase, the condition in which the heart
muscle will not respond to stimulation, is known as the refractory
period, or refractory phase. A similar conception has been applied
to the nerve cell. The experiments cited in the preceding para-
graph would indicate that, after the discharge of an impulse, the
cell falls into a refractory phase for a period of time lasting about
0.1 sec. The idea* is a convenient one, although we have no explana-
tion of what is the immediate cause of this temporary loss of irrita-
bility. Reasoning from analogy with the muscle, we might suppose
that it is due to some product of the chemical reaction that is
assumed to underlie nervous activity. Using this terminology,
it is probable that the cells in different parts of the nervous system
may have different refractory periods. In the case of the normal
nerve fiber (see p. 112) it will be recalled that the refractory period
is very brief, — say, 0.006 sec., — but varies with the condition of
the fiber, since in the narcotized fiber it may be as much as 0.1 sec.

CHAPTER VII.
REFLEX ACTIONS,

Definition and Historical. — By a reflex action we mean the
involuntary production of activity in some peripheral tissue through
the efferent nerve fibers connected with it in consequence of a
stimulation of afferent nerve fibers. The conversion of the sensory
or afferent impulse into a motor or efferent impulse is effected in
the nerve centers, and may be totally unconscious as well as invol-
untary,— for instance, the emptying of the gall-bladder during
digestion, or it may be accompanied by consciousness of the act,
as, for example, in the winking reflex when the eye is touched.
The application of the term reflex to such acts seems to have been
made first by Descartes* (1649), on the analogy of the reflection
of light, the sensory effect in these cases being reflected back, so
to speak, as a motor effect. The attention of the early physiologists
was directed to these involuntary movements and many instances
were collected, both in man and the lower animals. Their invol-
untary character was emphasized by the discovery that similar
movements are given by decapitated animals, — frogs, eels, etc.

Some of the earlier physiologists thought that the reflex might
occur in the anastomoses of the nerve trunks, but a convincing
proof that the central nervous system is the place of reflection
was given by Whytt (1751). He showed that in a decapitated frog
the reflex movements are abolished if the spinal cord is destroyed.
Modern interest in the subject was excited by the numerous works
of Marshall Hall (1832-57), who contributed a number of new
facts with regard to such acts, and formulated a view, not now
accepted, that these reflexes are mediated by a special set of fibers —
the excitomotor fibers.

In describing reflexes the older physiologists had in mind only
reflex movements, but at the present time we recognize that the
reflex act may affect not only the muscles, — voluntary, involuntary,
and cardiac, — but also the glands. We have to deal with reflex
secretions as well as reflex movements.

The Reflex Arc. — It is implied in the definition of a reflex
that both sensory and motor paths are concerned in the act. Ac-

* See Eckhard, " Geschichte der Entwickelung der Lehre von den Reflex-
erscheinungen," "Beitriige zur Anatomic u. Physiologic," Giessen, 1881, vol.
ix.

134

REFLEX ACTIONS.

135

cording to the neuron theory, therefore, the simplest reflex arc
must consist of two neurons: the sensory neuron, whose cell body
lies in one of the posterior root or cranial nerve ganglia, and a
motor neuron, whose nerve cell lies in the anterior horn of gray
matter of the cord or in the motor nucleus of a cranial nerve. The
reflex arc for the spinal cord is represented in Fig. 61. The arc
may, however, be more complex. The sensory fibers entering
through the posterior roots may pass upward through the entire
length of the cord to end in the medulla and on the way give off
a number of collaterals as represented in Fig. 62, or they
may make connections with intermediate cells which, in turn, are
connected with one or more motor neurons (Fig. 63). According

Fig. 61. — Schema to show the connection between the neuron of the posterior root and the
neuron of the anterior root, — the reflex arc.

to these schemata, one sensory fiber may establish reflex connections
with a number of different motor fibers, or, a fact which must be
borne in mind in studying some of the well-known reflex activities
of the cord and medulla especially, a sensory fiber carrying an
impulse which eventually reaches the cortex of the cerebrum and
gives rise to a conscious sensation may, by means of its collaterals,
connect with motor nuclei in the cord or medulla and thus at the
same time give origin to involuntary and even unconscious re-
flexes. Painful stimulation of the skin, for example, may give
us a conscious sensation of pain and at the same time reflexly
stimulate the vasomotor center and cause a constriction of the
small arteries. The fact that in this case two distinct events occur
does not necessitate the assumption that the impulses from the

136

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

skin are carried to the cord by two different varieties of fibers
It may well be that one variety of sensory neuron, the so-called
pain fibers, effects both results, because of the opportunities in
the cord for connections with different groups of nerve cells.

The Reflex Frog. — The motor reflexes from the spinal cord
can be studied most successfully upon a frog in which the brain
has been destroyed or whose head has been cut off. After such
an operation the animal may for a time suffer from shock, but
a vigorous animal will usually recover and after some hours will

Fig. 62. — Kolliker's schema to show
the direct reflex arc. It shows the pos-
terior root fiber (black) entering the
cord, dividing in Y. and connecting with
motor cells (red) by means of collater-

Fig. 63. — Kolliker's schema to
show the reflex arc with intercal-
ated tract cells. Posterior root fiber,
black; intercalated tract cell, blue;
motor cells, red.

exhibit reflex movements that are most interesting. The funda-
mental characteristics of reflex movements in their relations to the
place, intensity, and quality of the stimulus can be studied with
more ease upon an animal whose cord is thus severed from the
brain than upon a normal animal. In the latter case the connec-
tions in the nervous system are more complex and the reactions
are therefore less simple and less easily kept constant.

Spinal Reflex Movements. — The reflex movements obtained
from the spinal cord or from parts of the central nervous system

REFLEX ACTIONS. 137

may be divided into three groups by characteristics that are physio-
logically significant. These classes are: (1) Simple reflexes, or
those in which a single muscle is affected. The best example of
this group is perhaps the winking reflex, in which only the orbic-
ularis palpebrarum is concerned. (2) Co-ordinated reflexes, in
which a number of muscles react with their contractions so grad-
uated as to time and extent as to produce an orderly and useful
movement. (3) Convulsive reflexes, such as are seen in spasms,
in which a number of muscles— perhaps all the muscles — are con-
tracted convulsively, without co-ordination and with the pro-
duction of disorderly and useless movements. Of these groups,
the co-ordinated reflexes are by far the most interesting. They
can be obtained to perfection from the reflex frog. In such an
animal no spontaneous movements occur if the sensory surfaces are
entirely protected from stimulation. A sudden stimulus, however,
of sufficient strength applied to any part of the skin will give a
definite and practically invariable response in a movement which
has the appearance of an intentional effort to escape from or remove
the stimulus. If the toe is pinched the foot is withdrawn — in a
gentle manner if the stimulus is light, more rapidly and violently,
but still in a co-ordinated fashion, if the stimulus is strong. If
the animal is suspended and various spots on its skin are stimulated
by the application of bits of paper moistened with dilute acetic
acid the animal will make a neat and skillful movement of the
corresponding leg to remove the stimulating body. The reactions
may be varied in a number of ways, and in all cases the striking
features of the reflex response are, first, the seemingly purposeful
character of the movement, and, second, the almost mechanical
exactness with which a definite stimulus will give a definite response.
This definite relationship holds only for sensory stimulation of the
external integument, the skin and its organs. It is obvious, in
fact, that a muscular response can be effective only for stimuli
originating from the external surface. Stimuli from the interior
of the body exert their reactions, for the most part, upon the plain
musculature and the glands. The convulsive reflexes may be
produced by two different means : (1) By very intense sensory
stimulation. The reflex response in this case overflows, as it were,
into all the motor paths. A variation of this method is seen in the
well-known convulsive reaction that follows tickling. In this case
the stimulus, although not intense from an objective standpoint,
is obviously violent from the standpoint of its effectiveness in
sending into the central nervous system a series of maximal sensory
impulses. (2) By heightening the irritability of the central nervous
system. Upon the reflex frog this effect is obtained most readily
by the use of strychnin. A little strychnin injected under the

138 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

skin is soon absorbed and its effect is shown at first by a greater
sensitiveness to cutaneous stimulation, the slightest touch to
the foot causing its withdrawal. Soon, however, the response,
instead of being orderly and adapted to a useful end, becomes
convulsive. A mere touch of the skin or a current of air will throw
every muscle into contraction, and the extensors being stronger than
the flexors the animal's body becomes rigid in extension at every
stimulation. The explanation usually given for this result is that
the strychnin, acting upon some part of the nerve cells, increases
greatly their irritability, so that when a stimulus is sent into the
central nervous system along any sensory path from the skin it
apparently radiates throughout the cord and acts upon all the
motor cells. This latter supposition leads to the interesting con-
clusion that all the various motor neurons of the cord must be in
physiological connection, either direct or indirect, wdth all the
neurons supplying the cutaneous surface. The further fact that
under normal conditions the effect of a given sensory stimulus is
manifested only on a limited and practically constant number
of the motor neurons seems to imply, therefore, that normally the
paths to these neurons are more direct and the resistance, if we
may use a somewhat figurative term, is less than that offered by
other possible paths. Muscular spasms are observed under a number
of pathological conditions, — for instance, in hydrophobia. We are
at liberty to assume in such cases that the toxins produced by the
disease affect the irritability of the cells in much the same way as
the strychnin.

Theory of Co-ordinated Reflexes. — The purposeful character
of the co-ordinated reflexes in the frog gives the impression to the
observer of a conscious choice of movements on the part of the
brainless animal. Most physiologists, however, are content to see
in these reactions only an expression of the automatic activity
of a mechanism. It is assumed that the sensory impulses from
any part of the skin find, on reaching the cord, that the paths to
a certain group of motor neurons are more direct and offer less
resistance than any others. It is along these paths that the reflex
will take place, and we may further assume that these paths of
least resistance, as they have been called, are in part preformed
and in part are laid down by the repeated experiences of the indi-
vidual. That is, in each animal a definite structure may be sup-
posed to exist in the cord; each sensory neuron is connected with
a group of motor neurons, to some of them more directly than to
others, and we may imagine, therefore, a system of reflex apparatuses
or mechanisms which when properly stimulated will react always
in the same way. And, indeed, in spite of the adapted character
of the reflexes under consideration their automaton-like regularity
is an indication that their production is due to a fixed mechanical

REFLEX ACTIONS. 139

arrangement. Whether or not the reactions of the nervous system
in such cases are accompanied by any degree of consciousness can
not be proved or disproved, but the assumption of such an accom-
paniment does not seem necessary to explain the reaction.

Spinal Reflexes in the Mammals. — Experiments upon the lower
mammals, such as the dog, show that co-ordinated reflex move-
ments may be obtained from the lower portion of the cord after
severance of its connections with the brain. The spinal cord
may be severed, for instance, in the thoracic region and the animal
be kept alive and in good condition for an indefinite period. In
such an animal reflex movements of the hind legs or tail may be
obtained readily from slight sensory stimulation of the skin. The
knee-jerk and similar so-called deep reflexes are also retained. But
it is evident that these movements are not so complete nor so
distinctly adapted to a useful end as in the frog. The muscles of
the body supplied by the isolated part of the cord retain, however,
a normal irritability and exhibit no wasting. In man, on the
contrary, it is stated that after complete section of the cord the deep
reflexes, such as the knee-jerk, as well as the skin reflexes, are very
quickly lost. The muscles undergo wasting and soon lose their
irritability.* The monkeys exhibit in this respect a condition that
is somewhat intermediate between that of the dog and man. It
seems evident from these facts that in the tower animals, like the
frog, a much greater degree of independent activity is exhibited by
the cord than in the more highly developed animals. According to
the degree of development, the control of the muscles is assumed
more and more by the higher portions of the nervous system, and
the spinal cord becomes less important as a series of reflex centers,
its functions being more dependent upon its connections with the
higher centers.

Dependence of Co-ordinated Reflexes upon the Excitation
of the Normal Sensory Endings, — It is an interesting fact that
when a nerve trunk is stimulated directly in a reflex frog — the
sciatic nerve, for instance — the reflex movements are disorderly
and quite unlike those obtained by stimulating the skin. It is said
that if the skin be loosened and the nerve twigs arising from it be
stimulated, an operation that is quite possible in the frog, the re-
sponse is again a disorderly reflex, whereas the same fibers stimu-
lated through the skin give an orderly, co-ordinated movement.
The difference in response in these cases is probably not due to any
peculiarity in the nature of the sensory impulses originating in the
nerve endings of the skin, but more likely to a difference in their
strength and arrangement. When one stimulates a sensory nerve
trunk directly, — the ulnar nerve at the elbow in ourselves, for in-
* See Collier, " Brain," 1904, p. 38.

140 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

stance, — the resulting sensations are markedly different from those
obtained by stimulating the skin areas supplied by the same nerve ;
we have little or no sensations of touch or temperature, only pain
and a peculiar tingling in the fingers. In such an experiment the
stimulus applied to the trunk affects more or less equally all the
contained fibers, whereas in stimulation of the skin itself the effect
upon the cutaneous fibers of pressure, temperature, or pain pre-
dominates and presumably it is these fibers that normally are con-
nected in an efficient way with the reflex machinery in the nerve
centers.

Reflex Time. — Since in a reflex movement the nerve centers
are involved a determination of the total time between the appli-
cation of the stimulus and the beginning of the response gives a
means of ascertaining the time element concerned in the central
processes. Helmholtz, who first made experiments of this kind,
stated that the time required within the nerve centers might be as
much as twelve times as great as that estimated for the conduction
along the motor and sensory nerves involved in the reflex. Most
observers state that the time within the center varies with the
strength of the stimulus, being less the stronger the stimulus. It
varies also with the condition of the nerve centers, being lengthened
by fatigue and other conditions that depress the irritability of the
nerve cells. By reflex -time or reduced reflex time we may designate
the time required for the processes in the center, — that is, the total
time less that required for transmission of the impulse along the
motor and sensory fibers and the latent period of the muscle con-
traction. For the frog this is estimated as varying between
0.008 and 0.015 sec. In man the reflex time usually quoted is that
given by Exner for the winking of the eye. He stimulated one lid
electrically and recorded the reflex movement of the lid of the other
eye. The total time for the reflex was, on an average, from 0.0578
sec. to 0.0662 sec. He estimated that the time for transmission of
the impulse along the sensory and motor paths, together with the
latent period of the muscle, amounted to 0.0107 sec. So that the
true reflex time from his determinations varied between 0.0471 and
0.0555 sec. Mayhew,* using a more elaborate method, obtained
for the total time a mean figure equal to 0.0420 sec. If Exner's
correction is applied then the true reflex time according to this de-
termination is equal to 0.0313 sec.

Inhibition of Reflexes. — One of the most fundamental facts
regarding spinal reflexes is the demonstration that they can be
depressed or suppressed entirely — that is, inhibited — by other im-
pulses reaching the same part of the spinal cord. The most sig-
* Mayhew, " Journal of Exp. Medicine," 2, 35, 1897.

REFLEX ACTIONS. 141

nificant experiment in this connection is that made by Setschenow.*
If in a frog the entire brain or the cerebral hemispheres are re-
moved, then stimulation of the exposed cut surface — for instance,
by crystals of sodium chlorid — will depress greatly or perhaps
inhibit entirely the usual spinal reflexes that may be obtained by
cutaneous stimulation. On removal of the stimulating substance
from the cut surface by washing with a stream of physiological
saline (solution of sodium chlorid, 0.7 per cent.) the reflex activities
of the cord are again exhibited in a normal way. This experiment
accords with many facts which' indicate that the brain may inhibit
the activities of the spinal centers. In the reflex from tickling,
for -instance, we know that by a voluntary act we can repress the
muscular movements up to a certain point; so also the limited
control of the action of the respiratory and micturition centers
is a phenomenon of the same character. To explain such acts we
may assume the existence of a definite set of inhibitory fibers,
arising in parts of the brain and distributed to the spinal cord,
whose function is that of controlling the activities of the spinal
centers. In view of the fact, however, that there is no independent
proof of the existence of a separate set of inhibitory fibers within
the central nervous system — that is, a set of fibers whose specific
energy is that of inhibition — it is preferable to speak simply of
the inhibitory influence of the brain upon the cord, leaving unde-
cided the question as to whether this influence is exerted through
a special set of fibers, or is brought about by some variation in
the time relations, intensity, or quality of the nerve impulses.
Regarding the fact, however, there can be no question, and it
constitutes a most important factor in the interaction of the dif-
ferent parts of the nervous system. It is possible that this factor
explains why a normal frog gives reflexes that are so much less
constant and less predictable than in one with its brain removed.
A similar inhibition of spinal reflexes may be obtained by simul-
taneous stimulation of two different parts of the skin. The usual
reflex from pinching the toe of one leg may be inhibited in part
or completely by simultaneous stimulation of the other leg or
direct electrical stimulation of an exposed nerve trunk. A similar
interference is illustrated, perhaps, in the well-known device of
inhibiting an act of sneezing by a strong sensory stimulation from
some part of the skin, — for instance, by pressing upon the upper
lip. Inhibition of spinal reflexes by such means is not so constant
nor so effective as by stimulation of the central paths, but it forms
an interesting phenomenon which must be taken into account in
any hypothesis of the nature of inhibition that may be proposed.

* Setschenow, " Physiologische Studien iiber d. Hemmungs-Mechanismen
f. d. Reflexthatigkeit im Gehirn d. Frosches," Berlin, 1863.

142 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

A brief statement of the more or less unsatisfactory theories of
inhibition is given in connection with the inhibitory action of the
vagus nerve on the heart beat (see p. 539). It should be added,
however, in this connection that stimulation of the cord, and
probably of other parts of the nervous system, from two different
sources may result not only in an inhibition of the reflex normally
occurring from one of the stimuli, but under some circumstances
may give an augmentation or reinforcement of the reflex. A
striking example of this augmenting effect is given below in the
paragraph upon the knee-kick.

Influence of the Condition of the Cord on its Reflex Ac-
tivities.— The time and extent of the reflex responses may be
altered greatly by various influences, particularly by the action
of drugs. The effect in such cases is usually upon the nerve centers,
—that is, upon the cells themselves or upon the connections between
the terminal arborization and the dendrites — the process of conduc-
tion within the sensory and motor fibers being less easily affected.
A convenient method of studying such influences is that employed
by Tiirck. In this method the reflex frog is suspended, and the
tip of the longest toe is immersed to a definite point in a solution
of sulphuric acid of a strength of 0.1 to 0.2 per cent. If the time
between the immersion and the reflex withdrawal of the foot is
noted by a metronome, or by a record upon a kymograph, it will
be found to be quite constant, provided the conditions are kept
uniform. If the average time for this reflex is obtained from a
series of observations it is possible to inject various substances —
such as strychnin, chloroform, potassium bromid, quinin, etc. —
under the skin, and after absorption has taken place to determine
the effect by a new series of observations. So far as drugs are
concerned the results of such experiments belong rather to pharma-
cology than to physiology. The method in some cases brings out an
interesting difference in the effects of various kinds of stimulation.
Strychnin, for instance, as was stated above, increases greatly the
•delicacy of the reaction to pressure stimulation. At one stage in
its action before the convulsive responses are obtained the threshold
stimulus is greatly lowered, — mere contact with the toes causes a
rapid retraction of the leg; whereas in the normal reflex frog a
relatively large pressure is necessary to obtain a similar response.
At this stage in the action of the strychnin the effect of the acid
stimulus, on the contrary, may be markedly weakened so far as
the time element is concerned. If the action of the strychnin is
not too rapid, it is usually possible to find a point at which the
time for the reflex is diminished, but this effect quickly disappears
and the period between stimulus and response becomes markedly
lengthened at a time when the slightest mechanical stimulation gives

REFLEX ACTIONS. 143

a rapid reflex movement. This paradoxical result may depend pos-
sibly upon the variety of nerve fiber stimulated by the two kinds
of stimuli or may be connected with the fact that the acid
stimuli may bring about inhibitory as well as excitatory processes
in the cord.

Reflexes from Other Parts of the Nervous System. — Nu-
merous typical reflexes are known to occur in the brain. The
reflex effects upon the important centers in the medulla, such
as the vasomotor center, the respiratory center, and the cardio-
inhibitory center, the winking*' of the eye, sneezing, the light reflex
upon the sphincter muscle of the iris, and many other similar cases
might be enumerated. All of these reactions will be described
and discussed in their proper places. The conscious reactions of
the brain are not included among the reflexes by virtue of the defi-
nition which lays stress upon the involuntary characteristic of the
reflex response, but it should be remembered that, so far as the
nervous mechanism is concerned, these conscious reactions do not
differ from the true reflexes. When we voluntarily move a limb
the movement is guided and controlled by sensory impulses from the
muscles put into action. The fibers of muscle sense from these
muscles convey sensory impulses through a chain of neurons to
the cortex of the brain and there the impulses doubtless affect and
set into action the motor neurons through which the movement is
effected. So far as we know, the discharges from the efferent
neuron of the brain are not really automatic, but are conditioned
or originated by stimuli from other neurons; so that the activities
of the brain are carried on by a mechanism of one neuron acting
on another, just as in the case of the reflex arc. The added feature
of a psychical factor, a reaction in consciousness, enables us to draw
a line of distinction between these activities and those of so-called
pure reflexes; but the distinction is perhaps one of convenience
only, for, although the extremes may be far enough apart to suit
the definition, many intermediate instances may be found which
are difficult to classify. All skilled movements, for instance, such
as walking, singing, dancing, bicycle riding, and the like, — although
in the beginning obviously effected by voluntary co-ordination,
nevertheless in the end, in proportion to the skill obtained, become
more or less entirely reflex, — that is, involuntary. In learning
such movements one must, as the saying goes, establish his reflexes,
and the result can hardly be understood otherwise than by suppos-
ing that the continual adjustment of certain sensory impulses to
certain co-ordinated movements results in the formation of a more
or less complex reflex arc, a set of paths of least resistance.

Reflexes through Peripheral Ganglia — Axon Reflexes.—
Many attempts have been made by physiologists to ascertain

144

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

a

whether or not reflexes can occur through the peripheral nerve
ganglia, particularly those belonging to the sympathetic system.
With regard to the posterior root ganglia, it may be said that no
reflexes are possible through them. If the posterior root connect-
ing such a ganglion to the cord is severed stimulation of the sensory
area supplied by these ganglia causes no reflex response. Indeed,
according to our conception of the mechanism of a reflex, the pos-
terior root ganglia could not serve as reflex centers: they contain
apparently no efferent neurons. In the ganglia of the sympathetic
nerve and its appendages and in the similar
(o) ganglia contained in many of the organs the

nerve cells have dendritic processes, and, so
far as their histology is concerned, it would
seem possible that in any ganglion of this
type there might be sensory and motor neu-
rons so connected as to make the ganglion
an independent reflex center. Numerous
experiments have been made to determine
experimentally whether reflexes can be ob-
tained through such ganglia. Perhaps the
most successful of these experiments have
been made upon the inferior mesenteric
ganglion.

This ganglion may be isolated from all
connections with the central nervous system
and left attached to the bladder through the
two hypogastric nerves (see schema, Fig.
105) . If now one of these nerves is cut and
the central stump is stimulated a contraction
of the bladder follows. Obviously in this
case the impulse has traveled to the ganglion
and down the other hypogastric nerve; the
reaction has every appearance of being a true
reflex. Nevertheless, Langley and Ander-
son,* who have studied the matter with espe-
cial care, are convinced that in this and similar cases we have to do
with what they call pseudoreflexes or axon reflexes. The idea under-
lying this term may be explained in this way : Every sympathetic
ganglion is connected with the central nervous system, brain and
cord, by efferent spinal fibers, preganglionic fibers, which terminate
by arborization around the dendrites of the sympathetic cells. The
efferent fibers arising from the latter may be designated as post-
ganglionic fibers. These authors give reasons to believe that any
one preganglionic fiber, a, Fig. 64, may connect by collaterals with
* Langley and Anderson, " Journal of Physiology," 16, 410, 1894.

Fig. 64.— Schema to
show idea of an axon re-
flex : The preganglionic
fiber, a, sends branches
to two postganglionic
fibers, b, c. If stimulated
at x the impulse passes
backward in a direction
the reverse of normal and
falling into 6 and c gives
a pseudoreflex effect.

REFLEX ACTIONS. 145

several sympathetic cells. If such a fiber were stimulated at x,
then the impulse passing back along the axon in a direction the
reverse of normal would stimulate cells b and c, giving effects that
are apparently reflex, but which differ from true reflexes in that
the stimulating axon belongs to a motor neuron. Under normal
circumstances it is not probable that an effect of this kind can be
produced.

The Tonic Activity of the Spinal Cord. — In addition to the
definite reflex activities of the cord, each traceable to a distinct
sensory stimulus, there is evidence to show that many of its motor
neurons are in that state of more or less continuous activity which
we designate as tonic activity or tonus. There is abundant reason
for this belief in regard to many of the special centers of the cord
and brain, such as the vasomotor center, the center for the sphinc-
ter muscle of the iris, the centers for the sphincter muscles of the
bladder, the anus, etc. But the evidence includes the motor
neurons to the voluntary as well as the involuntary musculature.
In a decapitated frog the muscles take a definite position, and
Brondgeest showed that if such an animal is suspended, after cut-
ting the sciatic plexus in one leg, the leg on the uninjured side
takes a more flexed position. The explanation offered for this
result is that the muscles on the sound side are being innervated
by the motor neurons of the cord. Inasmuch as a result of this
kind cannot be obtained from a frog whose skin has been removed,
or in one in which the posterior roots have been severed it seems
evident that this tonic discharge from the motor neurons is due
to a constant inflow of impulses along the sensory paths. The
muscle tonus, in other words, is really a reflex tonus, which differs
from ordinary reflex movements only in the absence of a sudden,
visible contraction and in the more or less continuous character
of the innervation. In the section on animal heat the importance
of this constant innervation of the muscles as a source of heat is
further emphasized. The idea of a more or less continuous but
varying activity of the centers in the brain and cord in consequence
of the continuous inflow of impulses along the sensory paths fits
in very well with many facts observed in the peripheral organs, —
facts that will be referred to from time to time as the physiology
of these organs is considered.

Effects of Removal of the Spinal Cord. — Numerous investi-
gators have sectioned the cord partly or completely at various
levels. The general results of these experiments as regards loss
of sensation or voluntary movement are described in the next
section treating of the cord as a path of conduction to and from
the brain. But attention may be called here to some of the gen-

10

146 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

eral results obtained by Goltz* in some remarkable experiments
in which the entire cord was removed with the exception of the
cervical region and a small portion of the upper thoracic. In
making this experiment it was necessary to perform the operation
in several steps. That is, the cord was first sectioned in the upper
thoracic region and then in successive operations the lower tho-
racic, lumbar, and sacral regions were removed completely. Very
great care was necessary in the treatment of the animals after
these operations, but some survived and lived for long periods,
the digestive, circulatory, and excretory organs performing their
functions in a normal manner. The muscles of the hind limbs
and trunk, however, underwent complete atrophy, owing to the
destruction of their motor nerves. The blood-vessels also were
paralyzed after the first operations, but gradually their muscu-
lature again recovered tone, showing that, although under normal
conditions the tonic contraction of the vessels is under the in-
fluence of nerves arising from the cord, this tone may be re-estab-
lished in time after the severance of all spinal connections. Some
of the specific results of these experiments, bearing upon the re-
flexes of defecation, micturition, and parturition, will be described
later. Attention may be called here to the general results
illustrating the general functions of the cord.

In the first place, there was, of course, a total paralysis of volun-
tary movement in the muscles innervated normally through the
parts of the cord removed, and a complete loss of sensation in the
same regions, particularly of cutaneous and muscular sensibility.
In the second place, the visceral organs, including the blood-vessels,
were shown to be much more independent of the direct control of
the central nervous system. While these organs in the experiments
under consideration were still in connection with the sympathetic
ganglia and in part with the brain through the vagi, still their
connections with the central nervous system, particularly as
regards their sensory paths and the innervation of the blood-vessels,
were in largest part destroyed. The immediate effect of this
destruction would have been the death of the animal if the artificial
care of the observer had not replaced, in the beginning, the normal
control exercised by the nervous system through the spinal nerves;
but later this careful nursing was not required. While these organs,
therefore, are capable of a certain amount of independent activity
and co-ordination, they are normally controlled through the various
reflex activities of the brain and cord. In the third place, it is
noteworthy that the adaptability of the cordless portion of the
animal was distinctly less than normal. Its power of preserving a

* Goltz and Ewald, " Pfliiger's Archiv fur die gesammte Physiologie,"
63, 362, 1896.

REFLEX ACTIONS. 147

constant body temperature was more limited than in the normal
animal, and the susceptibility to inflammatory disturbances in the
visceral organs was greatly increased. It seems evident, from these
facts, that, although the animal was living, its power of adaptation to
marked changes in the external or internal environment was greatly
lessened, and this fact illustrates well the great general importance
of the spinal cord and brain as reflex certers controlling the nutri-
tion and co-ordinated activities of U j body tissues and organs.
This control is necessary under normal conditions for the success-
ful combination of the activities of the various organs. A large
part of this control is doubtless dependent upon the regulation of
the blood supply to the various organs. The mechanism by which
this is effected and the parts played by the cord and the brain
(medulla oblongata), respectively, will be described in the section
on circulation.

Knee-jerk. — Knee-jerk or knee-kick is the name commonly
given to the jerk of the foot when a light blow is struck upon the
patellar ligament just belo\v the knee. The jerk of the foot is
due to a contraction of the quadriceps femoris muscle. According
to Sherrington, the parts of this muscular mass chiefly concerned
are the m. vastus medialis and m. femoralis. In order to obtain
the muscular response it is usually necessary to put the quadriceps
under some tension by flexion of the leg. This end is obtained
most readily by crossing the knees or by allowing the leg to hang
freely when sitting on the edge of a bench or table. Under such
circumstances the jerk is obtained in the great majority of normal
persons, and this fact has made it an important diagnostic sign
in many diseases of the spinal cord. The importance of the
reaction for such purposes was first brought out by the work of
Erb and Westphal * in 1875.

Reinforcement of the Knee-jerk. — It was first shown by
Jendrassik (1883) that the extent of the jerk may be greatly aug-
mented if, at the time the blow is struck upon the tendon, a strong
voluntary movement is made by. the individual, such as squeezing
the hands together tightly or clenching the jaws. This phenomenon
was studied carefully in this country by Mitchell and Lewis, f who
ascertained that a similar augmentation may be produced by giving
the individual a simultaneous sensory stimulation. They desig-
nated the phenorrfenon as a reinforcement, and this name is gen-
erally employed by English writers, although occasionally the term
"Bahnung," introduced by Exner to describe a similar phenom-
enon, is also used. It is found that by a reinforcement the knee-

* Erb and Westphal, "Archiv f. Psychiatric," 1875, vol. v.

t Mitchell and Lewis, " American Journal of Med. Sciences," 92, 363, 1886.

148

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

jerk may be demonstrated in some individuals in whom the ordi-
nary blow upon the tendon fails to elicit a response. Bowditch and
Warren* studied the phenomenon of reinforcement and brought out
a fact of very great interest. They studied especially the time
interval between the blow upon the tendon and the reinforcing act
and found that if the latter preceded the blow by too great an inter-
val then, instead of an augmentation of the jerk, there was a dimi-
nution which they designated as negative reinforcement or inhi-
bition. This inhibiting effect began to appear when the reinforcing
act (hand-squeeze) preceded the blow by an interval of from 0.22
to 0.6 sec., and the maximum inhibiting effect was obtained at an

40-

30-

20-

10-

0

10-

20-

30-

mm

o

NORMAL

TIME

CXI" 02" 0.4"

0.7"

1.0"

17"

Fig. 65.— Showing in millimeters the amount by which the "reinforced" knee-kick
varied from the normal, the level of which is represented by the horizontal line at 0, "nor-
mal." The time intervals elapsing between the clenching of the hands (which constituted
the reinforcement) and the tap on the tendon are marked below. The reinforcement is
greatest when the two events are nearly simultaneous. At an interval of 0.4 sec. it'
amounts to nothing; during the next 0.6 sec. the height of the kick is actually diminished,
while after an interval of 1 sec. the negative reinforcement tends to disappear; and when
1.7 sec. is allowed to elapse the height of the kick ceases to be affected by the clenching of
the hands. — (Bowditch and Warren.)

interval of from 0.6 to 0.9 sec. Beyond this point the effect became
less noticeable, and at an interval of 1.7 to 2.5 sec. the reinforcing
act had no influence at all upon the jerk. These relations are
shown in the accompanying curve (Fig. 65). These authors con-
firmed also the fact that a sensory stimulus, such as a gentle blast
of air on the conjunctiva or the knee, may reinforce the jerk. The
physiological explanation of the reinforcement, negative and posi-
tive, is a matter of inference only, but the view usually held is that
it is due to "overflow." That is, many facts, such as strychnin
tetanus, indicate that the neuromuscular machinery of the entire
central nervous system is more or less directly connected and that

* Bowditch and Warren. " Journal of Physiology," 2, 25, 1890.

REFLEX ACTIONS. . 149

functional activity at one part will influence the irritability of the
remainder either in the direction of reinforcement (Bahnung) or
inhibition. We may conceive, therefore, that when the hands
are squeezed the motor impulses sent down from the cortex of the
brain to the upper portion of the cord overflow to some extent,
sufficient at least to alter the irritability of the other motor neurons
in the cord. Experimental stimulation of the cortex has given
similar results. Exner* found that when the motor center for the
foot in the cortex of a rabbit *was stimulated, the stimulation, even
if too weak to be effective itself, caused an increase in the contraction
brought about reflexly by a simultaneous stimulation of the skin
of the paw, and furthermore if these stimuli were so reduced in
strength that each was ineffective, then when applied together a
contraction was obtained. In this case an ineffective stimulus
from the cortex reaching the spinal cord increased the irritability
of the motor centers there so that a simultaneous reflex stimulus
from the foot, ineffective in itself, became effective.

Is the Knee-jerk a Reflex? — The most interesting question
in this connection is whether the jerk is a true reflex act or is due
to a direct mechanical stimulation of the muscle. Opinions are
divided upon this point. Those who believe that the jerk is a
reflex lay emphasis upon the undoubted fact that the integrity of
the reflex arc is absolutely essential to the response. The quad-
riceps receives its motor and sensory fibers through the anterior
crural nerve, and pathological lesions upon man as well as direct
experimental investigation upon monkeys prove that if either the
posterior or anterior roots of the third and fourth lumbar spinal
nerves are destroyed the knee-jerk disappears entirely. The oppo-
nents of the reflex view explain this fact by the theory that in
order for the quadriceps to respond it must be in a condition
of tonus. This tonus depends upon the reflex arc, the sensory
impulses from the muscle serving to keep it in that condition
of subdued contraction known as tone. On this view destruc-
tion of the reflex arc renders the muscle less irritable, so that it
will not respond by a contraction to the sudden mechanical exten-
sion or pull caused by the blow on the tendon. The adherents of
this view lay emphasis upon two facts: First, the knee-jerk is a
simple contraction, and not a tetanus, and, generally speaking,
the motor centers of the cord discharge a series of impulses when
stimulated. Second, the time for the jerk — that is, the interval
between the stimulus and the response — is too short for a reflex.
The determination of this time has been attempted by many ob-
servers for the purpose of deciding the controversy, but unfor-
tunately the results have been lacking in uniformity, varying, in
* Exner, "Archiv f. die gesaramte Physiologic/' 27, 412, 1882.

150 . PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

man, from 0.025 to 0.073 sec. Moreover, we have no definite basis
upon which to estimate what should be the time required if the
act were a genuine reflex. For the act of winking in man Exner
estimated a total time of 0.0578 sec., but May hew obtained a
smaller figure — 0.0471 sec. In the lower animals the results have
also been uncertain. Applegarth, making use of a dog with a
severed spinal cord, obtained for the time of the knee-jerk an
interval of 0.014 to 0.02 sec. Assuming a velocity of 100 ft. or
more per second, this would allow sufficient time for the impulse
to travel to the cord and back provided there was no delay in
the nerve centers. Waller and Gotch, using the rabbit, found the
time to be only 0.008 to 0.005 sec., — that is, just about the
latent period of a muscle contraction and too short a time for
a reflex. It is evident that more facts are necessary before a
positive statement can be made upon this point. In favor of
the reflex theory attention may be called to the fact that in
some cases a crossed reflex is obtained affecting the muscles of
the other leg. This apparently undoubted reflex shows that an
efficient sensory impulse has reached the cord, and, according to
our knowledge of reflexes, the effect in such cases should always
be most marked on its own side. It would seem to be unjustifiable
in these cases to suppose that the effect on the same side is not
reflex while on the opposite side it is reflex.

Conditions Influencing the Extent of the Knee-jerk. — The
effect of various normal conditions upon the knee-jerk has been
studied by a number of observers, particularly by Lombard.* The
results are most interesting in that they indicate very clearly that
the irritability of the spinal cord varies with almost every marked-
change in mental activity. During sleep the jerk disappears
and in mental conditions of a restful character its extent is relatively
small. In conditions of mental excitement or irritation, on the
contrary, the jerk becomes markedly increased. Lombard ob-
served also, in his own case, a daily rhythm, which is represented
in the chart given in Fig. 66. It would seem from his experiments
that the extent of the knee-jerk is a sensitive indicator of the
relative state of irritability of the nervous system: "The knee-
jerk is increased and diminished by whatever increases and di-
minishes the activity of the central nervous system as a whole/'
This general fact is supported, especially as regards mental activity,
by observations on other similar mechanisms, — such, for instance,
as the condition of the nervous centers controlling the bladder.

* Lombard, "The American Journal of Psychology," 1887, p. 1. See
also article "Knee-jerk" (Warren), "Wood's Ref. Handbook of Med. Sci-
ences," second edition, 1902.

REFLEX ACTIONS.

151

Use of the Knee-jerk and Spinal Reflexes as Diagnostic
Signs. — The fact that the knee-jerk depends on the integrity of
the reflex arc in the lumbar cord has made it useful as a diagnostic
indication in lesions of the cord, particularly, of course, for the
lumbar region. It is mainly on account of its practical value and
the ease with which it is ordinarily obtained that the phenom-
enon has been studied so extensively. In the disease known as
progressive locomotor ataxia the posterior root fibers in the pos-
terior columns in the lumba'r region are affected, and, as a con-
sequence, the jerk is diminished or abolished altogether according
to the stage of the disease. So also lesions affecting the anterior

April Otll 1887

**.

Fig. 66.— Lombard's figure to indicate the daily rhythm in the extent of the knee-
jerk and the effect of mental stimuli. The ordinates (0-110) represent the extent of the
kick in millimeters. Each dot represents a separate kick, while the heavy horizontal line
gives the average extent for the period indicated.

horns of the gray matter will destroy the reflex by cutting off the
motor path, while in other cases lesions in the brain or the lateral
columns of the cord affecting the pyramidal system of fibers may
be accompanied by an exaggeration of this and similar reflexes.
This latter fact agrees with the experimental results (see p. 141)
upon ablation of the brain. After such operations in the frog
and lower mammals at least the spinal reflexes may show a marked
increase. Interruption of the descending connections between brain
and cord at any point, therefore, may be accompanied by a strik-
ing increase in sensitiveness of the spinal reflexes. The explana-
tion usually given is that the inhibitory influences of the brain
centers upon the cord are thereby weakened or destroyed. The

152

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

explanation is incomplete in that it leaves undecided the question
as to whether this inhibitory influence is exerted through the or-
dinary motor paths or through a special set of inhibitory fibers.
Various motor reflexes whose motor centers are situated at differ-
ent levels in the cord may be used to a limited extent to diagnose
the condition of the cord at its various parts. Some of the most
generally known of these reflexes are given in the following table
and the location of the centers in the cord is shown in Fig. 67:

LOCALIZATION OF FUNCTION IN THE DIFFERENT SEGMENTS
OF THE SPINAL CORD.

(M. ALLEN STARR, slightly modified by Edinger.)*

SEGMENTS.

MUSCLES.

REFLEXES.

CUTANEOUS AREAS
INNERVATED.

Cervical ii-iii
C iv

M. sterno-cleido-
mastoideus.
M. trapezius.
Mm. scaleni et
colli.
Diaphragma.
Diaphragma.

Inspiratory reflex on
quick pressure be-
neath ribs.

Dilatation of the pu-

Neck and back of
head.

Neck.

C. v

M. supraspinatus.
M. infraspmatus.
M. deltoideus.
M. biceps brachii.
M. coracobrachi-
alis.
M. supinator
longus.
M. rhomboidei.
M. deltoideus.

pil on irritation of
the neck (C. iv-vii.)

Scapular reflex (C.

Upper part of
shoulder.
Outer side of arm.

Back of shoulder

C. vi

M. biceps brachii.
M. coracobrachi-
alis.
M. supinator
longus.
M. supinator
brevis.
M. pectoralis
major (pars
clavicularis).
M. serratus an-
terior.
Mm. rhomboidei.
M. brachialis
anticus.
M. teres minor.
M. biceps brachii.

v-T. i).
Tendon reflexes of.
the corresponding
muscles.

Tendon reflexes of the

and arm.
Outer side of
upper arm and
of the forearm.

Outer side of

M. brachialis
anticus.
M. pectoral is
major (pars
clavicularis) .

Mm. extensores la-
certi et brachii.
Tendon reflexes of
the muscles of the
wrist.

forearm.
Back of hand and
radial region.

* Taken from Barker's " Nervous System."

Acusticus
Vestibularis

Gustos
(cum Trigemino)

Pharynx

Larynx, Trachea
intestina

(ThoraUbdomerij

Regie colli „
Regio nuchae

Regio Nervi radialis
Regio N. median!
Regio N. ulnaris

anterior

Regio femoris

r\r

vn

Mil

IX

XI

WexaWoiinafe

* XII

jftedultalumbajs

Beflei crem*»f

i iateralis
( posterior
! mediana
' lateraiis
Scrotum, penis.
Perineum
Vesica
Rectumll
Anus

Musciiii faciei
Mm. pharyngis, palati
Mm. laryngis
Mm. linguae
Oesophagus
Sternocleidomastoideus
Mysculi colli et nuchae
Scaleni. Splenius
Cucullaris

Supra-, infraspinatus

, Supinator longus

Serratus anticus, Supinator brevis

Pectoralis major (portiociavicui.)

Teres minor

Pronatores, Brachialis internus

Triceps

Extensores carpi et digitor. longi

Pectoralis major (portio costalis)
Latissimus dorsi, teres major

Hexores carpi et digitor. longi ] g

Extensores pollicis '1

Interossei lumbricales /||

Thenar Hpthenar )~

Sartorius

Quadriceps femoris

Gluiaei. tensor fasc. lat.

Adductores femoris
Abductores femoris
Tibialis anticus
Gastrocnemius, Soleus

Biceps Semitendi-Semimembranosus
Obturator, pyriformis, quadratus femor.

Extensores digitorum
Peronei
Flexores digitorum

Interossei
Mm. perineales

Mm. vesicates
im. irectales

Fig. 67.

REFLEX ACTIONS.

153

LOCALIZATION OF FUNCTION IN THE DIFFERENT SEGMENTS OF THE SPINAL
CORD. — (Continued.}

SEGMENTS.

MUSCLES.

REFLEXES.

CUTANEOUS AREAS
INNERVATED.

C. vi (con-
tinued).

C. vii

M. serratus
anterior.
M. triceps brachii.
Mm. extensores
manus et digi-
torum.
Mm. pronatores.
M. triceps brachii
cap lit longum).
Mm. extensores
manus et digi-
torum.
M. flexores
manus.
Mm. pronatores
manus.
M. pectoralis
major (pars
sterno-costalis) .
M. subscapularis.
M. latissimus
dorsi.
M. teres major.
Mm. flexores
manus et digi-
torum.
Mm. m i n o r e s
manus.
Mm. extensores
pollicis.
Mm. m i n o r e s
manus.
Mm. eminent
thenar et hypo-
thenar.
Mm. dorsi.
Mm. abdominis.
Mm. erectores
spinae.
M. iliopsoas.
M. sartorius.
Mm. abdominis.

M. iliopsoas.
M. sartorius.
Mm. flexores genus.
M. quadriceps
femoris.
M. qu adri ceps
femoris.
Mm. rotatores
femoris (inward).
Mm. adductores
femoris.

4>

Blow upon the palm
of the hand causes
closure of the fin-
gers.
Palmar reflex (C.
vii-T. i).

Pupillary reflex.

Radial region of
hand.

Distribution of
N. medianus.

Ulnar region.

Skin of thorax,
back, abdomen,
and upper glu-
teal region.
Skin of pubic re-
gion.
Anterior part of
scrotum.
Outer side of hip.

Anterior and inner
side of thigh.

C. viii

Thoracic i . . .
T. ii-xii

Epigastric reflex (T.
iv-vii).
Abdominal reflex
(T. vii-xi).
Cremaster reflex
(L. i-iii).

Patellar tendon reflex
(L. ii-iv).

Lumbar i . . .
L. ii

L.iii

154

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

LOCALIZATION OF FUNCTION IN THE DIFFERENT SEGMENTS OF THE SPINAL
CORD. — (Continued.)

SEGMENTS.

MUSCLES.

REFLEXES.

CUTANEOUS AREAS
INNERVATED.

L. iv.

L. v

Sacral i-ii

S. iii-v.

Mm. abductores

femoris.
Mm. abductores

femoris.
M. t i b i a 1 i s

anterior.
Mm. flexores

genus (Ferrier?)
Mm. rotatores

femoris (out-

ward).
Mm. flexores

genus (Ferrier ?)
Mm. flexores

pedis.
Mm. extensores

digitorum.
Mm. peronsei.
Mm. flexores

pedis et digi-
torum.

M. peronsei.
Mm. m i n o r e s

pedis.
M. perinaei.

Gluteal reflex (L.
iv-v).

Plantar reflex.

Achilles tendon reflex.
Vesical and rectal
centers.

Inner side of thigh
and leg as far as
ankle; inner side
of foot

Back of hip and
thigh and outer
part of foot.

Back of thigh;
outer side of leg
and foot.

Skin over sacrum,
perineum, geni-
talia, and about
anus.

CHAPTER VIII.
THE SPINAL CORD AS A PATH OF CONDUCTION.

In addition to the varied 'and important functions performed
by the cord as a system of reflex centers controlling the activities
of numerous glands and visceral organs as well as the so-called
voluntary muscles, it is physiologically most important as a path-
way to and from the brain. All the fibers, numbering more than
half a million, that enter the cord through the posterior roots of
the spinal nerves bring in afferent impulses, which may be continued
upward by definite tracts that end eventually in the cortex of the
cerebrum, the cerebellum, or some other portion of the brain. On
the other hand, many of the efferent impulses originating reflexly
or otherwise in different parts of the brain are conducted downward
into the cord to emerge at one or another of the anterior roots of
the spinal nerves. The location and extent of these ascending and
descending paths form a part of the inner structure of the cord,
which is most important practically in medical diagnosis and which
has been the subject of a vast amount of experimental inquiry in
physiology, anatomy, pathology, and clinical medicine. In working'
out this inner architecture the neuron conception has been of the
greatest value, and the results are usually presented in terms of
these interconnecting units.

The Arrangement and Classification of the Nerve Cells
in the Gray Matter of the Cord. — Nerve cells are scattered
throughout the gray matter of the cord, but are arranged more
or less distinctly in groups or, considering the longitudinal aspect
of the cord, in columns the character of which varies somewhat in
the different regions. From the standpoint of physiological anatomy
these cells may be grouped into four classes: (1) The anterior
root cells, clustered in the anterior horn of gray matter (1, Fig. 68).
The axons of these cells pass out of the cord almost at once to
form the anterior or motor roots of the spinal nerves. (2) The
tract cells, so called because their axons instead of leaving the cord
by the spinal roots enter the white matter and, after passing upward
or downward, help to form the tracts into which this white matter
may be divided (2 and 3 of Fig. 68). These tract cells are found
throughout the gray matter, and according to the side on which the
axon enters into a tract they may be divided into three subgroups:

155

156 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

(a) Those whose axons enter the white matter on the same side of
the cord, the tautomeric tract cells of Van Gehuchten. (b) Those
whose axons pass through the anterior white commissure and thus
reach the tracts in the anterior or lateral columns of the other side.
These are known as commissural cells or the heteromeric tract
cells of Van Gehuchten. They form one obvious means for crossed
conduction in the cord, (c) Those whose axons divide into two,
one passing into the white matter of the same side, the other pass-
ing by way of the anterior commissure to reach the white matter
of the opposite side — the hecateromeric tract cells of Van Gehuch-
ten. (3) The Golgi cells of the second type — that is, cells whose

Dorsal

Fig. 68. — Schema of the structure of the cord. — (After 'Lenhossek.) On the right the
nerve cells; on the left the entering nerve fibers. Right side: 1, Motor cells, anterior
horn, giving rise to the fibers of the anterior root; 2, tract cells whose axons pass into the
white matter of the anterior and lateral columns; 3, commissural cells whose axons pass
chiefly through the anterior commissure to reach the anterior columns of the other side;
4, Golgi cells (second type), whose axons do not leave the gray matter, 5, tract cells whose
axons pass into the white matter of the posterior column. Left side: 1, Entering fibers of
the posterior root, ending, from within outward, as follows: Clarke's column, posterior
horn of opposite side, anterior horn same side (reflex arc), lateral horn of same side, pos-
terior horn of same side ; 2, collaterals from fibers in the anterior and lateral columns ; 3,
collaterals of descending pyramidal fibers ending around motor cells in anterior horn.

axons divide into a number of small branches like those of a
dendrite. The axons of these cells, therefore, do not become
medullated nerve fibers; they take no part in the formation of
the spinal roots or the tracts of white matter in the cord, but
terminate diffusely within the gray matter itself. (4) The pos-
terior root cells lying toward the base of the anterior horns. These
cells have been demonstrated in some of the lower vertebrates
(petromyzon — chick embryo), but their existence in the mammal
is still a question in some doubt; their axons pass out from the
cord by the posterior root and they form the anatomical evidence

SPINAL CORD AS A PATH OF CONDUCTION. 157

for the view that the posterior roots may contain some efferent fibers.
Some of the groups of tract cells have been given special names, —
such, for instance, as Clarke's column (columna vesicularis). This
group of cells lies at the inner angle of the posterior horn of gray
matter (5, Fig. 71), and forms a column usually described as
extending from the middle lumbar to the upper dorsal region.
The axons from these cells pass to the dorsal margin of the lateral
•columns on the same side to constitute an ascending tract of fibers
known as the tract of Flechsig, pr the dorsal or direct cerebellar tract.
General Relations of the Gray and White Matter in the
Cord. — Cross-sections of the cord at different levels show that
the relative amounts of gray and white matter differ considerably
at different levels, so that it is quite possible to recognize easily
from what region any given section is taken. At the cervical and
the lumbar enlargements the amounts of both gray and white
matter — that is, the total cross-area of the cord — show a sudden

•White matter. --------------- Gray matter. - Entire secHon.

s£omposite curves based on 4 Cases.

60
40
SO

100

• • V Y BUSH I B B K ¥ Y3 YD SM IX X XI XU I U JU KY I HH1HT

Fig. 69. — Curves to show the relative areas of the gray and white matter of the spinal
cord at different levels. — (Donaldson and Davis.) The Roman numerals along the abscissa
represent the origin of the different spinal nerves.

increase owing to the larger number of fibers arising at these levels.
The white matter, and therefore the total cross-area, shows also
a constant increase from below upward, due to the fact that in
the upper regions many fibers exist that have come into the cord
at a lower level or from the brain, those froni the latter region being
gradually distributed to the spinal nerves as we proceed downward.
In the accompanying figure a curve is presented showing the cross-
area of the cord and the relative amounts of gray and white matter
at each segment.

Tracts in the White Matter of the Cord, Methods of Deter-
mining. — The separation of the medullated fibers of the cord
into distinct tracts of fibers possessing different functions has
been accomplished in part by the combined results of investiga-
tions in anatomy, physiology, and pathology. The two methods
that have been employed most frequently and to the best advan-
tage are the method of secondary degeneration (Wallerian degen-

158 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

eration) and the method of myelinization. The method of second-
ary degeneration depends upon the fact that, when a fiber is cut
off from its cell of origin, the peripheral end degenerates in a few
days. If, therefore, a lesion, experimental or pathological, is made
in the cord at any level, those fibers that are affected undergo
degeneration: those with their cells below the lesion degenerate up-
ward, and those with their cells above the lesion degenerate down-
ward. According to the law of polarity of conduction in the neuron
a descending degeneration in the cord indicates motor or efferent
paths as regards the brain, and ascending degeneration indicates
sensory or afferent paths. It is obvious that localized lesions can
be used in this way to trace definite groups of fibers through the cord.
If, for instance, one exposes and cuts the posterior roots in one or
more of the lumbar nerves, the portions of the fibers entering the
cord will degenerate, and the path of some of these fibers may be
traced in this way upward to the medulla. The degenerated fibers
may be revealed histologically by the staining methods of Weigert
or of Marchi. The latter method (preservation in Miiller's fluid,
staining in osmic acid and Miiller's fluid) has proved to be espe-
cially useful; the degenerated fibers during a certain period give
a black color with this liquid, owing probably to the splitting up
of the lecithin in the myelin and the liberation of the fat from its
combination with the other portions of the molecule.* The mye-
linization method was introduced by Flechsig. It depends upon
the fact that in the embryo the nerve fibers as first formed have
no myelin sheath, and that this easily detected structure is in the
central nervous system assumed at about the same time by those
bundles or trac.ts of fibers that have a common course and func-
tion. By this means the origin and termination of certain tracts
may be worked out in the embryo or shortly after birth. The
well-known system of pyramidal fibers, for instance, is clearly
differentiated in the embryo late in intra-uterine life or at birth,
owing to the fact that the fibers composing it have not at that
time acquired their myelin sheaths. Flechsig assumes that the
development of the myelin marks the completed structure of the
nerve fiber and indicates, therefore, the time of its entrance into
full functional activity.

General Classification of the Tracts. — The tracts that have
been worked out in the white matter of the cord have been classified
in several ways. We have, in the first place, the division into as-
cending and descending tracts. This division rests upon the fact
that the axon conducts its impulses away from the cell of origin, and
consequently those neurons whose axons extend upward toward the

* See Halliburton, "The Chemical Side of Nervous Activity/' London.
1901; "Croonian Lectures."

SPINAL CORD AS A PATH OF CONDUCTION. 159

higher parts of the cord or brain are designated as ascending, since
normally the impulses conducted by them take this direction. They
constitute the afferent or sensory paths, and in case of injury to the
fiber or cell the secondary degeneration also extends upward. The
reverse, of course, holds true for the descending or motor paths.
The tracts may be divided also into long and short (or segmental)
tracts. The latter group comprises those tracts or fibers which
have only a short course in the white matter, extending over a dis-
tance of one or more spinal segments. Histologically the fibers of
these tracts take their origin from the tract cells in the gray matter
of the cord and after running in the white matter for a distance of
one or more segments they again enter the gray matter to terminate
around the dendritic processes of another neuron. These short
tracts may be ascending or descending, and the impulses that they
conduct are conveyed up or down the cord by a series of neurons,
each of whose axons runs only a short distance in the white matter,
and then conveys its impulse to another neuron whose axon in turn
extends for a segment or two in the white matter, and so on.
These tracts are sometimes described as association or short associa-
tion tracts, because they form the mechanism by which the activi-
ties of different segments of the cord are brought into association.
This method of conduction by segmental relays involving the par-
ticipation of a series of neurons may be regarded as the primitive
method. It indicates the original structure of the cord as a series
of segments, each more or less independent physiologically. The
short tracts in the mammalian cord lie close to the gray matter,
forming the bulk of what is known as the ground bundles. The
long tracts, on the contrary, are composed of those fibers, as-
cending or descending, which run a long distance, and, hi fact,
extend from the cord to some part of the brain. It is known,
however, that, although the tracts as tracts extend from brain
to cord, many of their constituent fibers may begin and end in the
cord or in the brain, as the case may be. Some of the fibers
of the long tracts are, therefore, so far as the cord is concerned,
simply long association tracts which connect different regions —
e. g., cervical and lumbar — of the cord by a single neuron, as the
short association tracts connect different segments of the same
region. It is said that in these long tracts those fibers that have
the shortest course lie to the inside — that is, nearest to the gray
matter.* From the results of comparative studies of the different
vertebrates we may conclude that the long tracts are a relatively
late development in their phylogenetic history, and that in the
most highly developed animals, man and the anthropoid apes,

* Sherrington and Laslett, "Journal of Physiology," 29, 188, 1903; and
Sherrington, ibid., 14, 255.

160

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

these long tracts are more conspicuous and form a larger percentage
of the total area of the cord. A physiological corollary of this
conclusion should be that in man the independent activity of the
cord is less marked than in the lower vertebrates, and this deduc-
tion is borne out by facts (see p. 139).

Specific Designation of the Long Spinal Tracts. — The tracts
that are most satisfactorily determined for the human spinal cord
are indicated schematically in Fig. 70.

They are named as follows : In the posterior column,

1. The tract or column of Goll — fasciculus gracilis.

2. The tract or column of Burdach — fasciculus cuneatus.

Pig. 70. — Schema of the tracts in the spinal cord (Kolliker) : g, Tract of Goll; 6, tract
of Burdach; pc, crossed pyramidal tract; pd, direct pyramidal tract; /, tract of Flechsig;
gr, tract of Gowers.

In the lateral column,

1. The crossed pyramidal tract, also known as the lateral
pyramidal tract or the fasciculus cerebrospinalis lateralis.

2. Flechsig's tract, known also as the direct cerebellar tract,
the dorsal cerebellar tract, or the fasciculus cerebellospinalis.

3. Gowers's tract, known also as the ventral cerebellar tract
or the fasciculus anterolateralis superficialis.

4. The anterolateral ground bundle, made up chiefly of short
association fibers.

In the anterior columns,

1. The direct pyramidal tract, known also as the anterior pyram-
idal tract or the fasciculus cerebrospinalis anterior.

SPINAL CORD AS A PATH OF CONDUCTION.

161

Of these tracts, those of Burdach and Goll, Flechsig and Gowers,
represent ascending or sensory paths, while the direct and the
crossed pyramidal tracts form a related descending or motor path.
It will be convenient to describe first the connections and physio-
logical significance of these tracts and then refer to the newer work
concerning less definitely established ascending and descending
paths.

The Termination in the Cord of the Fibers of the Posterior
Root. — All sensory fibers '
from the limbs and trunk
enter the cord through the
posterior roots. Inasmuch
as these roots are superfi-
cially connected with the
posterior columns, the older
observers naturally sup-
posed that these columns
form the pathway for
sensory impulses in the
cord. That this supposi-
tion is not entirely cor-
rect was proved by experi-
mental physiology. Section
of the posterior columns
causes little or no obvious
loss of sensations in the
parts below the lesion.
Histological investigation
has since shown that only
a portion of the fibers en-
tering through the posterior
root continue up the cord in
the posterior column; some
and indeed a large propor-
tion of the whole number
enter into the gray matter
and end around tract cells,
whence the path is con-
tinued upward by the axons of these latter cells, mainly in the
lateral or anterolateral columns. The several ways in which the
posterior root fibers may end in the cord are indicated in Fig. 71.

The posterior roots contain fibers of different diameters and

those of smallest size (1) are found collected into an area known

as the zone of Lissauer, lying between the periphery of the cord

and the tip of the posterior horn. These fibers enter the gray

11

Fig. 71. — Schema to show the terminations
of the entering fibers of the posterior root: 1,
Fibers entering zone of Lissauer and terminating
in posterior horn; 2, fiber terminating around a
tract cell whose axon passes into white column of
same side ; 3, fiber terminating around a tract cell
whose axon passes to opposite side (commissural
cell) ; 4, fiber terminating around motor cell of
anterior horn (reflex arc) ; 5, fiber terminating
in tract cell of column of Clarke; 6, fiber (exog-
enous) passing upward in posterior column to
terminate in the medulla oblongata.

162 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

matter chiefly in the posterior horn of the same side and end around
tract cells. The larger fibers of the root lying to the median side
fall into two groups: Those lying laterally (2, 3, 4) enter the gray
matter of the posterior horn and end in tract cells (2) whose axons
are distributed to the same side of the cord, or in tract cells whose
axons (3) pass to the other side through the anterior white com-
missure, or in the motor cells of the anterior horn, thus making a
typical reflex arc. Some of the fibers of this group may also pass
through the posterior gray commissure, to end in the gray matter
of the opposite side. The larger fibers lying nearest to the median
line enter the column of Burdach and run forward in the cord,
some of them (6) continuing upward to the medulla, and some of
them (5), after a shorter course, turning into the gray matter to end
in the cells of the column of Clarke. The axons of the cells in the
column of Clarke in turn pass out of the gray matter to constitute
the ascending path in the lateral column known as the dorsal cere-
bellar (Flechsig's) tract.

This general outline of the mode of ending in the cord of the
fibers of the posterior root is complicated further by the fact that
these fibers are supposed to give off collaterals after entering the cord.
The course of the typical fiber in the posterior root is represented
in Fig. 62. According to this diagram, the root fiber after entering
the cord makes a Y or T division, one branch passing downward
or posteriorly for a short distance, the other, longer division passing
upward or anteriorly. Each of these main stems may give off one
or more lateral branches, sensory collaterals. A main stem, there-
fore, which runs upward in the column of Burdach (6) to terminate
in the medulla oblongata may give off collaterals at various levels
which terminate in the gray matter of the cord, either around
tract cells or around the anterior root cells, forming in the latter
case a simple reflex arc. The existence of collaterals upon the root
fibers within the cord has been demonstrated in the human em-
bryo, but we have little exact information concerning their numeri-
cal value in the adult. The schema given in Fig. 71 must therefore
be accepted as an entirely diagrammatic representation of the chief
possibilities of the mode of ending of the fibers of the posterior root
by way of their collaterals as well as by way of the main stems.

Ascending (Afferent or Sensory) Paths in the Posterior
Columns. — The posterior columns are composed partly of fibers
derived directly from the posterior roots (6 in schema) and arising,
therefore, from the cells in the posterior root ganglia, and partly
from fibers that arise from tract cells in the gray matter of the cord
itself. . It is convenient to speak of the former group as exog-
enous fibers, using this term to designate nerve fibers which
arise from cells placed outside the cord; and the latter group as

SPINAL CORD AS A PATH OF CONDUCTION.

163

4™ Cervical

J&Dorsal

endogenous fibers — that is, fibers that have their cells of origin in
the gray matter of the cord. If we omit
a consideration of their collaterals the
course of the exogenous fibers is easily
understood. They come into the cord at
every posterior root, enter into the col-
umn of Burdach, and pass upward. The
fibers of this kind that enter at the lower
regions, sacral and lumbar, are, however,
gradually pushed toward the median line
by the exogenous fibers entering at higher
levels, so that in the upper thoracic or
cervical regions the columns of Goll are
composed mainly of exogenous fibers that
have entered the cord in the lumbar or
sacral region. These fibers continue up-
ward to end in two groups of cells that
lie on the dorsal side of the medulla
oblongata and are known, respectively,
as the nucleus of the fasciculus gracilis (or
nucleus of Goll) and the nucleus of the
fasciculus cuneatus (or nucleus of Bur-
dach). Their path forward from the
medulla is continued by new neurons
arising in these nuclei, and will be de-
scribed later. The course of these fibers
in the cord may be shown beautifully
by the method of secondary degeneration.
If one or more of the posterior roots of
the lumbar spinal nerves are cut, or
better still if the posterior columns are
severed in this region, the degeneration
will affect the exogenous fibers through-
out their course to the medulla, and it
will be seen that in the cervical region the
degenerated fibers are grouped in the
area of the column of Goll (see Fig. 72).
The endogenous fibers, so far as they are
ascending, represent afferent paths in
which two or more neurons are con-
cerned. The posterior root fibers con-
cerned in these paths end in the gray f rorn*

matter of the cord and thence the con- lumbosacrai plexus.— (Mott.)

... It will be noted that in the

dUCtlOn IS Continued bv One Or more cervical regions the degener-

„ m1 i T. i ,1 • ated area is confined to the

tract cells. The conduction by this set column of Goll.

Z^- Lumbar

164 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

of fibers may be on the same side of the cord as that on which the
root fibers entered, or it may be crossed, or using a convenient
terminology it may be homolateral or contralateral. The physio-
logical value of the ascending fibers in the posterior columns has been
investigated by a large number of observers. The physiologists
have employed the direct method of cutting the columns in the
thoracic or lumbar region and observing the effect upon the sensa-
tions of the parts below the lesion. The positive results of these
experiments have been difficult to interpret. Most of the older
observers found that there was no detectable change in the sensa-
tions of the parts below, but they paid attention only to cutaneous
sensations, and indeed chiefly to the sense of pain. Later observers*
have differed also in their description of the effects of this operation;
but most of them state that the animal shows an awkwardness
or lack of skill in the movements of the hind limbs, especially in
the finer movements, and this effect is interpreted to mean that
there is some loss of muscle sense. This conclusion is strength-
ened by the results of pathological anatomy. In the disease known
as tabes dorsalis the posterior columns of the cord in the lumbar
region are affected and the striking symptom of this condition is
an interference with the power of co-ordinating properly the move-
ments of the lower limbs, particularly in the act of maintaining
body 'equilibrium in standing and walking, — a condition known
as locomotor ataxia. So far as the cutaneous sensations are con-
cerned,— that is, the sensations of touch (pressure), pain, and tem-
perature,— all observers agree that the two latter are not affected,
while regarding touch opinions have differed radically. Schiff
contended that touch sensations are detectable as long as these
columns are intact and are seriously interfered with when they are
sectioned; but most of the results, pathological and experimental,
indicate that when the continuity of these fibers is destroyed the
sense of touch is still present in the parts supplied by the cord below
the lesion. To summarize, therefore, we may say that the evidence
at hand proves that the ascending fibers of the posterior column
do not convey impulses of pain or temperature, that if they convey
any touch (pressure) impulses they certainly do not form the only
path of conduction for this sense, and that most probably their
chief function is the conduction of impulses of muscle sense, — •
that is, they consist of sensory fibers from the voluntary muscles.
The muscle sensations thus aroused in the higher parts of the
brain are necessary to the proper co-ordination of the movements
of the muscles. Injury to these columns, therefore, while it does
not cause paralysis, is followed by disorderly — that is, ataxic —

* Borchert, "Archiv f. Physiologic," 1902, 389. See also Sherrington,
"Journal of Physiology," 14, 255, 1893.

SPINAL CORD AS A PATH OF CONDUCTION.

165

movements. On the histological side it has been shown, as stated
above, that the fibers, particularly the exogenous fibers, end in
nuclei of the medulla and thence are continued forward by the great
sensory tract known as the " fillet," to end eventually in that part
of the cortex of the cerebrum designated as the area of the body
senses.

Ascending (Afferent or Sensory) Paths in the Lateral
Columns. — The two best known ascending tracts in these columns
are those of Flechsig and of Gowers. The Flechsig bundle or dor-
sal cerebellar tract takes its origin in the upper lumbar region,
and is composed of axons connected with the tract cells of Clarke's
column. The impulses which its fibers convey are brought into
the cord through those fibers of the posterior root that end around
the cells of Clarke's column. A number of the fibers in this col-
umn end doubtless in the gray matter of the upper regions of the
cord, but most of them con-
tinue upward on the same side,
enter the inferior peduncle of
the cerebellum, and terminate
in the posterior and median
portions of the vermiform lobe,
mainly on the same side, but
partly also on the opposite
side. The tract of Gowers,
situated ventrally to Flechsig's
bundle (gr, Fig. 70), may ex-
tend forward into the anterior
columns along the periphery
of the cord. The two bundles
may be more or less intermin-
gled at the points of contact.
This tract begins also in the

upper lumbar region, its fibers arising on the same side from tract
cells situated in the anterior horn and the so-called intermediate
portions of the gray matter. Many of the fibers in this tract doubt-
less terminate in the cord itself, since the bundle does not increase
regularly in size as it passes up the cord. Most of the bundle
continues forward, however, along the ventral side of the pons,
gradually shifts more to the dorsal side, and at the level of the
superior peduncles of the cerebellum turns backward, for the most
part at least, and passes to the cerebellum by way of the superior
peduncles and the valve of Vieussens, to end in the vermiform lobe
chiefly on the same side, but to some extent on the opposite side *
(Fig. 73). Regarding the physiology of these two tracts there is

* For the literature upon these tracts see Van Gehuchten, " Le Nevraxe,"
3, 157, 1901.

a.e

Fig. 73. — To show the course of the fibers
of the cerebellar tracts of the cord (Mott) :
v.a.c., ventral tract (Gowers); d.a.c., dor-
sal tract (Flechsig); s.v., superior vermis;
P.C.Q., posterior corpora quadrigemina.

166 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

little experimental and not much clinical evidence. Some observers
have cut the tract of Flechsig in animals, but with no very obvious
effect except again a slight degree of ataxia in the movements
below the lesion and some loss of muscular tone.* This result
together with the fact that the bundle ends in the cerebellum
gives reason for believing that the fibers mediate muscular sensi-
bility. As we shall see, much evidence of various kinds connects
the cerebellum with the co-ordination of the muscles of the body
in the complex movements of standing and locomotion. This
power of co-ordination hi turn depends upon the sensory impulses
from the muscles, and since the fibers of the tract of Flechsig end
in the cerebellum, and since experimental lesion of them gives
no loss of cutaneous sensibility and some degree of ataxia, it seems
justifiable to conclude that these fibers are physiologically muscle-
sense fibers. The tract of Gowers has not been the subject of
much experimental study from the physiological side. Clinically
the tract may be involved in pathological or traumatic lesions of
the lateral columns. Gowers f himself gives a history of some such
cases which lead him to believe that this tract constitutes a path-
way for pain impulses, and this view or the view that it conducts
the impulses of both pain and temperature has been more or less
generally accepted. Little confidence, however, can be placed
in this conclusion, since the lesions in question were not strictly
confined to the column of Gowers. The only positive indication
that we have concerning the physiological value of these fibers is
given by their histology in the fact that they end for the most part
in the cerebellum. The cerebellum we know may be removed in
dogs and monkeys without loss of the sensation of pain, tempera-
ture, or touch, and this fact speaks strongly against the view that
either the tract of Flechsig or that of Gowers is concerned in the
conduction of these cutaneous sensations. From a physiological
standpoint we should be inclined to believe that both of these
tracts conduct the impulses of the deeper sensibilities, particularly
the sensations arising from the muscles, tendons, and joints.
It would seem, therefore, that all the long ascending tracts in the
posterior and lateral columns of the cord may be made up of fibers
of muscle sense, using this term in a wide sense to include the deep
sensibility of the joints, tendons, and muscles. The immense
importance of muscular sensibility in the maintenance of life and
in defense against enemies may explain, upon the doctrine of the
struggle for existence, why the long paths should have been devel-
oped first in connection with this sense.

*Bing, " Archiv fur Physiologie, " 1906, 250.
t Gowers, " Lancet," 1886.

SPINAL CORD AS A PATH OF CONDUCTION. 167

The Spinal Paths for the Cutaneous Senses (Touch, Pain,
and Temperature). — From the facts stated in the last two para-
graphs it would seem probable that the spinal paths for touch,
pain, and temperature must be along the short association tracts
of the ground bundles of the lateral and anterior columns. There
is evidence from the clinical side that the paths of conduction for
these senses are separate. In the pathological condition known
as syringomyelia cavities are formed in the cord affecting chiefly
the central gray matter and ^he contiguous portions of the white.
In these cases a frequent symptom is what is known as the dis-
sociation of sensations; the patient loses, in certain regions, the
sensations of pain and temperature (analgesia and thermo-anes-
thesia), but preserves that of pressure (touch). Facts of this kind
indicate that the paths of conduction for touch are separate from
those for pain and temperature, but little that is positive is known
regarding the exact location of these paths. The fibers of pain
and temperature probably end in the gray matter of the cord (pos-
terior horn) soon after their entrance, and the path is continued
upward by tract cells whose axons enter the ground bundles in the
lateral or anterolateral columns, most probably in the lateral col-
umns, so far at least as the lower animals are concerned,* but
the number of such neurons concerned in the conduction as far as
the medulla is not known. Regarding the path for the touch
impulses a singular amount of uncertainty prevails. This sense
is not lost in cases of syringomyelia in which the other cutaneous
senses are affected. On the other hand, the posterior columns,
as we have seen, may be completely sectioned in lower animals
without destroying or, indeed, affecting the sense of touch, and
in the case of man extensive pathological lesions of the same col-
umns are reported in which the sense of touch was not lost. Some
authors, therefore, have been led to believe that the touch impulses
may be conveyed up the cord by several paths: by the long asso-
ciation fibers of the posterior columns and by the short association
fibers of the lateral columns. Such a view receives little support
from the experimental work on the lower mammals. In these
animals the evidence tends to show that the conduction is by way
of the lateral or anterolateral columns, by means of tract cells and
short association tracts. The fact that in man the clinical evidence
seems to point to the posterior columns as a possible or indeed
probable path for these fibers may serve to exemplify the fact that
in these matters the various mammalia differ more or less according
to the degree of their development. It seems possible also that
some confusion may have resulted from a failure to differentiate
between true cutaneous touch (pressure) sensations and those
* For recent discussion see Bertholet, Le Nevraxe, 1906, vii.. 283.

168 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

designated by Head * as deep pressure sensations. This author has
shown that the latter are mediated through the afferent fibers to
the muscles and constitute apparently a part of the group of sensa-
tions described as muscle sense. The path for this deep sensibility
to touch probably lies in the posterior columns.

Homolateral and Contralateral Conduction of the Cuta-
neous Impulses. — Great interest, from the medical side, has
been shown in the question of the crossed or uncrossed conduc-
tion of the cutaneous impulses in the cord. The matter is nat-
urally one of importance in diagnosis. In human beings it was
pointed out by Brown-Sequard f that unilateral lesions of the
cord are followed by muscular paralysis below on the same side
and loss of cutaneous sensibility on the opposite side. This syn-
drome has been held clinically to establish the diagnosis of a uni-
lateral lesion, and has led to the view that, while the conduction
of the motor impulses is homolateral, that of the sensory impulses
is contralateral. Experimental work on lower animals, on the con-
trary, has not supported this view. While results in this direction
have varied, as would be expected from the intrinsic difficulties
connected with the interpretation of the sensations of an animal, the
general outcome has been to show that the sensory conduction is
bilateral, but mainly on the same side. That is, if the cord is
cut on one side only (hemisected) in the thoracic region, the sensi-
bility of the parts supplied below the lesion is impaired upon the
same side, but not completely abolished, showing that some
crossing has taken place.J It is possible that this crossing is more
complete in man than in the lower animals, although later studies
in man of unilateral lesions of the cord (Brown-Sequard paralysis)
indicate that the contralateral loss of cutaneous sensibility affects
chiefly the senses of pain and temperature; the loss of touch is not
complete, and muscular sensibility is affected only on the same
side. On the whole, it would seem that the crossing, of the sensory
fibers in the cord is only partial, and is more extensive in man
than in the lower animals. This partial crossing is probably com-
pleted in the brain, especially in the great sensory decussation in
the medulla.

The Descending (Efferent or Motor) Paths in the Antero-
lateral Column. — The main descending path in the cord is the
pyramidal system of fibers. In man, as shown in Fig. 70, there
are two fasciculi belonging to this system, — the direct and the
crossed pyramidal tracts. Both tracts arise from the anterior
pyramids on the ventral face of the medulla, whence the name of

* Head and Rivers, "Brain," 1905, 99.

t Brown-Sequard, "Journal de Physiologic, " 6, 124, 232, 581, 1863.

j Mott, "Brain," 1895, 1, and Bertholet, "Le NeVraxe," 1906, vii., 283.

SPINAL CORD AS A PATH OF CONDUCTION.

169

the pyramidal system. At the junction of the medulla and cord
the fibers of the pyramids decussate in part, forming a conspicuous
feature of the internal structure at this point known as the pyram-
idal decussation. According to the general schema of this decus-
sation (see Fig. 74), the larger number of the fibers in the pyramid
of one side pass over to form the
crossed pyramidal tract of the other
side of the cord (4, 5), while a
smaller part (3) continues down
on the same side to form the direct
pyramidal tract. Eventually, how-
ever, these latter fibers also cross
the mid-line in the anterior white
commissure, not, however, all at
once, as at the pyramidal decussa-
tion, but some at the level of each
spinal nerve. These pyramidal
fibers have their origin in the cortex
of the cerebral hemispheres in large
pyramidal cells ; some of them cross
the mid-line before reaching the
medulla to end around the cells of
origin of the cranial nerves; but
the greater number continue into
the cord and after crossing the
mid-line in the pyramidal decussa-
tion or in the anterior white com-
missure terminate around the motor
cells of the anterior horns, which
give rise to the motor roots of the
spinal nerves. Both tracts, the
crossed and the so-called direct,
continue throughout the length of
the cord, diminishing in area on the
way as some of their fibers termin-
ate in each segment. This system
of fibers is supposed to represent
the mechanism for effecting volun-
tary movements, and according to the general schema the volun-
tary motor path from cerebrum to muscle comprises two neurons,
—the pyramidal neuron and the spinal or the cranial neuron.
Moreover, as represented in the schema, the innervation is crossed,
the right side of the brain controlling the musculature of the left
side of the body and vice versa. As we shall see, however, when
we come to study the motor areas of the brain, this rule has im-

Fig. 74. — Schema representing
the course of the fibers of the pyram-
idal tract: 1, Fibers to the nuclei of
the cranial nerve; 2, uncrossed fibers
to the lateral pyramidal tract; 3, fi-
bers to the anterior pyramidal tract
crossing in the cord ; 4 and 5, fibers
that cross in the pyramidal decussa-
tion to make the lateral pyramidal
tract of the opposite side.

170 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

portant exceptions, and histologically there is proof that some of
the fibers in each pyramid (2 in Fig. 74) continue into and termi-
nate in the cord on the same side. The pyramidal system varies,
in an interesting way, in the extent of its development among the
different vertebrates. It reaches its highest development in man
and the anthropoid apes. In the other mammalia it is relatively
less important and the direct tract in the anterior columns is lack-
ing altogether. In the birds what represents the same system is
found in the anterior columns (Sandmeyer), while in the frog the
system does not exist at all.

The relative importance of the system in the different mammalia
is indicated in the accompanying table taken from Lenhossek,*
in which the area of the pyramidal system is given in percentage
of the total cross-area of the cord:

Mouse 1.14 per cent.

Guinea pig 3.0

Rabbit 5.3

Cat 7.76

Man 11.87

Evidently, therefore, the importance of the pyramidal system
varies in different animals, and it is necessary to bear this fact
in mind in applying the results of experiments on the lower animals
to man. In the lowest vertebrates there are undoubtedly motor
paths between the brain and cord through which so-called voluntary
movements are effected, but these are probably short paths in-
volving a number of neurons. The higher the position of the
animal in the phylogenetic scale, the more complete is the develop-
ment of the long pyramidal system; but even in the higher mam-
mals it is probable that motor paths, other than the pyramidal
system, connect the cortex and subcortical centers with the motor
nuclei in the cord. In the dog, for example, section of the pyramids
is not followed by complete paralysis, and, indeed, after such sections
stimulation of the motor areas of the cortex still causes definite
muscular movements.! One such indirect motor path is referred
to below in connection with the rubrospinal tract (Monakow's
bundle).

Less Weil-Known Tracts in the Cord. — In addition to the
tracts just described there are a number of others — mainly, descend-
ing tracts — concerning which our anatomical knowledge is less com-
plete, and the physiological value of which is entirely unknown or
at best is a matter of inference from the anatomical relations. {

* Lenhossek, " Bau des Nervensystems," second edition, 1895.

t Rothmann, "Zeitschrift f. klin. med.," vol. xlviii., 1903.

j Collier and Buzzard, "Brain," 1901, 177; and Fraser, "Journal of
Physiology," 28, 366, 1902. For summary and literature consult Van Ge-
huchten, "Anatomic du systeme nerveux de 1'homme," 4th ed., 1906.

SPINAL CORD AS A PATH OF CONDUCTION. 171

Descending Tracts in the Posterior Column — Comma Tract ;
Oval Field. — In the posterior columns several tracts of descending
fibers have been described. The comma tract of Schultze is
found in the cervical and the upper thoracic cord. The bundle
lies at the border-line between the columns of.Goll'and Burdach.
In the lower regions of the cord, lumbar and sacral, similar small
areas of descending fibers are found — oval field (Flechsig), median
triangle (Gombault and Philippe) — which represent possibly
different systems. It is probable that these fibers belong to the
group of long association fibers connecting distant portions of the
cord. Nothing is known regarding their physiology.

Descending Tracts in the Anterolateral Column. — The prepyram-
idal tract, known also as Monakow's bundle, the fasciculus inter-
mediolateralis, or the rubrospinal tract, is a conspicuous bundle
forming a wedge-shaped or triangular area in the lateral columns
between the crossed pyramidal tract and the tract of Gowers, or,
perhaps, more correctly speaking, forming the anterior portion
of the crossed pyramidal tract; the two systems being more or
less intermingled. The fibers composing this bundle are descending
fibers that take their origin in the midbrain in the cells of the red
nucleus. Shortly after their origin they cross to the opposite
side, and passing through the pon£ and medulla enter the spinal
cord in the lateral columns, in which they may be detected as far
as the sacral region. Its fibers terminate around cells lying in the
posterior part of the anterior horn of gray matter whose axons
in turn probably emerge through the anterior roots. This tract,
therefore, constitutes a crossed motor path from midbrain to the
anterior roots, and, since the red nucleus in turn is connected
with the cerebrum, either directly or by way of the cerebellum, it
represents a corticospinal motor path in addition to that offered
by the pyramidal system.

The vestibulospinal fibers lie anterior to the preceding tract
in the anterolateral ground bundle; they may extend into the
anterior column as far as the direct pyramidal tract. These fibers
originate in the nucleus of Deiters. In the cord the fibers end
around cells in the anterior horn. Since the Deiters nucleus forms
a termination for the sensory fibers of the vestibular branch of the
eighth cranial nerve, and since these fibers are believed to give us
a sense of the position of the body and to be concerned in the reflex
adjustment of the muscles in the movements used to maintain
equilibrium, their connection in Deiters' nucleus with a spinal motor
path becomes very significant as furnishing a reflex arc through
which sensory impressions from the vestibular apparatus in the ear
may automatically control the musculature of the body. A number
of other descending paths in the anterior and lateral columns have

172 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

been described, such as Helweg's bundle or the olivospinal tract,
lying on the margin of the cord at the junction of the anterior and
the lateral columns and supposed to arise in the olivary bodies;
the anterior and the lateral reticulospinal tracts arising from cells
in the reticular formation of medulla, pons, and midbrain; and
the continuation into the cord of the important posterior longitu-
dinal bundle which extends from the midbrain through to the cord
and connects the motor nuclei of the cranial nerves with the
motor centers of the cord. Concerning these and similar tracts
our physiological knowledge is scanty, and it is not possible at
present to employ them with certainty in explaining the activity
of the neuromuscular apparatus.

CHAPTER IX.

THE GENERAL PHYSIOLOGY OF THE CEREBRUM
AND ITS MOTOR FUNCTIONS.

From the time of Galen in the second century of the Christian
era the brain has been recognized as the organ of intelligence and
conscious sensations. Galen established this view not only by
anatomical dissections, confirming the older work of the Alexandrian
school (third century B.C.) in regard to the origin from the brain
of the cranial nerves, but also by numerous vivisection experiments
upon lower animals. All modern work has confirmed this belief
and has tended to show that in the cerebral hemispheres and, indeed,
in the cortex of gray matter lies the seat of consciousness.
It is perhaps still an open question as to the existence of a
conscious or psychical factor in the activities of other parts of the
nervous system, but there is no doubt that the highest develop-
ment of psychical activity in man is associated with the cortical mat-
ter of the cerebrum. In the young infant the dawn of its mental
powers is connected with and dependent on the development of the
normal cortical structure, while in extreme age the failure in the
mental faculties goes hand in hand with an atrophy of the elements
of the cortex. If this cortex were removed all the intelligence, sen-
sation, and thought that we recognize as characterizing the highest
psychical life of man would be destroyed, and abnormalities in the
structure of this cortical material are accepted as the immediate
causal factor of those perversions in reasoning and in character
which are exhibited by the insane or the degenerate. The cortical
gray matter, therefore, is the chief organ of the psychical life, the
tissue through whose activity the objective changes in the external
world, so far as they affect our sense organs, are converted into
the subjective changes of consciousness. The nature of this reac-
tion constitutes the most difficult problem of physiology and psy-
chology, a problem which it is generally believed is beyond the
possibility of a satisfactory scientific explanation. For it is held
that the methods of science are applicable only to the investiga-
tion of the objective — that is, the physical and chemical — changes
within the nervous matter, while the psychical reaction is of a nature
that cannot be approached through the conceptions or methods
of physical science. In other words, there is a physicochemical

173

174 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

mechanism in the brain matter which is capable of giving us a
reaction in consciousness. The methods of physiology are adapted
to the investigation of the nature of this mechanism, but the reac-
tion in consciousness deals with a something which so far as we
know is not matter or energy, and which, therefore, is not within
the scope of physiological or, indeed, scientific explanation. In
what follows, therefore, attention is called only to the mechanical
side, — the facts that have been discovered regarding the anatomical
structure and the physical and chemical properties of the nervous
mechanism.

The Histology of the Cortex. — The finer structure of the
different regions of the cortex has been the subject of much investi-
gation, but in this connection it is only necessary to recall the
elementary facts so far as they are useful in physiological explana-
tions. Leaving aside minor differences in the shape and stratifica-
tion of the cells, it is an interesting fact that the cortex everywhere
has a similar structure. It consists of four or five layers more or
less clearly distinguishable (see Fig. 75) :

1. The molecular layer, lying immediately beneath the pia
mater, and having a thickness bf about 0.25 mm. In this layer,
in addition to the supporting neuroglia, there are found a number
of very small nerve cells of several types lying with their processes
parallel to the surface of the brain. The axons and dendrites of
these small cells terminate within the layer, so that they take no
direct part in the formation of the white matter of the brain, but
have, so to speak, a distributive or associative function. In this
layer, also, end many of the dendrites of the larger nerve cells of
the deeper layers and the terminal arborization of entering nerve
fibers (axons) from other regions. It must be conceived, there-
fore, as containing a fine feltwork of nerve fibrils, — dendrites and
axons or their collaterals,— and as a region, therefore, in which
many of the incoming impulses along afferent fibers are, so to
speak, distributed into outgoing ones. On histological grounds
Cajal was inclined to believe that this layer represents the location
of the most important psychical reactions.

2. The layer of small pyramidal cells of about the same thick-
ness as the last. This layer contains a number of small nerve
cells, mostly of the pyramidal type, with the apex directed toward
the external surface. The dendrites from the apical process termi-
nate in the molecular layer, while the axon arising from the basal
side of the cell passes inwardly to constitute one of the nerve
fibers of the medullary portion of the cerebrum.

3. The layer of large pyramidal cells. This layer, much thicker
(1 mm.) than the preceding, is not sharply differentiated from it.
It contains large pyramidal cells, particularly in the Rolandic area.

GENERAL PHYSIOLOGY OF THE CEREBRUM.

175

Their form and connections are, in general,
the same as those given for the small
pyramidal cells.

4. The layer of fusiform or polymor-
phic nerve cells. A small layer of cells
whose form is more irregular than that of
the pyramidal cells, but whose axons also
pass into the medullary portion of the
cerebrum, while their dendrites stretch
externally into the layers of pyramidal
cells. In this layer are found also some
cells belonging to the second type of
Golgi (Mart mot ti cells). The axis cylin-
der processes from these latter cells, in-
stead of becoming medullated fibers of
the white matter of the cerebrum, pass
toward the external surface, to end in
the pyramidal or molecular layer in a
number of minute branches.

5. The medulla of the cerebrum. The
white matter of the cerebrum begins
immediately below the last-named layer,
and consists (1) of nerve fibers which
originate from the pyramidal and poly-
morphic cells immediately exterior to it,
and which carry outgoing impulses from
that part of the cortex, and (2) of fibers
arising elsewhere in the cortex or in the
lower portions of the brain, which ter-
minate in the cortex and carry the
incoming impulses, — impulses which are
afferent as regards that part of the cor-
tex. The fibers in this white matter may
be classified under three heads: First,
the projection system (A, B, C, D, and
E of Fig. 76), comprising those fibers,
afferent and efferent, which connect the
cortex with underlying parts of the cen-
tral nervous system, — the spinal cord,
medulla, pons, midbrain, or thalamus.
This great projection system emerges, for
the most part, through the internal cap-
sule and the crura of the cerebrum.
Certain parts of the cortex are seemingly
lacking in a projection system; the fibers

m

Matte,

n

IV

Fig. 75. — To show the
structure of the cortex cere-
bri (Dejerine) : I, The molec-
ular layer; II, the layer of
vertical fusiform cells; ///,
the layer of small pyramidal
cells; IV, the layer of large
pyramidal cells; V, the layer
of polymorphic cells.

176

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

Fig. 76. — Schema of the projection fibers of the cerebrum and of the peduncles of the
cerebellum; lateral view of the internal1 capsule: A, Tract from the frontal gyri to the pons
nuclei, and so to the cerebellum (frontal cerebro-cortico-pontal tract) ; B, the motor
(pyramidal) tract; C, the sensory (body sense) tract; D, the visual tract; E, the auditory
tract; F, the fibers of the superior peduncle of the cerebellum; G, fibers of the middle
peduncle uniting with A in the pons; H, fibers of the inferior peduncle of the cerebellum;
J, fibers between the auditory nucleus and the inferior quaarigeminal body; K, motor
(pyramidal) decussa^n in the bulb; Vt, fourth ventricle. The numerals refer to the
cranial nerves. — (Modified from Starr.)

Fig. 77. — Lateral view of a human hemisphere, showing the bundles of association
fibers (Starr): A, A, Between adjacent gyri; B, between frontal and occipital areas; C,
between frontal and temporal areas, cingulum ; D, between frontal and temporal areas,
fasciculus uncinatus; E, between occipital and temporal areas, fasciculus longitudinalis
inferior; C.N, caudate nucleus; O.T, optic thalamus.

GENERAL PHYSIOLOGY OF THE CEREBRUM. 177

arising from these parts do not enter the capsule to make connec-
tion with the motor and sensory paths, below, but pass to other
parts of the cortex, forming a part of the system of association
fibers. Second, the association system, which may be defined as
comprising those fibers which connect one part of the cortex with
another (Fig. 77). There are short association tracts (A, A) con-
necting neighboring convolutions and long tracts passing from one
lobe to another. Third, the commissural system, consisting of as-
sociation fibers that cross the mid-line and connect portions of one
cerebral hemisphere with the cortex of the other. These fibers
make up the commissural bands known in gross anatomy as the
corpus callosum, anterior white commissure, fornix, etc.

Physiological Deductions from the Histology of the Cortex.
— Cajal* especially lays stress upon some anatomical features which
seem to justify certain generalizations of a physiological nature. In
the first place, every part of the cortex receives incoming impulses
and gives rise to outgoing impulses. Every part of the cortex is,
therefore, both a termination of some afferent path and the begin-
ning of some efferent path; it is, in other words, a reflex arc of
a greater or less degree of complexity. We may suppose that
every efferent discharge from any part of the cortex is occasioned
by afferent impressions reaching that point from some other part
of the nervous system. Whether or not there is such a thing as
absolutely spontaneous mental activity cannot be determined by
physiology, but on the anatomical side at least all the structures
exhibit connections that fit them for reflex stimulation, and many
of our apparently spontaneous acts must be of this character.
Secondly, all parts of the cortex exhibit an essentially similar
structure. Modern physiology has recognized clearly that different
parts of the cerebrum have different functions, but the differentia-
tion in structure which usually accompanies a specialization in
function is not very evident. Definite differences in the thickness
of the layers, in the size or shape of the cells, have been pointed out,
but it is perhaps something of a disappointment to find so little
of an anatomical distinction between structures whose reaction in
consciousness is so widely separated. It would seem that the
structural peculiarities must lie chiefly in the ultimate chemical
composition and physical properties of the protoplasm. In the
third place, the central nervous system throughout the verte-
brates is constructed upon the same lines, a mechanism of intercon-
necting neurons. There is a vast difference in the mental activity
of a frog and a man, but the cortex of the cerebrum shows a funda-
mental similarity in structure in the two cases. The chief difference
that comparative anatomy is able to show is that in the higher

* Cajal, "Les nouvelles idees sur la structure du systeme nerveux, etc.,"
Paris, 1894.
12

178

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

animals the greater mental development is associated with a greater
complexity and richness in the connections of the neurons. As
shown in Figs. 78 and 79, the number of processes, particularly
the dendritic processes, is much greater in the cortical cells
of the higher animals; or, to put this fact in another way, the
number of cells in the cortex of the higher animals is much less
for an area of the same size than in lower animals. The amount
of in-between substance or the richness of the network of processes

Fig. 78. — A-D, Showing the phylogenetic development of mature nerve cells in a
series of vertebrates: a-e, the ontogenetic development of growing cells in a typical mam-
mal (in both cases only pyramidal cells from the cerebrum are shown) ; A, frog; B, lizard;
C, rat; D, man; a, neuroblast without dendrites; b, commencing dendrites; c, dendrites
further developed; d, first appearance of collateral branches; e, further development of
collaterals and dendrites. — (From Ramdn y Cajal.)

is increased. This anatomical fact would indicate that the greater
mental activity in the higher animals is dependent, in part, upon
the richer interconnection of the nerve cells, or, expressed physio-
logically, our mental processes are characterized by their more
numerous and complex associations. A visual or auditory stim-
ulus that, in the frog, for instance, may call forth a comparatively
simple motor response, may in man, on account of the numerous
associations with the memory records of past experiences, lead to

GENERAL PHYSIOLOGY OF THE CEREBRUM.

179

psychical and motor responses of a much more intricate and in-
direct character.

Extirpation of the Cerebrum.— One of the methods used in
physiology to determine the general functional value of the cerebral
hemispheres has been to remove them completely, by surgical
operation, and to study the effect upon the psychical responses of
the animal. Upon the cold-blooded animals and the birds the
operation may be performed with ease, but in these animals the
positive results are not striking and the experiments are valuable

* J

•4W

Fi£. /9. — Sections through corresponding parts of the cortex in: a, Man; ft, dog;
and c, mole, to show the greater separation of the nerve cells in the higher animals.—
(Bethe, after Nissl.)

chiefly for their negative results. If the cerebral hemispheres are
removed from the frog, for example, the animal after recovering
from the immediate effects of the operation — that is, the effects
of the anesthetic and the shock — shows surprisingly little difference
from the normal animal. It maintains a normal posture and shows
no loss at all in its power of equilibration. When placed on its
back it quickly regains its usual position. If thrown into water

180 PHYSIOLOGY OP CENTRAL NERVOUS SYSTEM.

it swims to a solid support and crawls out like a normal animal.
It jumps when stimulated and is careful to avoid obstacles placed
in its way, showing that its visual reflexes are not impaired. It
is said, however, that the more complicated reactions that depend
upon the memory of past experiences or the instincts are absent or
imperfect. This latter peculiarity is manifested most impressively
in birds (pigeons) after removal of a part or all of the cerebrum. As
a result of such an operation, the nervous, active animal is changed
at once to a stupid, lethargic creature which reacts only when
stimulated. It sits in a drowsy attitude, with its head drawn in
to the shoulders, its eyes closed, and its feathers slightly erected;
occasionally it will open its eyes, stretch the neck, gape, preen
its feathers perhaps, and then sink back into its somnolent attitude.
The animal in this condition maintains its equilibrium perfectly,
flies well if thrown into the air and perches comfortably upon a
narrow support. It may be kept alive apparently indefinitely by
appropriate feeding and so long as it is well fed retains its stupid
and impassive appearance. If allowed to starve for a while it
becomes restless from the effects of hunger, may walk to and fro,
and peck aimlessly at the ground. If surrounded by grain it may
peck at the separate grains, but never actually seizes one in its
beak and swallows it. The striking defect in these animals is the
loss of those responses that depend upon memory of past or in-
herited experiences. Its motor reactions are all of a simple kind.
If placed upon a hot plate it will, for a time, lift first one foot, then
the other, and finally squat, but never flies away. When dosing
a loud noise awakens it, but it exhibits no signs of fear, and
quickly relapses into somnolence when the auditory stimulus ceases.
The one positive conclusion that we may draw from the behavibr
of these animals is that in them the cerebrum is the place in which
the memory records are stored, and that when it is removed the
actions of the animal when stimulated become much more direct
and predictable, since the stimulus awakens no associations with
past experiences. The complete removal of the cerebrum in mam-
mals is attended with more difficulty. When taken out at once
by a single operation the animal survives but a short time and
the permanent effects of the operation cannot be detected. Goltz,*
however, has succeeded, in dogs, in removing by a peculiar operation
all of the cerebral cortex. The operation was performed in sev-
eral successive stages with an interval of several months between.
In the most successful experiment the animal was kept alive for
a year and a half and the postmortem examination showed that-
all of the cortex had been removed except a small portion of the
tip of the temporal lobe, and this latter, since its connection with
* Goltz, " Archiv f. die gesammte Physiologic," 51, 570, 1892.

GENERAL PHYSIOLOGY OF THE CEREBRUM. 181

the other parts of the brain had been destroyed, was, of course,
functionless. In addition, a large part of the corpora striata and
optic thalami and a small portion of the midbrain had been re-
moved. The behavior of this animal was studied carefully. After
the immediate effects of the operation — paralysis, etc. — had disap-
peared the animal moved easily ; in fact, showed a tendency to keep
moving continually. There was no permanent paralysis of the so-
called voluntary movements. He answered to sensory stimuli of
various kinds, but not in an intelligent way. If, for instance, a
painful stimulus was applied to the skin, he would growl or bark,
and turn his head toward the place stimulated ; but did not attempt
to bite. No caressing could arouse signs of pleasure, and no
threatening signs of fear or anger. Like the pigeon, the most con-
spicuous defect in the animal was a lack of intelligent response, — •
that is, the responses to sensory stimuli were simple, and evidently
did not involve complex associations with past experiences. His
memory records, for the most part, had been destroyed. Goltz
records that when starved he showed signs of hunger, and that
eventually he learned to feed himself when his nose was brought
into contact with the food, although he was not able to recognize
food placed near him. He would reject food with a disagreeable
taste. When sleeping he gave no signs of dreaming, differing in
this respect from normal dogs.

Localization of Functions in the Cerebrum. — When the
belief was established that the cerebrum is the organ of the higher
psychical activities there arose naturally the question whether dif-
ferent parts of the cortex have different functions corresponding
to the various faculties of the mind, or whether the cerebrum is
functionally equivalent throughout, in the same sense, for instance,
as the liver. This question of the localization of functions in the
brain (cerebrum) has been much debated, but the most interesting
and important discussions upon the subject belong to the nine-
teenth century. About the beginning of the century Franz Joseph
Gall, at that time a physician in Vienna, began to teach publicly his
well-known system of cranioscopy or, as it was later designated by
his chief disciple (Spurzheim), system of phrenology.* Gall, from his
early youth, was possessed with the idea that the different faculties
of the mind are mediated through different parts of the brain, that
in it we have to deal not with a single, but with a plurality of
organs. This belief was in opposition to the current ideas of his
times and Gall devoted his entire life to an earnest effort to estab-
lish and popularize his views. He and his disciples contributed
many very important facts to our knowledge of the finer anatomy
of the brain; but, so far as the view of separate organs in the

* Gall (and Spurzheim), " Recherches sur la systeme nerveux en general
et sur celui du cerveau en particulier," 1810-19.

182 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

cerebrum is concerned, the methods that he employed, although
perhaps the only ones that he could make use of at that time,
have since been demonstrated to be fallacious when used as he
used them. He conceived that the more developed any given
mental quality is the larger will be the organ representing it in
the cerebrum, and since the cranium fits closely to the cerebrum
the relative prominence of the parts of the cerebrum may be judged
by a study of the exterior of the skull. This method of study con-
stituted the essential feature of cranioscopy or phrenology, and
by observation upon people with particularly marked mental
qualities Gall and his disciples supposed that they had located the
organs for thirty-five different faculties. While the general idea
of this method may be defended, it is obvious that the application
of it scientifically, so that positive and demonstrable results can
be obtained, is practically impossible. The system of phrenology
and its methods quickly fell into disrepute, since they were ex-
ploited chiefly by frauds and charlatans. Gall's ideas in the
beginning excited the greatest interest, but it seems that he was
never able to convince the majority of the scientific men of his day
of the conclusiveness of his results. At the time that he was
teaching his doctrines in Paris, where he spent the latter years of
his life, Flourens began his celebrated experimental work upon the
functions of the brain, — work which was mainly instrumental in
convincing physiologists that the cerebrum is a single organ,
functionally equivalent in all of its parts.* Flourens' chief ex-
periments were made upon pigeons, and in these animals he found
that successive ablations of parts of the cerebrum from before
backward or from side to side were not followed by a corresponding
series of defects in the animals' psychical life. On the contrary,
when the quantity of brain substance removed was sufficiently
large, all these qualities went at once. The choice of animals
for these experiments was an unfortunate one, but the results
were corroborated in part by a number of instances in which human
beings by accident or wounds in battle had lost a part of the brain
without any apparent defect in their mental powers. Therefore
toward the middle of the nineteenth century the prevalent view
in physiology was that the cerebrum is functionally equivalent in
all of its parts. One fact was known in medicine at that time
which distinctly contradicted this belief, — namely, that an injury
to the posterior portion of the third frontal convolution in man,
on the left side, causes a loss of articulate speech (motor aphasia).
But this fact, so significant to us now, was not properly valued at
the time. The beginning of our modern views of- cerebral localiza-

* Flourens, " Recherches experimentales sur les proprietes et les fonctions
du systeme nerveux dans les animaux vertebres," 1824.

GENERAL PHYSIOLOGY OF THE CEREBRUM.

183

tion is found in the work of Fritsch and Hitzig* (1870), in which
they exposed and stimulated electrically the cortex cerebri in
dogs. They observed that stimulation of certain definite areas,
particularly in the sigmoid gyrus, gave distinct and constant
movements in the limbs, face, etc. (see Fig. 80). This work
was- followed quickly by experiments of a similar kind made
by numerous observers, in which the cerebrum was stimulated in
various animals and finally in
man. In addition, the method
of ablation of these areas was
employed with subsequent
study of the animal in regard
to the motor or sensory de-
fects resulting therefrom, and
the results obtained were
further extended by careful
autopsies upon human beings
in whom paralyses of various
kinds and sensory defects were
associated with more or less
definite lesions of the cerebrum.
The first outcome of this work
was to lead to an extreme view
of localization of function in
the brain, in which the differ-
ent motor and sensory areas
were definitely circumscribed
and separated one from the
other, making the cerebrum a
plurality of organs, to use
Gall's term. The more recent

Fig. 80. — To sh9\v the motor areas in the
dog's brain as originally determined by
Fritsch and Hitzig: s, Sigmoid gyrus; A, center
for the neck muscles; -F, center for the ex-
tensors and adductors of the forelimb; +,
center for the flexors and rotation of fore-
limb; #. center for the hind limb; O — O,
center for the muscles innervated by the
facial.

work has tended to modify
these extreme views of local-
ization and to emphasize the
fact that histologically and
physiologically the entire cere-
brum is connected so inti-
mately, part to part, that, although the different regions mediate
different functions, nevertheless an injury or defect in one part
may influence to some extent the functional value of all other
regions in the organ. The general idea of a localization of func-
tion has been established definitely, but the modern view is that
the cerebrum is composed of a plurality of organs, not completely

* Fritsch and Hitzig, " Archiv f. Anatomie und Physiologic und wissen-
schaftliche Medizin," 1870, 300.

184

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

separated one from the other as taught by Gall, but intimately
associated and to a certain extent dependent one on another for
their full functional importance.

The Motor Area. — The first experiments of Fritsch and Hitzig
disclosed the location of a cortical region in the dog which upon
stimulation gave definite movements. The later experiments of
Ferrier, Schafer, Horsley, and Beevor, particularly upon the apes,
gave reason for believing that this motor area surrounds the fissure,
of Rolando and extends inward upon the mesial surface of the cere-
brum. Its exact boundaries marked out by careful stimulation of

yf J<*w Opening Vo cal Mastication,
oj~fQ,u> cords

Fig. 81. — Location of motor areas in brain of chimpanzee. — (Sherrington and Green-
baum.) The extent of the motor areas is indicated by stippling; it lies entirely in front
of the fissure of Rolando (sulcus centralis). Much of the motor area is hidden in the sulci.
The regions marked eyes indicate the areas whose stimulation gives conjugate movements
of the eyeballs. It is doubtful, however, whether these represent motor areas proper.

the region in monkeys was more or less verified upon man, since in
operations upon the brain it was often necessary to stimulate the
cortex in order to localize a given motor area. By these means
charts have been made showing the cortical area for the musculature
of each part of the body. It was found that in general the distri-
bution of the areas lies along the fissure of Rolando and follows the
order of the cranial and spinal nerves. Within each area smaller
centers may be located by careful stimulation; thus, the hand and
arm area may be subdivided into centers for the wrist, fingers,
thumb, etc. More recently Sherrington and Greenbaum,* making

* " Reports of the Thompson- Yates and Johnston Laboratories," 4, 351,
1902; 5, 55, 1903.

GENERAL PHYSIOLOGY OF THE CEREBRUM.

185

use of electrical stimulation, unipolar method, have explored care-
fully the motor areas in the monkey. They state that these areas do
not extend back of the Rolandic fissure, but lie chiefly along the
anterior central convolution, as represented in Figs. 81 and 82,
extending for only a small distance on to the mesial surface of the
cerebrum. The area thus delimited by physiological experiments
is the region from which arises the pyramidal system of fibers,
and clinical experience has shown that lesions in this part of the
cortex are accompanied by % paralysis of the muscles on the other

Sulc. Central. Anu3 £ Vagina,
Sutecottoso \ — ' SuUi.frecentr.marg.

Sulc.cdicj,rin

C.S.8. del.

Fig. 82. — To show extension of motor areas on to the mesial surface, brain of chim-
panzee.— (Sherrington and Ureenbaum). Mesial surface of left hemisphere: Stippled region
marked LEG gives the motor area for lower limb; /, s, and h indicate regions from which
movements were obtained occasionally with strong stimuli; /, foot and leg; s, shoulder and
chest; h, thumb and fingers. The shaded area marked EYES indicates a region stimulation
of which gives conjugate movements of the eyes.

side, particularly in the limbs. Pathological or experimental
lesions here, moreover, are followed by a degeneration of the
pyramidal neurons, — a degeneration which extends to the ter-
mination of the neurons in the cord. With these data we can con-
struct a fairly complete account of the mechanism of voluntary
movements. The initial outgoing or efferent impulses arise in the
large pyramidal cells of the motor areas and proceed along the
axons of their neurons to the motor nuclei of the cranial or spinal
nerves. The neurons of the pyramidal tract constitute the motor
tract for voluntary movements; a lesion anywhere along this tract
causes paralysis, more or less complete and on the other side of
the body in general, if the lesion is anterior to the decussation.
The path of the motor fibers is represented in the schema given in
Fig. 83. Arising in the cortex, they take the following route
(see also Fig. 76, B):

186 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

1. Corona radiata.

2. Internal capsule.

3. Cms cerebri (pes).

4. Pons Varolii, in which they are broken into a number of
smaller bundles by the fibers of the middle peduncle of the

cerebellum. In this region, also, some of the fibers cross the
mid-line, to end in the motor nuclei of the cranial nerves:
Third, fourth, fifth, sixth, and seventh.

5. Anterior pyramids.

6. Pyramidal decussation.

7. Direct and crossed pyramidal tracts in the cord.

After ending in the motor nuclei of the cranial or spinal nerves the
path is continued by a second neuron from these nuclei to the mus-
cles. The entire path involves, therefore, two neurons, and injury
to either will cause paralysis of the corresponding muscles.

Difference in the Paralysis from Injury to the Spinal and the
Pyramidal Neuron. — With regard to the musculature of the limbs
especially a difference has been observed in the paralysis caused by
injury to the spinal and pyramidal neurons, respectively. Lesions of
the anterior root cells in the cord or of the axons arising from them
cause complete paralysis of the corresponding muscles, since these
muscles are then removed not only from voluntary control, but also
from reflex effects. The muscles are entirely relaxed and in time ex-
hibit a more or less complete atrophy. When the pyramidal neurons
are affected, as in the familiar condition of hemiplegia resulting
from a unilateral lesion of the motor cortex, there is paralysis as
regards voluntary control, but, the spinal neuron being intact, the
muscles are still subject to reflex stimulation through the cord,
especially to the so-called tonic impulses. Under these conditions,
especially if the lesion is in the cord, it is frequently noticed that the
paralyzed muscles are thrown into a state of continuous contraction,
contracture, in which they exhibit a spastic rigidity. This fact,
therefore, may be used in diagnosing the general location of the
lesion. A satisfactory explanation of the cause of the contraction
has not been furnished. It may be due to uncontrolled reflex
excitation of the spinal neurons, or, as suggested by Van Gehuchten,
to the action of the indirect motor path by way of the rubrospinal
tract.

Is the Pyramidal Tract the Only Means of Voluntary
(Cortical) Control of the Muscles? — Much discussion has arisen
regarding this question. It is, in fact, one of those questions
of nervous mechanism in which experiments upon lower ani-
mals must be applied with caution to the conditions in man.
As we have seen, the entire cerebral cortex may be removed
from the frog, the pigeon, and the dog without causing permanent

GENERAL PHYSIOLOGY OF THE CEREBRUM.

187

paralysis, although in the animal last named there is at first a more
or less marked loss of voluntary control. But in man and the higher
types of the monkey the pyramidal system is more completely
developed, and corresponding with this fact it is found that the
paralysis from lesion of the motor cortex is more permanent. In
fact, observations upon men in whom
it has been necessary to remove
parts of the motor area by surgical
operation indicate that the voluntary /'/
control of the muscles is lost or im- j'?^
paired permanently. It would seem, 1%-J
therefore, that in an animal as high
in the scale as the dog voluntary
control of the muscles can be main-
tained through tracts other than the
pyramidal system, tracts, perhaps,
such as Monakow's bundle (rubro-
spinal tract) , arising in the midbrain
(see p. 171). In man, however,
along with the more complete de-
velopment of the pyramidal system,
the efficacy of the phylogenetically
older motor systems is correspond-
ingly reduced.

The Crossed Control of the
Muscles and Bilateral Represen-
tation in the Cortex. — It has been
known from very ancient times that
an injury to the brain on one side
is accompanied by a paralysis of
voluntary movement on the other
side of the body, a condition known
as hemiplegia. The facts given
above regarding the origin and course

Fig. 83. — Schema representing
the course of the fibers of the pyram-
idal tract: 1, Fibers to the nuclei of
the cranial nerve; 2, uncrossed fibers
to the lateral pyramidal tract; 3, fi-
Of the DVramidal fibers explain the bers to the anterior pyramidal tract
"J crossing in the cord; 4 and 5, fibers

that cross in the pyramidal decussa-
tion to make the lateral pyramidal
tract of the opposite side.

crossed character of the paralysis
quite satisfactorily. The schema
thus presented to us is, however,

not entirely without exception. In cases of hemiplegia in which
the whole motor area of one side is included it is known that the
paralysis on the other side does not involve all the muscles, and,
in the second place, it is said that there is some muscular weakness
on the same side. The paralysis in hemiplegia affects but little,
if at all, those muscles of the trunk which are accustomed to act
in unison, — the muscles of inspiration, for instance, the diaphragm,

188 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

abdominal and intercostal muscles, and the muscles of the larynx.
It would appear that these muscles are bilaterally represented in
the cortex; so that if one side of the brain is intact the muscles of
both sides are still under voluntary control. The mechanism of
this bilateral representation is not definitely known; one may
conceive several possibilities. The motor area on each side may
send down a double set of pyramidal fibers, one of which crosses
and the other remains on the same side, or the fibers may
bifurcate. Or it is possible that the bilateral control is due
to commissural connections between the lower centers in the
cord. Some evidence in favor of the former view is found in the
undoubted histological fact brought out by Mellus and others, that
small unilateral lesions in the motor area — the center of the great
toe in the monkey, for instance — are followed by degeneration in
the lateral pyramidal tract in the cord on both sides, showing that
some portions of the motor area send fibers to both sides of the
body. In cases of hemiplegia it may be added that the muscles
of the limbs are not all equally affected.

Are the Motor Areas Only Motor in Function? — The great
number of nerve cells in the cortex in addition to the large pyram-
idal cells that give origin to the fibers of the pyramidal tract make
it possible histologically that other functions may be mediated
in the same region. This possibility has been kept in view since
the early experiments of Munk, in which he showed that lesions in
the Rolandic region are followed by disturbances in what are
designated as the body sensations, muscular and cutaneous sensi-
bility, but especially the former. It was suggested, therefore,
at one time that one and the same spot in the cortex might
serve as the origin of the motor impulses to a given muscle and
as the cortical termination of the sensory impulses coming from
the same muscle, the reaction in consciousness, the muscular sensa-
tions, being mediated perhaps through cells other than those
giving rise to the pyramidal fibers. Recent physiological and clin-
ical work has, however, not tended to support this view. The
motor areas appear to be confined to the region in front of the fis-
sure of Rolando, while the cortical area, which gives rise to that
kind of consciousness that we designate in general as body sensi-
bility, extends back of the Rolandic fissure in the posterior central
gyrus. Whether, on the other hand, the sense areas for the body
(cutaneous and muscular) extend forward into the cortex of
the frontal lobe is not clearly shown by experimental or clinical
evidence. Flechsig, from his studies upon the time of myelini-
zation of the afferent fibers in the embryo brain, concludes that
this is the case, and that therefore the motor and sensory areas
overlap for a part at least of their extent (see p. 212 and Fig. 92).

GENERAL PHYSIOLOGY OF THE CEREBRUM. 189

In the motor area there are numerous connections by afferent
fibers, association tracts, with other parts of the brain. By
this means the motor area, without doubt, is brought into rela-
tion with many other parts of the cortex, and the sensations or
perceptions aroused elsewhere may react upon the motor paths.
A voluntary movement, however simple it may be, is a psychological
act of some complexity. The mental processes that lead to and
originate the motor discharge cannot be located in the cortex, but
the immediate origin of the- motor impulse lies most probably, in
the areas along the anterior margin of the fissure of Rolando.

CHAPTER X.

THE SENSE AREAS AND THE ASSOCIATION AREAS OF
THE CORTEX.

The delimitation of the sensory areas in the cortex is a matter
of very considerable difficulty, owing partly to the fact that the
determination of the presence or absence of certain states of con-
sciousness in the animal or person under observation cannot be
made except by indirect means, and partly no doubt to the fact
that the organization of the sensory mechanism in the brain is
more complex and diffuse than in the case of the motor apparatus.
Moreover, the distinction between what we may call simple sensa-
tions and the more complex psychical representations and judg-
ments of which these sensations form a necessary constituent can-
not be made clearly, even by the individual in whom the reactions
occur. We recognize in ourselves different stages in the degree of
consciousness aroused by sensory reactions. Our visual and
auditory sensations are clearly differentiated; but many of the
lower senses escape recognition in the individual himself, since the
state of consciousness accompanying them is of a lower order.
Our muscular sensations, for instance, are so indefinite as to be
practically subconscious. They are most important to us in every
act of our lives, yet the uninformed person is unconscious of the
existence of such a sensation, and if deprived of it would recognize
the defect only in the consequent loss of control of the voluntary
muscular movements. In the attempts to determine in what part
of the brain the various sensations are mediated every possible
method of inquiry has been used : the anatomical course of the
sensory paths, physiological experiments of stimulation and ablation,
and observations upon individuals with pathological or traumatic
lesions in the brain. In the long run, the study of neuropatholog-
ical cases in man must give us the last word, because in such cases
the estimate of the sensory defect can be made with most accuracy
and because in man the specialization of the psychical functions
has reached its highest development. The results that have been
obtained are perhaps the most definite in the case of the higher
senses, vision and hearing, since defects in these senses are recog-
nized most clearly, and the anatomical mechanisms involved have
proved to be more accessible to investigation.

190

SENSE AREAS AND ASSOCIATION AREAS. 191

The Body-sense Area. — In his early experiments Munk in-
sisted that lesions of the cortex involving the Rolandic area are
accompanied by a state of anesthesia on the other side of the body,
hemianesthesia, particularly as regards the tactile and muscular
sensations. It is not necessary, perhaps, to go into the details
of the long controversy that arose in connection with this point.
Both the clinical and the experimental evidence has been contra-
dictory in the hands of different observers, but the tendency of
recent studies has been to phow, as stated above, that, whereas
the motor areas lie anterior to the fissure of Rolando, the sensory
areas concerned with the cutaneous and muscular sensations extend
posterior to this fissure.* Positive cases are recorded in which lesions
involving the anterior central convolutions were accompanied by
paralysis on the other side, hemiplegia, without any detectable
disturbance of sensibility, and, on the other hand, lesions in the
posterior central, and neighboring parietal convolutions, in which
there was a hemianesthesia more or less distinctly marked without
any paralysis. Such cases tend to support the view that the motor
and body sense areas, although contiguous, do not overlap. f On
the other hand, the embryological evidence, as furnished by Flechsig,
indicates that the sense areas may extend in front of the Rolandic-
fissure (p. 212) and overlap the motor areas in part. At present,
perhaps, one is justified in saying only that the region immediately
posterior to the Rolandic fissure is entirely sensory. Regarding
the sensory defects associated with lesions of the parietal lobe
posterior to the Rolandic fissure (posterior central convolution,
supramarginal, superior, and possibly inferior parietal convolutions),
it seems probable that they involve chiefly the muscular sense,
pressure and temperature sense, and the judgments or perceptions
based upon these sensations, while the sense of pain is but little
affected. Monakow gives the order in which sensory defects mani-
fest themselves after such lesions, as follows: The localizing space
and muscle sense are chiefly affected,- — in fact, almost lost on the
opposite side; the temperature and pressure sense may be affected,
while the pain sense is retained or but slightly affected. The
clinicians have observed that the most positive and invariable
symptom of lesions in this region is a condition of astereognosis, —
that is, a diminution in the stereognostic sense or perception. By
the stereognostic perception is meant the power to judge concerning
the form and consistency of external objects when handled, and it
must be regarded as a perception based upon localized sensations of
touch and temperature in combination with muscular sensibility.

* Consult Monakow, "Ergebnisse der Physiologic," 1902, vol. i, part I,
p. 621.

t Mills, American Neurological Association, 1901.

192

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

On the whole, therefore, we must infer that the cortex in this
postrolandic area is concerned with the finer and more conscious
interpretations of the sensations of pressure, temperature, and
muscular conditions, and especially the higher type of these sensa-
tions which we can project or localize accurately. The definite
part of the cortex, if any, concerned in the primary conscious
mediation of the sense of pain and in the more general sensations

Fissure of Rolando

Internal or Median Fillet

Fig. 84. — Schema representing the origin and course of the fibers of the median fillet, — the
intercentral paths of the fibers of body sense.

of pressure and temperature — that is, the so-called common or, to
use Head's term, protopathic sensations (p. 260)— has not been
definitely localized.

The Histological Evidence. Course of the " Fillet."— On
the histological side there is very strong corroborative evidence for
the view that cortical centers for the sensory fibers of the body
in general lie in the parietal lobe in the region indicated above.
This evidence is connected with the path taken by the sensory

SENSE AREAS AND ASSOCIATION AREAS. 193

fibers in the cord, especially those of the posterior columns, after
ending in .the nucleus gracilis and nucleus cuneatus of the medulla.
This path is represented in a schematic way in the accompanying
diagram (Fig. 84). The second sensory neurons arise in the nuclei
mentioned. For the most part, at least, these new neurons run
ventrally, as internal arciform fibers, cross the mid-line, and then
pass forward or anteriorly. The crossing occurs mainly just in
front of — that is, cephalad to — the pyramidal decussation, forming
thus a sensory decussation,,, which explains the crossed sensory
control, as the pyramidal decussation explains the crossed motor
control of the cerebrum in relation to the body. After this decussa-
tion the sensory fibers form a longitudinal bundle -on each side

Fig. 85. — Cross-section through midbrain (Kdlliker) to. show the position of the fillet (L, L):
." . Nr, The red nucleus; Snt the^substantia nigra; Pp, the crus.

'

known as the jnedian fillet, lemniscuSi or laqueus, which in the pons
lies just dorsal to the pyramidal fibers. m

The fillet fibers may be traced' forward (see Fig. 85) as far as
the anterior colliculus of the corpora quadrigemina and the thal-
amus, the important termination being in the thalamus (ventral
or lateral nucleus) . Those neurons that end in the thalamus
are continued forward by a third set of neurons, which end in the
parietal lobe of the cerebrum (see Fig. 76, C). On its way
through the medulla and pons -the fillet tract is believed to receive
accessions of sensory fibers from the sensory nuclei of the cranial
nerves of the opposite side. The course of .the fillet has been
traced by various means, but especially by the method of myeliniza-
13

194 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

tion during embryonic life and by degeneration consequent upon
long-standing disuse. As was stated in the section upon Nerve De-
generation, injury to an axon is followed quickly by degeneration of
the peripheral end, and much more slowly by a degeneration of the
central end and the nerve cell itself, when the path is not again
established. Certain long-standing cystic lesions (porencephaly)
in the parietal cortex have resulted in an atrophic degeneration of
the fillet fibers, thus adding materially to the evidence that this
sensory tract ends eventually in the region indicated.* Further
evidence of the same character is found in the observations made
by Campbell f upon cases of tabes dorsalis. The lesion in such
cases is in the posterior columns of the spinal cord, but eventually
the whole upward path is affected and degenerative changes are
found in the cells of the posterior central convolution.

From the connections of the fillet with the tracts of the pos-
terior columns of the cord it is evident that it forms one pathway
at least for the fibers of muscle sense. Whether or not the fibers
of pressure, pain, and temperature take the same route is not
known, but it seems probable at least from the known connections
of the fillet with the sensory nuclei of the cranial nerves and with
the sensory tracts of the lateral as well as the posterior columns
of the cord. The fillet ends chiefly in the thalamus, before passing
on to the cortex, and here, as in other similar cases, we have the
possibility that the lower centers, in addition to the reflex connec-
tions which they make, may mediate also some form of conscious
reaction. While the general tendency has been to confine the
conscious quality of the central reactions to the cortex, there is
no proof that the lower centers are entirely lacking in this property.
In Goltz's dog without cerebral cortex, for instance, the animal-
responded to various sensory stimuli, and when hungry gave
evidence, so far as his actions were concerned, of experiencing
the sensations of hunger; but whether or not these actions were
associated with conscious sensations is hidden from us, and we can
hope to arrive at positive conclusions upon this point only by obser-
vations upon man himself.

The Center for Vision.— The location in the cortex of the
general area for vision has been established by anatomical, physio-
logical, and clinical evidence. The physiologists have experimented
chiefly by the method of ablation. Munk, Ferrier, and later ob-
servers have found that removal of both occipital lobes is followed
by defects in vision. According to Munk, removal of both occip-
ital lobes is followed by complete loss of visual sensations, or, as he
expresses it, by cortical blindness. Goltz, however, contends that in

* Hosel, 'Archiv f. Psychiatrie, " 24, 452, 1892.

t Campbell, ' Histological Studies on Localisation of Cerebral Functions, "
Cambridge, 1905.

SENSE AREAS AND ASSOCIATION AREAS. 195

the dog at least removal of the entire cerebral cortex leaves the
animal with some degree of vision, since he will close his eyes if a
strong light is thrown upon them. All the experiments upon the
higher mammals (monkeys) and clinical experience upon man
tends, however, to support the view of Munk. Complete removal
of the occipital lobes is followed by apparently total blindness.
If any degree of vision remains it is not sufficient for recogni-
tion of familiar objects or for directing the movements. In an
animal in this condition tjje pupil is constricted when light is
thrown upon the eye; but this reaction we may regard as a reflex
through the midbrain, and there is no reason to believe that it is
accompanied by a visual sensation. When the injury to the occip-
ital cortex is unilateral the blindness affects symmetrical halves of
the two eyes, a condition known as hemiopia. Destruction of the
right occipital lobe causes blindness in the two right halves of the
eyes, or, in accordance with the law of projection of retinal stimuli,
in the two left halves of the normal visual field when the eyes
are fixed upon any object. Destruction of the left occipital lobe
is followed by blindness in the two left halves of the retinas or the
right halves of the visual field. This result of physiological ex-
periments is borne out by clinical experience. Any unilateral
injury to the occipital lobes is followed by a condition of hemiopia
more or less complete according to the extent of the lesion. Obser-
vation, however, has shown that this general symmetrical relation
has one interesting and peculiar exception. The most important
part of the retina in vision is the region of the fovea centralis,
whose projection into the visual field constitutes the field of direct
or central vision. It is said that the hemiopia from unilateral
lesions of the cortex does not involve this part of the retina.

The Histoloqical Evidence. — The histological results supple-
ment in a very satisfactory way the findings from physiology and
pathology. The retina itself, considered from an embryological
standpoint, is an outgrowth from the brain vesicles, and is there-
fore an outlying portion of the central nervous system. The optic
fibers, in terms of the neuron doctrine, must be considered as
axons of the nerve cells in the retina. If, therefore, an eye is enu-
cleated or an optic nerve is cut the fibers connected with the
brain undergo secondary degeneration and their course can be
traced microscopically to the brain. By this means it has been
shown that in man and the mammalia there is a partial decus-
sation of the optic fibers in the chiasma. The fibers from the
inner side of each retina cross at this point to the opposite optic
tract; those from the outer side of the retina do not decussate,
but pass into the optic tract of the same side. The fibers of the
optic tract end mainly in tne gray matter of the external genicu-

196 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

late body, but some pass also to the optic thalamus (pulvinar) and
some to the anterior colliculus of the corpora quadrigemina. These
locations, therefore, particularly the external geniculates, must be
considered as the primary optic centers. From these points the path
is continued toward the cortex by new neurons whose axons consti-
tute a special bundle, the optic radiation, lying in the posterior limb
of the internal capsule (see Fig. 76, D). A schema representing

Occipital lobe.

Optic radiation.
Superior colliculus. (

Lateral or external geniculate.
Optic thalamus.

Optic tract.

Optic chiasm.
Optic nerve.
c- Retina. •

Fie 86 -Diagram to indicate the general course of the fibers of the. optic nerves and the
bilateral connection between cortex and retina.

this course of 'the optic fibers is given in the accompanying diagram
(Fig "8Q). According to this schema, the general relations of each
occipital' lobe to the retinas of the two eyes is such that the right
occipital cortex represents the cortical center for the two right
halves of the retinas, while the left occipital lobe is the center for
the two left halves of each retina,— a relation that agrees completely
with the results of experimental physiology and clinical studies.
In addition to the fibers described, which may be regarded as the
visual fibers proper, there are other fibers in the optic tracts and

. SENSE AREAS AND ASSOCIATION AREAS. 197

optic 'nerves whose" physiological value is not entirely clear. The
fibers of this kind that have been described are: (1) Posterior or
Gudden's commissure. Fibers that pass from one optic tract to
the other along the posterior border of the chiasma. These fibers
form a commissural band connecting the two internal (or median)
geniculate bodies, and possibly also the inferior colliculi. It
seems probable that they belong to the central auditory path
rather than to the visual system. (2) Fibers passing from the
chiasma into the floor of the third ventricle. The further course
of these fibers is not clearly known, but it is possible that they make
connections with the nuclei of the third nerve. They will be referred
to in the section on vision in connection with the light reflex of
the iris. (3) An anterior commissure. Several observers have
claimed that there is a commissural band along the anterior margin
of the chiasma which connects one optic nerve or retina with the
other.

There are many points in connection with the course of the
optic fibers and the physiology of the different parts of the occip-
ital cortex which are unknown and require further investigation.
Some of these points may be referred to briefly.

The Amount of Decussation in the Chiasma. — According
to the schema given above, half of the fibers in each optic nerve
decussate in the chiasma. There is, however, no positive proof
that the division of the fibers is so symmetrically made. In the
lower vertebrates, — fishes, amphibia, reptiles, and most birds — •
the crossing is said to be complete, while in the mammalia a certain
proportion of the fibers remain in the optic tract of the same side.
In a general way, it would appear that the higher the animal is
in the scale of development the larger is the number of fibers that
do not cross in the chiasma. At least it is true that a larger num-
ber remain uncrossed in man than in any of the mammalia, and it is
also possible or probable that the extent of decussation in man
shows individual differences. There seems to be no acceptable
suggestion regarding the physiological value of this partial decus-
sation other than that of a probable relation to binocular vision. It
has been used to explain the physiological fact that simultaneous
stimulation of symmetrical points in the two retinas gives us a
single visual sensation.

The Projection or Localization of the Retina on the
Occipital Cortex. — It would seem most probable that the paths
from each spot in the retina terminate in a definite region of
the occipital cortex, and attempts have been made, by various
methods to determine this relation. According to Henschen,* the
visual paths in man end around the calcarine fissure on the
*Henschen, "Brain," 1893, 170.

198

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

LEFT RETINA

RIGHT RETIW

mesial surface of the brain, and this portion of the occipital lobe
should be regarded as the true cortical center for vision, the re-
mainder of the occipital cortex being perhaps the seat of visual
memories or associations. There seems to be much evidence
indeed that the immediate ending of the optic paths lies in this
region. Thus, Donaldson* found, upon examination of the brain
of Laura Bridgman, — the blind deaf-mute, that the cuneus espe-
cially showed marked atrophy, and clinical cases of lesions of the
cuneus have been found to be associated with a marked degree of
hemiopia. So also Flechsig,f by means of the myelinization
method, finds that the optic fibers end chiefly along the margin
of the calcarine fissure. It has been assumed that the fibers

from the fovea of the retina
end in this region, — according
to some authors (Henschen)
along the anterior third of the
fissure, according to others
(Schmid and LaqueurJ) along
the posterior portion of the
fissure. Moreover, since uni-
lateral lesions of the occipital
lobe, however extensive, do
not cause complete blindness
of the foveal region, it has
been supposed that this im-
portant part of the retina is
bilaterally represented in the
cortex, as indicated in the ac-
companying diagram (Fig. 87) ;
so that complete foveal blind-
ness— that is, blindness of the
centers of the visual fields — can

Fig. 87.— Diagram showing the probable , nopnr whpn hnth OPpinitfll

relati9ns between the parts of the retina and Only OCC T \V IM

the visual area of the cortex. — (From Schd- 1/VKoa aro ininrprl in tnp rpo*inn

7«r.) The bilateral representation of the looeS are H^UTC

fovea is indicated by the course of the dotted of ^he calcarine fissure. While
lines. .

the general opinion seems to

be that this last-named region is the main cortical ending of the
retinal fibers, especially of those arising from the foveal area, other
observers contend that the entire occipital cortex, lateral as well as
mesial surfaces, must be regarded as the cortical termination of the
visual paths, and that even the foveal portion of the retina is con-
nected with a wide area in this lobe. Monakow, for instance, ^points

* Donaldson, "American Journal of Psychology," 1892, 4.
f Flechsig, "Localization der geistigen Vorgange," Leipzig,
j Schmid and Laqueur, "Virchow's Archiv," 158, 1900.

1896.

SENSE AREAS AND ASSOCIATION AREAS. 199

out that, while extensive lesions of the occipital cortex on both
sides, leave, with a few exceptions, some degree of central vision,
no cases are reported of cortical lesions involving only or mainly
the vision in the macular region. He therefore argues that, while
the paths from the retina to the lower visual centers (external
geniculate) may be isolated, the further connections with the
cortex must be widespread. The cortical center for distinct vision
according to this view is not limited to a narrow area, but must
involve a large region in the occipital cortex. It is difficult to
reconcile this view with the ideas of isolated conduction and specific
function of each part of the cortex, and it is very evident that the
projection of the retinas upon the cortex is a question that must
be left for further observation and experiment. Some light was
supposed to be thrown upon the subject from the results of stimula-
tion of the occipital cortex. Stimulation of this kind causes move-
ments of the eyes, and the movements vary with the place stimu-
lated.* Stimulation of the upper border of the lobe causes move-
ments of the eyes downward, stimulation of the lower border move-
ments upward and of intermediate regions movements to the side.
Assuming that the direction of the movement is associated with
movements toward that part of the visual field from which a
normal visual stimulus would come, it is evident that movements
of the eyes downward would imply stimulation of the upper half
of the retina, since objects in the lower part of the visual field
form their image on the upper half of the retina. Following this
suggestion, the projection of the retinas on the occipital lobes, or
the cortical representation of the retinas on the occipital cortex
might be represented by a definite schema. Such a definite rela-
tionship, however, as stated above, is not borne out by clinical facts.
The fact that stimulation of the occipital cortex causes definite
movements of the eyeballs seems, however, to be demonstrated and
it implies that there are efferent fibers in the optic radiation running
from the occipital cortex to the midbrain, where they make con-
nections with the motor nuclei of the third, fourth, and sixth cranial
nerves.

The Function of the Lower Visual Centers. — The first
ending of the optic fibers lies in the external geniculate and to a
lesser extent in the thalamus and superior colliculus. It is con-
ceivable, of course, that some degree of visual sensation may be
mediated through these centers. Goltz observed that in dogs with
the cerebrum removed the animals showed a constriction of the
pupils when a bright light was thrown upon the eyes, or even closed
the eyes. It is the general belief that reactions of this kind are me-
chanical reflexes accompanied by no higher psychical reaction than
*Schafer, "Brain," 11, 1, 1889, and 13, 165, 1890.

200 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

in the case of spinal reflexes. The existence in the midbrain of the
motor nuclei of the third nerve, and of the posterior longitudinal
bundle through which connections are established with the motor
nuclei of other cranial nerves, furnishes us with a possible reflex
arc through which the visual impulses brought into the lower optic
centers, especially the superior colliculus, may cause co-ordinated
movements of the eyes or of the head. • Usually it is assumed that
conscious visual sensations, and especially visual associations and
memories, are aroused only after the impulses reach the occipital
cortex. In the fishes the midbrain forms the final ending of the
optic fibers, and in these animals, therefore, whatever psychical
activity accompanies the visual processes must be mediated through
this portion of the brain. In the higher animals, however, the
development of a cerebral cortex is followed by the evolution of the
optic radiation, and as the connections of the occipital cortex
increase in importance, those of the midbrain (with the optic fibers)
dwindle correspondingly. Here, as in other cases, the psychical
activity is concentrated in the portions of the brain lying most
anteriorly, and doubtless the degree of consciousness is greatly
intensified in the higher animals in correspondence with the devel-
opment of the cerebral cortex whose striking characteristic is its
capacity to evoke a psychical reaction.

The Auditory Center. — The location of the auditory area has
been investigated along lines similar to those used for the visual
center. The experimental physiological work has yielded varying
results in the hands of different observers. Munk and Ferrier
placed the cortical center for hearing in the temporal lobe, and
in spite of negative results by Schafer and others this localization
has been shown to be substantially correct. Entire ablation of
both temporal lobes is followed by complete deafness. Ablation
on one side, however, is followed only by impairment of hearing,
and in the light of the results from histology and from the clinical
side it seems probable that the connections of the auditory cortex
with the ear follow the general schema of the optical system rather
than that of the body senses. That is, it is probable that the
auditory fibers from each ear end partly on the same side and
partly or mainly on the opposite side of the cerebrum. The exact
portion of the temporal lobe that serves as the immediate organ
of auditory sensations cannot be determined with certainty, but
it seems certain that it lies mainly. in the superior temporal gyrus,
and the transverse gyri extending 'from this into the fissure of
Sylvius.

The Histological Evidence. — On the histological side the paths of
the auditory fibers have been followed with a large measure of suc-
cess, although in many details the opinions of the different investi-

SENSE AREAS AND ASSOCIATION AREAS.

201

gators vary considerably. The eighth cranial nerve springs from the
bulb by two roots: the external and the internal. The former has
been shown to supply, mainly at least, the cochlear portion of the
internal ear, and is, therefore, the auditory nerve proper. This
division is spoken of as the cochlear branch. The internal root sup-
plies mainly the vestibular branch of the internal ear, and is there-
fore spoken of as the vestibular branch (see Fig. 88) . It seems cer-
tain that the latter is not an auditory nerve, but is concerned

Posterior nucleus.

Deiters's nucleus.

Dorsal nucleus.
Ventral nucleus.

Cochlear branch.

Vestibular branch.

Semicircular
canals.

Scarpa's ganglion.
Cochlea.

Spiral ganglion.
Fig. 88.— The medullary nuclei of the eighth nerve.— (From Poirier and Charpy.)

with peculiar sensations from the semicircular canals and vestibule
that have an important influence on muscular activity, especially
in complex movements. The central course of these two roots is
quite as distinct as their peripheral distribution, — a fact that bears
out the supposition that they mediate different functions. The
vestibular branch ends in the nucleus of Deiters, the nucleus of
Bechterew, and the nucleus fastigii of the cerebellum. Through
these nuclei reflex connections are made with the motor centers
of the cord and midbrain, and probably also with the cerebellum.
The path is not known to be continued forward to the cerebrum.
The central course of the cochlear branch is indicated schematically

202

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

in Figs. 88 and 89. The fibers constituting this branch arise from
nerve cells in the modiolus of the cochlea, — the spiral ganglion.
These cells, like those in the posterior root ganglia, are bipolar.
One axon passes peripherally to end around the sense cells of the
cochlea, at which point the sound waves arouse the nerve impulses.
The other axon passes toward the pons, forming one of the fibers
of the cochlear branch. On entering the pons these cochlear
branches end in two nuclei, one lying ventral to the restiform
body and known as the ventral or accessory nucleus (V.n., Fig. 89),
and one dorsally, known as the dorsal nucleus or the tuberculum
acusticum (D.n.). From these nuclei the path is continued by sec-
ondary sensory neurons, and its further course toward the brain is
still a matter of much uncertainty in regard to many of the de-
tails.* The general course of the fibers, however, is known. Those
axons that arise from the accessory nucleus pass mainly to the oppo-
site side by slightly different routes (Fig. 89). Some strike directly
across toward the vental side of the pons, forming a conspicuous
band of transverse fibers that has long been known as the corpus

trapezoideum ; others
pass dorsally around
the restiform body and
then course downward
through the tegmental
region to enter the cor-
pus trapezoideum. The
fibers of this cross band
end, according to some
observers, in certain nu-
clei of gray matter on the
opposite side of the pons,
especially in the superior
olivary body and the
trapezoidal nucleus, and
thence the path forward
is continued by a third
neuron. Certainly from
the level of the superior
olivary body the audi-
tory fibers enter a dis-
tinct tract long known
to the anatomist and des-
ignated as the lateral
fillet or lateral lemniscus.

Authors differ as to whether the auditory fibers of this tract arise

from nerve cells in the superior olivary and neighboring nuclei, or

* For literature see Van Gehuchten, " Le Nevraxe/' 4, 253, 1903.

Fig. 89. — Diagram to show central course of
auditory fibers (modified from Van Gehuchten) :
D.n., Dorsal nucleus giving rise to the fibers that
form the auditory striae («.«.); V.n., the ventral nu-
cleus, giving origin to the fibers of the corpus trape-
zoideum (c.tr.); s.o., superior olivary nucleus; l.f.,
lateral fillet; n.s., nucleus of the lateral fillet; t.g.x.,
the inferior colliculus.

SENSE AREAS AND ASSOCIATION AREAS. 203

are the fibers from the accessory nucleus which pass by the superior
olivary body without ending and then bend to run forward in a
longitudinal direction. This last view is represented in the schema
(Fig. 89). The secondary sensory fibers that arise in the tubercu-
lum acusticum pass dorsally and then transversely, forming a
band of fibers that comes so near to the surface of the floor of the
fourth ventricle as to form a structure visible to the eye and known
as the medullary or auditory striae. The fibers of this system dip
inward at the raphe, cross thef, mid-line, and a part of them at least
eventually reach the lateral fillet of the other side either with or
without ending first around the cells of the superior olivary nucleus.
According to the description of some authors, the fibers from the
accessory nucleus and tuberculum acusticum do not all cross the
mid-line to reach the lateral fillet of the other side; some of them
pass into the lateral fillet of the same side; so that the relations of
the fibers of the cochlear nerves to the lateral fillet resemble, in the
matter of crossing, the relations of the optic fibers to the optic
tract. After entering the lateral fillet the auditory fibers pass
forward toward the midbrain and end in part in the gray matter of
the inferior colliculus, of the median or internal geniculate, and,
according to Van Gehuchten, in a small mass of nerve cells in the
midbrain known as the superior nucleus of the fillet. From this
second or third termination another set of fibers, the auditory
radiation, continues forward through the posterior extremity of
the internal capsule to end in the superior temporal gyrus (see
Fig. 76, E). According to Flechsig,* who has studied the course
of these fibers in the embryo by the myelinization method, the
main group passes from the internal geniculates to the transverse
gyri of the temporal lobe within the fissure of Sylvius. The in-
ternal geniculates, in man at least, have therefore the function
of a subordinate auditory center, as the external geniculates have
the function of a subordinate visual center. The internal genic-
ulates are connected with the inferior colliculus, and also, it will
be remembered, with each other, by commissural fibers (Gudden's
commissure) that pass along the optic tracts and the posterior
margin of the chiasma. The auditory path, therefore, involves
the following structures: The spiral ganglion, the cochlear nerve,
accessory nucleus and tuberculum acusticum, corpus trapezoideum,
medullary striae, superior olivary, lateral fillet, inferior colliculus,
median geniculate, Gudden's commissure, auditory radiation, and
temporal cortex.

The Motor Responses from the Auditory Cortex. — Accord-
ing to Ferrier, stimulation of the cortex of the temporal lobe (infe-
rior convolution) causes definite movements, such as pricking of
* Flechsig, " Localisation der geistigen Vorgiinge," Leipzig, 1896.

204 PH.YSIOLOGY OF CENTRAL NERVOUS SYSTEM.

the ears and turning of the head and eyes to the opposite side.
As in the case of the visual area, therefore, we must suppose that
distinct motor paths originate in the auditory region, and it is
natural to suppose that these paths give a means for cortical reflex
movements, folio wing upon auditory stimulation.

The Olfactory Center. — The olfactory sense is quite un-
equally developed in different mammals. Broca divided them from
this standpoint into two classes: the osmatic and the anosmatic
group, the latter including the cetacea (whales, porpoise, dolphin).
The osmatic group in turn has been divided into the microsmatic
and macrosmatic animals, the latter class including those animals
in which the sense of smell is highly developed, such as the dog
and rabbit, while the former includes those animals, such as man,
in which this sense is relatively rudimentary.* The peripheral end-
organ of smell consists of the olfactory epithelium in the upper
portion of the nasal chambers. The physiology of this organ will
be considered in the section on special senses. The epithelial
cells of which it consists are comparable to bipolar ganglion
cells. The processes or hairs that project into the nasal chamber
are acted upon by the olfactory stimuli, and the impulses thus
aroused are conveyed by the basal processes of the cells, the olfac-
tory fibers, through the cribriform plate of the ethmoid bone into
the olfactory bulb.

The Olfactory Bulb and its Connections. — The olfactory
bulbs are outgrowths from and portions of the cerebral hemi-
spheres. Each bulb is connected with the cerebral hemispheres
by its olfactory tract. The connections established by the fibers
of this tract are widespread, complicated, and in part incom-
pletely known. All those portions of the brain connected with
the sense of smell are sometimes grouped together as the rhinen-
cephalon. According to von Kolliker, the parts included under
this designation are, .in addition to the olfactory bulb and tract,
Ammon's horn, the fascia dentata, the hippocampal lobe, the fornix,
the septum lucidum, and the anterior commissure. The schematic
connections of the olfactory fibers are as follows (Fig. 90) : After
entering the olfactory lobe the fibers terminate in certain globular
bodies, the glomeruli olfactorii (5), whose diameter varies from 0.1 to
0.3 mm. Here connections are made by contact with the dendrites
of nerve cells of the olfactory lobe, the mitral and brush cells ((7).
The axons of these cells pass toward the brain in the olfactory tract.
Three bundles of these fibers are distinguished: (1) The precommis-
sural bundle, the fibers of which terminate in part in nerve cells sit-
uated in the tract itself, but, for the most part, enter the anterior
commissure and pass to the same or the opposite side, to end in the
* See Barker, "The Nervous System," 1899, for references to literature.

SENSE AREAS AND ASSOCIATION AREAS.

205

hippocampal lobes or other gray matter belonging to the rhinen-
cephalon. (2) The mesial bundle, the fibers of which terminate
in the gray matter adjacent to the base of the olfactory tract,
the tuberculum olfactorium, whence the path is probably continued
by other neurons to the region of the hippocampal lobe. (3) The
lateral tract, whose fibers seem to pass to the hippocampal lobe of
the same side. According to Van Gehuchten,* none of the fibers
of the anterior commissure arise from the nerve cells in the olfactory
bulb. He considers that the fibers in the olfactory portion of this
commissure constitute an association system connecting the olfac-
tory lobe of one side with the olfactory bulb of the other side.

\

Fig. 90. — Diagram of the central course of the olfactory fibers: /, Olfactory bulb;
II, olfactory tract; ///, cortex of the hippocampal lobe (gyfus uncinatus); IV, anterior
commissure, olfactory portion; A, olfactory epithelial cells of nose (their fibers, olfactory
nerve fibers, terminate in the glomeruli of the bulb) ; B, glomeruli of olfactory bulb where
the olfactory fibers come in contact with the dendrites of the. mitral cells; C, mitral and
brush cells; 1, 2, 3, axons from the mitral cells constituting the fibers of the olfactory
tract. Fibers 3, which enter the commissure, arise, according to some observers, from
cells in the olfactory lobe near the base of the tract.

The Cortical Center for Smell. — So far as the histological
evidence goes, it tends to show that the chief cortical termination
of the olfactory paths is 'found in the hippocampal lobe, especially
its distal portion, the gyrus uncinatus. The experimental evi-
dence from the side of physiology points in the same direction.
.Ferrier states that electrical stimulation in this region is followed by

* Van Gehuchten, "Le NeVraxe," 6, 191, 1904.

206 PHYSIOLOGY OP CENTRAL NERVOUS SYSTEM.

a torsion of the lips and nostrils of the same side, muscular move-
ments that accompany usually strong olfactory sensations. On
the other hand, ablations of these regions are followed by defects
in the sense of smell. The experimental evidence is not very
satisfactory, owing to the technical difficulties in operating upon
these portions of the brain without at the same time involving
neighboring regions. There is some clinical evidence also that
lesions in this region involve the sense of smell. Thus Carbonieri
records that a tumor in this portion of the temporal lobe occa-
sioned epileptic attacks which were accompanied by nauseating
odors.

The Cortical Center for Taste Sensations. — Practically
nothing definite is known concerning the central paths and cortical
termination of the taste fibers. The course of these fibers in the
peripheral nerves has been much investigated and the facts are
mentioned in the section upon "special senses." It is usually
assumed, although without much decisive proof, that the cortical
center lies also in the hippocampal convolution posterior to the
area of olfaction. Experimental lesions in this region, according
to Ferrier, are accompanied by disturbances of the sense of taste.
On embryological grounds Flechsig supposes that the cortical
center may lie in the posterior portion of the gyrus fornicatus
(6, Fig. 94).

Aphasia. — The term aphasia means literally the loss of the
power of speech. It was used originally to indicate the condition of
those who from accident or disease affecting the brain had lost in
part or entirely the power of expressing themselves in spoken words,
but the term as a general expression is now extended to include
those who are unable to understand spoken or written language, -^
that is, those who are word-blind or word-deaf. It is usual, there-
fore, to distinguish sensory aphasia from motor aphasia. By the
latter term is meant the condition of those who are unable to speak,
and by sensory aphasia those who are unable to understand the
written, printed, or spoken symbols of words.

Motor Aphasia. — A condition of motor aphasia not infrequently
results from injuries to the head or from hemorrhage in the region
of the middle cerebral artery. The first exact knowledge of the
portion of the brain involved seems to have been obtained by
Bouillaud (1825) as the result of numerous autopsies.

(It is a curious fact that Bouillaud's observations were inspired by the work
of Gall. Gall having observed, as he thought, that individuals who are fluent
speakers or who have retentive memories are characterized by projecting eyes,
concluded that this peculiarity is due to the larger size of the lower part of the
frontal lobe, and he therefore located the faculty of speech in this region of the
brain. In spite of the vagaries into which he was led by his false methods Gall
made many most important contributions to our knowledge of the anatomy of
the brain and the cord. The discovery of the location of the center of speech,

SENSE AREAS AND ASSOCIATION AREAS. 207

however, cannot be rightly placed to his credit, since his reasons for its location
were, so far as we know, entirely unjustified. It cannot be reckoned as more
than a coincidence that in this particular his phrenological localization was
afterward in a measure justified by facts.)

The essential truth of Bouillaud's observations was established
by other observers, and Broca especially located the part of the
brain involved in these lesions in the posterior part of the third or
inferior frontal convolution. This region is, therefore, frequently
known as Broca's convolution or Broca's center. Subsequent ob-
servations have abundantly 'confirmed this localization, and what
is designated as the " speech center" is placed in the inferior frontal
convolution in the gyrus surrounding the anterior or ascending
limb of the fissure of Sylvius (S, Fig. 91); although many authors
insist that this localization is too limited, and that defects in the
power of speech may result not only from injuries to this region
but also from lesions of contiguous areas, including the island
of Reil. Autopsies have shown that in right-handed persons
the speech center is placed or is functional usually in the left cere-
bral hemisphere, while in the case of left-handed individuals
aphasia and paralysis are produced by lesions involving the right
side of the brain. This region is not the direct cortical motor
center for the muscles of speech. It is possible that aphasia may
exist without paralysis of these latter muscles. It is rather the
memory center of the motor innervations necessary to form the
appropriate sounds or words with which we have learned to ex-
press certain concepts. The child is taught to express certain
ideas by definite words, and the memory apparatus through which
these associations are transmitted to the motor apparatus may
be conceived as located in the speech center. Lesions of any kind
affecting this area will therefore destroy more or less the ability to
use appropriately spoken words, and clinical experience shows that
motor aphasia may be exhibited in all degrees of completeness and
in many curious varieties. The individual may retain the power to
use a limited number of words, with which he expresses his whole
range of ideas, as, for instance, in the case described by Broca,*
in which the individual retained for the expression of numbers only
the word three, and was obliged to make this word do duty for all
numerical concepts. Other cases are recorded in which the patient
had lost only the power to use names — that is, nouns (Marie) —
or could remember only the initial letters. Others still in which
words could be used only when associated with musical memories,
as in singing. It does not seem to be certain whether or not, in
the case of complete lesion of the center on one side, the ability

*Exner, " Hermann's Handbuch der Physiologic," vol. iii, part u, p. 342.
Consult for older literature.

208

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

to speak can be again acquired by education of new centers.*
Some recorded cases seem to indicate that this re-education is
possible in the young, while in the old it is more difficult or impos-
sible. We express our thoughts not only in spoken but also in
written symbols. As this latter form of expression involves a
different set of muscles and a different educational experience,
it is natural to assume that the complex associations concerned, or,
to use a convenient expression, the memory centers, should involve
a different part of the cortex. It is, in fact, observed that in some
aphasics the loss of the power of writing, a condition designated
as agraphia, is the characteristic defect, rather than the loss of the
ability to use articulate language. The area in which the motor
'associations for the act of writing are located has been placed

in the middle or sec^
ond frontal convolu-
tion contiguous to "the
cortical motor centers
for the muscles of the
arm 'and hand (W;
Fig. 91).

Sensory ''Aphasia. —
In sensory aphasia f
(amnesia) the individ-
ual suffers from an
inability to under-
stand spoken or writ-
ten language, and as
the cortical centers for
hearing and seeing are.
situated in distinct
parts of the brain, we
should expect that the
mechanism for the

'association, in one case of visual memories of- verbal symbols with
certain concepts and in the other case of auditory memories, should
also be located in separate regions. Inability to understand spoken
language, or word-deafness, is, in fact, usually attributed -to a
lesion involving the- first temporal convolution- contiguous -to the
cortical sense of hearing (H, Fig. 91), while loss of power to under-
stand written or printed language, word-blindness, is traced to
lesions involving the inferior parietal convolution, the gyrus angu-
laris, contiguous to the occipital visual center (V ', Fig. 91). These
* See Mills, "Journal of the Amer. Med. Assoc.," 1904, xliii.
t Consult Starr, "Aphasia," "Transactions of the Congress of American
Physicians and Surgeons," vol. i, p. 329, 1888; also Monakow, "Gehirn-
pathologie, 1906.

Fig. 91. — Lateral view of a human hemisphere;
cortical area V, damage to which produces "mind-
blindness" (word-blindness); cortical area H, damage
to which produces "mind-deafness" (word-deafness);
cortical area S, damage to which causes the loss of-
audible speech ; cortical area W, damage to which abol-
ishes the power of writing. — (Donaldson.)

SENSE AREAS AND ASSOCIATION AREAS. 209

two conditions may occur together, but cases are recorded in which
they existed independently. It may be imagined that the individual
suffering from word-blindness alone is essentially in the condition
of one who attempts to read a foreign language. The power of
vision exists, but the verbal symbols have no associations, therefore
no meaning. So one who is word-deaf alone may be compared to
the normal individual who is spoken to in a foreign tongue. The
words are heard, but they have no associations with past experience.

The general facts regarding aphasia illustrate excellently the
prevalent conception of cerebral localization. The understanding
and the use of spoken or written language is, so to speak, a mental
whole, both from the standpoint of education and of use. To
understand or to express certain conceptions implies the use of
definite words, and our visual, auditory, and motor experiences are
combined in these symbols. Each phase of this complex may be
cultivated more or less separately; in the case of the unlettered
man, for instance, the written or printed symbols form no part
in the associations connected with his verbal concepts. Corre-
sponding to these facts we have, on the anatomical side, a portion
of the brain in which the auditory memories are organized, — that
is, connected in some way with a definite arrangement of nerve
cells and their processes, another part in which the visual memories
are organized, and other parts in which the motor memories as
regards speaking or writing are laid down in some definite form.
Each part is a distinct center, but their combined use in intellectual
life would imply that they are connected by association fibers, so
that, although fundamentally distinct, they are practically com-
bined in their activity. Corresponding with this conception it is
found from clinical experience that aphasics, although the lesion
may affect only one of these various centers, suffer a deterioration,
more or less pronounced, of their general intellectual capacity.
We may believe that the varying gifts of individuals, in the matter
of the use of language, rest partly on the amount of training re-
ceived and partly on the inborn character and completeness of
the nervous machinery in the different centers.

The Association Areas. — According to the views presented
above, it will be seen that the motor and sense areas occupy only
a small portion of the cortex, forming islands, as has been said,
surrounded by much larger areas. Flechsig* has designated these
latter areas as association areas, and has advocated the view that
they are the portions of the cortex in which the higher and more
complex mental activities are mediated, the true organs of thought.
His views as to the relations and physiological significance of these
areas have been based chiefly on the study of the embryo brain

* Flechsig, "Gehirn und Seele," Leipzig, 1896; also, "Archives de neurol-
ogie," vol. ii, 1900.
14

210 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

with reference to the time of acquisition of the myelin sheaths.
Thus he finds that the fibers to the sense areas acquire their myelin,
and therefore according to his view become fully functional before
those distributed to the association areas. Moreover, in the em-
bryo, at least, these latter areas are not supplied with projection
fibers, — that is, they are not connected directly with the under-
lying parts of the nervous systems. Their connections are with
the various sense centers and motor centers of the cortex.

The association areas may be regarded therefore as the regions
in which the different sense impressions are synthesized into complex
perceptions or concepts. The foundations of all knowledge are
to be found in the sensations aroused through the various sense
organs; through these avenues alone can our consciousness come
into relation with the external or the internal (somatic) world,
and the union of these sense impressions into organized knowledge
is, according to Flechsig, the general function of the association
areas. This function of the association areas is indicated by the
anatomical fact that they are connected wdth the various sense
centers by tracts of association fibers, suggesting thus a mechanism
by which the sense qualities from these separate sense centers may
be combined in consciousness to form a mental image of a complex
nature. The sequence of phenomena in the external world is or-
derly, and, corresponding to this fact, the reflection of these phenom-
ena in the sequence and combinations of sensations is also orderly.
In the association areas our memory records of past experiences
and their connections are laid down in some, as yet unknown,
material change in the network of nerve cells and fibers. Here,
as elsewhere in the nervous system, it may be supposed that the
efficiency of the nervous machine^- is conditioned partly by the
completeness and character of training, but largely also by the
inborn character of the machinery itself. The very marked differ-
ences among intelligent and cultivated persons — for instance, in
the matter of musical memory and the power of appreciating and
reproducing musical harmonies — cannot be attributed to differences
in training alone. The gifted person in this respect is one who is
born with a certain portion of his brain more highly organized than
that of most of his fellow-men. This general conception that the
special capacities of talented individuals rest chiefly upon inborn
differences in structure or organization of the brain may be re-
garded as one outcome of the modern doctrine of localization of
functions in this organ. In the beginning of the nineteenth century
it seems to have been the general view that those who had a high
degree of mental capacity might direct their activity with equal
success in any direction according to the training received. A man
who could walk fifty miles to the north, it was said, could just as

SENSE AREAS AND ASSOCIATION AREAS. 211

easily walk fifty miles to the south, and a man whose training
made him an eminent mathematician might with different training
have made an equally eminent soldier or statesman. In our day,
however, with our ideas of the organization of the brain cortex,
and our knowledge that different parts of this cortex give different
reactions in consciousness, it seems to follow that special talents
are due to differences in organization of special parts of the
cortex.

Subdivision of the Association Areas. — On anatomical grounds
Flechsig distinguishes three (or four) association areas: The frontal
or anterior (35, Fig. 94), which lies in front of the motor area;
the median or insular, — that is, the cortex of the island of Reil;
and the posterior, which lies back of the body feeling area, extending
to the occipital lobe and also laterally into the temporal lobe.
This area Flechsig suggests may be subdivided into a parietal area,
34, Fig. 94, and a temporal area, 36, Fig. 94. The greater relative
development of these areas is one of the features distinguishing
the human brain from those of the lower mammals. In accordance
with the general conception of localization of functions Flechsig
suggests that these areas have different functions, — that is, take
different parts in the complex of mental activity. Basing his
views upon the nature of the association tracts connecting
them with the sense centers, he suggests that the posterior area
is concerned particularly in the organization of the experiences
founded upon visual and auditory sensations, and shows especial
development in cases of talents, such as those of the musician,
which rest upon these experiences. The anterior area, being in
closer connection with the body sense area, may possibly be espe-
cially concerned in the organization of experiences based upon the
internal sensations (bodily appetites and desires). In this part
of the brain possibly arises the conception of individuality, the
idea of the self as distinguished from the external world. And in
alterations or defective development of this portion of the brain
may lie possibly the physical explanation of mental and moral
degeneracy. This general idea is borne out in a measure by his-
tological studies of the brains of those who are mentally deficient
(amentia) or mentally deranged (dementia). It is stated* that
the brain in such cases shows a distinct wasting of the cortex and
that the maximum focus of this change is found in the prefrontal
lobes (anterior association area). In the case of the idiotic this
area is distinctly undeveloped and in the insane the atrophy is
marked in proportion to the degree of dementia. Regarding the
peculiar functions of the cortex of the island of Reil there are no
facts sufficiently distinct to warrant even a provisional statement.
* Bolton, "Brain," 1903, p. 215.

212 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

The area is much more developed in man than in the lower mam-
mals, and its connections with other parts of the cortex by means
of association tracts are such as to lead to the supposition that
its general functions are of the higher synthetic character attributed
to the association areas in general.

By way of caution it should be stated that the general . ideas developed
above in accordance with Flechsig's views do not meet with universal accep-
tance. Some of the most experienced observers are unwilling to admit that
such a degree of localization of the psychical activities really exists. They
contend that the whole cortex may be concerned in mediating the highest
mental processes, and quote post-mortem examinations of carefully studied
cases in support of this view. We must recognize, in fact, that the schemata
designed to show the distribution of the higher psychical activities in the
cortex represent at present only hypotheses which need satisfactory con-
firmation before they can be finally accepted. We may feel considerable
confidence in the localizations of the motor areas and of some, at least, of the
sensory areas, but in the matter of the more complex mental acts, failure
in which expresses itself in the conditions of aphasia, dementia, perversions,
etc., our knowledge is incomplete, both as regards analysis of the symptoms
and the localities affected in the brain.

The Development of the Cortical Areas. — In a recent report
Flechsig* gives the results of an extensive study of the time of
myelinization of the fibers in the cerebrum of man from the fourth
month of intra-uterine to the fourth month of extra-uterine life.
The first areas to develop in the cortex are the primary sense
centers (smell, cutaneous and muscle sense, sight, hearing, and
touch), and later in connection with these centers systems of motor
fibers appear. There are thus formed seven primary zones, sensory
and motor, to which he gives the name of projection areas. The
location of these areas is shown in part in Figs. 92 and 93, 2 ($, &},
5, 6, 7 (76), 8, 15. Two areas connected with the olfactory sense
are not shown in these figures; they appear in the anterior per-
forate lamina on the base of the brain and in the uncinate gyms.
Later there is developed around these primary zones areas that
Flechsig calls marginal or border zones, which have no projection
fibers, but which are connected by short association fibers with
one or more of the primary projection zones, 14, 16 to 33, in Figs.
94 and 95. These areas all develop after birth; and from a
physiological standpoint may be regarded perhaps as the seat of
the organized memories connected with the primary sense centers.
It is injuries in these centers which may be supposed to produce
the various kinds of aphasia described above. Thus, areas 17, 20,
and 24 form border areas to the primary area of sight (5); 16 has
the same relation to 2, 18 to /, and 14, Ub with 7. Later still
the great association areas— 34, 35, 36, Figs. 94 and 95 — acquire
their myelinated fibers. These latter centers, as indicated above, may

* Flechsig " Berichte der mathematisch-physischen Klasse der konigl.
Sachs. Gesellschaft der Wissenschaften zu Leipzig," 1904. For a summary of
the results of this work see Sabin, " The Johns Hopkins Hospital Bulletin,"
February, 1905.

SENSE AREAS AND ASSOCIATION AREAS. 213

.-ritaS^"

J

Fig. 92. — Lateral surface of the brain, showing the primordial areas, both sensory and
automatic, in dotted zones. — (Flechsig.)

H \

Fig. 93. — Same zones on the mesial surface of the brain. — (Flechsig).

214

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

Fig. 94. — Lateral surfaces of the brain, showing the primordial and marginal zones.

— (Flechsig.)

Fig- 95. — Same areas on the mesial surface. — (Flechsig.)

SENSE AREAS AND ASSOCIATION AREAS. 215

be considered as association areas with more complex connections,
and they serve to mediate therefore the higher psychical activities.
Flechsig, in his recent report, designates these areas from an anatom-
ical point as terminal or central zones. As the result of his his-
tological work, as far as it has progressed, he distinguishes
thirty-six areas in the cortex in which the myelinization of the
fibers occurs separately, and in which, therefore, by inference,
different physiological activities are mediated. These 36 areas
are subdivided as follows: *

I. Primary areas.

la. Primary projection areas (1, 2, 4, 5, 6, 7, 8 (15}t seven or
eight in number, and provided with projection fibers —
sensory and motor.

16. Primary areas without projection fibers (3, 9, 10, 11, 12, 13)
and apparently without association fibers. Functions un-
certain.
II. Association areas.

IP* Intermediate or border areas, 14, 16-33, provided with

short association fibers.

II&* Terminal or central areas, 34, 35, 36, provided with long
association fibers.

Histological Differentiation in Cortical Structure. — While
the general structure of the cortex is everywhere similar, detailed
examination has shown differences in the shape of the cells, the
thickness and number of the strata, the calibre of the fibers, etc.,
which are said to be constant for any given region. By this means
it is possible to divide the cerebral cortex into a number of areas
whose structures are sufficiently distinct to be recognized with some
certainty. Reasoning from analogy we should infer that a differen-
tiation in structure implies a subdivision of physiological activity,
and to this extent this recent hist o logical work supports the view
of a localized distribution of function in the cortex. Campbell,*
in a very thorough investigation of this kind, has succeeded in
separating some fifteen or sixteen different areas, and the results
obtained by him support in a general way the localizations described
in the preceding pages. Thus the cortex in the postcentral con-
volution (body-sense area) has a structure distinctly different
from that of the precentral convolution (motor area), the latter
being characterized among other things by the presence of giant
pyramidal cells (Betz cells). In the occipital lobes the region
round the calcarine fissure (visuosensory) has a structure different
from that of the contiguous cortex (visuopsychic) , and a similar
difference is claimed for the auditory region. Campbell calls
attention to the fact that the extreme end of the frontal lobe
(prefrontal region) has a comparatively undeveloped structure.

* Campbell, " Histological Studies on Localisation of Cerebral Functions,"
Cambridge, 1905.

216 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

The Corpus Callosum.— The corpus callosum is the most
conspicuous of the bands of commissural fibers that connect one
cerebral hemisphere with the other. Similar tracts of the same
general nature are the anterior commissure, the fornix, the
psalterium, etc. The position and great development of the corpus
callosum has made it the object of experimental as well as anatomical
investigation. When the corpus is divided by a section along the
longitudinal fissure (v. Koranyi) no perceptible effect of either a
motor or sensory nature is observed in the animal. When it is
stimulated electrically (Mott and Schafer) from above symmetrical
movements on the two sides of the body may be obtained. If
the motor cortex on one side is removed stimulation in the longi-
tudinal fissures causes movements only on the side controlled

Fig. 96. — -Diagram to show the composition of the corpus callosum as a system of com-
missural fibers, without projection fibers. — (Cajal.)

by the uninjured cortex. These facts are in harmony with the
results of histological studies, which indicate that the fibers of the
corpus callosum do not enter directly into the internal capsules
to be distributed to underlying portions of the brain, but are truly
commissural and connect portions of the cortex of one hemisphere
with the cortex of the other side. This relation is indicated in the
accompanying diagram (Fig. 96). So far as the motor regions are
concerned, there is some evidence that the connection thus es-
tablished is between symmetrical parts of the cortex (Muratoff), —
that is, between parts having similar functions, — and we may per-
haps regard the corpus as a means by which the functional
activities of the two sides of the cerebrum are associated.

The Corpora Striata and Optic Thalami. — The numerous
masses of gray matter found in the cerebrum beneath the cortex,

SENSE AREAS AND ASSOCIATION AREAS. 217

in the thalamencephalon, and in the midbrain have each, of course,
specific functions, but, in general, it may be said that they are
intercalated on the afferent or efferent paths to or from the cortex.
Their physiology is included, therefore, in the description of the
functions mediated by these paths. For instance, the external
geniculate bodies form part of the optic path. In addition, how-
ever, these masses of cells contain in many cases reflex arcs of a
more or less complicated kind, through which afferent impulses
are converted into efferent impulses that affect the musculature
or the glandular tissues of the body. The large nuclei constituting
the corpora striata (nucleus caudatus and n. lenticularis) and the
optic thalami have been frequently studied experimentally to as-
certain whether they have specific functions independently of their
relations to the cortex. These efforts have given uncertain results.
Older experiments (Nothnagel), in which the attempt was made to
destroy these nuclei by the localized injection of chromic acid, are
probably unreliable, as the destruction involved also the projection
fibers passing to the cortex. Lesions of the nucleus caudatus are said
to be accompanied always by a rise in body temperature and an
increase in heat production, and stimulation of the same nucleus
gives a very marked rise in blood-pressure. These facts indicate
a possible connection of this nucleus with heat and vasomotor
regulation. Other observers have supposed that these nuclei are
especially concerned in the co-ordination of the muscles concerned
in involuntary or unconscious movements. On the anatomical side
we have the striking fact that the nuclei of the corpora striata
have few connections with the cortex, but, on the other hand,
send an independent system of projection fibers into the brain stem.
Embryologically these structures are developed from the wall of
the forebrain and would seem to have a physiological importance
similar to that of the cortex itself, but experimental and clinical
facts are at present insufficient to justify any hypothesis as to their
special functions. With regard to the various nuclei of the optic
thalamus it is known that they form abundant connections with
the sensory areas of the cortex cerebri, and from this standpoint
they may be regarded as consisting of subcenters with a proba-
bility, however, that reflexes may occur through them (subcortical
reflexes) independently of the cortex. Numerous fibers have been
traced from the thalamus to the body sense area (Flechsig).

CHAPTER XI.

THE FUNCTIONS OF THE CEREBELLUM, THE PONS,
AND THE MEDULLA.

The functions of the cerebellum are, in some respects, less satis-
factorily known than those of any other part of the central nervous
system. Many theories have been held. Most of these views
have been attempts to assign to the organ a single function of a
definite character, but latterly the insufficiency of the theories
proposed has led observers to attribute to the cerebellum general
properties the nature of which can not be expressed satisfactorily
in a single phrase. Before attempting to give a summary of exist-
ing views it will be helpful to recall briefly the important facts re-
garding its structure and relations, so far as they are known and can
be used to explain its functional value.

Anatomical Structure and Relations of the Cerebellum. —
The finer histology of the cerebellar cortex is represented in Fig. 97.
Three layers may be distinguished. The external molecular
layer (A), the middle granular layer (B), and the internal medullary
layer consisting of the white matter or medullated nerve fibers,
afferent and efferent (C). Between the molecular and granular
layers lie the large and characteristic Purkinje cells (a). The.
dendrites of these cells branch profusely in the molecular layer;
their axons pass into the medullary layer. From the standpoint
of the neuron doctrine these cells, so far as the cerebellum is con-
cerned, are efferent. They form, indeed, the sole efferent system
of the cerebellar cortex. The afferent fibers of the cerebellum end
in both the granular and the molecular layers. Those that termi-
nate in the granular layer — designated by Cajal as moss fibers,
have at their terminations and points of branching curious clumps
of small processes; they probably connect with the dendrites of the
nerve cells in this layer. Those that pass deeper into the molec-
ular layer come into connection with the dendrites of the Purkinje
cells, around which, indeed, they seem to twine, so that Cajal desig-
nated them as climbing fibers. The granular layer (B) contains
numerous granules (g} or small nerve cells. These cells are spherical,
and have a relatively large nucleus and a small amount of cyto-
plasm. Their dendrites are few and short; their axons run into
the molecular layer, divide in T, and the two branches then run

218

CEREBELLUM, PONS, AND MEDULLA.

219

parallel to the surface and doubtless make connections with the den-
drites of the Purkinje cells as well as with the cells of the molecular
layer. A few larger nerve cells of Golgi's second type (/) are found
also in the granular layer. In the molecular layer are, found two
types of cells : the larger basket cells (6) whose axons terminate in a
group of small branches that inclose the body of the Purkinje cells,
and a number of smaller cells (e), situated more superficially,
whose axons pass longitudinally in the molecular layer and termi-
nate in arborizations or baskets that doubtless make connections
with the dendrites of the Purkinje cells.

Fig. 97. — Histology of the cerebellum. — (From Obersteiner .)

A consideration of this peculiar and intricate structure enables
us to comprehend that the cerebellar cortex presents a reflex arc
of a very considerable degree of complexity. The incoming im-
pulses through the moss and climbing fibers may pass at once to the
Purkinje cells and lead to efferent discharges, or they may end in
the cells of the granular or molecular layer and thus be distributed
to the Purkinje cells in a more indirect way. In addition to the
cortex the cerebellum contains several masses of gray matter in
its interior: the large dentate nucleus in the center of each hemi-
sphere and the group of nuclei lying in or near the middle of the

220 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

medullary substance of the vermiform lobe (nucleus fastigii, n.
globosi, and the n. embolif ormis) . The axons of the Purkinje
cells of the cortex terminate in these subcortical nuclei, and the
efferent path from the cerebellum is then continued by new neurons.
Thus, the fibers of the superior peduncles of the cerebellum arise
chiefly from the dentate nuclei, and only indirectly from the cor-
tex. The anatomical connections, afferent and efferent, between
the cerebellum and other parts of the nervous system are very com-
plex and not yet entirely known. Without attempting to recall
all of these connections, which will be found described in works upon
anatomy or neurology, emphasis may be laid upon those which are
at present helpful in discussing the physiology of the organ.

1. Connections with the Afferent Paths of the Cord. — Through
the inferior peduncles the cerebellum receives afferent fibers from the
spinal cord and the medulla. The tract of Flechsig undoubtedly
terminates in the cerebellum, and according to some observers the
fibers of the posterior columns after ending in the n. gracilis and
n. cuneatus are continued in part to the cerebellum by nerve fibers
passing by way of the inferior peduncles. Ascending fibers arising
in the reticular formation of the medulla and the olivary nucleus
also take this path to the cerebellum, and, on the other hand, prob-
ably make connections with the sensory tracts of the cord or the
sensory nuclei of the medulla. Another afferent tract of the cord,
that of Gowers, enters the cerebellum by way of the superior
peduncles. The nature of the sensory impulses conveyed in this
way to the cerebellum is not entirely understood, but it seems
certain that some of them, at least, are what we designate as im-
pulses of the muscle sense, and this fact, as we shall see, throws
some light on the specific functional importance of the cerebellum.

2. Connections with the Vestibular Branch of the Eighth Cranial
Nerve. — This branch, arising in the semicircular canals and utriculus
and sacculus, ends in the pons in several nuclei (Deiters', Bech-
terew's) and also in the n. fastigii of the cerebellum. These nuclei
in turn are connected with other parts of the central nervous system,
but the details are not yet completely known. The connections
that have been most clearly established are those made with the
motor centers. From Deiters' nucleus the vestibulospinal tract
arises and passes to the cord to connect with the motor centers of
the spinal nerves, while Bechterew's nucleus is said to give origin
to a bundle which runs with the posterior longitudinal fasciculus
and may make connections with the motor nuclei of the cranial
nerves. In how far the vestibular nuclei may make afferent con-
nections with the cerebellum is undecided, but it seems probable
that such tracts exist, in view of the fact that destruction of the
semicircular canals and severe lesions of the cerebellum cause
motor disturbances that are strikingly similar.

CEREBELLUM, PONS, AND MEDULLA.

221

3. Connections with the Cortex of the Cerebrum. — The cerebellar
cortex is connected with the cerebral cortex by the large system
known as the cortico-ponto-cerebellar tract (see Fig. 76, A). The
fibers of this tract arise in the motor area of the cerebrum or in
the frontal cortex anterior to the motor area, descend in the internal

Fig. 98. — Diagram to indicate a possible descending path from cerebrum to cord in ad-
dition to the pyramidal system, the secondary or cerebellar motor path (Van Gehuchten).
The path is indirect and comprises the following units : 1. The cortico-ponto-cerebellar
path, represented as arising in the motor area of the cerebrum and passing down with the
pyramidal system to end in the pons, thence continued through the middle peduncles to the
cerebellar cortex of opposite side. 2. The path from the cerebellar cortex to the dentate
nucleus. 3. The path from the dentate nucleus to the red nucleus passing by way of the
superior peduncles. 4. The path from the red nucleus to the motor cells of the spinal cord
(rubro-spinal tract).

capsule and crus cerebri, and end in the gray matter of the pons.
Thence new axons continue the path across the mid-line and to
the cerebellar cortex by way of the middle peduncle. The tract
would seem to convey efferent impulses from the cerebral cortex
(motor region) of one side to the cerebellar cortex of the opposite
side. A second possible connection with the cerebrum is made

222 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

by way of the thalamus. Fibers arising in the dentate nucleus
emerge by way of the superior peduncles and connect with the
red nucleus in the subthalamic region and perhaps also with the
thalamus. The latter fibers may be continued forward to the
cortex of the cerebrum and thus constitute an afferent path from
cerebellum to cerebrum. Those fibers, on the contrary, which end
in the red nucleus are brought into reflex connection with the
motor bundle (rubrospinal tract), extending from the red nucleus
to the motor centers in the spinal cord. Making use of the connec-
tions described above, Van Gehuchten pictures an indirect motor
path from the cortex of the cerebrum to the motor nerves by way
of the cerebellum (see Fig. 98). The motor impulses descend by
way of the cortico-ponto-cerebellar path to the cerebellar cortex,
thence to the dentate nucleus, thence to the red nucleus, and then,
by way of the rubrospinal tract, to the motor nuclei of the spinal
nerves.

Theories Concerning the Functions of the Cerebellum.—
Modern views concerning the functions of the cerebellum may be
classified under three general heads: First, those that consider it
a general co-ordinating center or organ for the muscular movements
and especially for those concerned in equilibrium and locomotion.
This view, first proposed essentially by Flourens (1824), has been
adopted by many, perhaps by most, writers since his time. The
manner in which the organ serves to co-ordinate these movements
has been explained in various ways. According to the older ob-
servers, it was supposed so to arrange or group the various motor
impulses that they reached the lower motor centers in the cord
in the necessary combination for co-ordinated contractions. Ac-
cording to more recent observers, this synergetic action is exer-'
cised not directly on the motor side of the reflex but on the sensory
side. The numerous sensory paths connected with the organ,
especially those of the muscular sense, and those from the vestibular
nerve, suggest the view that in the complex cortex of the cerebel-
lum these afferent impulses act upon nervous combinations whose
discharges in turn are conveyed to the motor centers in a definite
and orderly sequence. Either point of view assumes that there
are in the cerebellum certain distinct mechanisms — that is, combi-
nations of neurons that are essentially reflex centers, and that in
all of our more complex bodily movements these mechanisms
intervene. The second general set of theories regarding the cere-
bellum assumes that this organ is essentially the center or a center
for the muscle sense. This view is connected usually with the name
of Lussana,* but has been supported since in one sense or another
* Lussana. See " Journal de la physiol. de I'homme," 5, 418, 1862.

CEKEBELLUM, PONS, AND MEDULLA. 223

by many observers.* It is, in fact, not essentially different per-
haps from the second phase of the first group of theories. Those
who have expressed their idea of the physiology of the cerebellum
by saying that it is a center of the muscle sense have, in recent
times at least, recognized that this sense has a cortical center also in
the cerebrum. The view can not assume, therefore, a conscious
muscle sense mediated by the cerebellum, but only that the muscle
sense fibers have a cortical termination therein and that the cerebel-
lar activity thus aroused is in some way necessary to the orderly
adjustment of complex voluntary movements. According to an-
other point of view, the cerebellum is a great augmenting organ for
the neuromuscular system. It is added on, as it were, to the cere-
brospinal motor system and serves not to co-ordinate the motor
discharges, but to increase their strength or effectiveness. This
general view, first proposed by Weir Mitchell (1869), has been sup-
ported by Luys, and especially, although with important modifica-
tions, by Luciani.t Some of the details of the work of the latter
observer are given below.

Experimental Work Up on the Cerebellum. — Rolando, and par-
ticularly Flourens, gave the direction to modern experimentation
in this subject. The latter observer made numerous observations,
especially on pigeons, in regard to the effect of removing all or a
part of the cerebellum. He describes in detail the striking results
of such an operation. When all or a large part of the organ is re-
moved the animal shows a most distressing inability to stand or
move. There seems to be no muscular paralysis, but, at first,
a total lack of power to co-ordinate properly the contractions of the
various muscles involved in maintaining equilibrium. The animal
takes a most abnormal position, with the head retracted and
twisted, and any attempt to move is followed by violent disorderly
contractions that may result in a series of involuntary somersaults.
The animal is totally unable to fly. When the injury to the cere-
bellum is less the effect upon the movements is either too slight
to be noticed or is shown in a greater or less uncertainty in its
movements. When it attempts to walk, for instance, it exhibits
a staggering, drunken gait, a condition designated as cerebellar
ataxia. Similar operations on mammals give in general the same
results. If the operation is unilateral, — that is, affects only one
hemisphere, — the animal (dog) exhibits forced movements, such
as a tendency to roll around the long axis of his body toward the
injured side and subsequently movements in a circle toward the same

* See Lewandowsky, "Archiv f. Physiologic," 1903, 129.

t For the literature of the cerebellum see Luciani, "II cervelleto," Florence,
1891; German translation, "Das Kleinhirn," 1893. Also Luciani, article,
"Das Kleinhirn" in "Ergebnisse der Physiologic/' vol. iii, part n, p. 259, 1904.

224 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

side. In man there are several cases on record in which the organ
was shown by autopsy to be largely or completely atrophied and
numerous cases of tumors affecting the cerebellum. In the latter
group of cases there may be certain marked subjective symptoms,
such as headache, and especially vertigo, and also a certain degree
of ataxia or awkwardness and uncertainty of movement. So also
in the cases of atrophy, in which probably the condition developed
slowly through a number of years, a degree of ataxia was exhibited,
especially when the movements were rapid and forced. In the
ataxic condition resulting from tabetic lesions of the posterior col-
umns the effect upon the movements is increased by covering up
the eyes (Romberg's symptom), the individual being then deprived
of his visual stimuli as well as those coming by way of the muscular
and cutaneous nerves. In cerebellar ataxia, however, the effect
is not increased by closure of the eyes, a result which is probably
explained by the fact that the individual still possesses his paths
of muscular and cutaneous sensibility to the cerebrum, and these
senses may be used in the reflex adjustments of voluntary move-
ments.

Interpretation of the Experimental and Clinical Results.—
Flourens was led by the striking results of his operations on pigeons
to suggest the view that the cerebellum is an organ for the co-
ordination of the movements of equilibrium and locomotion.
Objections were raised to this view. Some observers (Dalton,
Weir Mitchell) found that if the pigeons from which the cerebellum
had been removed wrere kept long enough the effects first observed
gradually disappeared, so that finally the animals were able to
move or fly with no marked difference from the normal animal
•except that fatigue was shown much more quickly. Hence the
view advocated by Mitchell that the essential function of the
cerebellum is that of an augmenting apparatus for the voluntary
movements. With regard, to this view it may be remarked in
passing that pigeons with the cerebral hemispheres removed exhibit
apparently as a permanent symptom the same tendency to rapid
fatigue after sustained muscular effort. By the same logical process
therefore one might conclude that one function of the cerebrum
is that of an augmenting organ to the motor discharges from the
cerebellum or midbrain. So also the cases of complete or nearly
complete atrophy of the cerebellum in human beings in which no
evil result followed other than a slight degree of cerebellar ataxia
have been used as an argument against the view that this organ
is necessary to the co-ordination of the complex voluntary move-
ments. The view that the cerebellum has essentially a direct
co-ordinating function has been criticized most seriously by Luciani.
This observer made a series of long-continued and most careful

CEREBELLUM, PONS, AND MEDULLA. 225

observations upon dogs and monkeys in which the entire cere-
bellum or certain definite parts had been removed. He lays stress
upon the fact that the violent disturbance of movement is tem-
porary and is slowly recovered from in time. He was led, therefore,
to view these disturbances as due primarily not to the loss of the nor-
mal functional activity of the organ, but to irritations resulting from
the operation. When this stage of irritation is passed the real
defects which indicate the true function of the cerebellum become
apparent. These defects exhibit themselves as a loss of power
in the neuromuscular apparatus of the complex voluntary move-
ments, and he analyzes these results under three heads: First,
a loss of force in the muscular contractions, — a condition of asthenia ;
second, a loss of tone in the muscles of the limbs and trunk, par-
ticularly in the hind limbs, — a condition of atonia; and, third, a
loss of steadiness in the muscular contractions, — a condition of
astasia. The astasia manifests itself in a tremor of the muscles
when voluntarily contracted, especially in movements requiring
much exertion. Luciani supposes that this tremor is due to an
alteration — that is, a slowing — of the rhythm of discharges of the
impulses from the motor centers. The functions of the cerebellum
on his theory are expressed, therefore, by saying that it is an aug-
menting organ for the activity of the neuromuscular apparatus ; and
that, so far as this augmenting or strengthening activity can be ana-
lyzed, it consists in an increase in the energy of the motor discharges
(sthenic action), an increase in the tension or tone of the motor
centers and their connected muscles (tonic action), and an increase
in the rhythm of the motor impulses (static action) so that nor-
mally the muscular contractions are of the nature of complete
tetani. Luciani believes that this action of the cerebellum is
continuous, although varying in intensity, and that it affects all
of the musculature of the body, and not simply the muscles con-
cerned in body equilibrium. This constant motor activity is in
turn dependent upon a constant inflow of sensory impulses into
the cerebellum along its afferent connections, particularly upon the
impulses from the vestibular portion of the internal ear, and those
from the muscle sense fibers and perhaps also from the fibers of
the cutaneous senses. The constant augmenting activity of the
cerebellum is therefore a species of reflex effect, — a reflex tonus
which affects all the musculature. Whether the cerebellar mechan-
ism is especially arranged to co-ordinate its effect upon the neuro-
muscular apparatus, — that is, in some way to adapt the move-
ments to a definite end — Luciani leaves an open question. He
does not believe that a lack of co-ordination (cerebellar ataxia)
is necessarily present in cerebellar lesions ; but admits that, if this
symptom is an invariable one, it would be necessary to add to

15

226 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

the general augmenting activity of the cerebellum also a general
adaptive or co-ordinating activity. It is precisely this latter feature
which stands out in the minds of most physiologists as the
characteristic function of the cerebellum, while Luciani considers
that it is not demonstrated by clinical or experimental facts, and
that even if demonstrated it would have to be considered as a
part — perhaps a subordinate part — of the functional influence of
this organ.

Conclusions as to the General Functions of the Cerebel-
lum.— It is evident that an authoritative statement of the function
or functions of the cerebellum is impossible. It seems quite clear,
however, that the organ exerts a regulating influence of some kind
upon the neuromuscular apparatus of our so-called voluntary
movements. The precise nature of the regulating influence is in
dispute, and one who reads the literature finds it difficult at times
to separate clearly the different theories proposed, since some
authors are content with general statements and others attempt
a more specific analysis. On- the whole, it seems desirable at
present to hold to the general idea, introduced by Flourens, that
the cerebellum is a central organ for co-ordination of voluntary
movements, particularly the more complex movements necessary
in equilibrium and locomotion. Instead, however, of assuming
with Flourens that the cerebellum contains a co-ordinating principle,
an expression that means nothing at present, we may assume that
it exerts its co-ordinating influence by virtue of the definite nervous
mechanisms contained in it — that is, by nervous complexes which,
on the afferent side, are connected with the peripheral sensory
nerves to the vestibule of the ear, the muscles, and the skin, and on
the efferent side are in direct or indirect relations with the motor
areas of the brain as well as the motor centers in the cord. These
mechanisms are inherited structures, but, like other nervous mechan-
isms, they are developed by use. The many muscular contractions
made in our ordinary movements of equilibrium are learned by ex-
perience, and the effects of this training are felt mainly upon these
cerebellar paths or mechanisms. We regard the speech center in the
cerebrum as a collection of nervous mechanisms in which are stored
or preserved the connections necessary to the motor presentation
of thoughts, a memory center for the spoken symbols of our con-
cepts; it is possible that in the same way we may regard the cere-
bellum as a memory center of the muscular movements concerned
in equilibrium. The relations of the cerebellum with the motor
areas of the cerebrum and the motor centers in the cord are evidently
quite complex and far from being fully understood. Moreover, this
relationship must vary considerably in different animals. Removal
of the cerebrum from a pigeon leaves an animal with almost perfect

CEREBELLUM, PONS, AND MEDULLA. 227

power of controlling its equilibrium. In the dog a similar operation
is followed by a longer period of inability to control perfectly the
movements of locomotion, and it is probable that in man after such
an operation the power of locomotion would be acquired more slowly,
if at all. On the other hand, the violent effect upon such move-
ments caused by the removal of the cerebellum in the pigeon is less
evident in the dog, and, if we may judge from the incomplete data
of clinical neurology, very much less evident in man. In man the
motor control of the voluntary muscular system through the cere-
brum is more highly developed than in the lower animals.

The most important objection to the view that the cerebellum
is an organ of co-ordination for the movements of equilibrium
and locomotion is that in the bird as well as in man the animal
eventually learns to carry out these movements after loss of the
cerebellum. This fact is clear proof that the cerebellum is not
the only mechanism through which such co-ordination is possible ;
but it is no valid objection to the view that normally this control
is effected through this organ. The sensory tracts on which this
co-ordination depends make connection with the thalamus or cere-
brum as well as the cerebellum, and when the latter arc is broken
the higher centers may be used to replace its functions in part
at least. The replacement is not complete, since even in man loss
of the cerebellum is followed by a permanent condition of slight
ataxia. Lewandowsky's* suggestion that normally in man the
finer, more conscious movements of the body are controlled directly
from the cerebrum, while the subconscious or dimly conscious
movements of locomotion and equilibrium are regulated through
the cerebellar centers seems to be in accord with the facts known.

The Psychical Functions of the Cerebellum. — In the cerebel-
lum, as in the other nerve centers below the cerebrum, we have to
consider the possibility of a psychical or conscious side to the activity
of the organ. It seems clear, however, that the degree of conscious-
ness, if any, exhibited by the cerebellum is of a much lower order
than that shown by the cerebrum. All observers agree that there
is no marked loss of sensations, but Luciani, Russell, and others
state their belief that in some indefinable way the mentality of
the animal is affected by removal of the cerebellum. Whatever
functions of this kind are present we can define only by the un-
satisfactory term of subconscious rather than unconscious. As far
as can be determined, this effect is felt mainly upon the muscular
sense and the sense of direction.

Localization of Function in the Cerebellum. — All observers
agree that so far as the influence of the cerebellum on the muscula-

* Lewandowsky, " Archiv f. Physiologic," 1903, 129; see also Kohnstamm,
"Archiv f. d. gesammte Physiologic," 89, 240, 1902.

228 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

ture of the body is concerned, it is homolateral, — that is, each half
of the cerebellum is connected with its own half of the body.
The connection with the motor areas of the brain is the re-
verse, the right half of the cerebrum being in relation with
the left half of the cerebellum. These relations are in the main
borne out by the anatomical course of the motor and sensory paths
described above. But those who have operated upon the cere-
bellum by the method of ablation agree entirely in the statement
that by this method at least no evidence is obtained of a localization
of function in the cerebellar hemispheres. There is no reason to
believe that extirpation of definite areas in the hemispheres affects
definite groups of muscles either on the sensory or the motor side.
We are forced to conclude, therefore, that localization is absent
and that regarding the cerebellum we must believe, as was formerly
believed regarding the cerebrum, that each half is everywhere func-
tionally equivalent. The effect of ablations is dependent not upon
the part removed, but rather upon the quantity. It is to be doubted,
perhaps, whether this view will stand the test of more complete
investigations, for some data exist that suggest the possibility of
a localization. It is observed, for instance, that the effects of
ablation upon the movements of the animal are more marked the
closer the injury is to the mid-line,* — that is, the more the vermi-
form lobe is involved. The possibility of a more or less definite
localization is suggested also by the effects of stimulation of the
cerebellar cortex. Ferrier especially has described definite move-
ments of the eyes, head, or limbs following electrical excitation of
definite regions of the cortex; but this indication has not been
developed by later experimenters with sufficient success to lead
to positive conclusions.

The Medulla Oblongata. — In the medulla oblongata we must
recognize a region of special physiological importance in that it
is the seat of certain centers which control the activity of the
circulatory and respiratory organs. If the medulla is severed
from the portion of the brain lying anterior to it the animal con-
tinues to live for a considerable period. The respiratory move-
ments are performed rhythmically, and the blood-vessels retain
their tone so as to maintain an approximately normal blood-pressure.
On the contrary, destruction of the medulla, or severance of its
connections with the underlying parts, is followed by a cessation
of respiration and a loss of tone in the arteries, either of which
results in the rapid death of the organism as a whole. The portions
of the medulla which exercise these important functions are desig-
nated, respectively, as the respiratory and the vasomotor or vaso-
constrictor centers. Their location and to some extent their con-
* Lewandowsky, loc. cit.

Fig. 99. — Nuclei of origin of motor and primary terminal sensory nuclei of cerebral
nerves (Held) : Schematically lepresented in a supposedly transparent brain .stem viewed
from behind. (Nuclei and roots of motor nerves in light red, of sensory nerves in
purple. Cochlear nerve in yellow.) 4, nucleus of the third nerve (n. oculomotorii);
5, nucleus of the fourth nerve (n. trochlearis); 6, the fourth nerve; 7, the descending
(motor) root of the fifth nerve; 8, the principal motor nucleus of the fifth nerve;
9, thesemilunar ganglion (g. Gasseri); 26, the ascending (sensory) root of the fifth
nerve; 14, nucleus of the sixth cranial nerve; 15, nucleus of the facial (seventh)
nerve; 16, the facial nerve; 34, 33, nucleus of the vestibular branch of the eighth cranial
nerve; 32, ventral nucleus of the cochlear branch of the eighth nerve: 27, dorsal nucleus
of the cochlear branch of the eighth nerve; 19, 29, the glossopharyngeal nerve; 18, 28, the
vagus nerve; 20, motor nuclei of vagus and glossopharyngeal (nucleus ambiguus and
nucleus dorsalis); 23, 24, nucleus of the alse cinerese, the solitary bundle and its nucleus;
17, the eleventh or spinal accessory nerve; 22, nucleus of the spinal accessory; 21, nucleus
of the hypoglossal nerve. — (From Spalteholz, "Human Anatomy.")

CEREBELLUM, PONS, AND MEDULLA. 229

nections have been determined by physiological experiments, but
so far it has not been possible to mark out histologically the exact
groups of cells concerned. The position and physiological properties
of these centers are described in the sections on respiration and
circulation. These centers are of especial importance because of
their wide connections with the body, their essentially independent
activity in reference to the higher parts of the brain, and the abso-
lutely necessary character of the regulations they effect. In the
development of the brain the- functions originally mediated by the
lower parts have been transferred more and more to the higher
parts, especially in regard to conscious sensation and motion, and
the so-called higher psychical activities. But the unconscious and
involuntary regulation of the organs of circulation and respiration
and to a certain extent of the other visceral organs has been cen-
tralized, as it were, in the medulla. In addition to the control
of the respiration and circulation other important reflex activities
are effected through the medulla by means of the vagus nerve,
which has its nucleus of origin in this part of the brain. Such, for
instance, are the reflex control of the heart through the cardio-
inhibitory center and of the motions and secretions of the alimentary
canal.

The Nuclei of Origin and the Functions of the Cranial
Nerves. — The origin, course, anatomical and physiological relations
of the first or olfactory, second or optic, and eighth or auditory
nerves have been referred to in the preceding pages. For the
sake of completeness the origin and functions of the other cranial
nerves may be summarized briefly in this connection.

The Third Cranial Nerve (N. Oculomotorius) . — This nerve arises
from the base of the brain on the median side of the corresponding
cms cerebri. It is a motor nerve supplying fibers to four of the
extrinsic muscles of the eyeballs, — namely, the internal rectus, the
superior rectus, the inferior rectus, and the inferior oblique — and
to the levator palpebrse. It innervates also two important intrinsic
muscles of the eyeball, the ciliary muscle used in accommodating
the eye in near vision, and the sphincter of the iris which controls
in part the size of the pupil. These two latter muscles belong to
the type of plain muscle, and the fibers of the third nerve which
innervate them terminate in the ciliary ganglion, whence the path
is continued by sympathetic nerve fibers (postganglionic fibers) to the
muscles. In the interior of the brain the fibers of the third nerve
arise from a conspicuous nucleus or collection of nuclei situated in
the central gray matter of the midbrain at the level of the superior
colliculus. The fibers for the ciliary muscle and sphincter pupillse
arise more anteriorly than those for the extrinsic muscles. His-
tologically three parts at least may be distinguished, as shown in

230

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

Fig. 100,— namely, the lateral (or principal) nucleus, which gives
origin chiefly to the fibers innervating the extrinsic muscles; the
median nucleus; and the nucleus of Edinger-Westphal. According
to Bernheimer * the large median nucleus gives rise to the fibers
that innervate the ciliary muscles, while the Edinger-Westphal
nuclei (accessory nuclei) control the movements of the sphincter
muscle of the iris. Some of the fibers, particularly those from
the lateral nucleus to the inferior rectus, the internal rectus, and
the inferior oblique, cross the mid-line and emerge in the nerve
of the opposite side.

Edinger-Westphal nucleus.
Principal nucleus
Median nucleus.

Nucleus of 4th nerve.

Fig. 100. — Nuclei of origin of the third and fourth nerves. — (From Poirier and Charpy.)

The Fourth Cranial Nerve (N. Trochlearis) . — This nerve emerges
from the brain in the anterior medullary velum (valve of Vieussens)
just posterior to the inferior colliculus. It curves around the crus
cerebri to reach the base of the brain. It is a motor nerve, and
supplies fibers to the superior oblique muscle of the eyeball. In
the interior of the brain the fibers arise from a nucleus in the central
gray matter just posterior to that of the third nerve (Fig. 100).
The fibers pass dorsalward toward the velum and make a com-
plete decussation before emerging.

The Fifth Cranial Nerve (N. Trigeminus). — This nerve arises
from the side of the pons by two roots, a small motor root, portio

* Bernheimer, in " Graefe-Saemisch's Handbuch der ees. Augenheilkunde."
2ded., I., 41.

CEREBELLUM, PONS, AND MEDULLA.

231

minor, and a large sensory root, portio major. It is, therefore, a
mixed motor and sensory nerve, supplying motor fibers to the

Fig. 101. — Diagram showing the average area of distribution of the sensory fibers of the
trigeminal nerve. — (Gushing.)

N. opht.

; Principal
1 motor
i nucleus.

Descending
spinal root.

N. max. sup. N. max. inf.

Fig. 102. — Nuclei of origin of the fifth cranial nerve. — (From Poirier and Charpy, after

Van Gehuchten.)

muscles of mastication and sensory fibers of pressure, pain, and
temperature to the face, the forepart of the scalp, the eye, nose,
portions of the ear, mouth, and tongue, and to the dura mater

232 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

(Fig. 101). In the interior of the brain the motor portion, portio
minor, arises partly from a small nucleus in the pons and partly
from a long column of cells extending along the lower margin of the
central gray matter throughout the midbrain. This column and
the fibers arising from it constitute the descending motor root of the
fifth nerve (see Fig. 102). The sensory fibers originate from the nerve
cells in the Gasserian ganglion (g. semilunare). The branch that
enters the brain ends partly in a collection of cells in the pons, the
so-called sensory nucleus, and partly in a column of cells extending
posteriorly throughout the length of the medulla. These cells
and the fibers ending in them constitute the descending spinal root
of the fifth nerve (see Fig. 99).

The Sixth Cranial Nerve (N. Abducens). — This nerve arises from
the base of the brain at the posterior edge of the pons. It is a motor
nerve, and supplies fibers to the external rectus muscle of the eye-
ball. In the interior of the brain its fibers originate in a small spheri-
cal nucleus lying beneath the floor of the fourth ventricle. Con-
nections have been traced between this nucleus and the pyramidal
tract of the opposite side (Fig. 99).

The Seventh Cranial Nerve (N. Facialis). — This nerve appears
on the base of the brain at the posterior margin of the pons, lateral
and somewhat posterior to the emergence of the sixth nerve. It is
mainly a motor nerve, but carries some sensory fibers (fibers of
taste and general sensibility) received through the n. intermedius of
Wrisberg. The motor fibers of the nerve supply the muscles of the
face, part of the scalp, and the ear, including its intrinsic muscles,
and in addition secretory fibers are supplied to the submaxillary
and sublingual glands. Within the brain these fibers arise from a
conspicuous nucleus in the tegmental region of the pons lying
ventral to the nucleus of the sixth, beneath the middle of the fourth
ventricle (Fig. 99). The sensory fibers of the nerve of Wrisberg
originate in the nerve cells of the geniculate ganglion.

The Ninth Cranial Nerve (N. Glossopharyngeus) arises from the
side of the medulla, — the restiform body. It is a mixed nerve,
supplying motor fibers to the muscles of the pharynx and the base
of the tongue and secretory fibers to the parotid gland. Within
the brain these fibers arise from two motor nuclei common to this
and the tenth nerve, — namely, a dorsal nucleus below the floor of
the fourth ventricle and a smaller ventral nucleus, n. ambiguus,
in the reticular substance of the tegmentum (Fig. 99). The sensory
fibers supply in part the mucous membrane of the tongue and
pharynx, the tympanic cavity, and the Eustachian tube. These
fibers arise from cells in the two ganglia on the trunk of the nerve,
the ganglion superius and g. petrosum. The branches from these
cells that pass into the medulla terminate in the nucleus of the ala
cinerea.

CEREBELLUM, PONS, AND MEDULLA. 233

The Tenth Cranial Nerve (N. Vagus or Pneumogastricus) . — This
nerve arises from the side of the medulla posterior to the origin of
the glossopharyngeal nerve. It is also a mixed nerve, with an
extensive distribution to the respiratory and digestive organs and
the heart. Its efferent or motor fibers arise within the brain from
the same masses of cells that give rise to the motor fibers of the
glossopharyngeal. These fibers supply the intrinsic muscles of the
larynx, esophagus, stomach, small intestine, and part of the large
intestine. Inhibitory fibers *are carried to the heart and secretory
fibers to the gastric and pancreatic glands. Its sensory or afferent
fibers are distributed to the mucous membrane of the larynx,
trachea, and lungs, and to the mucous membrane of the esophagus,
stomach, intestines, and gall-bladder and ducts. These fibers
arise from cells in the ganglia on the trunk of the nerve, the gan-
glion jugulare and g. nodosum. The branches from these cells that
pass into the medulla terminate in the gray matter of the ala cinerea.

The Eleventh Cranial Nerve (N. Accessorius) . — This nerve is
usually described as arising by upper roots from the medulla, and
by a series of lower roots from the spinal cord as low as the fifth
to the seventh cervical segment. It is a motor nerve, supplying
fibers to the sternomastoid and trapezius muscles. The medullary
branches arise from the posterior portion of the dorsal motor
nucleus which gives origin to the vagus, while the spinal branches
originate from cells in the anterior horn of the gray matter of the
cord (Fig. 99).

The Twelfth Crainal Nerve (N. Hypoglossus). — This nerve arises
from the medulla in the furrow between the anterior pyramid and
the olivary body. It is a motor nerve, supplying the muscles of
the tongue and the extrinsic muscles of the larynx and hyoid bone.
Within the brain these fibers originate from a distinct nucleus
lying in the floor of the fourth ventricle near the mid-line (Fig. 99).

CHAPTER XII.

THE SYMPATHETIC OR AUTONOMIC NERVOUS
SYSTEM.

The chain of nerve ganglia extending on each side of the spinal
column to the coccyx is known as the sympathetic nervous system.
This name was given to the structure under the misapprehension
that it constitutes a nerve pathway through which so-called sym-
pathetic— or, as we now designate them, reflex actions of distant
organs are effected. It was supposed to arise from the brain by
branches connected with the fifth and sixth cranial nerves.* We
now know that this system consists of a series of ganglia or col-
lections of nerve cells connected with each other and connected also
with the spinal nerves. Strictly speaking, the term sympathetic
system is applicable only to the chain of ganglia which begins with
the superior cervical ganglion at the base of the skull and ends
with the ganglion coccygeum. There are, however, other outlying
nerve ganglia with or without specific names which from a physio-
logical and indeed from an anatomical standpoint belong to the same
group. In the abdomen we have the so-called prevertebral ganglia,
the semilunar ganglion from which arises the celiac plexus, the
superior mesenteric, and the inferior mesenteric ganglion giving
rise to the hypogastric nerve. These ganglia lie ventral to the
sympathetic trunk, but are in direct connection with it. In the
head region the ciliary, spheno palatine, and otic ganglia are
also of the same type. More peripherally are numerous other
ganglia lying in or around the various visceral organs, such as the
submaxillary ganglion near the duct from the corresponding gland,
the cardiac ganglia in the heart, and the extensive system of nerve
cells in the walls of the alimentary canal known as the plexuses
of Meissner and Auerbach. With the exception, perhaps, of this-
last system, whose histological structure and connections are not
satisfactorily known, all of these ganglia are frequently designated
as sympathetic, and from a physiological as well as an anatomical
standpoint may be considered with the ganglia of the sympathetic
trunk or chain. Langley, who has contributed greatly to our
knowledge of the finer anatomy and the physiology of this system,
has recently proposed a different classification. |

* Charles Bell, "The Nervous System of the Human Body," third edi-
tion, London, 1844, p. 9.

tSchafer's "Text-book of Physiology," 1900, vol. ii ; " Ergebnisse der
Physiologic," 1903, vol. ii, part n, p. 823 ; also " Brain," 1903, vol. xxvi.

234

SYMPATHETIC NERVOUS SYSTEM.

235

Autonomic Nervous System. — According to Langley, the
efferent fibers from the nerve cells of the sympathetic and re-
lated ganglia supply the plain muscle tissues,
the cardiac muscles, and the glands, — that is,
the organs of the involuntary or, according to
an old nomenclature, the vegetative processes
of the body. He proposes for this entire sys-
tem of efferent fibers the term autonomic, to
indicate that they possess a certain independ-
ence of the central nervous system. The au-
tonomic system is contrasted physiologically
and anatomically with the efferent spinal and
cranial fibers that supply the striated or volun-
tary muscles: physiologically in the fact that
this latter group of fibers is entirely dependent
upon activities of the central nervous system,
and anatomically in the fact that the auto-
nomic fibers, although arising ultimately from
the central nervous system, all pass to their pe-
ripheral tissues by way of sympathetic nerve
cells. The autonomic path consists of two
neurons : one belonging to the central nervous
system, whose axon emerges in one of the spinal
or cranial nerves and ends around the dendrites
of a sympathetic cell ; and one occurring in some
one of the numerous sympathetic ganglia, whose
axon passes to the peripheral tissue. The first
axon is spoken of as the preganglionic fiber, the
second as the postganglionic fiber. Their con-
nections are represented in the accompanying
schema (Fig. 103).

Physiological and anatomical investigations
have shown that autonomic nerve fibers arise
from four regions in the central nervous system
(Fig. 104) : First, from the midbrain, emerging

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Fig. 103. — Schema to show the general relation between
the preganglionic and postganglionic fibers of the autonomic
paths.

Fig. 104.— Illus-
trating the central ori-
gin of the autonomic
fibers. — (Langley.)

236 PHYSIOLOGY OP CENTRAL NERVOUS SYSTEM.

in the third cranial nerve and passing via the ciliary ganglion;
second, from the bulbar region, emerging in the seventh, ninth, and
tenth cranial nerves; third, from the thoracic spinal nerves (first
thoracic to fourth or fifth lumbar) and passing in general via the
ganglia of the sympathetic chain; fourth, from the sacral region
by way of the so-called nervus erigens supplying the descending
colon, rectum, anus, and genital organs. The autonomic fibers at
their origin in the central nervous system — that is, while pregan-
glionic fibers — are all possessed of a small medullated sheath,
having a diameter of 1.8 p. to 4 //. The postganglionic fiber is in
most cases non-medullated, but this is by no means an invariable
rule. In many cases the axons from sympathetic cells possess
distinct, although small, myelin sheaths.

The Nicotin Method. — The course of the autonomic fibers
has been traced in many cases to their corresponding sympathetic
nerve cells partly by the method of secondary degeneration and
partly by the use of nicotin, as first described by Langley and
Dickinson.* These authors have shown that after the use of
nicotin, either injected into the circulation or painted upon the
ganglion, stimulation of the preganglionic fiber in any part of its
course fails to give any response, while stimulation of the post-
ganglionic fiber, on the contrary, is still effective. It would seem,
therefore, that the nicotin paralyzes the connection of the pre-
ganglionic fiber with the sympathetic nerve cell, and by means
of the local application of the drug it is possible in many cases
to pick out the ganglion in which the preganglionic fiber really
ends. For it often happens that in the sympathetic trunk this
fiber will pass through several ganglia before making final con-
nections with a sympathetic cell. So far, the course of these
fibers has been traced most successfully in the case of the nerves
supplying the sweat glands, blood-vessels, and especially the erector
muscles of the hairs, the so-called pilomotor nerve fibers. The
visible result of stimulation in the last case gives a ready means
of determining the presence of the fibers.

General Course of the Autonomic Fibers Arising from the
Spinal Nerves. — It has long been known that the spinal nerves
are connected with many of the ganglia of the sympathetic chain
by fine branches known as the rami communicantes. In the tho-
racic and lumbar regions (first thoracic to second or fourth lumbar)
these rami consist of two parts, a white and a gray ramus, the
difference in color being due to the fact that the white rami are
composed almost entirely of medullated fibers, while the gray rami
are largely non-medullated. In the cervical, lower lumbar, and
sacral regions the rami consist only of the gray part. Physiological
*" Proceedings, Royal Society," 1889, 46, 423.

SYMPATHETIC NERVOUS SYSTEM. 237

experiments show that the white rami consist of preganglionic
fibers that arise from nerve cells in the spinal cord, pass out by
way of the anterior roots, enter the white ramus, and thus reach
the sympathetic chain. On entering this latter the fiber may
not end at once in the ganglion at which it enters, but may pass up
or down in the chain for some distance. Eventually, however, it
ends around a sympathetic nerve cell and the path is then con-
tinued by the axon from this cell as the postganglionic fiber. The
gray rami consist of these latter fibers, which return from the sym-
pathetic chain to the spinal herves and are then distributed to the
areas supplied by these nerves, particularly the cutaneous areas,
since the skin branches are the ones that supply the sweat glands,
the blood-vessels, and the erector muscles of the hairs. It will be
noted that the fibers that pass from a given spinal nerve — say, the
twelfth thoracic — by a white ramus to enter the sympathetic chain
do not return as postganglionic fibers by the gray ramus to the
same spinal nerve. On the contrary, the gray ramus of the twelfth
thoracic may consist of the postganglionic portion of autonomic
fibers that enter the sympathetic through a white ramus of
one of the higher thoracic nerves. In general, we may say
that there is a great outflow of autonomic fibers, including
vasomotor, sweat, and pilomotor fibers, in the white rami commu-
nicantes from the first or second thoracic to the second or fourth
lumbar nerves. Those of these fibers that are to be distributed to
the skin areas of the body — head, limbs, and trunk — return by way
of the gray rami to the various spinal nerves and are distributed with
these nerves, the distribution being somewhat different in different
animals and for the different varieties of fibers. Those fibers that
are distributed eventually to the blood-vessels, glands, and walls
of the viscera have a different course from those supplying the
glands, blood-vessels, and plain muscle of the head region. For
the head region the fibers after entering the sympathetic chain pass
upward along the cervical sympathetic to end in the superior
cervical ganglion; thence the path is continued by postganglionic
fibers which emerge by the various plexuses that arise from this
ganglion. For the abdominal and pelvic viscera the fibers (particu-
larly the rich supply of vasoconstrictor fibers), after entering the
sympathetic chain, emerge, still as preganglionic fibers, by the
splanchnic nerves that run to the celiac ganglion or in the branches
connecting with the inferior mesenteric ganglia, and then become
postganglionic fibers (see Fig. 105). The details of the course of
the vasomotor, sweat, visceromotor fibers to the different regions,
the cardiac fibers, etc., will be given in the appropriate sections.

General Course of the Autonomic Fibers Arising from the
Brain. — These fibers leave the brain in the third, seventh, ninth,

238

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

tenth, and eleventh cranial nerves.

I.c

Fig. 105. — Diagram giving a schematic
representation of the course of the autonomic
<sympathetic) fibers arising from the thoracico-
lumbar and sacral regions of the cord. The
preganglionic fiber is represented in red, the
ppstganglionic in black lines. The arrows in-
dicate the normal direction of the nerve im-
pulses or nerve conduction. S.c., Superior
cervical ganglion; I.e., inferior cervical gan-
glion; T, the first thoracic ganglion; Sp., the
splanchnic nerve; C., the semilunar or celiac
ganglion ; m., the inferior mesenteric ganglion ;
h., the hypogastric nerves; N.E., the nervus
•erigens. The numerals indicate the corre-
sponding spinal nerves.

Those that emerge in the third
nerve end, as preganglionic fi-
bers, in the ciliary ganglion.
Their postganglionic fibers
leave this ganglion in the short
ciliary nerves and innervate
the plain muscle of the" sphinc-
ter of the iris and the ciliary
muscle. The fibers that emerge
in the seventh and ninth
nerves probably supply the
glands and blood-vessels (vaso-
dilator fibers) of the mucous
membrane of the nose and
mouth. Some of these fibers
reach the fifth nerve by way
of anastomosing branches and
are distributed with it. Their
preganglionic portion termi-
nates in some of the ganglia
belonging to the sympathetic
type which are found in this
region, such as the sphenopal-
atine and otic ganglia, and the
submaxillary and sublingual
ganglia for the fibers dis-
tributed to the glands of the
same name. The autonomic
fibers that arise with the tenth
(and the eleventh) nerves are
distributed through the vagus.
Physiologically these fibers
consist of motor fibers (vis-
ceromotor fibers) to the mus-
culature of the esophagus,
stomach, small intestine, and
large intestine as far as the
descending colon, motor fibers
to the bronchial musculature,
inhibitory fibers to the heart,
and secretory fibers to the
gastric and pancreatic glands.
The ganglia in which the pre-
ganglionic portions end have
not been definitelv located,

SYMPATHETIC NERVOUS SYSTEM. 239

but probably they comprise the small and, for the most part, un-
named local ganglia found in or near the organs innervated.

General Course of the Autonomic Fibers Arising from the
Sacral Cord. — The autonomic fibers of this region emerge from
the cord in the anterior roots of the sacral nerves, — second to
fourth. The branches from these roots unite to form the so-called
nervus erigens (pelvic nerve), which loses itself in the pelvic plexus
without making connections with the sympathetic chain of ganglia.
The pelvic plexus is formed in part also from the hypogastric nerve
arising from the inferior mesenteric ganglion. Through this latter
path autonomic fibers from the upper lumbar region enter the
plexus (Fig. 105). The autonomic fibers of the nervus erigens
supply vasodilator fibers to the external genital organs, and in
the male constitute the physiological mechanism for erection;
whence the name. They supply, also, vasodilator fibers to rectum
and anus and motor fibers to the plain muscles of the colon de-
scendens, rectum, and anus. The'preganglionic parts of these
fibers end in small sympathetic ganglia in the pelvic plexus or in
the neighborhood of the organs supplied.

Normal Mode of Stimulation of the Autonomic Nerve Fibers.
• — In distinction from the nerve fibers ~ innervating the skeletal
muscles practically the whole set of autonomic fibers is removed
from the control of the will. An apparent exception to this general
statement is found in the fact that the ciliary muscle of the eye is
seemingly under voluntary control. We must suppose that under
normal conditions they are always excited reflexly, and the course
of the afferent fibers concerned in these reflexes and the nature of
the effective sensory stimulus in each case are important in the con-
sideration of each of the physiological mechanisms involved. Most
of these mechanisms, as we shall find, work reflexly — that is,
without voluntary initiation — and, for the most part, uncon-
sciously,— for instance, the movements of the intestines, the secre-
tion of the digestive glands, and the contraction and dilatation of
the arteries. The autonomic nerve fibers control, therefore, the
unconscious co-ordinated actions, the so-called vegetative processes,
of the body. There is no apparent reason in the anatomical ar-
rangements why these fibers should be free from voluntary control.
Their distinguishing characteristic in comparison with the nerves
for the voluntary movements is the fact that they all terminate
first in sympathetic nerve cells; but this fact gives no explanation
of the absence of conscious control by the will. We are justified in
saying that nerve paths that pass through sympathetic nerve cells
cannot be excited voluntarily; but the immediate reason for this
fact is probably to be found in the ultimate point of origin of these
paths in the central nervous system. What we designate as vol-

240 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

untary motor paths arise in a definite region of the cortex, — the
motor area in the frontal lobe. Our motor conceptions or ideas
can affect the efferent paths arising in this region, but not those,
apparently, which originate in other parts of the brain.

CHAPTER XIII.

THE PHYSIOLOGY OF SLEEP.

t

The state of more or less complete unconsciousness which we
designate as sleep forms a part of the physiology of the brain which
naturally has attracted much attention, and the theoretical explana-
tions that have been advanced at one time or another are exceed-
ingly numerous. The same condition occurs in many, if not all, of
the other mammalia, and, indeed, in all living things there occur
periods of rest alternating with periods of activity. Whether these
periods of rest are essentially similar in nature to sleep in man
is a question in general physiology that can be solved only when
we know more of the chemistry of living matter. Within the human
body there are other tissues that exhibit periods of rest alternating
with periods of activity, — the gland cells, for example. The secret-
ing cells of the pancreas have a period of activity in which the
destructive processes exceed the constructive, and a period of rest
in which these relations are reversed. We may compare this con-
dition in the gland cells with that in the brain. Sleep, from this
standpoint, is a period of comparative rest or inactivity, during
which the constructive or anabolic processes are in excess of the
disassimilatory changes. The period of sleep is a period of re-
cuperation, and doubtless all tissues have these alternating
phases. To explain sleep fundamentally, therefore, it would be
necessary to understand the chemical changes of anabolism and
catabolism, and an explanation of the sleep of the brain tissues
would doubtless explain the similar phenomenon in other tissues.
But what the physiologists desire first, and have attempted to
determine, is an explanation of why this condition comes on with
a certain periodical regularity, — an explanation, in other words, of
the mechanism of sleep, the change or changes in the brain or the
body which reduce the metabolism of the brain tissue to such
an extent that it falls below the level necessary to cause conscious-
ness.

Physiological Relations during Sleep. — The central and most
important fact of sleep is the partial or complete loss of conscious-
ness, and this phenomenon may be referred directly to a lessened
metabolic activity in the brain tissue, presumably in the cortex
cerebri. During sleep the following changes have been recorded:

16 241

242 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

The respirations become slower and deeper and the costal respiration
(respiration by elevation of the ribs) predominates over the ab-
dominal or diaphragmatic respiration as compared with the waking
condition. The respiratory movements also show frequently a
tendency to become periodic, — that is, to increase and decrease
regularly in groups after the manner of the Cheyne-Stokes type
of breathing. The expiration is frequently shorter and more audi-
ble than in the respirations of the waking hours. The eyeballs
roll upward and inward and the pupil is constricted. According
to Lombard's observations, the knee-kick decreases or disappears
entirely during sleep. Some of the constant secretions are dimin-
ished in amount, — as, for instance, the urine, the tears, and the
secretion of the mucous glands in the nasal or pharyngeal mem-
brane. One of the familiar signs of a sleepy condition is the dry ness
of the surface of the eyes, a condition that leads to the rubbing
of the eyes. It is sometimes stated that the digestive secretions
are diminished during sleep, but the statement does not seem to
rest upon satisfactory observations, and may be doubted. The
pulse-rate decreases during sleep and there are also certain sig-
nificant changes in the distribution of blood in the body owing
to a diminished vascular tone in the skin vessels. These latter
changes will be referred to more in detail below. The physiological
oxidations are also decreased, as shown by the diminished output
of carbon dioxid. On the whole, however, the physiological activities
of the body go on much as in the waking condition. Those changes
in activity that do occur are, in the main, an indirect result of
the partial or complete cessation of activity in the brain. One
might say that while the cortex of the brain sleeps — that is, is
inactive — most of the other organs of the body may be awake and
maintain their normal activity. Another fact of interest is that
the entire cortex does not fall asleep at the same instant nor
always to the same extent. Ordinarily as sleep sets in the power
to make conscious movements is lost first and the auditory sen-
sibility last, and on awakening the reverse relation holds. The
individual may be conscious of sound sensations before he is
sufficiently awake to make voluntary movements.

The Intensity of Sleep. — The intensity of sleep — that is, the
depth of unconsciousness — has been studied by the simple device
of ascertaining the intensity of the sensory stimulus necessary to
awaken the sleeper. Kohlschutter * used for this purpose a pendu-
lum falling against a sounding plate. At intervals of a half-hour
during the period of sleep the auditory stimuli thus produced were
increased in intensity until waking was caused. His results are
expressed in the curve shown in Fig. 106, in which the intensity
* Kohlschiitter, "Zeitschrift f. rationelle Medicin," 1863.

THE PHYSIOLOGY OF SLEEP.

243

of the sleep is represented by the height of the ordinates. According
to this curve, the greatest intensity is reached about an hour after
the beginning, and from the second to the third hour onward the
depth of sleep is very slight. The activities of the brain lie just
below the threshold of consciousness. It appears also from this
curve that the recuperative effect of sleep is not proportional to
its intensity. The long period from the third to the eighth hour,
in which the depth of sleep is so slight is presumably as important
in restoring the brain to its normal waking irritability as the deeper
period up to the third hour. It is probable that the curve of in-
tensity of sleep varies somewhat with the individual and also with
surrounding conditions. That individual variations occur is indi-

STRE1NGTH OF STIMULUS
800

100

HOURS 0,5 UO L5 Z.O 2.5 3.0 3.5 4.0 45 5.0 5-5 6.0 6& 7.0 7.5 7.8

Fig. 106. — Curve illustrating the strength of an auditory stimulus (a ball falling from
a height) necessary to awaken a sleeping pers9n. The hours marked below. The tests
were made at half-hour intervals. The curve indicates that the distance through which
it was necessary to drop the ball increased during the first hour, and then diminished, at
first very rapidly, then slowly. — (Kohlschiitter.)

cated by the results obtained by two other observers, Monninghoff
and Piesbergen,* who used the same general method as was em-
ployed by Kohlschutter. The sleeper was awakened by auditory
stimuli produced by dropping a lead ball from varying heights upon
a lead plate. Only two experiments were made each night, and
the curves constructed represent, therefore, composites from several
periods of sleep. One of the curves obtained is represented in
Fig. 107. According to this curve, the maximum intensity is
reached between the first and second hours, and between the fourth
and the fifth hour there is a second slight increase in intensity,
giving a second maximum in the curve. This latter feature of a
* Monninghoff and Piesbergen, "Zeitschrift f. Biologic," 19, 1, 1883.

244

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

Fig. 107. — Curve of intensity of sleep according to Monninghpff and Piesbergen. The
figures along the abscissa represent time in hours from the beginning of sleep; those along
the prdinate the relative intensity of sleep measured in milligram -millimeters, expressing
the intensity of sound of a falling body necessary to awaken the sleeper.

t\K. 108. — Curve of intensity of sleep in a child of three years and eight months, as deter-
mined by Czerny.

THE PHYSIOLOGY OF SLEEP. 245

second increase in intensity toward morning is very apparent also
in some interesting curves obtained by Czerny from children of
different ages. His method of awakening the sleeper was to use
induction shocks of varying intensities. In children of four years
with a normal period of sleep of about twelve hours the curve shows
a very marked increase in intensity toward morning, as shown
in Fig. 108. Curves made by similar experimental methods are
reported by Ho well and by Michelson.* The striking feature about
all the curves is the sharp increase in intensity shortly after falling
asleep, the maximum being reached at the first or second hour of
slumber. Subsequently the curve again falls rapidly and the sleep
is light, but may show a greater or less increase in intensity toward
the end of the period.

Changes in the Circulation during Sleep. — That the circula-
tion undergoes distinct and characteristic changes during sleep
has been shown upon man by phlethysmographic observations and
upon the lower animals by direct kymographic experiments.
Using very young dogs, Tarchanofff has been able to measure
their blood-pressure while sleeping. He finds that the pressure
in the aorta falls by an amount equal to twenty to fifty millimeters
of mercury during sleep, and that the same general fact is true
for man is shown by the sphygmomanometric observations reported
by Brush and Fayerweather.J Making use of patients with a
trephine hole in the skull, Mosso § has been able to show that during
sleep the volume of the brain diminishes, while that of the arm
or foot increases. The apparent explanation of this fact is that
the blood-vessels in the body dilate, and receive, therefore, more
blood, while a smaller amount flows to the brain. The volume
of the foot or hands was measured in these experiments by incasing
it in a plethysmograph (see section on circulation). The author ||
has extended these observations so as to obtain a plethysmographic
record of the volume of the hand and part of the forearm during
a period of normal sleep. One of the records thus obtained is given
in Fig. 109. The amount of dilatation is given by the ordinates
below the base line. Granting that the increase in volume of the
hand and arm is caused by an increase in the volume of blood
contained in their blood-vessels, the curve shows that during and
after the onset of sleep the blood-vessels in the arm slowly dilate
until between one and two hours after the beginning of sleep.

* Howell, "Journal of Experimental Medicine," 2, 313, 1897. Michel-
Bon, "Dissertation," Dorpat, 1891.

fTarchanoff, "Archives italiennes de biologic," 21, 318, 1894.

J Brush and Fayerweather, "American Journal of Physiology," 5, 199,
1901.

§ Mosso, "Ueber den Kreislauf des Blutes im menschlichen Gehirn," 1881.

II Howell, loc. cit.

246

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

After this maximum is reached the arm remains more or less of
the same volume for a certain period or else diminishes in volume

very gradually. Shortly before waking,
however, the arm begins to diminish
more rapidly in size, owing doubt-
less to the contraction of its blood-
vessels; so that at the time of awak-
ing it has practically the same volume
as at the beginning of sleep. If, on
the basis of Mosso's experiments,
quoted above, we assume that the
blood-flow in the brain stands in a
reciprocal relation to that in the arm,
this curve may be taken to indicate
that before and after the onset of sleep
the blood-flow through the brain di-
minishes rapidly to a certain point
and that before awaking the blood-flow
begins to increase again until it reaches
normal proportions.

Effect of Sensory Stimulation.—
That sensory stimuli of various kinds
affect a sleeping individual without
entirely awaking him is shown by the
movements that may be caused in this
way, and also by the nature of the
dreams which may be provoked. It is
very interesting to find from plethys-
mographic observations that all kinds
of sensory stimulations from with-
out and from within are liable to
affect the circulation of the blood
during sleep. As shown by the plethys-
mograph, the volume of the arm dimin-
ishes more or less in proportion to the
* intensity of the stimulus, and the
£ probable interpretation of this fact is
that the sensory stimulus acts reflexly
upon the vasomotor center in the
medulla and causes through it a con-
traction of the blood-vessels. In the
curve shown in Fig. 109 most of the

irregularities were traceable to causes of this kind, — noises
in the building or street or other sensory stimuli. The
same fact is exhibited in a striking way by the curves given in

THE PHYSIOLOGY OF SLEEP.

247

Fig. 110. In these experiments the recorder attached to the
plethysmograph to register the changes in volume was of a differ-
ent kind (tambour) and the record reads in a reverse way to that
shown in Fig. 109, — that is, a dilatation is recorded by a rise in
the curve and a constriction by a fall. The recorder being more
sensitive, the volume changes in the arm due to the heart beat are
clearly indicated. The legends attached to the illustration explain
the results of the experiments.

Theories of Sleep. — Many hypotheses have been advanced
to explain the nature and c'ausation of sleep. Confining ourselves
to the more recent hypotheses that attempt to explain the immediate

,r

Fig. 110. — Sleep: A, effect of external impression (music box), insufficient to awaken
sleeper, — a marked diminution in volume of the arm ; B, effect of external impression
(music box) sufficient to awaken sleeper; a stronger diminution in volume followed by
dilatation as the subject again fell asleep.

cause of the production of the condition, the following brief de-
scription will suffice to show the nature of the theories proposed :

1. The Accumulation of Acid Waste Products. — Preyer* and
also Obersteiner have suggested that the accumulation of acid
waste products in the blood brings on a gradually increasing loss of
irritability or fatigue in the brain cells which results finally in a
depression of their activity sufficient to cause unconsciousness. It
is known that functional activity in the muscle is accompanied by
the formation of acid waste products, especially sarcolactic acid,

* Preyer, " Centralblatt f. d. med. Wiss.," 13, 577, 1875; and Obersteiner,
"Allgemeine Zeitschrift f. Psychiatric," 29, 224, 1872-73.

248 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

and that if not removed as quickly as formed these products cause
a diminution and finally a loss of irritability. The central nerve
tissues in activity show also an acid reaction. Moreover, if lactic
acid or its sodium salt is injected into the blood it brings on a con-
dition of fatigue and finally a state of unconsciousness. The theory,
therefore, supposes that during the waking hours the constant
activity of the muscles and nervous system results in a gradual
accumulation of these waste products, since their oxidation and
removal does not keep pace with their production. The end-
result is a diminishing irritability of the central nervous system,
especially perhaps of the cortex, which results finally in invol-
untary sleep, although normally the accumulation is not carried
to this extreme, since it is our habit to induce sleep, when the
sensations of sleepiness become apparent, by withdrawing ourselves
from excitations, mental or sensory.

2. Consumption of the Intramolecular Oxygen. — Pfliiger* suggests
that the cause of sleep lies essentially in the fact that the brain cells
during the waking hours use up their store of oxygen more rapidly
than it can be replaced by the absorption of oxygen from the blood.
The result is a gradual reduction in irritability; so that when
external stimuli are withdrawn the oxidations in the cells sink
below the level necessary to arouse consciousness. During sleep
the store of intramolecular oxygen — that is, the oxygen syntheti-
cally combined by anabolic processes to form the irritable living
matter — is again replenished.

3. The Neuron Theory. — Duval, f Cajal, and others have applied
the neuron doctrine to explain the occurrence of sleep. According
to the neuron conception, the connection between the cells in the
cortex and the incoming impulses along the afferent paths is made by
the contact of the terminal arborizations of the afferent fibers with
the dendrites of the cell. Assuming that these latter processes are
contractile, Duval supposes that sleep is caused mechanically by
their retraction, which results in breaking the connections and
thus withdrawing the brain cells from the possibility of external
stimulation. Conductivity is re-established upon awaking by the
elongation and intermingling of the processes again re-establishing
physiological connections. The numerous efforts made to demon-
strate the fact of a retraction of the dendritic processes by histo-
logical examinations of brains during sleep or narcosis have, how-
ever, not been successful.

4. Anemia Theories of Sleep. — Numerous facts in physiology
make it practically certain that during sleep there is a diminished

* Pfluger, "Archiv f. d. gesammte Physiologic," 10, 468, 1875.
t Duval, " Comptes rendus de la soc. de biol.," February, 1895; and Cajal,
•'Archiv f. Anat. (u. Physiol.)," 375, 1895.

THE PHYSIOLOGY OF SLEEP. 249

flow of blood through the brain, a condition of cerebral anemia.
In animals with the brain exposed or with a glass window in the
skull it has been observed directly that the flow of blood to the
cortex is diminished during sleep. Mosso's plethysmographic experi-
ments mentioned above have been given a similar interpretation,
and Tarchanoff s observations upon sleeping dogs, as well as direct
determinations upon man by Brush and Fayerweather, show that
the arterial pressure falls during sleep. Inasmuch as the lessened
pressure in the arteries is accpmpanied by a dilatation of the vessels
of the skin, as shown by the plethysmograph, it is probable, when
the facts previously mentioned are taken into consideration, that
the diminished pressure in the arteries forces less blood through
the brain and more through the dilated vessels of the skin. In
fact, as is explained in the section on circulation, it is probable
that the blood-flow through the brain is normally regulated in-
directly by the circulation in other parts of the body. Constriction
of blood-vessels elsewhere increases arterial pressure and shunts
more blood through the brain, and vice versa. This general view
is in accord with the fact that sensory stimuli and increased mental
activity are accompanied by a constriction of the blood-vessels
(of the skin) and a rise of arterial pressure, while, on the other
hand, mental inactivity and especially sleep are accompanied by
a dilatation of the blood-vessels of the body (skin vessels) and a
fall of arterial pressure. All of our facts, therefore, point to an
anemic condition of the brain during sleep, and some physiologists
have believed that this condition precedes and causes the state
of sleep, while others take the opposite view that it follows and
is merely one result of sleep. On the basis of the plethysmographic
experiments mentioned above the author* has proposed a theory
of sleep in which the diminished flow of blood to the brain is ex-
plained and is assumed to be the chief factor in bringing on sleep.
The theory assumes that the periodicity of sleep is dependent
mainly upon a rhythmical loss of tone in the vasomotor center in
the medulla in consequence of fatigue from continued activity
during the waking hours. That is, the vasomotor center is in
constant action during this period; the continued flow of sensory
stimuli and the constant activity of the brain act reflexly on this
center and through it cause a constriction of the blood-vessels of
the body, particularly of the skin, by means of which the blood-
flow through the brain is maintained with an adequate velocity.
In consequence of this varying but constant activity the center
undergoes fatigue; stronger and stronger stimulation is necessary
to maintain its normal tone, and eventually its .effect on the blood-
pressure becomes insufficient to maintain an adequate flow through
* Howell, "Journal of Experimental Medicine," 2, 313, 1897.

250 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

the brain and unconsciousness or sleep results, even against one's
desires, as is shown by the experience of those who have attempted
to keep awake much beyond the habitual period. Ordinarily,
however, this fatigue of the vasomotor center and its resulting
tendency to a cessation of activity is favored by our voluntary
withdrawal of stimulation. Our preparations for sleep, closure of
eyes, darkened and if possible quiet room, cessation from disturbing
thoughts, result in a diminution of the sensory and mental stimuli
that normally play upon the vasomotor center. The cessation
of such stimuli may, indeed, at any time be all that is necessary
to bring about a partial loss of activity in this center, a les-
sened flow of blood through the brain, .and a period of sleep which,
however, is usually short. If, however, the vasomotor center has
been previously fatigued, as may be supposed to be the case at the
•end of the day, the withdrawal of these stimuli permits it to fall
into a more complete state of inactivity, and the diminution of
blood-flow to the brain and the state of unconsciousness is longer
lasting, — lasts indeed, according to the curves of which an example
is given in Fig. 109, until the gradual resumption of activity in the
vasomotor center brings about a constriction of the blood-vessels
of the body and thus drives enough blood through the brain to
cause spontaneous awakening. A third factor which must aid in
the production of unconsciousness as a result of the lessened flow
of blood, and in the return of consciousness in connection with
the increased flow of blood, is the greater or less fatigue of the
cortical cells themselves after a day's activity, and their greater
irritability after a night's rest. Many factors, therefore, co-oper-
ate in the development of the normal state of sleep lasting for
six to eight hours out of twenty-four, but the central factor which .
explains its rapid onset, involving nearly simultaneously all . the
conscious areas of the brain, whether previously fatigued or not,
and the equally sudden restoration to consciousness of the entire
cortex, is to be found in the amount of blood-flow to the brain.
Under normal conditions this is the factor that stands in most
immediate relation to that appearance and disappearance of full
consciousness which mark for us the limits of sleep. A similar
view is advocated by Hill,* who believes, however, that the regu-
lation of the blood-flow through the brain is effected through the
vasomotor control of the splanchnic area, whereas the author's
view is that the regulation is effected mainly through variations
in the cutaneous circulation, — that is, for the normal occurrence
of sleep. The drowsiness that follows a heavy meal is probably due
mainly to the mechanical effect of a dilatation of the blood-vessels of

* Hill, "The Physiology and Pathology of the Cerebral Circulation," Lon-
don, 1896.

THE PHYSIOLOGY OF SLEEP. 251

the viscera and the consequent diminution in the blood-flow through
the brain; but the sleep that occurs at the end of the day is un-
doubtedly connected with a dilatation of the blood-vessels of the
skin of the trunk and extremities. What the condition in the vis-
ceral organs may be at such times we have at present no means
of knowing.

Hypnotic Sleep. — The sleep that can be produced by so-called
suggestion, the sleep of hypnotism, has been studied by means
of the plethysmographic rnethod.* The result, so far as the
volume of the arm and hand is concerned, shows that in this con-
dition, unlike normal sleep, there is a marked diminution in volume,
and, therefore, we may believe, an increased constriction of the
blood-vessels of the skin. This observation accords with the
blanched appearance of the skin of the extremities, and with the
statement that in deep hypnotic sleep the skin does not bleed
readily when pricked with a needle. In view of our limited knowl-
edge, however, it would be hazardous to base any comparison
between normal and hypnotic sleep upon this single fact.

* Walden, "American Journal of Physiology," 4, 124, 1900-1901.

SECTION III.
THE SPECIAL SENSES.

CHAPTER XIV.

CLASSIFICATION OF THE SENSES AND GENERAL
STATEMENTS.

Under the general term sense organ we may include not only
the peripheral organ on which the stimulus acts, but also the sensory
path through which the impulses are conveyed to the central
nervous system and the cortical center by means of which the
reaction in consciousness is mediated.

Classification of the Senses. — In general, we attempt to
distinguish the various sense organs by the differences in their
end reaction hi consciousness. Each sense organ gives a different
kind of response, the nature and distinctive features of which
are recognized subjectively. The conscious sensations are said
to differ in quality or modality. The qualitative difference in
some cases is very distinct, — the difference between sensations of
sound and of vision, for instance, — and on this subjective difference
we base our efforts to give specific names to the sense organs con-
cerned. This means of classification is not, however, applicable
in all cases. While many of our sensations are so distinct in quality
that we can recognize them and name them without difficulty,
others are of a more obscure character. In addition to our sensa-
tions of vision, hearing, smell, taste, pressure, temperature, and
pain, there are doubtless many other sensations whose conscious-
reaction is less distinct in quality and for which our subjective
means of recognition and classification are less satisfactory or
entirely inadequate. Such, for instance, are the sensations from
the muscles, from the semicircular canals and the vestibular sacs
of the ear, and from many of the visceral organs. For the recogni-
tion and classification of these senses and sense organs it is neces-
sary to fall back upon the methods of anatomical and physiological
analysis, methods which in many respects are uncertain. So also-
within the limits of any sensation of a given quality or modality,.

252

CLASSIFICATION OF THE SENSES. 253

we distinguish certain subqualities. In vision we have many dif-
ferent qualities which we designate by special names, — the series
•of different colors, for example. In sound sensations we distinguish
different tones and different qualities of tones. But here, again,
the subjective mark is often so indistinct in consciousness
that it cannot be used satisfactorily for purposes of classifica-
tion. In the odor sensations we distinguish many different quali-
ties, each recognizable at the time that it is experienced, but their
characteristics are so fugitive that so far it has not been possible
to name them or group them in any satisfactory way. In studying
the qualities of the various sensations, so far as they are recogniz-
able, the effort of physiology has been to connect them with some
definite anatomical or physiological peculiarity in the sense organs
concerned. The final explanation of the differences in quality
involves a study of the nature and properties of consciousness
itself, — a subject which as yet has not been undertaken by physi-
ology. At present we accept the fact of consciousness and the
fact that there are different kinds or qualities of consciousness,
and our investigations are directed only toward ascertaining
the anatomical, physical, and chemical properties of the organs
involved in the production of these subjective changes.

In former times it was customary to divide the sensations into
two different groups, — the special and the common senses, — the
former including the so-called five senses of man, — namely, sight,
hearing, touch, taste, and smell, — while under the latter were
grouped all other sensations of less distinctive qualities. In physi-
ology the belief that man has only five special senses has, however,
long been abandoned. The sense of touch as ordinarily understood
has been shown to consist of two or rather three distinct senses:
pressure, heat and cold, and the sense of pain exhibited by the
skin is in all essential respects as special and characteristic as those
just named. There is, however, no certain standard as to what
shall constitute a special in contradistinction to a common sense;
so that a classification based on this nomenclature is unsatis-
factory. In one respect, however, our senses show a difference
which may be used as a basis for dividing them into two general
groups. This difference lies in the manner of projection. We may
assume that all of our sensations are aroused directly in the brain.
In that organ take place the final changes which react in con-
sciousness. But in no case are we conscious that this is the case.
On the contrary, we project our sensations either to the exterior
of the body or to some peripheral organ in the body, the
effort being apparently to project them to the place where experi-
ence has taught us that the acting stimulus arises. We may
divide the senses, therefore, into two great groups: (1) The

254 THE SPECIAL SENSES.

external or rather the exterior senses, or those in which the sensa-
tions are projected to the exterior of the body, and which form,
therefore, the means through which we become acquainted with the
outside world. The exterior senses include sight, hearing, taste,
smell, pressure, and temperature (heat and cold). (2) The internal
or interior senses, or those in which the sensations are projected to
the interior of the body. It is through these senses that we acquire
a knowledge of the condition of our body and perhaps also a knowl-
edge of ourselves as an existence or organism distinct from the ex-
ternal world. Among the interior senses we must include pain,
muscle sense, the sensations from the semicircular canals and ves-
tibule of the internal ear, hunger, thirst, sexual sense, fatigue, and
in addition perhaps other less definite sensations from the visceral
organs. This line of demarcation, although it holds so well in
most cases, is not absolutely distinctive. The temperature sense,
for instance, is, so to speak, on the border line between the two
groups; we may project this sensation either to the exterior or
to the interior according to circumstances. When the temperature
nerves are excited simultaneously with the pressure nerves, we
project the sensation to the exterior, to the stimulating body. If
the skin is touched by a hot or cold solid object we speak of the
object as being hot or cold. If, however, the same nerves are
stimulated by warm gases or even liquids under conditions that
do not involve the pressure sense we refer the change to ourselves, —
we are hot or cold, as the case may be. So also when the skin is
heated by the blood the resulting sensation is projected to the
skin. It would seem that the habit of projection is acquired by
experience, and that those senses whose organs are habitually
affected by objects from without we learn to project to the object
giving rise to the stimulus.

The Doctrine of Specific Nerve Energies. — The term specific
nerve energy we owe to Johannes Miiller (1801-1858). The term
is in some respects unfortunate, as at present in the physical sci-
ences the word energy is used to designate certain specific properties
of matter. The phrase specific nerve energy in physiology, however,
is intended to designate the fact that each sensory unit arouses or
mediates its own specific quality of sensation, the specific energy of
the optic apparatus being visual sensations, of the auditory apparatus
sound sensations, etc., and each sensory nerve or apparatus can
give no other than its own quality of sensation. Whether this
specificity in the reaction of each sensory nerve is due to some pecu-
liarity in the nerve itself or its peripheral end-organ, or to a pecu-
liarity of the part of the brain in which it terminates Miiller left
an open question, although he called attention to the fact that
the central ending is capable of giving its specific effect in con-

CLASSIFICATION OF THE SENSES. 255

sciousness independently of the conducting nerve fibers. With
regard to this latter question the opinions of physiologists still
differ. Most physiologists, perhaps, adopt the view that the
specific reaction in consciousness is due to the central ending, — •
that, in other words, the different sensory parts of the cortex
give different kinds or qualities of consciousness, while the sensory
nerve fibers are simply conductors of nerve impulses, which,
however much they may differ in intensity, are qualitatively
the same in all nerve fibers*. According to this view, it would
result, as du Bois-Reymond expressed it, that, if the auditory
nerve fibers were attached to the visual center and the optic
fibers to the auditory center, we would see the thunder and hear
the lightning. Each typical sense-organ from this standpoint
consists of three essential parts: the central ending, which deter-
mines the quality of the sensation; the peripheral end-organ,
retina, cochlea, etc., which determines whether or not any given
form of stimulus shall be effective and which in most cases is con-
structed so as to be responsive to a special form of stimulus desig-
nated as its adequate stimulus; and of connecting neurons whose
only function is to conduct the nerve impulses originating in the
end-organ. The fact, therefore, that the light waves can stimulate
the rods and cones of the retina, but are an inadequate stimulus-
probably to the hair cells of the cochlea or the taste buds of the
tongue, is due to a peculiarity in structure of the rods and cones;
but the fact that the impulses conducted by the optic fibers arouse
a peculiar modality of sensation is not due to any peculiarity in
structure in these fibers or in the rods and cones, but to a charac-
teristic structure of the optic centers. The positive experimental
evidence for the correctness of this view is not conclusive, but, on
the whole, is impressive. Such facts as the following may be noted:

1. When sensory nerve fibers are stimulated otherwise than
through their end-organs each reacts, if it reacts at all, according
to its specific energy, — that is, it produces its own quality of sensa-
tion. When the optic nerve is cut, for instance, the mechanical
stimulus causes a flash of light ; when the chorda tympani is stimu-
lated in the tympanic cavity by mechanical, electrical, or chemical
stimuli sensations of taste are aroused.

2. Mechanical pressure upon the peripheral nerves distributed to
the skin may cause a loss of some of the cutaneous senses in certain
areas of the skin with a retention of others. Thus the senses of
pressure and temperature may be lost and that of pain retained,
or pain may be lost and pressure retained. Such facts agree with
the view that each sense has its own set of nerve fibers ; those that
mediate pain can not by a mere modification of the stimulus give
also a sense of pressure.

3. The only objective manifestation of a nerve impulse that we

256 THE SPECIAL SENSES.

can study in the nerve itself is the electrical change that accom-
panies it or that perhaps constitutes its essence. This electrical
change is qualitatively the same in -all kinds of nerve fibers, and this
fact agrees with the view that the nerve impulse is qualitatively the
same in all fibers.

So far as the sensory nerve fibers are concerned, the chief ob-
jection to this view of the doctrine of specific nerve energies is
found perhaps in the difficulty or impossibility of applying it to
the explanation of color vision. According to the strict interpreta-
tion of the view, each fundamental color sense, being distinct in
quality, should be mediated by its own set of nerve fibers. When
Helmholtz first formulated his theory of color vision he spoke,
therefore, of three kinds of nerve fibers, — the red, the green, and
the violet, — each when stimulated alone giving its own specific
sensation and not capable of giving any other. The facts accumu-
lated regarding color vision, however, seem to show that this view
will not hold. One and the same cone, with its connecting fiber,
may give rise to any or all of the primary color sensations, and,
unless we choose to further subdivide the nerve unit and assume
that the separate nerve fibrils of which the axis cylinder is composed
constitute the separate conductors for the primary sense qualities,
it would seem to be impossible to apply the doctrine of specific
energies to this case. Not too much weight should be given per-
haps to this objection. For it must be remembered that all of our
present theories of color vision are unsatisfactory, and possibly
when we attain to the right point of view the facts may not be
so difficult to interpret in terms of this theory of specific energies.

The alternative view proposed in place of the doctrine of
specific nerve energies assumes that the nerve impulses may
vary in quality as well as in intensity, and that therefore one and
the same nerve fiber may arouse different qualities of sensation and
have different end effects according to the character of the impulse
conveyed. This point of view is not capable of much discussion,
since there are no positive facts that support it. It is logically
satisfactory in meeting the cases in which the former view seems
to be unsatisfactory. It is difficult, however, in our ignorance of
the nature of the nerve impulse to imagine in what respects it may
possibly differ in character.

The Weber-Fechner (Psychophysical) Law. — One difficulty
that has been encountered in the physiological study of sensory
nerves is that the end reaction cannot be measured with exactness.
With efferent nerves the end reaction is a contraction or secretion
that can be estimated quantitatively in terms of our physical and
chemical units of measurement. But the end reaction of a sensory
nerve is a state of consciousness for which we have no standard of

CLASSIFICATION OF THE SENSES.

257

measurement. Weber, in studying the relation between the
strength of the stimulus and the amount of the resulting sensation,
availed himself of the method of the least detectible change in sen-
sation ; that is, he determined the increase in stimulus at different
levels necessary to cause a just perceptible increase in the sensation.
By means of this method he arrived at the significant result that
the increase in stimulus necessary to cause this change is, within
physiological limits, a definite fractional increment of the acting
stimulus. If, for instance^- with a weight of 30 gms. upon
the finger it requires an increment of -fa — that is, one additional
gram — to make a just perceptible difference in the pressure sensa-

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Fig. 111. — Curve to indicate the Weber-Fechner law of a logarithmical relation be-
tween excitation and sensation. — (From Waller.') The excitations are indicated along the
abscissas, the sensations along the ordinates. The increase in sensation is represented as tak-
ing place in equal steps, "the minimal perceptible difference," while the corresponding
excitations require an increasing increment of i at each step, namely 1, 1.33, 1.77, 2.37,
etc. That is, for equal increments of sensation increasing increments of stimulation are
necessary.

tlon, then, with a weight of 60 gms. upon the finger the addition
of another gram would not be perceived ; it would require again an
increment of -^ — that is, 2 gms. — to make a just perceptible dif-
ference in sensation. This relationship is known as Weber's law.
While its exactness has often been disputed, it seems to be generally
admitted that for a median range of stimulation the law expresses
the approximate relation between the two variables considered.
Fechner attempted to give this law a more quantitative and ex-
tensive application by assuming that just perceptible differences
in sensation represent actually equal amounts of sensation. Ac-
cepting this assumption, we can express the relationship between
stimulus and sensation as determined by Weber's experiments by

17

258 THE SPECIAL SENSES.

saying that for the sensation to increase by equal amounts, — that is,
by arithmetical progression, — the stimulus must vary according
to a certain factor, — that is, by geometrical progression. The
sensation may be regarded as a geometrical function of the
stimulus. If the relation between stimulus and sensation is repre-
sented as a curve in which the ordinates express the sensation in-
creasing by equal amounts, and the abscissas the corresponding
stimuli increasing at each interval by J, a result is obtained such as
is represented in the accompanying figure (Fig. 111). A curve of
this kind is a logarithmical curve, and Fechner expressed the rela-
tionship between stimulus and sensation in what has been called the
psychophysical law, — namely, that the sensation varies as the
logarithm of the stimulus. From the physiological standpoint it is
important to bear in mind, as has been emphasized by Waller,* that
several steps intervene between the action of the external stimulus
and the production of the conscious sensation. The external stim-
ulus acts first on the end-organ, this in turn upon the sensory nerve
fiber, producing a nerve impulse which finally in the brain gives the
conscious reaction. It is a question, therefore, whether the logarith-
mical relation of the stimulus holds between it and the reaction of the
end-organ or between the internal stimulus — that is, the sensory
nerve impulse — and the psychical reaction. This author has given
some facts obtained by recording the action current in the optic
nerve, the retina being stimulated by known intensities of light,
which indicate that the relation observed is between the external
stimulus and the internal stimulus, — that is, the sensory nerve
impulse.

* Waller, "Brain," 201, 1895.

CHAPTER XV.
CUTANEOUS AND INTERNAL SENSATIONS.

According to the older views, the sensory nerves of the skin give
sensations of touch. Modern physiology has shown, however, that
these nerves mediate at least four different qualities of sensation, —
namely, pressure, warmth, cold, and pain. Our so-called touch
sensations are usually compound, consisting of a pressure and a
temperature component and also very frequently an element of
muscle sense when muscular efforts are involved, as, for instance, hi
measuring weights or resistances. The four sensory qualities enu-
merated constitute the cutaneous senses, and they are present, or,
to speak more accurately, the nerves through which these senses are
mediated are present not only over the general cutaneous surface,
but also in those membranes — such as the mucous membrane of
the mouth and the rectum (stomodeum and proctodeum) — which
embryologically are formed from the epiblast. The surfaces in the
interior of the body, on the contrary, — such as the membranes
of the alimentary canal, muscles, fasciae, etc., — have only
nerves of pain, but no sense of touch or temperature. Of these
cutaneous senses, three — pressure, warmth, and cold — may be
grouped with the exterior senses, the sensations being projected to
the exterior of the body, into the substance causing the stimulation;
although, as was mentioned above, the temperature sensations
under conditions — ^fever, vascular dilatation, etc. — may be pro-
jected to parts of the skin itself and be felt as changes in ourselves.
The temperature sensations are, in fact, projected to the exterior
whenever they are combined with pressure sensations, the latter
serving, as it were, as the dominant sense. The pain sense, on the
other hand, belongs to the group of interior senses, the sensations
being always projected into our own body and being felt as changes
in ourselves. In the matter of the classification of the cutaneous
senses and, indeed, the body senses in general a new point of view
has been suggested by Head and Rivers.* These authors made a
careful study of the loss of sensations after division of the cutaneous
nerves, and of the subsequent gradual and separate return of these
sensations following upon suture of the divided ends. They
find that in skin areas made completely anesthetic there is present
*Head and Rivers, "Brain," 1905, 99.
259

260 THE SPECIAL SENSES.

a deep or subcutaneous sensibility to pressure and movements,
a sensibility which must be mediated through sensory fibers
contained in the nerves to the muscles. In the skin itself there
are present two kinds of sensory fibers. One variety conveys
sensations of pain and of extreme changes in temperature, but
the sensations are imperfectly localized. This kind of sensation
is found in the viscera also, and it may be considered from the
functional standpoint as a defensive agency toward pathological
changes in the tissues; it is designated as protopathic sensibility.
The second group of fibers responds to stimulations by light
pressures and small differences in temperature. These fibers
regenerate after lesions much more slowly than the protopathic
variety, and since the sensations mediated by them are localized
very exactly they furnish us the means for making fine discrim-
inations of touch and temperature. For this reason they are
described as an epicritic system and the corresponding sensations
are designated as epicritic sensibility. This system of fibers is
not found in the other organs, and it constitutes, therefore, the
special characteristic of the skin area.

The Punctiform Distribution of the Cutaneous Senses.—
A most interesting feet in regard to the cutaneous senses is that
they are not distributed uniformly over the whole skin, but are
present in discrete points or spots. This fact was first clearly
established by Blix,* although it was discovered independently
by Goldscheider and in this country by Donaldson. These ob-
servers paid attention chiefly to the warm and cold spots. The
existence of these spots may be demonstrated easily by anyone
upon himself by moving a metallic point gently over the skin.
If the point has a temperature below that of the skin it will be
noticed that at certain spots it arouses simply a feeling of contact
or pressure, while at other spots it gives a distinct . sensation of
coldness. If, on the other hand, the point is warmer than the
skin it will at certain spots give a sensation of warmth. On mark-
ing the cold and warm spots thus obtained it is found that they
occupy different positions on the skin. Elaborate charts have
been made of the warm and cold spots on different regions
of the skin, the apparatus usually employed being a metal
tube through which water of any desired temperature may be
circulated. The temperature of the skin, whatever it may be,
forms the zero line; any object of a higher temperature stimulates
only the warm spots, while one of a lower temperature acts upon
the cold spots. The pressure sense and the pain sense are also
distributed in a punctiform manner; they have been studied most

* Blix, "Zeitschrift f. Biologic," 20, 141, 1884; Donaldson, "Mind," 39
1, 1885. See also Goldscheider, "Archiv f. Physiologic," 1885, suppl. volume

CUTANEOUS AND INTERNAL SENSATIONS.

261

carefully by von Frey.* To determine the location of the pressure
points he used fine hairs of different diameters fastened to a wooden
handle. The cross-areas of these hairs are determined by measure-
ments under the microscope, and the pressure exerted by each is
measured by pressing it upon the scale pan of a balance. The
quotient of the pressure exerted divided by the cross-area of the

hair in square millimeters, - —2, reduces the pressure to a uniform

Fig. 112. — Representation of the distribution of cold and warm spots on the volar
surface of forearm in a space 2 cms. by 4 cms. The red dots represent the cold spots as
tested at a temperature of 10° C. The black dots represent the warm spots as tested at a
temperature of 41° to 48° C.

unit of area. For the pain points fine needles may be employed
or stiff hairs similar to those used for the pressure points. From
the experiments made there seems to be no doubt that each of
the four cutaneous senses has its own spots of distribution in the
skin, those for pain being most numerous and those for warmth
the least numerous. There is some reason for believing also that
the nerve endings mediating the pain sense lie most superficially
in the skin and those for the warm sense the deepest.

* Von Frey, " Konigl. Sachsischen Gesellschaft der Wissenchaften. Math.-
phys. Klasse," 1894-95-96.

262 THE SPECIAL SENSES.

Specific Nerve Energies of the Cutaneous Nerves. — Many
attempts have been made to determine whether the doctrine of
specific nerve energies applies to these cutaneous senses; that is,
whether each sense has its own nerve fibers capable of giving only its
own quality of sensation. The evidence, on the whole, is favorable
to this view. According to some observers, electrical or mechanical
stimulation of the different points calls forth for each its character-
istic reaction. Donaldson has found that cocain applied to the
eye or throat destroys the senses of pain and pressure, but leaves
those of heat and cold, which again supports the view of separate
fibers for each sense. In addition there are a number of interesting
pathological cases which point in the same direction. In some
lesions of the cord — syringomyelia, for instance — the senses in the
skin of the parts below are dissociated, — that is, there may be loss
of pain and temperature in a certain area with a retention of the
pressure sense, — a fact which indicates that these senses have
separate paths and therefore separate nerve fibers. Still more
interesting cases of dissociation are reported as the result of the
compression of peripheral nerve trunks. Thus, Barker* describes
his own case, in which, as the result of the pressure of a cervical
rib upon some of the cords of the brachial plexus, there was a region
in the arm lacking in the pressure and temperature senses, but retain-
ing the sense of pain. He quotes other cases in which the reverse
dissociation occurred, pressure sense alone remaining. The simplest
explanation of these facts is the view that each pressure, pain,
warm, and cold spot is supplied by its own nerve fiber, and that
each, when stimulated, reacts, if it reacts at all, only with its own
peculiar quality of sensation. According to this view, artificial
stimulation, if properly controlled, of the trunks of the nerves
supplying the skin should be capable of bringing out these different
sense qualities. Experiments made with this point in view have
not, however, been very successful. Mechanical or electrical stimu-
lation of the ulnar nerve, for instance, gives usually only pain sensa-
tions, although if the stimulus is feeble contact sensations are
aroused. The method, however, is probably at fault. In the case
of amputated fingers or limbs a more decisive result is obtained.
As is well known, individuals after such operations may for many
years have sensations of their lost fingers or limbs. In such cases
the pressure in the stump of the wound acting upon the central
ends of the sensory fibers arouses sensations which are projected
in the usual way, and give the feeling that would be experienced
if the lost parts were still there and were stimulated in the normal
manner.

* Barker, "Journal of Experimental Medicine/' 1, 348, 1896.

CUTANEOUS AND INTERNAL SENSATIONS. 263

The Temperature Senses. — The main facts regarding the
distribution of heat and cold spots have been determined. In gen-
eral, the cold spots are more numerous than the warm spots, and
react more promptly to their adequate stimulus. The cold spots
or the cold sense may be present in places devoid of the sense of
warmth; thus, it is said that the glans penis possesses only the
cold sense. The threshold stimulus varies also in different parts
of the skin, the tip of the tongue requiring the smallest stimulus
to arouse a sensation, and the eyelids, forehead, cheeks, lips, limbs,
and trunk following in the order named. According to Goldscheider,
the spots on most portions of the skin form chains that have a some-
what radiate arrangement with reference to the hair follicles. The
temperature points possess each its adequate stimulus, that for the
cold spot being temperatures lower than the skin or of the terminal
organ of the cold nerves, that for the heat spots temperatures higher
than their own. Apparently, therefore, one end-organ is excited
by a diminution in the atomic movements of its organ, and the
other by an increase. Nothing is known, however, of the exact
nature of the stimulating process. From the standpoint of specific
nerve energies it is most interesting to find that these points, particu-
larly the cold spots, may be stimulated by other than their adequate
stimuli. Mechanical and electrical stimulation has in the hands of
several observers been efficient in causing a sensation of cold upon
a cold spot and of heat upon a warm spot. Some chemical stimuli
are also effective. Menthol applied to the skin gives a cold sensa-
tion, while, on the other hand, if the arm be plunged into a jar of
carbon-dioxid gas a distinct warm sensation will be experienced.
A curious effect of this kind is what is known as the paradoxical cold
reaction. It is produced by applying a very warm object, with a
temperature of 40° to 60° C., to a cold spot. In many cases this
spot is stimulated and a cold sensation is felt. The same result
may be felt at the instant of entering a hot bath. Many efforts
have been made to determine whether there is a specific kind of
end-organ for each of these senses. Numerous observers have
cut out the skin from cold or hot spots and examined the removed
part carefully by histological methods. The general result has been
that no distinctive end-organs have been found. Von Frey, how-
ever, believes that, although the heat spots are supplied simply
by a terminal end plexus, the cold spots in some places at least have
as a special end-organ the end-bulbs of Krause. This conclusion is
based upon the fact that these end-bulbs are found in places, such
as the glans penis and conjunctiva, where the cold sense is espe-
cially prominent or exclusively present.

The Sense of Pressure. — The pressure points are smaller and
more numerous than the cold or warm spots. Von Frey has shown

264 THE SPECIAL SENSES.

that in those portions of the body that are supplied with hairs
the pressure points lie over the hair follicles. The pressure nerve
fibers, in fact, terminate in a ring surrounding the hair follicle,
this form of termination serving as an end-organ. On account of
their position they are stimulated by any pressure exerted upon
the hair. The hair, indeed, acts like a lever and transmits any pres-
sure applied to it with increased intensity, acting, therefore, as re-
gards the pressure organ somewhat like the ear-bones in the case
of the endings of the auditory nerve. In parts of the body not
furnished with hairs the tactile or Meissner corpuscles are found
and these structures doubtless function as pressure end-organs.
They are particularly abundant in the parts of the hand and feet in
which a delicate sense of pressure is present in spite of a much thick-
ened epidermis. It has been estimated that for the entire surface
of the body, excluding the head region, there are about 500,000
of these pressure points. These points are close together on those
parts, such as the tongue and fingers, which have a delicate tactile
sense and more widely scattered where the sense is less developed.
The Threshold Stimulus and the Localizing Power. — The
delicacy of the sense of pressure may be measured by determining
the minimal pressure necessary to arouse a sensation, — that is,
the threshold stimulus, — or it may be estimated in terms of the
power of discriminating two contiguous stimuli, — that is, the mini-
mal distance that two points must be apart in order for the sensa-
tions to be recognized as distinct. The two methods of measure-
ment do not coincide. As determined by the threshold stimulus,
the greatest delicacy is exhibited by the skin of the face, the fore-
head, and temples. According to the older methods of measure-
ment, the forehead will perceive a pressure of 2 mgs., while the skin
of the tips of the fingers needs a pressure of from 5 to 15 mgs. to
arouse a perceptible sensation. The back of the hand or the arm
is more sensitive from this standpoint than the tips of the fingers.
When measured by the power of discriminating two points —
that is, the localizing sense — the tips of the fingers are far more
sensitive than the skin of the face or of the arm. This latter prop-
erty, in fact, stands in relation to the closeness of the pressure
points to one another. The localizing sense may be determined
by Weber's method of using a pair of compasses with blunt points.
For any given area of the skin the power of discrimination or local-
ization is expressed in terms of the number of millimeters between
the two points at which they are just distinguished as two separate
sensations when applied simultaneously to the skin. Instruments
made for this purpose are designated as esthesiometers. They
carry two points the distance of which apart can be readily adjusted
and read off on a scale. The most satisfactory form of esthesiom-

CUTANEOUS AND INTERNAL SENSATIONS. 265

eter is that devised by von Frey. The two points in this case are
made by long, rather stiff hairs whose pressure can be made quite
uniform. According to the older measurements, the localizing
sense of different parts of the skin varies greatly, as is shown by the
accompanying table:

Tip of the tongue 1.1 mms.

Tip of finger, palmar surface 2.3

Second phalanx finger, palmar surface 4.5

First phalanx finger, palmar surface 5.5

Third phalanx finger, dorsal surface 6.8

Middle of palm 8to9

Second phalanx finger, dorsal surface 11.3

Forehead 22.6

Back of the hand 31.6

Forearm 40.6

Sternum 45

Along the spine 54

Middle of neck or back 67.7

The tips of the tongue and the fingers are, therefore, the most
delicate surfaces, and that the tongue surpasses the fingers in this
respect is easily within the experience of everyone who will recall
the ease with which small objects between the teeth are detected by
the tongue as compared with the fingers. From the above data it
is evident also that the whole skin may be imagined as composed
of a mosaic of areas of different sizes, the sensory circles of Weber,
in each of which two or more simultaneous stimulations of the pres-
sure nerves give only one pressure sensation. The size of these
areas, particularly where they are large, may be reduced by practice,
as is shown by the increased tactile sensibility of the blind. The
fact that we can recognize two simultaneous pressure stimuli of the
skin as two distinct sensations implies that the two sensations have
some recognizable difference in consciousness. This difference is
spoken of as the local sign. We may believe that every sensitive
point upon the skin has its own distinctive local sign or quality, and
that by experience we have learned to project each local sign more
or less accurately to its proper place on the skin surface. Two points
on this surface that are a great distance apart are easily recognized
as different ; but as we bring the points closer together the difference
becomes less marked and finally disappears when the distance
corresponds to the area of the sensory circle for the part of the skin
investigated, for instance, 1 mm. for the tongue, 22 mms. for the
forehead, etc. The ultimate limit of the power of discrimination
was assumed by Weber to depend upon the area of distribution of
a single nerve fiber. Assuming that each nerve fiber at its termi-
nation spreads over a certain skin area, it was suggested that the
size of this area forms a limit to the power of discrimination,
since two stimuli within it would affect a single fiber and therefore
would give a single sensation.

266 THE SPECIAL SENSES.

This view, however, has not been supposed to accord with the
facts even when the additional supposition was made that the local
signs of two adjacent fibers may not be distinct enough for us to
recognize them as separate and that practically there must be a
number of intervening unstimulated areas, the number varying
according to the sensitiveness of the area. Von Frey has, however,
given a new method of testing the localizing sense of the skin, the
results of which seem to accord with this anatomical explanation.
If instead of applying the two points simultaneously they are
applied in succession, at an interval of one second, the individual can
distinguish the difference when two neighboring pressure points are
stimulated. Each pressure point in the skin, therefore, has a local
sign, which enables us to distinguish it from all others, and by this
method the ultimate sensory circles on the skin become much
smaller than when measured by the usual method of Weber. The
center of each is a pressure point and the area is determined by the
distance from this center at which an isolated stimulation of this
point can be obtained. It seems probable, moreover, that each of
these pressure points is connected to the brain by a separate nerve
path, possibly a single fiber, and that this anatomical arrangement
determines the limitation of the localizing sense for different regions
of the skin.

The Pain Sense. — Pain is probably the sense that is most widely
distributed in the body. It is present throughout the skin, and
under certain conditions may be aroused by stimulation of sensory
nerves in the various visceral organs, and indeed in all of the mem-
branes of the body. Our knowledge of the physiological properties
of the end-organs and nerves mediating this sense is chiefly limited
to the skin, and for cutaneous pain at least the evidence, as stated
above, is very strongly in favor of the view that there exists a special
set of fibers which have a specific energy for pain. All recent ob-
servers agree that the pain sense has a punctiform distribution in
the skin, the pain points being even more numerous than the pres-
sure points. The threshold stimulus of these points in various
regions may be determined by von Frey's stimulating hairs, and
experiments of this kind show, as we should expect, that it varies
greatly. The cornea, for instance, gives sensations of pain with
much weaker stimuli than in the case of the finger tips. In general,
however, the threshold stimulus is much higher for the pain than
for the pressure points. Histological examination of the pain points
indicates that there is no special end-organ, the stimulus taking
effect upon the free endings of the nerve fibers. Any of the usual
forms of artificial nerve stimuli may affect these endings if of suf-
ficient intensity, and, as is well known, stimuli applied to sensory

CUTANEOUS AND INTERNAL SENSATIONS. 267

nerve trunks affect these fibers with especial ease. A temperature
of 50° to 70° C. applied to an afferent nerve will cause violent pain
sensations, but has no effect upon the motor nerve fibers in the same
trunk. Mechanical stimulation gives usually only pain sensations,
and the results of inflammatory changes, as in neuritis or neuralgia,
are equally marked.

Localization or Projection of Pain Sensations. — Under normal
conditions cutaneous pains are projected with accuracy to the point
stimulated, and it is possible' that this result is due in part at least
to the training acquired in connection with concomitant (epicritic)
pressure sensations, the latter acting as a guide or aid in the pro-
jection. Thus in the cases referred to above, in which a portion
" of the skin had lost the sense of pressure and temperature, but
retained that of pain, it was found that the localization was very
incomplete. Pain arising in the internal organs, on the contrary,
is located very inaccurately. The pain from a severe toothache,
for example, may be projected quite diffusely to the side of the face.
A very interesting fact in this connection is that such pains are
often referred to points on the skin and may be accompanied by
skin areas of tenderness. Pains of this kind that are misreferred
to the surface of the body are designated as reflected pains. It has
been shown by Head * and others that the different visceral organs
have, in this respect, a more or less definite relation to certain
areas of the skin. Pains arising from stimuli acting upon the
intestines are located in the skin of the back, loins, and abdomen
in the area supplied by the ninth, tenth, and eleventh dorsal
spinal nerves; pains from irritations in the stomach are located
in the skin over the ensiform cartilage; those from the heart in the
scapular region, and so on. The explanation offered for this
misref erence is that the pain is referred to the skin region that is
supplied from the spinal segment from which the organ in question
receives its sensory fibers, the misref erence being due to a diffusion
in the nerve centers. As Head expresses it, "when a painful
stimulus is applied to a part of low sensibility in close central
connection with a part of much greater sensibility the pain pro-
duced is felt in the part of higher sensibility rather than in the part
of lower sensibility to which the stimulus was actually applied/'
It is interesting that affections of the serous cavities — e. g., the
peritoneum — do not cause reflected pains or cutaneous tenderness
as in the case of the viscera. Another notable fact in this connec-
tion is the occurrence of the condition known as allochiria. When
from any cause one or other of the cutaneous senses is depressed
in a given area stimulation in this region may give sensations
which are referred to the symmetrical area on the other side of
*Head, "Brain," 16, 1, 1893, and 24, 345, 1901.

268 THE SPECIAL SENSES.

the body, or, if this also is involved, it may be referred to the area
next above or below in the spinal order. The above law, according
to which projection is made to the area of high sensibility most
closely connected with the area of low sensibility, seems to hold
in this case also.

The Muscle Sense. — The existence of a special set of sensory
nerve fibers distributed to the muscles was clearly recognized by
some of the older physiologists. Charles Bell,* for example, says:
"Between the brain and the muscles there is a circle of nerves; one
nerve conveys the influence from the brain to the muscle; another
gives the sense of the condition of the muscle to the brain." The
conclusive proof of the existence of such fibers, however, has only
been furnished within recent years. It has been demonstrated
that there are special sensory endings in the muscles, the so-called
muscle spindles, and in the attached tendons, the tendon spindles
or tendon organs of Golgi. The muscle spindles are found most
frequently in the neighborhood of the tendons, at tendinous inter-
sections or under aponeuroses. Sherringtonf has shown that the
nerve fibers in them do not degenerate after section of the anterior
roots of the corresponding spinal nerves and are therefore derived
from the posterior roots. In the muscles of the limbs he estimates
that from one-half to one-third of the fibers in the muscular nerve
branches are sensory, and that most of these sensory fibers end in
the muscle spindles. On the physiological and clinical side facts of
various kinds have accumulated that make clear the existence of
this group of sensory fibers and emphasize their essential importance
in the co-ordination of our muscular movements. It has been shown
that stimulation of the nerves distributed to the muscles or mechani-
cal stimulation of the muscles themselves causes a depressor effect
upon blood-pressure, thus demonstrating the presence of afferent
fibers in the muscles. As described in the section upon the central
nervous system, the numerous experiments upon the effect of section
of the posterior and lateral columns of the cord and observations
upon the results of pathological lesions of the posterior columns
(tabes dorsalis) give results which are interpreted to mean that fibers
of muscular sensibility form the most important group in the
posterior columns and constitute, as well, perhaps, the long, ascend-
ing fibers in the tracts of Flechsig and Gowers in the lateral col-
umns. It is believed, therefore, that our so-called voluntary muscles
are richly supplied with afferent fibers and that the impulses carried
by these fibers to the brain are necessary for the proper contraction
of the muscles and particularly for the adequate combination of
the contractions of groups of muscles in the co-ordinated movements

* Bell, "The Nervous System of the Human Body," third edition, Lon-
don, 1844, p. 200.

t Sherrington, " Journal of Physiology," 17, 237, 1894.

CUTANEOUS AND INTERNAL SENSATIONS. 269

of equilibrium. Indeed, section of the posterior roots of the spinal
nerves supplying a given region is followed by a loss of control
of the muscles in this region hardly less complete than the paralysis
produced by direct section of the anterior roots; the muscles not
only lose their tonicity in consequence of the dropping out of the
reflex sensory stimuli from the skin and muscles of the region, but
they are apparently withdrawn from voluntary control in spite of
the maintenance of their normal motor connections. Within the
central nervous system the fibers of muscle sense end in part in
the cerebellum and in part ''pass forward, by way of the median
fillet, to end in the cerebrum. In the cerebrum they end in the
cortex of the parietal lobe in the region of the posterior central
convolution. There is reason to believe that this cortical sense
area of the muscle sense is connected by association fibers with
the motor areas lying anterior to the fissure of Rolando, and we
have thus a reflex arc, — or, as Bell expressed it, a circle of nerves
between the muscles and the brain. It is probable that a similar
arc or circle is formed by the connections through the cerebellum,
and still a third one of a lower order by the connections in the
spinal cord. In the higher animals the impulses received in the
cerebellum through the fibers of muscle sense, in connection with
those received from the semicircular canals and vestibular sacs
of the ear, furnish the sensory basis for the cerebellar control of
muscular movements, particularly of the synergetic combination
necessary in locomotion. Through the circle or arc in the cortex
of the cerebrum it may be supposed that our characteristic volun-
tary movements are effected, and it may be doubted whether a
so-called voluntary contraction can be made when this circle is
broken on the sensory side. Whether or not this latter suggestion
is true it seems to be beyond doubt that adequately controlled
voluntary movements depend for their adaptation upon the
inflow of sensory impulses along the fibers of muscle sense. We
have a certain consciousness of the condition of our muscles at
all times, and if we were deprived of this knowledge we should be
unable to control them properly, perhaps unable to use them
voluntarily.

The Quality of the Muscle Sense. — Our conscious realization
of muscular sensibility is not distinct. Under ordinary conditions
the untrained person is unaware of the presence of such a sense;
but physiological analysis enables us to realize its existence. What
we designate as the feeling of resistance and of weight depends
usually partly upon the pressure sense, but largely upon the muscle
sense. As Head has pointed out (p. 259), we still possess a certain
sensibility to pressure, even after our cutaneous nerves are com-
pletely anesthetized, — so that a pressure upon the skin is recognized

270 THE SPECIAL SENSES.

and located. This deep sensibility to touch or pressure must
be mediated through the sensory nerves of the muscles, and it
constitutes one form of the conscious reaction of the nerve fibers
of muscle sense. In estimating the difference in weight between
two bodies our judgment is much more exact if the bodies are lifted
by muscular effort, as is our custom, than if they are simply allowed
to press upon the skin; and in all calculations of resistance to effort
it is the amount of muscular contraction exerted that furnishes us
with the chief sensory basis for our judgments. So also in the judg-
ments of distance based upon visual impressions it is believed that
for close objects, particularly, the muscle sense connected with the
extrinsic and intrinsic musculature of the eyeballs plays a funda-
mental part. Doubtless also this sense takes an essential part
in the primitive formation of our conceptions of space, since it
may be assumed that the continual movements of the extremities
in connection with our visual and tactile impressions furnish essen-
tial data upon which we build our perceptions of distance and
size, our judgments of spatial relations. As is explained in the
chapter on the physiology of the ear, the sensations from the semi-
circular canals and vestibular sacs co-operate in giving data for
these fundamental conceptions, and it is not possible for us to
disentangle the parts taken by these senses separately in building
up our knowledge of the external world. The muscle sense is
reckoned usually among the internal (or common) senses, — that is,
those which are projected to the interior of the body and are felt
as changes in ourselves. A little reflection, however, demonstrates
that, like the temperature sense, it may under conditions be pro-
jected to the exterior and be interpreted as a quality of external
objects. Weight and resistance, for example, are attributed to
the objects giving rise to the feeling of muscular effort, and it may
be said, perhaps, that, as in the case of temperature, the feeling
is projected more or less clearly to the exterior when it is combined
with the pressure sense which acts as the predominating or guiding
factor in the projection. In excessive muscular effort the quality
of the muscle sensation undergoes a change and becomes strong
enough to make a distinct and peculiar impression upon our con-
sciousness. We designate this feeling as fatigue, but there is no
question apparently that this sensation is mediated through the
same nerve fibers that ordinarily give us our muscular sensibility.

Sensations of Hunger and Thirst. — Hunger and thirst are
typical interior (or common) sensations. We feel them as changes
in ourselves. Neither sense has been the direct object of much
experimental investigation, and what knowledge we possess is there-
fore derived largely from accidental or pathological sources. Hunger
in its mild form is designated as appetite. It occurs normally at a

CUTANEOUS AND INTERNAL SENSATIONS. 271

certain interval after meals, and is referred or projected more or
less accurately to the stomach. It is not known whether this sense
is mediated by a special set of sensory fibers distributed to the
mucous membrane of the stomach, or whether, perhaps, it
may be a quality of the sensory impressions from the muscular
coat. The former view seems more probable, especially when it is
remembered that loss of appetite or anorexia is so frequently an
accompaniment of pathological changes in the membrane of the
stomach. The nervous mechanism through which this sense is me-
diated is of most essential importance and deserves more careful
study at the hands of physiologists and pathologists. Under ordi-
nary conditions of life all of the regulation of the amount and quality
of the food necessary to the proper nutrition of the body and the
maintenance of body equilibrium is effected through this sense. Its
striking influence upon the body at large is well illustrated in the case
of animals (pigeons, dogs) deprived of their cerebrum. During the
period of fasting these animals show all the external signs of hunger
and keep in continual, restless movement that seems to imply a con-
stantly acting sensory stimulus. We may assume that appetite
has its sensory origin, its peripheral nerve endings in the stomach,
and that these endings are excited in some unknown way when the
stomach is empty. This gastric hunger, as it might be called,
disappears, or the appetite is appeased when the stomach is filled.
This fact in itself would indicate that the stimulus has a local
origin in the stomach, and is not dependent upon any general
change in the nutritive condition of the body. The appetite is
satisfied by filling the stomach with food long before this food
is actually absorbed and distributed to the tissues. The inges-
tion of totally indigestible material would probably have temporarily
a similar result. The exact nature of the conditions that lead
to or cause a stimulation of the sensory nerves of appetite in the
stomach remains unexplained. The well-known fact that muscular
exercise and low temperatures and particularly a combination of
the two cause a marked augmentation of the appetite would suggest
that the sensory stimulus is influenced by the extent or character
of the oxidations in the muscular tissues, and that, therefore, some
substance may be formed as the result of these oxidations which
affects the sensory nerves of the stomach. The same general sug-
gestion is contained in the fact that diabetics exhibit an abnormal
appetite in spite of abundant feeding. In these individuals the
carbohydrate food escapes oxidation more or less completely, and
the metabolism, particularly in the muscles, involves, therefore,
to a greater extent, the oxidation of proteid material, — a fact which
may stand in some relation to the abnormal appetite that is observed.
The complexity of the nervous apparatus that controls the the appe-

272 THE SPECIAL SENSES.

tite is shown also by many facts from the experiences of life and from
the results of laboratory investigations. For example, it is found
that large amounts of gelatin in the diet, although at first accepted
willingly, soon provoke a feeling of dislike and aversion to this
particular foodstuff such as cannot be overcome. An animal will
starve rather than use the gelatin, although all of our direct physio-
logical evidence would indicate that this substance is an efficient
food, playing much the same part as the fats or carbohydrates.
A fact of this kind indicates that the sensory apparatus of the appe-
tite is influenced in some specific way by the metabolism of this
particular material. So also the feeling of satiety and aversion for
food that follows overfeeding indicates something more than a sim-
ple removal of the sensations of appetite ; it implies an active state,
due possibly to the excitation of sensory fibers of a different char-
acter. With regard to the -effects of prolonged starvation, the
pangs of hunger that are felt at first do not seem to increase in in-
tensity to such an extent as to cause actual suffering. The testi-
mony of the " prof essional fasters," at least, seems to show that, if
water is provided, prolonged deprivation of food is not accompanied
by the intense discomfort or suffering popularly associated with
the idea of complete starvation.

The Sense of Thirst. — Our sensations of thirst are projected
more or less accurately to the pharynx, and the facts that we know
would seem to indicate that the sensory nerves of this region have
the important function of mediating this sense. The water con-
tents of the body are subject to great changes. Through the lungs,
the skin, and the kidneys water is lost continually in amounts that
vary with the conditions of life. This loss affects the blood directly,
but is doubtless made good, so far as this tissue is concerned, by a
call upon the great mass of water contained in the storehouse of the
tissues. To restore the body tissues to their normal equilibrium
in water we ingest large quantities, and the control of this regula-
tion is effected through the sense of thirst. We -know little or
nothing about the nervous apparatus involved; but it may be
assumed that when the water content falls below a certain amount
the nerve fibers in the pharyngeal membrane (fibers of the glosso-
pharyngeal nerve) are stimulated and give us the sensation of
thirst. That we have in this membrane a special end-organ of
thirst is indicated, moreover, by the fact that local drying in this
region, from dry or salty food, or dry and dusty air, produces a
sensation of thirst that may be appeased by moistening the mem-
brane with a small amount of water not in itself sufficient to relieve
a genuine water need of the body. Our normal thirst sensations
might be designated, therefore, as pharyngeal thirst, to indicate
the probable origin of the sensory stimuli. Prolonged deprivation

CUTANEOUS AND INTERNAL SENSATIONS. 273

of water, however, must affect the water content of all the tissues,
and under these conditions sensations are experienced whose quality
is not that of simple thirst alone, but of pain or suffering. All ac-
counts agree that complete deprivation of water for long periods
induces intense discomfort, anguish, and possibly mental troubles,
and we may suppose that under these conditions sensory nerves
are stimulated in many tissues, and that the metabolism in the ner-
vous system in addition is directly affected by the loss of water.
It is interesting to note that/ while in diseases due to a general in-
fection, loss of appetite, anorexia, is a frequent symptom, there is
no corresponding loss of the sense of thirst. Even in hydrophobia
the patient experiences the sensations of thirst, although unable to
drink water.

18

CHAPTER XVI.
SENSATIONS OF TASTE AND SMELL.

The sense of taste is mediated by nerve fibers distributed to
parts of the buccal cavity and particularly to parts of the tongue.
The most sensitive regions are the tip, the borders, and the posterior
portion of the dorsum of the tongue in the region of the circum-
vallate papillae. Taste buds and a sense of taste are described also
for the soft palate, the epiglottis, and even for the larynx. The
sense is not present uniformly over the entire dorsum of the tongue.
On the contrary, it has an irregular, punctiform distribution over
most of this region with the exception of the parts mentioned above.

The Nerves of Taste. — The anterior two-thirds of the tongue
are supplied with sensory fibers from the lingual nerve, a branch
of the inferior maxillary division of the fifth nerve, and the posterior
third from the glossopharyngeal. The taste fibers for these regions,
therefore, are supplied immediately through these nerves. It has
been shown, moreover, that the taste fibers carried in the lingual
are brought to it through the chorda tympani nerve, which arises
from the seventh cranial nerve and joins the lingual soon after
emerging from the tympanic cavity of the ear. There has been
much discussion as to the origin of these taste fibers from the brain.
At first sight it would seem that the fibers for the posterior third
of the tongue must have their origin from the brain in the glosso-
pharyngeal and those for the anterior two-thirds in the sensory
portion of the facial. Many surgeons have reported, however, that
complete extirpation of the Gasserian ganglion of the fifth nerve
is followed by complete loss of taste in the corresponding side of
the tongue, and others have described a loss of taste for the anterior
two-thirds following a similar operation. Some authors have
asserted, therefore, that all the taste fibers originate or rather end
in the sensory nucleus of the fifth, while others believe that the
fibers running in the chorda tympani, at least, take their origin in
the fifth nerve. It is supposed by these authors that the fibers
reach the Gasserian ganglion by a circuitous route, as is indicated
in the diagram given in Fig. 113. Those that run in the lingual
and chorda tympani nerves are assumed to pass to the ganglion
by way of the great superficial petrosal and Vidian nerves and
MeckeFs ganglion, while those that are contained in the glosso-

274

SENSATIONS OF TASTE AND SMELL.

275

pharyngeal reach the same ganglion through the nerve of Jacobson,
the small superficial petrosal, and the otic ganglion. A recent re-
port by Gushing,* of the results of removal of the Gasserian gan-
glion in thirteen cases, throws much doubt upon these views. This
author made careful examinations of the sense of taste, not only
immediately after the operation, but for a long period subsequently.
He states that in no case was there any effect upon the sense of taste
in the posterior third of the tongue. We may believe, therefore, that
the taste fibers of this part ,arise immediately from the ganglion
cells in the petrosal ganglion and enter the brain with the roots of
the nerve to terminate in its sensory nucleus in the medulla.

tyltauin.

Fig. 113. — Schema to show the course of the taste fibers from tongue to brain. —
(Cws/ungr.) The dotted lines represent the course as indicated by Cushing's observations.
The full black lines indicate the paths by which some authors have supposed that these
fibers enter the brain in the trigeminal nerve.

Regarding the anterior two-thirds of the tongue, the lingual region,
it was found that in some cases there was at first a loss of acuity of
taste or even an entire disappearance of the sense, but subsequently
it returned. It would seem, therefore, that the loss of taste de-
scribed after removal of the Gasserian ganglion is an incidental
result the cause of which is not entirely clear. Gushing attributes
it to a postoperative degeneration and swelling in the fibers of the
lingual nerve, which affect the conductivity of the intermingled
fibers of the chorda tympani. Since, however, there is no perma-

* Gushing, " Bulletin of the Johns Hopkins Hospital," 14, 71, 1903. Gives
also the surgical literature.

276

THE SPECIAL SENSES.

nent loss of taste in this region, it follows that the taste fibers do
not pass through the Gasserian ganglion. We may assume, there-
fore, that they originate directly in the nerve cells of the geniculate
ganglion and enter the brain with the fibers of the portio intermedia
of the seventh nerve.

The End-organ of the Taste Fibers. — In the circumvallate
papilla?, in some of the fungiform papilla?, and in certain portions
of the fauces, palate, epiglottis, or even the vocal cords there are
found the organs known as taste buds which are believed to act
as peripheral organs of taste. These curious structures are repre-
sented in Fig. 114. They are oval bodies with an external layer
of tegmental or cortical cells, and they contain in the interior a

number of elongated cells
each of which ends in a hair-
like process which projects
through the central taste
pore of the organ. These
latter cells may be consid-
ered as the true sense cells;
the hair-like process con-
stitutes probably the part
that is stimulated directly
by sapid substances. The
impulse thus aroused is
communicated through the
body of the cell to the
endings of the taste fibers
which terminate around
these cells by terminal
arborizations of the same
general type as in the case
of the hair cells in the
cochlea.

Classification of Taste Sensations. — Our taste sensations
are very numerous, but it has been shown that there are four
primary or fundamental sensations, — namely, sweet, bitter, acid,
and salty, and that all other tastes are combinations of these
primary sensations, or combinations of one or more of them with
sensations of odor or with sensations derived from stimulation of
the so-called nerves of common sensibility in the tongue. Thus,
the taste of pepper may be resolved into a slight odor sensation
and a sensation due to stimulation of the fibers of general sensi-
bility,— that is, it gives no taste sensation proper. The taste of
alum may be considered as a combination of a salty taste with
common sensibilitv. Combinations of sweet and acid tastes, sweet

Fig. 114. — Section through one of the taste
buds of the papilla foliata of the rabbit (from
Quain, after Ranvier), highly magnified: p, Gus-
tatory pore: 8, gustatory cell; r, sustentacular
cell ; m, leucocyte containing granules ; e, super-
ficial epithelial cells; n, nerve fibers.

SENSATIONS OF TASTE AND SMELL. 277

and bitter tastes, etc., form a part of our daily experience, and
in the fused or compound sensation that results from such com-
binations one may usually recognize without difficulty the con-
stituent parts. The seemingly great variety of our taste sensations
is largely due to the fact that we confuse them or combine them
with simultaneous odor sensations. Thus, the flavors in fruits and
the bouquet of wines are due to odor sensations which we designate
ordinarily as tastes, since they are experienced at the time these
objects are ingested. If care is taken to shut off the nasal cavities
during the act of ingestion even imperfectly, as by holding the
nose, the so-called taste disappears in large measure. Very dis-
agreeable tastes are usually, as a matter of fact, due to unpleasant
odor sensations. On the other hand, some volatile substances
which enter the mouth through the nostrils and stimulate the
taste organs are interpreted by us as odors. The odor of chloro-
form, for instance, is largely due to stimulation of the sweet taste
in the tongue.

Distribution and Specific Energy of the Fundamental
Taste Sensations. — Regarding the distribution of the funda-
mental taste sensations over the tongue and palate there seem
to be many individual differences. In general, however, it may
be said that the bitter taste is more developed at the back of
the tongue and the adjacent or posterior regions; at the tip of
the tongue the bitter sense is less marked or in cases may be absent
altogether. On the contrary, in this latter region the sweet taste
is well developed. On this account it may happen that substances
which when first taken into the mouth give a not unpleasant sweet
taste subsequently when swallowed cause disagreeably bitter sen-
sations, like the little book of the evangelist, which in the mouth
was "sweet as honey, and as soon as I had eaten it, my belly was
bitter." Oehrwall * has made an interesting series of experiments
in which he stimulated separately a number of fungiform papilla?
on the surface of the tongue. Each papilla was stimulated sepa-
rately for its fundamental taste senses of sweet, bitter, and acid,
by using drops of solutions of sugar, quinin, and tartaric acid. Of
the 125 papilla? thus examined, 27 gave no reaction at all, although
sensitive to pressure and temperature. In the 98 papilla? that
reacted to the sapid stimulation it was found that 60 gave taste
sensations of all three qualities, 4 gave only sweet' and bitter, 7 only
bitter and acid, 12 only sweet and acid, 12 only acid, and 3 only
sweet. None was found to give only a bitter sensation. These
facts bear directly upon the question of the specific energy of the
taste fibers. It is possible that the four fundamental taste qualities
may be mediated by four different end-organs and four separate
* Oehrwal], "Skandinavisches Archiv f. Physiologic," 2, 1, 1890.

278 THE SPECIAL SENSES.

sets of nerve fibers, each giving, when stimulated, only its own
quality of sensation. On the other hand, it is possible that one and
the same nerve fiber might give different qualities of sensation
according to the nature and mode of action of the sapid substances.
The fact, as shown by OehrwalFs experiments, that there are sensory
spots upon the tongue which will not react to some kinds of sapid
substance, but do react to others, and perhaps only to one particular
kind, speaks strongly in favor of the view that there are different
end-organs and nerve fibers for each fundamental taste. This view
is still further supported by the fact that certain chemically pure sub-
stance ; give different tastes according to the part of the tongue
upon which they are placed. Thus, sodium sulphate (Guyot) may
taste salty upon the tip of the tongue and bitter when placed upon
the posterior part. A better instance still is given by solutions of

a bromin substitution product of saccharin, the chemical name

f
for which is parabrom-benzoic sulphinid: C6H3Br -j

-

I feO 2

When this substance is placed upon the tip of the tongue it gives a
sweet sensation, while upon the posterior region it gives only a bitter
taste together with a sensation of astringency (Howell and Kastle).
Extracts of the leaves of a tropical plant, Gymnema silvestre, applied
to the tongue, destroy the sense of taste for sweet and bitter sub-
stances (Shore), and this fact may be explained most satisfactorily
by assuming that this substance exercises a selective action upon
taste terminals in the tongue, paralyzing those for the bitter
and the sweet substances. Finally, the fact that electrical, me-
chanical, or chemical stimulation of the chorda tympani, where it
passes through the tympanic cavity, may arouse taste sensations is
proof that the taste sensation in general is not due to a peculiar kind
of impulse that can be aroused only by the action of sapid bodies
upon the terminals in the tongue, but, on the contrary, that it is a
specific energy of these fibers, and depends for its quality, there-
fore, upon the specific reaction of the terminations in the brain.

Method of Sapid Stimulation. — In order that sapid substances
may react upon the taste terminals it is necessary, in the first place,
that they shall be in solution. It is impossible to taste with a dry
tongue. We may assume, therefore, that the stimulation consists
essentially in a chemical reaction between the sapid substance and
the terminal of the taste fiber, — for instance, the hair process of
the sense cells in the taste buds, — and the question naturally arises
whether the distinctive reactions corresponding to the separate
taste qualities can be referred to a definite chemical structure in the
sapid bodies. Are there certain chemical groups which possess the
property of reacting specifically with the end-organs? Experience
shows that substances of very different chemical constitution may

SENSATIONS OF TASTE AND SMELL. 279

excite the same taste. Thus, sugar, saccharin, and sugar of lead
(lead acetate) all give a sweet taste, while, on the other hand,
starch (soluble starch), which stands so close in structure to the
sugars, has no effect upon the taste terminals. It is interesting
to remember that the taste nerves may be stimulated by sapid sub-
stances dissolved in the blood as well as when applied to the ex-
terior of the tongue. A sweet taste may be experienced in diabetes
from the sugar in the blood, or a bitter taste in jaundice from the
bile.

The Threshold Stimulus. — The determination of the threshold
stimulus for different sapid substances is made by ascertaining the
minimal concentration of the solution which is capable of arousing
a taste sensation. The delicacy of the sense of taste is influenced,
however, by certain accessory conditions which must be taken into
account. Thus, the temperature of the solution is an important
condition. Very cold or very hot solutions do not react, — that is,
the extremes of temperature seem to diminish or destroy the sensi-
tiveness of the end-organ. A temperature between 10° and 30° C.
gives the optimum reaction. So also the delicacy of the sense of
taste is increased by rubbing the sapid solution against the tongue.
Doubtless this mechanical action facilitates the penetration of the
sapid body into the mucous membrane, but it seems also to in-
crease the irritability of the end-organ. It is our habit in tasting
bodies with the tongue to rub this organ against the hard palate.
With regard to the threshold stimulus such results as the following
are reported:

Salty (sodium chlorid). 0.25 gm. in 100 c.c. H2O — detectible on tip of

tongue.
Sweet (sugar) 0.50 detectible on tip of

tongue.
Acid (HC1) 0.007 " " " detectible on border of

tongue.
Bitter (quinin) 0.00005 " " " " detectible on root of

tongue.

The very great sensitiveness of the tongue to bitter substances is
evident from this table.

The Olfactory Organ. — The end-organ for the olfactory sense
lies in the upper part of the nose, and consists of elongated, epithe-
lial-like cells, each of which bears on its free end a tuft of six to
eight hair-like processes, while at its basal end it is continued into
a nerve fiber that passes through the cribriform plate of the ethmoid
bone and ends in the olfactory bulb. These olfactory sense cells
lie among supporting epithelial cells of a columnar shape (Fig.
115). At the free edge of the cells there is a limiting membrane
through which the olfactory hairs project. The olfactory sense

280

THE SPECIAL SENSES.

cells are essentially nerve cells, and in this respect resemble the
sense cells in the retina, the rods and cones, rather than those of the
ear or of the organs of taste. The distribution of the olfactory
cells, according to v. Brunn, is confined to the nasal septum and a
portion of the upper turbinatebone. The area covered in each nos-
tril corresponds to about 250 square millimeters. The epithelium
of the lower and middle turbinates and the floor of the nostrils is
composed of the usual ciliated cells found in the respiratory passages,
while the so-called vestibular region of the nose, the part roofed in

by the cartilage, is covered
by a stratified pavement
epithelium corresponding in
structure with that of the
skin. These latter portions
of the nose are supplied
with sensory fibers derived
from the fifth or trigeminal
nerve. We must consider
the 500 sq. mm. of olfac-
tory epithelium as the
olfactory sense organ com-
parable physiologically and
perhaps anatomically to the
rod and cone layer of the
retina. The connections of
these cells with the central
nervous system have al-
ready been described (p.
205). It will be remem-
bered that the fine, non-
medullated fibers springing
from the basal end of the
sense cells enter the olfac-
tory bulb and end in ter-
minal arborizations in the olfactory glomeruli, where they make con-
nections by contact with the dendrites of the mitral cells of the
bulb. Through the axons of these mitral cells the impulses are con-
ducted along the olfactory tract to their various terminations in the
olfactory lobe itself, either of the same or of the opposite side, and
eventually also in the cortical region, the uncinate gyrus, of the
hippocampal lobe. As regards the olfactory sense cells, the nerve
cells in the olfactory bulb might be compared with the nerve gan-
glion layer of the retina, and the nerve fibers of the olfactory tract
with the fibers of the optic nerve.

The Mechanism of Smelling. — Odoriferous substances to

Fig. 1 15. — Cells of the olfactory region (after
v. Brunn): a, a, Olfactory cells; 6, 6, epithelial
cells; nt n, central process prolonged as an olfac-
tory nerve fibril; Z, Z, nucleus; c, knob-like clear
termination of peripheral process; h, h, bunch of
olfactory hairs.

SENSATIONS OF TASTE AND SMELL. 281

affect the olfactory cells must, of course, penetrate into the upper
part of the nasal chamber. This end is attained during inspiration,
either by simple diffusion or by currents produced by the act of
sniffing. It may also happen by way of the posterior nares. In
fact, the flavors of many foods, fruits, wine, etc., are olfactory rather
than gustatory sensations. When such food is swallowed the poste-
rior nares are shut off from the pharynx by the soft palate, but in
the expiration succeeding the swallow the odor of the food is con-
veyed to the olfactory end-organ. Flavors are perceived, therefore,
not during the act of swallowing, but subsequently, and if the nostrils
are blocked, as in coryza, foods lose much of their flavor. Simply
holding the nose will destroy much of the so-called taste of fruits
or the bouquet of wines.*

Nature of the Olfactory Stimulus. — The fact that smells are
transmitted through space like light and sound has suggested the
possibility that they may depend upon a vibratory movement of
some medium. This view, although occasionally defended in
modern times, is apparently entirely incompatible with the facts.
The usual view is that odoriferous bodies emit particles which, as
a rule at least, are in gaseous form. These particles are con-
veyed to the olfactory epithelium by currents in the air or by
simple gaseous diffusion, and after solution in the moisture of
the membrane act chemically upon the sensitive hairs of the sense
cells. All vapors or gases are, however, not capable of acting as
stimuli to these cells; so that evidently the odoriferous character
depends upon some peculiarity of structure. It is assumed that
there are certain groups, "odoriphore groups," which are character-
istic of all odoriferous substances and by virtue of which these
substances react with the special form of protoplasm found in
the hair cells. Hay craft f has formulated certain fundamental
conceptions bearing upon the relation between chemical structure
and odoriferous stimulation. He has shown that the power to
cause smell, like other physical properties, is a periodic function of
the atomic weight — that in the periodic system, according to Men-
dele jeff, the elements in certain groups are characterized by their
odoriferous properties; for instance, the second, fourth, and sixth
members — sulphur, selenium, and tellurium — of the sixth group.
Moreover, in organic compounds belonging to an homologous series
the smell gradually changes and, indeed, increases in the higher
members of the series, — that is, in those having a more complex
molecular structure.

The Qualities of the Olfactory Sensations. — While we dis-

* For many interesting facts concerning smelling and the literature to
1895 see Zwaardemaker, "Die Physiologic des Geruchs," Leipzig, 1895.
fHaycraft, "Brain," 1888, p. 166.

282 THE SPECIAL SENSES.

tinguish a great many different kinds of odors, it has been found
difficult, indeed impossible, to classify them very satisfactorily
into groups. That is, it is not possible to pick out what might be
called the fundamental odor sensations. This sense was doubtless
used by primitive man chiefly in detecting and test ing food, in protect-
ing himself from noxious surroundings, and perhaps also in controll-
ing his social relations. The olfactory sensations, in accordance with
this use made of them, give either pleasant or unpleasant sensa-
tions in a more marked and universal way than in the case of vision
or hearing, approaching, in this respect, rather the purely sensual
characteristics of the lower senses, the bodily appetites. Mankind
has been content to classify odors as agreeable and disagreeable,
and to designate the many different qualities of odors by the
names of the substances which in his individual experience
usually give rise to them. A number of observers have proposed
classifications more or less complete in character. One of the latest
and perhaps the best is that suggested by Zwaardemaker on the basis
of the nomenclatures introduced by previous observers. Adopting
first the general grouping into pure odors, odors mixed with sensa-
tions of common sensibility from the mucous membrane of the nose,
and odors mixed or confused with tastes, he separates the pure odors
or odors proper into nine classes, as follows:

I. Odores aetherei or ethereal odors, such as are given by the fruits, which

depend upon the presence of ethereal substances or esters.
II. Odores aromatici or aromatic odors, which are typified by camphor
and citron, bitter almond and the resinous bodies. This class is
divided into five subgroups.

III. Odores fragrantes, the fragrant or balsamic odors, comprising the vari-
ous flower odors or perfumes. The class falls into three subgroups.
IV. Odores ambrosiaci, the ambrosial odors, typified by amber and musk.
This odor is present in the flesh, blood, or excrement of some ani-
mals, being referable in the last instance to the bile.

V. Odores alliacei or garlic odors, such as are found in the onion, garlic,
sulphur, selenium and tellurium compounds. They fall into three
subgroups.

VI. Odores empyreumatici or the burning odors, the odors given by roasted
coffee, baked bread, tobacco smoke, etc. The odors of benzol, phenol,
and the products of dry distillation of wood come into this class.
VII. Odores hircini or goat odors. The odor of this animal arises from the
caproic and caprylic acid contained in the sweat ; cheese, sweat,
spermatic and vaginal secretions give odors of a similar quality.
VIII. Odores tetri or repulsive odors, such as are given by many of the nar-
cotic plants and acanthus.

IX. Odores nauseosi or nauseating or fetid odors, such as are given by feces
and certain plants and the products of putrefaction.

While the classification serves to emphasize a number of marked
resemblances or relations that exist among the odors, it does not
rest wholly upon a subjective kinship, — that is, the different odors
brought together in one class do not in all cases arouse in us sensa-

SENSATIONS OF TASTE AND SMELL. 283

lions that seem to be of related quality. It is not impossible, how-
ever, that further analysis may succeed in showing that there are
certain fundamental qualities in our numerous odor sensations.
Our position regarding the odors is similar to that which formerly
prevailed in the case of the taste sensations. It was thought to be
impossible to classify these latter satisfactorily on the basis of a few
fundamental sensations, but it is now universally accepted that all
of our true gustatory sensations show one or more of four primary
taste qualities. As was said,, above, our odor sensations are classi-
fied in ordinary life as agreeable or disagreeable, and, indeed,
Haller, the great physiologist of the eighteenth century, divided
odors along this line into three classes: (1) the agreeable or am-
brosial, (2) the disagreeable or fetid, and (3) the mixed odors. In
many cases, no doubt, the agreeableness or disagreeableness of an
odor depends solely upon the associations connected with it. If
the associative memories aroused are unpleasant the odor is dis-
agreeable. Thus, the odor of musk, so pleasant to most persons,
produces most disagreeable sensations in others, on account of past
associations. It is possible, however, that there is some funda-
mental difference in physiological reaction between such odors as
those of putrefaction and of a violet which may be considered as the
cause of the difference in psychical effect. It has been suggested, for
instance, that they may affect the circulation in the brain in opposite
ways, one producing an increased, the other a decreased flow.
This improbable supposition has been shown to be devoid of foun-
dation by the observations of Shields.* In his experiments the vascu-
lar supply to the skin of the arm was determined by plethysmo-
graphic methods, and it was found that both pleasant (heliotrope
perfume) and unpleasant (putrefactive) odors give a similar vascu-
lar reaction. Each class, if it acts at all, causes, as a rule, a con-
striction of the skin vessels, such as is obtained normally from in-
creased mental activity, — a reaction usually interpreted to mean a
greater flow of blood to the brain.

Fatigue of the Olfactory Apparatus. — It is a matter of
common observation that many odors, such as the perfumes of
flowers, quickly cease to give a noticeable sensation when the stimu-
lation is continued. This result is usually attributed to fatigue
of the sense cells in the end-organ and it is noticeable chiefly with
faint odors. One who sits in an ill-ventilated room occupied by
many persons may be quite unconscious of the unpleasant odor
from the vitiated air, while to a newcomer it is most distinct.

Threshold Stimulus— Delicacy of the Olfactory Sense. —
The extraordinary delicacy of the sense of smell in some of the lower
animals is seemingly beyond the power of objective measurement or
* Shields, " Journal of Experimental Medicine," 1, 1896.

284

THE SPECIAL SENSES.

expression. The ability of a dog, for instance, to follow the trail of
a given person depends undoubtedly upon the recognition of the
individual odor, and the actual amount of olfactory material left
upon the ground which serves as the stimulus must be infinitesi-
mally small. Even in ourselves the actual amount of olfactory
material which suffices to give a distinct sensation is often beyond
our means of determination except by the aid of calculation. It
is recognized in chemical work, for instance, that traces of known
substances too small to give the ordinary chemical reactions may be
detected easily by the sense of smell. By taking known amounts

Fig. 116. — Zwaardemaker's olfactometer.

of odoriferous substances and diluting them to known extents it is
possible to express in weights the minimal amount of each substance
that can cause a sensation. By this method such figures as the
following are obtained: Camphor is perceived in a dilution of 1 part
to 400,000; musk, 1 part to 8,000,000; vanillin, 1 part to 10,000,000;
while, according to the experiments of Fischer and Penzoldt,
mercaptan may be detected in a dilution of -^ -$-^ -^^ of a milli-
gram in 1 liter of air or -rg-o-TroinroT of a milligram in 50 c.c. of air.
Various methods have been proposed to determine the relative
delicacy of the olfactory sense in different persons, and these methods
have some application in the clinical diagnosis of certain cases.
Zwaardemaker has devised a simple apparatus, the olfactometer,
the principle of which is illustrated in Fig. 116. It consists of an
outside cylinder — the olfactory cylinder, whose inner surface is of
porous material which can be filled with a known strength of olfac-
tory solution — and an inside tube, smelling tube. This latter is
applied to the nose and where it runs inside the cylinder it is gradu-

SENSATIONS OF TASTE AND SMELL. 285

ated in centimeters. It is evident that the further out the inner
tube is pulled the greater will be the amount of olfactory substance
which will be exposed to the incoming air of an inspiration.

Conflict of Olfactory Sensations. — When different odors are
inhaled simultaneously through the two nostrils they may give rise
to the phenomenon of a conflict of the olfactory fields similar to that
described for the visual fields. That is, we perceive first one then
the other without obtaining a fused or compound sensation. The
result depends largely on the odors selected. In some cases one
odor may predominate in consciousness to the entire suppression
of the other, — a phenomenon which also has an analogy in binocular
sensations. It is well known, also, that certain odors antagonize or
neutralize others. It is said, for instance, that the odor of iodoform,
usually so persistent and so disagreeable, may be neutralized by the
addition of Peru balsam, and that the odor of carbolic acid may
destroy that of putrefactive processes. Whether the neutralization
is of a chemical nature or is physiological does not seem to have
been definitely ascertained.

Olfactory Associations. — Personal experience shows clearly
that olfactory sensations arouse numerous associations — our
olfactory memories are good. On the anatomical side the cortical
center in the hippocampal lobe is known to be widely connected
with other parts of the cerebrum, and we have in this fact a basis for
the extensive associations connected with odors. In animals like
the dog, with highly developed olfactory organs, it is evident that
this sense must play a correspondingly large part in the psychical
life. In such animals as well as among the invertebrates it is in-
timately connected with the sexual reflexes, and some remnant of
this relationship is obvious among human beings. Among the so-
called special senses that of smell is perhaps the one most closely
connected with the bodily appetites, and overgratification or over-
indulgence of this sense, according to historical evidence, has at least
been associated with periods of marked decadence of virtue among
•civilized nations.

PHYSIOLOGY OF THE EYE.

The eye is the peripheral organ of vision. By means of its
peculiar physical structure rays of light from external objects are
focused upon the retina and there set up nerve impulses that are
transmitted by the fibers of the optic nerve and optic tract to the
visual center in the cortex of the brain. In this last organ is
aroused that reaction in consciousness which we designate as a
visual sensation. In studying the physiology of vision we may
consider the eye, first, as an optical instrument physically adapted
to form an image on the retina and provided with certain physi-
ological mechanisms for its regulation; secondly, we may study
the properties of the retina in relation to its reactions to light,
and lastly, the visual sensations themselves, or the physiology
of the visual center in the brain.

CHAPTER XVII.

THE EYE AS AN OPTICAL INSTRUMENT— DIOPTRICS
OF THE EYE.

Formation of an Image by a Biconvex Lens. — That the re-
fractive surfaces of the eye form an image of external objects upon
the retinal surface is a necessary conclusion from its physical struc-
ture; The fact may be demonstrated directly, however, by ob-
servation upon the excised eye of an albino rabbit. The thin coats
of such an eye are semi transparent, and if the eye is placed in a tube
of blackened paper and held in front of one's own eyes it can be seen
readily that a small, inverted image of external objects is formed
upon the retinal surface, just as an inverted image of the exterior is
formed upon the ground glass plate of a photographic camera. This
image is formed in the eye by virtue of the refractive surfaces of the
cornea and the lens. The curved surfaces of these transparent bodies
act substantially like a convex glass lens, and the physics of the
formation of an image by such a lens may be used to explain the
refractive processes in the eye. To understand the formation
of an image by a biconvex lens the following physical facts must be

286

DIOPTRICS OF THE EYE.

287

borne in mind. Parallel rays of light falling upon one surface of the
lens are brought to a point or focus (F) behind the other surface
(Fig. 117). This focus for parallel rays is the principal focus and
the distance of this point from the lens is the principal focal dis-
tance. This distance depends upon the curvature of the lens and
its refractive power, as measured by the refractive index of the
material of which it is composed. Parallel rays are given theo-
retically by a source of light *at an infinite distance in front of the
lens, but practically objects not nearer than about twenty feet
give rays so little divergent that they may be considered as par-

Fig. 117. — Diagrams to illustrate the refraction of light by a convex lens : a., Refrac-
tion of parallel rays ; 6., refraction of divergent rays ; c., refraction of divergent rays from
a luminous point nearer than the principal focal distance.

allel. On the other hand, if a luminous object is placed at F the
rays from it that strike upon the lens will emerge from the other
surface as parallel rays of light. If a luminous point (/, Fig. 117)
is placed in front of such a lens at a distance greater than the
principal focal distance, but not so far as to give practically
parallel rays, the cone of diverging rays from it that impinges
upon the surface of the lens will be brought to a focus (/') further
away than the principal focus. Conversely the rays from a
luminous point at /' will be brought to a focus at /. These points,
/ and /', are therefore spoken of as conjugate foci. All luminous

288

THE SPECIAL SENSES.

points within the limits specified will have their corresponding
conjugate foci, at which their images will be formed by the lens.
Lastly, if a luminous point is placed at v, Fig. 117, nearer to the
lens than the principal focal distance, the cone of strongly di-
vergent rays that falls upon the lens, although refracted, is still
divergent after leaving the lens on the other side and consequently
is not focused and forms no real image of the point. For every lens
there is a point known as the optical center, and for biconvex lenses
this point lies within the lens, o. The line joining this center and
the principal focus is the principal axis of the lens (o-F, Fig. 117).
All other straight lines passing through the optical center are known
as secondary axes. Rays of light that are coincident with any of these
secondary axes suffer no angular deviation in passing through the
lens; they emerge parallel to their line of entrance and practically
unchanged in direction. Moreover, any luminous point not on the

Fig. 118. — Diagrams to illustrate the formation of an image by a biconvex lens: a, For-
mation of the image of a point; b, formation of the images of a. series of points.

principal axis will have its image (conjugate focus) formed some-
where upon the secondary axis drawn from this point through the
optical center. The exact position of the image of such a point
can be determined by the following construction (Fig. 118) : Let A
represent the luminous point in question. It will throw a cone of
rays upon the lens, the limiting rays of which may be represented by
A-b and A-c. One of these rays, A-p, will be parallel to the prin-
cipal axis, and will therefore pass through the principal focus, F.
If this distance is determined and is indicated properly in the
construction, the line A-p may be drawn, as indicated, so as to
pass through F after leaving the lens. The point at which the

DIOPTRICS OF THE EYE. 289

prolongation of this line cuts the secondary axis, A-o, marks the
conjugate focus of A and gives the position at which all of the
rays will be focused to form the image, a. In calculating the
position of the image of any object in front of the lens the same
method may be followed, the construction being drawn to de-
termine the images for two or more limiting points, as shown
in Fig. 118. Let A-B be an arrow in front of the lens. The image
of A will be formed at a on the secondary axis A-o, and the image of
B at 6 along the secondary axis B-o. The images of the intervening
points will, of course, lie between a and b; so that the image of the
entire object will be that of an inverted arrow. This image may be
caught on a screen at the distance indicated by the construction if
the latter is drawn to scale. The principal focus of a convex lens
may be determined experimentally or it may be calculated from the
formula ~ - + ~ = y, in which / represents the principal focal dis-
tance and p and pl, the conjugate foci for an object farther away
than the principal focal distance. That is, if the distance of the
object from the lens, p, is known, and the distance of its image, p1,
is determined experimentally, the principal focal distance of the
lens, /, may be determined by the formula, or if any two of the fac-
tors, p, p1, and /, are known the third may be reckoned from the
formula.

Formation of an Image by the Eye. — As stated above, the re-
fractive surfaces of the eye act essentially like a convex lens. As a
matter of fact, these refractive surfaces are more complex than
in the case of the biconvex lens. In the latter the rays of light
suffer refraction at two points only. Where they enter the lens
they pass from a rarer to a denser medium and where they leave the
lens they pass from a denser to a rarer medium. At these two
points, therefore, they are refracted. In the eye there is a larger
series of refractive surfaces. The light is refracted at the anterior
surface of the cornea, where it passes from the air into the denser
medium of the cornea ; at the anterior surface of the lens, where it
again enters a denser medium; and at the posterior surface of the
lens, where it enters the less dense vitreous humor. The relative
refractive powers of these different media have been determined
and are expressed in terms of their refractive indices, that of air
being taken as unity.*

The three points at which the light is refracted are indicated

* The term index of refraction expresses the constant ratio between the
angles of incidence and of refraction, or specifically between the sine of the

angle of incidence and the sine of the angle of refraction: -: = index of

smer

refraction.

19

290

THE SPECIAL SENSES.

Fig. 119. — Diagram to illustrate the surfaces
in the eye at which the rays of light are chiefly
refracted.

Index of refraction for air = 1

Index of refraction for cornea and aqueous hu-
mor = 1.3365

Index of refraction for crystalline lens = 1.4371

Index of refraction for vitreous humor = 1.3365

in the accompanying schema (Fig. 119). The refractive surfaces
of the eye may be considered as being composed of a concavo-convex
lens, the cornea and aqueous humor, and a biconvex lens, the
crystalline lens. In a system of this kind, composed of several
refractive media, it has been shown that to construct geometrically

the path of the rays it is
necessary to know six
points ; these are the six car-
dinal points or optical con-
stants of Gauss, — namely,
the anterior and the poste-
rior focal distance, the two
nodal points, and the two
principal points. So far
as the eye is concerned, it
has been shown that the
path of the rays of light

may be represented with sufficient accuracy by employing what is
known as the reduced schematic eye of Listing, in which the
refraction is supposed to take place at a single convex surface
separating two media, the air on one side and the media of the eye
on the other, the latter having a refractive index of 1.33 (see Fig.
120). In this reduced eye the position of the ideal refracting
surface c' lies in the aqueous humor, at a distance of 2.1 mms. from
the anterior surface of the
cornea, and the position of
the nodal point or optical
center — that is, the center
of curvature of the ideal
refracting surface lies in
the crystalline lens at n, a
distance of 7.3 mms. from
the anterior surface of the
cornea. The principal fo-
cal distance for this refract-
ing surface lies at a dis-
tance of 20.7 mms., which
would be equivalent to
22.8 mms. (20.7 -f 2.1)
from the actual surface of the cornea and 15.5 mms. (22.8 — 7.3)
from the nodal point. In the eye at rest this principal focal
distance coincides with the retina, since the refracting surfaces

Fig. 120. — Diagram to illustrate the reduced
or schematic eye with a single refracting surface
separating two media of different densities: c',
the ideal refracting surface situated 2.1 mms.
behind the anterior surface of real cornea; n,
the nodal point, or center 9f curvature of the
surface c', and 15.5 mms. in front of retina.
The eyeball is supposed to be filled with a uni-
form substance having a refractive index of 1.33,
equal to that of the vitreous humor.

DIOPTRICS OF THE EYE. 291

in the normal resting eye are so formed that parallel rays (rays
from distant objects) are brought to a focus on the retina. To
show the formation of the image of an external object on the retina
it suffices, therefore, to use a construction such as is represented in
Fig. 121. Secondary axes are drawn from the limiting points of the
object — A and B — through the nodal point. Where these axes
cut the retina the retinal image of the object will be formed. That
is, all the rays of light proceeding from A that penetrate the eye will
be focused at a, and all proceeding from B at 6. The image on
the retina will therefore be inverted and will be smaller than the
object. The angle formed at the nodal point by the lines A-n and
B-n is known as the visual angle; it varies inversely with the dis-
tance of the object from the eye.

The Inversion of the Image on the Retina. — Although the
images of external objects on the retina are inverted, we see them
erect. This fact is easily understood when we remember that our
actual visual sensations take place in the brain and that the pro-
jection of these sensations to the exterior is a secondary act that has
been learned from experience. Experience has taught us to project
the visual sensation arising from the stimulus of any given point on
the retina to that part of
the external world from
which the stimulus arises,
— that is, to the lumin-
ous point giving origin to
the light rays. Accord-
ing to the physical prin-
ciples described above,
the image of such a point

must be formed On the Fig. 121.— Diagram to illustrate the construc-

, • « .1 i tion necessary to determine the location and size of

retina where the second- the retinal image.
ary axis from that point

through the nodal point touches the retina. In projecting this
retinal stimulus outward to its source, therefore, we have learned
to project it back, as it were, along the line of its secondary axis,
In Fig. 121 the retinal stimulus at a is projected outward along
the line a-n-A, and to such a distance as, from other sources, we
estimate the object A to be. This law of projection is fixed by
experience, but it implies, as will be noted, that we are conscious
of the differences in sensation aroused by stimulation of different
parts of the retina. Considering the retina as a sensory surface,
— like the skin, for instance, — each point, speaking in general terms,
may be assumed to be connected with a definite portion of the
cortex, and the sensation aroused by the stimulation of these dif-
ferent points must differ to some extent in consciousness, each has

292 THE SPECIAL SENSES.

its local sign. The sensations arising from each of these points we
have learned to project outward into the external world along the
line from it to the nodal point of the eye, because under the normal
conditions of life this point is stimulated only by external objects
situated on this line. This law of projection is so firmly fixed that
if a given point in the retina is stimulated in some unusual way
we still project the resulting sensation outward according to the
law, and thus make a false projection and interpretation. For
instance, if the little finger is inserted into the inner and lower angle
of the eye and is pressed upon the eyeball the edge of the retina is
stimulated mechanically. One experiences, in consequence, a
visual sensation, known as a phosphene, consisting of a dark-blue
spot surrounded by a light halo. This sensation, however, is
projected out toward the upper and outer angle of the eye, accord-
ing to the law of projection, since normally this part of the retina
is only stimulated by light coming from such a direction. A similar
error in projection is obtained by holding objects so close to the eye
that a physical inverted image cannot be formed, but only an erect
shadow image. This experiment may be performed as follows:
Hold the head of a pin close to the eye, and, in order that a sharp
shadow may be thrown, allow the light to fall on this pin through
a pinhole in a card held somewhat farther from the eye. By this
means an erect shadow of the pin, lying in the circle of light from
the hole, will be thrown on the eye. This shadow image will be
projected outward according to the usual law, and consequently
will appear inverted.

The Size of the Retinal Image. — The size of the image of an
object on the retina may be reckoned easily, provided the size of the
object and its distance from the eye is known. As will be seen from
the construction given in Fig. 121, the triangles A-n-B and a-n-b are
symmetrical ; consequently we have the ratio :

A-B : a-b : : A-n : a-n or

A-B A-n

— r— = : that is

a-b a-n '

Size of object Distance of object from nodal point.
Size of image s " Distance of image from nodal point.

As was stated above, the distance of the image from the nodal
point — that is, the distance of the retina from the nodal point-
may be placed at 15.5 or 15 mms. Consequently, three of the factors
in the above equation being known, it is easily solved for the un-
known factor — namely, the size of the image on the retina. To
take a concrete example; suppose it is desired to know the size on
the retina of the image made by an object 120 feet high at a distance
of one mile (5280 feet). If we designate the size of the image as x

DIOPTRICS OF THE EYE. 293

and substitute the known values for the other terms of the equation,

120 5280 u • u • u *u j-

we have — = -^ -, or x = 0.341 mm., which is about the diam-
eter of the fovea centralis. The retinal image of the object in
this case would be, in round numbers, about -nnrVinr °f the actual
size of the object.

Accommodation of the Eye for Objects at Different Dis-
tances.— The normal or, as it is sometimes named, the emmetropic
eye, is arranged to focus parallel rays more or less accurately upon
the retina. That is, the refractive media have such curvatures and
densities that parallel, or substantially parallel rays are brought to
a focus upon the retinal surface. When objects are brought closer
to the eye, however, the rays proceeding from them become more
and more divergent. If the eye remains unchanged the refracted
rays cut the retina before coming to a focus — so that each
luminous point in the object, instead of forming a point upon the

Fig. 122.— Diagram explaining the change in the position of the image reflected from the
anterior surface of the crystalline lens. — (Williams, after Danders.)

retina, forms a circle, known as a diffusion circle. As this
is true for each point of the object, the retinal image as a whole
is blurred. We know, however, that up to a certain point
at least this blurring does not occur when the object is brought
closer to the eyes. The eye, in fact, accommodates itself to the
nearer object so as to obtain a clear focus. In a photographic
camera this accommodation or focusing is effected by moving the
ground glass plate farther away as the object is brought closer to the

294 THE SPECIAL SENSES.

lens. In the eye the same result is obtained by increasing the curva-
ture and therefore the refractive power of the lens. That a change
in the lens is the essential factor in accommodation for near objects
is demonstrated by a simple and conclusive experiment devised by
Helmholtz with the aid of what are known as the images of Pur-
kinje. The principle of this experiment is represented by the dia-
gram given in Fig. 122. The eye to be observed is relaxed;
that is, gazes into the distance. A lighted candle is held to one
side as represented, and the observer places his eye so as to
catch the light of the candle when reflected from the observed eye.
With a little practice and under the right conditions of illumina-
tion the observer will be able to see three images of the candle re-

A B

Fig. 123. — Reflected images of a candle flame as seen in the pupil of an eye at rest and
accommodated for near objects. — (Williams.)

fleeted from the observed eye as from a mirror: one, the brightest,
is reflected from the convex surface of the cornea (a, Fig. 123, A}',
one much dimmer and of larger size is reflected from the convex
surface of the lens (6, Fig. 123, A). This image is larger and
fainter because the reflecting surface is less curved. The third
image (c, Fig. 123, A) is inverted and is smaller and brighter
than the second. This image is reflected from the posterior
surface of the lens, which acts, in this instance, like a concave
mirror. If now the observed eye gazes at a near object it will
be noted (Fig. 123, B] that the first image does not change at
all, the third image also remains practically the same, but the
middle image (b) becomes smaller and approaches nearer to the
first (a). This result can only mean that in the act of accom-
modation the anterior surface of the lens becomes more convex.
In this way its refractive power is increased and the more diver-
gent rays from the near object are focused on the retina. Helm-
holtz has shown that the curvature of the posterior surface of the
lens is also increased slightly; but the change is so slight that the
increased refractive power is referred chiefly to the change in the
anterior surface. The means by which the change is effected

DIOPTRICS OF THE EYE. 295

was first explained satisfactorily by Helmholtz.* He attributed
it to the contraction of the ciliary muscle. This small muscle,
composed of plain muscle fibers, is found within the eyeball, lying
between the choroid and the sclerotic coat at the point at which the
sclerotic passes into the cornea and the choroid falls into the ciliary
processes. Some of its fibers take a more or less circular direction
around the eyeball, resembling thus a sphincter muscle, while others
take a radial direction in the,, plane of the meridians of the eye and
have their insertion in the choroid coat (Fig. 124). When this
muscle contracts the radial fibers especially will pull forward the
choroid coat. The effect of this change in the choroid is to loosen
the pull of the suspensory ligament (zonula Zinnii) on the lens and
this organ then bulges forward by its own elasticity. The theory
assumes that in a condition of rest the suspensory ligament, which
runs from the ciliary processes to the capsule of the lens, exerts a

Ciliary Border

process, of iris. Ciliary muscle.

Pigment
epithelium

Ora serrata.

Fig. 124. — Meridional section of eyeball after removal of sclerotic coat, cornea, and iris,
to show the position of the ciliary muscle. — (Schultze.)

tension upon the lens which keeps it flattened, particularly along
its anterior surface, since the ligament is attached more to this side.
When this tension is relieved indirectly by the contraction of the
ciliary muscle the elasticity of the lens, or rather of the capsule of
the lens, causes it to assume a more spherical shape along its anterior
surface, and the amount of this change is proportional to the
extent of contraction of the muscle. Other theories have been
proposed to explain the way in which the contraction of the ciliary

* Helmholtz, "Handbuch der physiologischen Optik," second edition.
1896.

296 THE SPECIAL SENSES.

muscle effects a change in the curvature of the lens,* but none is
so simple and, on the whole, so satisfactory as the one suggested
bv Helmholtz.

It is interesting to note that in fishes accommodation is effected in a
different way, namely, by movements of the lens forward and backward.
In these animals the eye when at rest is accommodated for near vision, and
to see objects at a distance the refractive power of the eye is diminished by
the contraction of a special muscle, retractor lentis, which pulls the lens toward
the retina, f

Limit of the Power of Accommodation — Near Point of
Distinct Vision. — When an object is brought closer and closer to
the eye a point will be reached at which it is impossible by the
strongest contraction of the ciliary muscle to obtain a clear image
of the object. The rays from it are so divergent that the refractive
surfaces are unable to bring them to a focus on the retina. Each
luminous point makes a diffusion circle on the retina, and the
whole image is indistinct. The distance at which the eye is just
able to accommodate and within which distinct vision is impos-
sible is called the near point. Observation shows that this near
point varies steadily with age and becomes rapidly greater in dis-
tance between the fortieth and the fiftieth year. In the case of the
normal eye the recession of the near point varies so regularly with
age that its determination may be used to estimate the age of the
individual. Figures of this kind are given :

AGE.
10

NE
7 en

AR POINT.
i. or 2.76 in
3.94
5.61
8.66
15.75
39.37

20

10 '

30

14 '

40

22 '

50

40 '

60..

. 100 '

This gradual lengthening of the near point is explained usually
by the supposition that the lens loses its elasticity, so that con-
traction of the ciliary muscle has less and less effect in causing an
increase in its curvature. The process starts very early in life,
and is one of the many facts which show that senescence begins
practically with birth. The change in near point in early life is so
slight as to escape notice, but after it reaches a distance of about
25 cm. (about 10 inches) the fact obtrudes itself upon us in the use
of our eyes for near objects, — reading, for example. The condition
is then designated as old-sightedness or presbyopia. Most normal
eyes become so distinctly presbyopic between the fortieth and the
fiftieth year as to require the use of glasses in reading. If no other
defect exists in the eye, this deficiency of the lens is readily over-

* See Tscherning, " Optique physiologique," Paris, 1898 ; and Schoen,
" Archiv f. die gesammte Physiologic," 59, 427, 1895.

fSee Beer, "Wiener klinische Wochenschrift, " 1898, No. 12.

DIOPTRICS OF THE EYE. 297

come by using suitable convex glasses to aid the eye in focusing
the rays. It is obvious that in such cases the glasses need not be
used except for near work.

Far Point of Distinct Vision. — The normal eye is so adjusted
that parallel rays are brought to a focus on the retina. The far
point is therefore theoretically at infinity. Objects at a great
distance are seen distinctly, as far as their size permits, without
accommodation, — that is, with the eye at rest. Practically it is
found that objects at a distance of 6 to 10 meters (20 to 30 feet) send
rays that are sufficiently parallel to focus on the retina without
muscular effort on the part of the eyes, and this distance, therefore,
measures the practical far point, punctum remotum, of the normal
eye. The rays at this distance are, in reality, somewhat divergent,
and that they produce a distinct image without an act of accom-
modation may be due to the fact that the rods and cones, the really
sensitive part of the retina, do not form a mathematical plane, but
have a certain thickness or depth. In the fovea centralis, for in-
stance, the cones have a length estimated (Greeff) at 85 // (0.085
mm.), and since the displacement of the focus of an object moved
from an infinite distance (parallel rays) to 6 or 10 meters from the
eye is less than this amount, the focused image would continue to
fall on some part of the cones without the aid of the mechanism of
accommodation.

The Refractive Power of the Eye and the Range of Accom-
modation.— The refractive power of lenses is expressed usually
in terms of their principal focal distance, a lens with a distance
of one meter being taken as the unit and designated as having a
refractive power of one diopter, 1 D. Compared with this unit,
the refractive power of lenses is expressed in terms of the recipro-
cal of their principal focal distance measured in meters; thus,
a lens with a principal focal distance of y1^ meter is a lens of 10
diopters, 10 D., and one with a focal distance of 10 meters is
^ diopter (0.1 D.). The anterior principal focal distance of
the combination of refractive surfaces in the eye is 15.5 mms. or
^o meters. The reciprocal of this length of focus. -^ or 64.5 D.,
expresses the refractive power of the eye under the normal con-
ditions in which the rays are refracted into the dense vitreous
humor. The anterior focal length of the cornea alone is given as
23.3 mm., which would correspond to a power of 42.9 D., while the
anterior focal length of the lens alone is equal to 50.6 mm. or about
20 D. In the combined system, therefore, the action of the cornea
is more important than that of the lens. Removal of the lens, as
in cataract operations, does not lessen the refractive power of the

298 THE SPECIAL SENSES.

eye so much as when the action of the cornea is destroyed, as
happens for the most part when the head is immersed in water.
The total refractive power of the eye is increased by the act of
accommodation, on account of the greater curvature of the lens.
As stated in a preceding paragraph the extent of accommodation
varies with age.. At 10 years the range is from infinity, when the
eye is at rest, to 7 ctm. when the maximum accommodation is
used. In this case, therefore, the refractive power is increased
from 64.5 D. to 78.5 D., since a distance of 7 ctm., T^- meter, is
equivalent to -^ or 14 + D. The decreasing range of accom-
modation as age increases is expressed conveniently in tha number
of diopters which may be added to the refractive power of the
eye by the action of the ciliary muscle.

The following table illustrates the usual range of accom-
modation for different ages :

Range of accommodation
Years. in diopters.

10 14

15 12

20 10

25 8.5

30 7

35 5.5

40 4.5

45 3.5

50 2.5

55 1.75

60 • 1

65 0.7-)

70 , 0.25

Optical Defects of the Normal Eye. — The refractive surfaces
of the eye exhibit some of the optical defects commonly noticed
in lenses, particularly those defects known as chromatic and spherical
aberration. White light is composed of ether waves of different
lengths and different rapidities of vibration, the shortest waves being
those at the violet end of the spectrum and the longest those at the
red end. In passing through a prism or lens these waves are re-
fracted unequally and are therefore more or less dispersed accord-
ing to the character of the refracting medium. The short, rapid
waves at the violet end are refracted the most and are brought to
a focus before the longer, red waves, so that the image shows
fringes of color instead of being pure white. This phenomenon
is known as chromatic aberration. Lenses used for scientific
purposes are corrected for this defect or made achromatic by a
combination of lenses of crown and flint glass so placed that the
dispersive power of one neutralizes that of the other. The eye
exhibits this defect, but not to such an extent as to be noticeable
in ordinary vision. If, however, an object is in focus when viewed

DIOPTRICS OF THE EYE. 299

by red light it can be shown that the focus must be changed if the
same object is illuminated by violet light. Helmholtz estimates
that if the media of the eye possess the same dispersive power as
water the rays of violet light must be brought to a focus at about
0.434 mm. in front of that of the red rays.

Spherical aberration depends upon the fact that the rays near the
circumference of a lens are refracted more and therefore are brought
to a focus sooner than those entering nearest the center. This
defect may be noticed in an uncorrected lens by the fact that
when the center of the image is in exact focus its margins are
slightly out of focus and vice versa. The defect is usually cor-
rected, as in photography, by use of a diaphragm to cut off
the rays from the periphery of the lens. In the eye both spher-
ical and chromatic aberrations are remedied to a large extent by
a similar device. The iris constitutes an adjustable diaphragm,
which is reflexly narrowed as the light increases in intensity and
thus cuts off the rays that would go through the periphery of
the lens. The interesting physiological control of the movements
of the iris is described below. In the eye the defect of spherical
aberration is counteracted also by the peculiar structure of the
crystalline lens. This organ is composed of concentric layers
whose density increases toward the center. The result of this
arrangement is that the center of the lens is more refractive than the
periphery, and the tendency of the latter portion to refract more
strongly is more or less neutralized. A third optical defect of the
eye consists in the fact that its refractive surfaces are not absolutely
centered, — that is, the centers of curvature of the cornea and of the
anterior and the posterior surfaces of the lens do not lie in the same
straight line. Moreover, the optical axis of the system does not
coincide exactly with the line of sight. By the latter term we mean the
line from the point looked at to the fovea centralis or the part of the
fovea on which the image of the point falls. This line of sight or
visual axis makes an angle of about five degrees with the optical
axis. The system would be more perfect as an optical apparatus
if the two axes coincided.

Abnormalities in the Refraction of the Eye — Ametropia.—
The eye that is normal and in which parallel rays focus on the
retina when the eye is at rest is designated as emme tropic. Any
abnormality in the refractive surfaces or the shape of the eyeball
prevents this exact focusing of parallel rays and makes the eye
ametropic. The most common refractive troubles of the eye
are due to short-sightedness or myopia, far-sightedness or hyper-
metropia, astigmatism, and old-sightedness or presbyopia. Some
description of these conditions is useful to emphasize by contrast

300 THE SPECIAL SENSES.

the mode of action of the dioptric mechanism in the normal eye,
but for a full description of the extent and complexity of these
defects reference must be made to special treatises upon the
errors of refraction in the eye.

In myopia or near-sightedness parallel rays of light are brought
to a focus before reaching the retina. Consequently when the rays
fall upon the retina each point forms a diffusion circle and the image
is indistinct. This defect may be due to an abnormally great cur-
vature of the refractive surfaces, the cornea or the lens, or to an ab-
normal length of the eyeball in its anteroposterior diameter. The
latter cause is the more common. The defect may be congenital,
but usually it is acquired, and in the latter case its cause is generally
attributed to a weakness in the coats of the eyeball. The interior
of the eye is under some pressure, intra-ocular tension, which is
estimated to be equal to the pressure of a column of mercury 25 to 30
mms. in height. This tension is increased by strong convergence of
the eyeballs in looking at near objects. If the coats of the eye are
weak or become so from disease or malnutrition they may yield
somewhat to this pressure and the eyeball become lengthened in the
anteroposterior diameter. The condition as regards refraction of
parallel rays is represented then by the diagram B, in Fig. 125.
The retina is farther away than the principal focal distance of the
refractive surfaces, and if the defect is excessive even diverging
rays may not be focused. The obvious remedy for such a condition
is to use concave lenses before the eyes for distant vision. By this
means, if the lenses are properly chosen, the rays will be given such
an amount of divergence that the focus will be thrown back to the
retina. As compared with the normal or emme tropic eye, the
myopic eye has its far point of distinct vision — that is, the farthest
point that can be seen distinctly without an effort of accommo-
tion — less than twenty feet from the eye, the exact distance depend-
ing upon the extent of the myopia. On the contrary, the near point
of distinct vision — that is, the nearest point at which distinct vision
can be obtained with the aid of the muscles of accommodation — is
closer than in the normal eye. Much of the prevalent myopia in the
young is attributed by oculists to bad methods in reading, such as
insufficient lighting, small print, and a faulty position of the book.
Such conditions lead to an excessive muscular effort and thus
aggravate any tendency that exists toward the development of a
near-sighted condition.

In hypermetropia the conditions are the opposite of those in
myopia. Parallel rays of light after refraction in the eye cut the
retina before they come to a focus. The principal focal distance, in
other words, is behind the retina. In this case, also, each point

DIOPTRICS OF THE EYE.

301

of a distant object will make upon the retina, when the eye is not
accommodated, a diffusion circle, and the image consequently is
blurred. This defect may be caused by a lessened curvature or
refractive power in the cornea or lens, but in the majority of cases
it is referable to a diminution in the anteroposterior diameter of
the eyeball. This condi-
tion is usually congenital:
the eyeball from birth is
smaller than the normal.
The path of the parallel
rays in this case is repre-
sented in the diagram (7,
Fig. 125. When such an
eye looks at a distant ob-
ject a clear image may be
obtained only by using the
ciliary muscle, and to pre-
vent this constant strain
upon the muscle of accom-
modation convex glasses
must be worn. Glasses of
this kind converge the
rays and if properly chosen
will bring parallel rays to
a focus without the con-
stant aid of accommoda-
tion. It is obvious that
in the hypermetropic eye
there is no far point of

Fig. 125. — Diagram showing the difference be-
tween normal (A), myopic (B), and hypermetropic
(C) eyes. In B and C the dotted lines represent the
path of the rays after correction by glasses. — (Bow-
ditch.)

distinct vision when the
eye is at rest, since some
accommodation must be
used to bring even parallel rays to a focus. The near point of
distinct vision will be farther away than in the normal eye, since
accommodation begins when the rays are parallel and its limits
are reached with a less degree of divergence; hence the name of
far-sightedness .

Presbyopia or old-sightedness has been referred to above. It
is due to a gradual failure in the effectiveness of accommodation
with increasing age, and is attributed usually to a progressive in-
crease of rigidity in the lens. The near point of distinct vision
recedes farther and farther from the eye, and consequently in close
work convex glasses must be worn to aid the accommodation. It
is obvious that this effect of old age will be less noticeable in the

302 THE SPECIAL SENSES.

myopic than in the emmetropic eye, since in the former the greater
length of the eyeball requires less accommodation in near vision and
the failure of the lens to refract is therefore not felt so soon What
is known as second-sight in the old may be brought about by
the late development of a myopic condition, — that is, by a change
in the length of the eyeball or by a swelling of the crystalline
lens, — and in such a case convex glasses for near work may be
dispensed with.

Astigmatism. — In a perfectly normal or ideal eye the refractive
surfaces, cornea, anterior and posterior surfaces of the lens, are
sections of true spheres, and, all the meridians being of equal
curvature, the refraction along these different meridians is equal.
Such an eye will bring the cone of rays proceeding from a luminous
point to a focal point on the retina, barring the disturbing influence
of chromatic and spherical aberration. If, however, one or all of the
refractive surfaces have unequal curvatures along different merid-
ians, then it is obvious that the rays from a luminous point can not
be brought to a focal point, since the rays along the meridian of
greater curvature will be brought to a focus first and begin to diverge
before the rays along the lesser curvature are focused. Such a
condition is designated as astigmatism (from a, not, and rfT^a,
point). The effect may be illustrated by the diagram in Fig. 126,
which represents the refraction of the rays from a luminous point by
a planoconvex lens whose curvature along the vertical meridian is
greater than along the horizontal meridian.

The rays along the vertical meridian are brought to a focus
first at G, but those from the horizontal meridian are still converging;
so that a screen placed at this point will give the image of a horizontal'
line (a-a'). The rays along the horizontal meridian are brought to a
focus at B, but those from focus G have by this time spread out
in a vertical plane, so that a screen placed at this point will give
the image of a vertical line (b-c). In between the images will be
elliptical or circular, as represented in the diagram. In the eye
astigmatism may be due to an inequality in curvature of either the
cornea or the lens, and may be either regular or irregular. By
regular astigmatism is meant that condition in which while the
curvature along each individual meridian is equal throughout its
course, the curvatures of the different meridians vary and in such
a way that the meridians of greatest and least curvature are at
right angles to each other or approximately so. Ordinary astig-
matism is of the regular variety, and is usually attributed to a
defect in the curvature of the cornea. If the astigmatism is such
that the vertical meridian has the greatest curvature it is termed
"with the rule," since usually this meridian is slightly more

DIOPTRICS OF THE EYE.

303

curved than the horizontal one. If, on the contrary, the cur-
vature along the horizontal meridian is greater, the astigmatism
is " against the rule." The meridians of greatest and least curva-
ture may not lie in the vertical and horizontal planes, but in some
of the oblique planes; but so long as they are at right angles the
astigmatism is regular. It is evident that such a condition may
be corrected by the use of cylindrical lenses, so chosen as to in-
crease the refraction along,, the meridian in which the cornea
has the least curvature, in which case a convex or plus cylinder is
used, or, on the other hand, to diminish appropriately the refraction
along the meridian of greatest curvature, in which case a concave
or minus cylinder is used. An eye that suffers from a marked

Fig. 126. — Schema to illustrate the paths of the rays of light in a cornea showing
regular astigmatism. — (McKendrick.) The lower line of figures represents the section 01
the cone of light, or the images obtained at different distances. The image varies from a
horizontal to a vertical line, but at no place can a point be obtained at which rays along
all meridians are focused.

degree of astigmatism cannot focus distinctly at the same time
lines that are at right angles to each other; hence the use of a
series of lines whose images are formed along the different meridians
of the eye, as shown in Fig. 127, will reveal this defect if it exists.
If the eye is directed to the center of intersection of the lines some
of the lines appear distinct while those at right angles to them
are blurred. A normal eye can be thrown into an astigmatic con-
dition by approximating the eyelids closely. In this position the
tears make a concave cylindrical lens, which alters the curvature
along the vertical meridian. What is known as irregular astig-
matism is due to the fact that the meridians of greatest and least
curvature are not at approximately right angles, or, as is more

304

THE SPECIAL SENSES.

commonly the case, it is due to an irregularity in the curvature
along some one meridian, such as may be produced by a scar upon
the cornea. This condition may be produced from a variety of
causes affecting either the cornea or the lens, and practically it
can not be corrected by the use of lenses. As Helmholtz has shown,

a small degree of irregular
astigmatism is present nor-
mally, owing to a certain
asymmetry in the curvature
of the lens. This defect is
made apparent in the visual
sensations caused by a point
of light, such as is furnished,
for instance, by a fixed star.
The retinal image in these
cases, instead of being a sym-
metrical point, is a radiate
figure the exact form of
which may vary in different
eyes. For this reason the
fixed stars give us the well-
known star-shaped image

Fig. 127. — Astigmatic chart.

instead of a clearly defined

point.

Innervation and Physiological Control of the Ciliary Muscle
and the Muscles of the Iris. — From an optical point of view the
iris plays the part of a diaphragm. It is, moreover, an adjustable
diaphragm the aperture of which — that is, the size of the pupil —
is varied reflexly according to the conditions of illumination. Its
adjustments are made possible by the fact that it contains within
its substance two bands of muscular tissue, one, the sphincter
muscle, forming a circular ring whose contraction diminishes the
aperture of the pupil, and the other a dilator muscle whose contrac-
tion widens the pupil. Each of these muscles possesses its own
nerve fibers that arise ultimately from the brain, and through these
fibers reflex movements of great delicacy are effected. The sphinc-
ter pupillae is a well-defined band of plain muscle whose width
varies, according to the state of contraction, from 0.6 to 1.2 mms.;
it forms a ring lying just on the margin of the pupil, and it is im-
bedded in the stroma of the iris. The histological differentiation
of the dilator pupillse is much less distinct. For a long time its
existence was the subject of controversy, but it is now conceded
that such a muscle is present in the form of a layer of elongated
spindle-like cells which lie close to the pigment layer of the iris and

DIOPTRICS OF THE EYE.

305

form radial bundles stretching from the ciliary border of the iris
toward the pupillary orifice.* Both of these muscles are supplied
by autonomic nerve fibers — that is, the motor nerve path comprises
a preganglionic fiber, arising from the central nervous system,
and a postganglionic fiber, arising from a sympathetic ganglion.
Anatomically it can be shown that the sphincter muscle is supplied
by the short ciliary nerves arising from the ciliary ganglion,
which supply also the *
muscle of accommoda-
tion, the ciliary muscle;
while the dilator muscle
is supplied by the long
ciliary nerves that arise
from the ophthalmic
branch of the fifth cra-
nial nerve, as represented
in Fig. 128. The entire
course of the motor
paths, preganglionic and
postganglionic fibers, is
represented diagrammat-
ically in Fig. 129. The
motor fibers to the ciliary
muscle and sphincter
pupillae arise in the mid-
brain in the nucleus of
origin of the third cranial
nerve, and indeed in a
special part of this nu-
cleus lying most ante-
riorly. They leave the
third nerve in the orbit
and end within the sub-
stance of the ciliarj- gan-

lc

Course of constrictor nerve fibers,
Course of dilator nerve fibers,- -

Fig. 128.— Diagrammatic representation of the

nerves governing the pupil (after Foster) : II, Optic
gJlOn, Whence the path nerve; c.g, ciliary ganglion; r.b, its short root from
,• -II *"i motor ocuh nerve; sum its svmDathetic root* rl

IS Continued by Sympa- its long root from V, ip£thkl£<5SS Branch ofoph-
thpflP fnn«to-p no-linn I'M "lalmic division of fifth nerve; s.c, short ciliary
V POb LgdJlgllOniC ; nerves; l.c, long ciliary nerves.

fibers emerging from the

ganglion in the short ciliary nerves. The fibers to the dilator
muscle have a very different path. They arise also in the brain,
most probably in the midbrain, although their exact origin has
not been determined satisfactorily, and pass down the spinal

*For a physiological proof and the literature of the controversy see
Langley and Anderson, "Journal of Physiology/' 13, 554, 1892. For the
histological proof, Grunert, "Archives of Ophthalmology/' 30, 377, 1901.
20

306

THE SPECIAL SENSES.

cord to terminate in the lower cervical region. From this point
the path is continued by spinal neurons which leave the cord in the
eighth cervical and the first and second thoracic spinal nerves and
pass by way of the corresponding rami communicantes into the
sympathetic chain at the level of the first thoracic ganglion. From
this point the fibers pass upward in the cervical sympathetic with-
out terminating until they reach the superior cervical ganglion near
the base of the skull. From this ganglion the path is continued
by sympathetic (postganglionic) fibers which pass to the Gasserian
ganglion and unite with its ophthalmic branch. Subsequently
they leave the ophthalmic nerve in the long ciliary branches. These
fibers under normal conditions are in constant (tonic) activity, so
that if the path is interrupted at any point by section of the cervical

Gasserian

jossena/t ^ — v Ojbhttalmie branck off U Long cdiaru nerves.
Ganglion,. \ X i '*»•/»

V f~ . <.-„ l^DUabr

\fir~ T^fc*

Su]yeriorCe>

Fig. 129. — Schema showing the path of the preganglionic and ppstganglionic fibers
to the ciliary muscle and to the sphincter and dilator muscles of the iris. — (Modified from
Schultz.) The course of the long ciliary nerves is represented very diagrammatically.

sympathetic, for instance — the pupil is seen to contract. This
constant activity may be referred directly to the activity of the
spinal neurons whose cells lie in the spinal cord in the lower cervical
and upper thoracic region. The cells in question constitute what
is sometimes called the lower ciliospinal center of Budge.

The Accommodation Reflex and the Light Reflex of the
Sphincter Muscle. — When the eye is accommodated for a near
object by the contraction of the ciliary muscle there is always a
simultaneous contraction of the sphincter pupillse whereby the
pupil is narrowed. The act is one of obvious value in vision, since
by diaphragming down the lens the focus is improved and more
exact vision, such as is needed in close work, is obtained. The act
is usually spoken of as the accommodation reflex, but in reality it

DIOPTRICS OF THE EYE. 307

is rather what is known as an associated movement. The voluntary
effort inaugurated in the brain affects the cranial centers for both
muscles, and under normal conditions they always act together, —
a fact which implies a close connection of their centers. An example
of a similar associated action is seen in the effect of the respiratory
movements on the rate of heart beat, the inspiratory discharge
from the respirator}7 center being accompanied by an associated
effect upon the cardio-inhioitory center whereby the heart rate
is quickened. In the particular case that we are dealing with
three muscular acts, in fact, are usually associated, for every act
of accommodation under normal circumstances is accompanied
not only by a constriction of the pupil, but also by a convergence
of the eyeballs, due to a contraction of the internal rectus muscle
in each eye.

The light reflex is observed when light is thrown into the eye.
As is well known, the pupil dilates in darkness or dim lights and
contracts to a pin-point upon strong illumination of the retina.
The value of this reflex is also obvious. In the dim light the total
illumination and therefore the visual power of the retina is aided
by an enlarged pupil, but in strong lights the illumination may be
diminished with advantage by diaphragming, since the optical
image on the retina is thereby improved on account of the diminu-
tion in spherical aberration. The reflex arc involved in this act is
known in part. The afferent path is along the optic nerve; the
efferent path back to the sphincter is through the third nerve
and ciliary ganglion ; injury to either of these paths diminishes or
destroys the reflex. The reflex is also lost in some cases in which
neither of these paths seems to be involved. In tabes dorsalis
(locomotor ataxia) and general paresis, for instance, the pupil
of the eye is constricted and does not give the light reflex, but
still shows the accommodation reflex. Such a condition is known
as the Argyll Robertson pupil. Some question exists, there-
fore, as to the nature of the connections in the brain between the
afferent impulses and the motor center in the nucleus of the third
nerve. According to some authors (Gudden, v. Bechterew), the
afferent light reflex fibers are a set of fibers distinct from the visual
fibers proper. They arise in the retina and pass backward in the
optic nerve, but leave the optic tracts at the chiasma to enter the
walls of the third ventricle and thus reach the nucleus of the third
nerve. This view, however, finds no support in the histological
structure of the retina. Under normal conditions the light reflex
is bilateral, — that is, light thrown upon one retina only will cause
constriction of the pupil in both eyes. In those of the lower ani-
mals whose optic nerves cross completely in the chiasma the light
reflex, on the contrary, is unilateral, affecting only the eye that

308 THE SPECIAL SENSES.

is stimulated.* We may conclude, therefore, that the bilaterality
of the reflex in the higher animals is dependent upon the partial
decussation of the optic fibers in the chiasma, a sensory stimulus
upon one retina giving rise to impulses which are conveyed to the
two sides of the brain. It is possible, however, that in addition
commissural connections may exist between the central connections,
— the motor centers in the midbrain. It is usually stated that
the effect of the light upon the sphincter muscle is greatest when
the retina is stimulated at or near the fovea and that it varies
directly with the intensity of the light and the area illuminated.t
The Action of Drugs upon the Iris. — The condition of con-
striction of the pupil is frequently designated as miosis (mi-o'-sis)
and the condition of dilatation as mydriasis (myd-ri'-as-is). Many
drugs are known which, when applied directly to the absorptive
surfaces of the eye or when injected into the circulation, affect
the muscles of the iris and therefore vary the size of the pupil.
Those drugs that cause miosis are spoken of as miotics, and those
that produce mydriasis as mydriatics. Atropin, the active prin-
ciple of belladonna, homatropin, and cocain are well-known myd-
riatics, while physostigmin (eserin) and muscarin or pilocarpin are
examples of the miotics. There has been much question as to the
precise action of these drugs. For an adequate discussion of this
question the student is referred to works on pharmacology; but
it may be said that the evidence from the physiological sidej indi-
cates that atropin causes mydriasis by paralyzing the endings of
the constrictor nerve fibers in the sphincter muscle, while phy-
sostigmin and muscarin cause miosis by stimulation of the endings-
of these same fibers. In the case of cocain it is probable that the
drug first stimulates mainly the endings of the dilator fibers in the
dilator muscles, and in stronger doses causes additional mydriasis
by paralyzing the constrictor fibers. The stronger mydriatics
paralyze not only the sphincter pupillse, but also the similarly
innervated ciliary muscle, thus destroying the power of accom-
modation. When atropin is applied to the eye the individual is
unable to use his eyes for near work — reading, for example — until
the effect of the drug has worn off. In ophthalmological literature
this condition of paralysis of the ciliary muscle is spoken of as
cycloplegia, and most of the mydriatic drugs are also cycloplegics.
On the contrary, the stronger miotics stimulate the ciliary muscle,
and therefore during their period of action throw the eye into a
condition of forced accommodation.

* Steinach, "Archiv f. d. gesammte Physiologic," 47, 313, 1890.
fSee Abelsdorff and Feilchenfell, "Zeitschrift f. Psychologic und Phys-
iologic des Sinnesorgane," 34, 111, 1904.

J Schultz, "Archiv f. Physiologic," 1898, 47.

DIOPTRICS OF THE EYE. 309

In the above description of the innervation of the iris and the causes of
mydriasis and miosis the simplest explanations offered have been adopted.
It should be added, however, that some facts are known which indicate that
the conditions are more complex. Thus, Meltzer and Auer* have shown
that in mammals the application of solutions of adrenalin to the eye has no
effect on the iris and the same is true after section of the cervical sympathetic.
But if the superior cervical ganglion is removed the adrenalin causes a maxi-
mal mydriasis. This paradoxical dilatation indicates that the ganglion
has some specific influence upon the iris in addition to serving as part of the
pathway for the pupillodilator fibers, since as long as it is present it prevents
the adrenalin from acting upon the musculature of the iris.

The Balanced Action of the Sphincter and Dilator Muscles
of the Iris. — It would seem that under normal conditions both the
sphincter and the dilator muscle are kept more or less in tonic
activity by impulses received through their respective motor fibers.
They thus balance each other, to speak figuratively, and a mechan-
ism of this kind in which two opposing actions are in play is in a
condition to respond promptly and smoothly to an excess of stimu-
lation from either side. The two muscles, in fact, act as antago-
nists in the same manner as the flexor and extensor muscles around
a joint. At the same time this relation adds some difficulties to
the explanation of specific reactions, since it is evident that a dila-
tation of the pupil may be caused either by a contraction of the
dilator muscle or a loss of tone (inhibition) in the sphincter, while
in constriction of the pupil the effect may result either from a con-
traction of the sphincter or an inhibition of the dilator; or, last,
the contraction of one muscle may always be accompanied by an
inhibition of its antagonist, as is supposed to be the case with the
flexor and extensor muscles of the limbs. Andersonf has given
some evidence to show that the dilatation of the pupil in cats is
due to a double action of this sort, the pupillodilator muscle con-
tracting first and subsequently the tone of the constrictors suf-
fering an inhibition. Alterations in the size of the pupil take place
not only under the conditions described above — namely, the light
and the accommodation reflex and the action of drugs, — but also
under many other circumstances, normal and pathological. In
sleep, for instance, the eyes roll upward and inward and the pupils
are constricted. It would seem probable that the miosis in this case
is due to a cessation in tonic activity on the part of the dilator
muscle rather than to an active contraction of the sphincter muscle,
the state of sleep being characterized by a diminution in activity
in the central nervous system. Emotional states also affect the
size of the pupil and thus aid in giving the facial expressions char-
acteristic of these conditions. Writers speak of the eyes dilating
with terror or darkening with emotions of deep pleasure. This pupil-

* Meltzer and Auer, "American Journal of Physiology," 11, 28, and 40, 1904.
t " Journal of Physiology," 30, 15, 1903.

310 THE SPECIAL SENSES.

lary accompaniment of the emotional states may occur even when
it is a matter of memory rather than immediate experience. The
explanation of this mydriasis can hardly be obtained by experi-
ment, but reasoning from analogy we know that strong emotional
states are usually accompanied by more or less distinct inhibitory
effects on motor centers, and perhaps in this case the reaction is
most satisfactorily explained by attributing it to an inhibition of
the constrictor center in the midbrain.

Intraocular Pressure. — The liquids in the interior of the
eye are normally under a pressure, the average value of which
may be estimated at 25 mms. of mercury. In consequence of
this internal pressure the eyeball is tense and its external surface,
including the cornea, shows a regular curvature. It is obvious
that folds or creases in the cornea would entirely destroy its use-
fulness, so far as the formation of an image is concerned. The
amount of the intraocular pressure may be measured by thrusting
a tubular needle, properly connected with a manometer, into the
anterior chamber of the eye. The liquid in the interior of the
eyeball may be considered as tissue lymph, and like the lymph
elsewhere it is derived from the blood-plasma. Investigation
has shown that the lymph is formed in the ciliary processes, but
in this as in other cases there is a difference of opinion as to whether
the production is due to so-called secretory or to mechanical
causes, such as filtration. The facts that are known seem to
be explicable from the mechanical point of view.* We may
suppose that the liquid filters into the eye through the vessels
in the ciliary processes, and, on the other hand, drains off at the
angle of the anterior chamber through the canal of Schlemm.
The intraocular pressure rises until, under its influence, the out-
flow just balances the inflow. It is evident from this point of
view that intraocular pressure will be increased by any change
that will augment the production of the liquid at the ciliary
processes, such as a rise of blood-pressure, or by any interference
with the outflow, such as might arise from a blocking of the canal
of Schlemm. Certain pathological conditions (glaucoma) are
characterized by an abnormally high intraocular tension, the
difference from the normal being such that it is easily recognized
by pressure with the fingers.

Methods of Determining the Refraction of the Eye. — The condition
of the eye as regards its refraction may be determined by the use of
suitable charts and a series of spherical and cylindrical lenses. The results
by such a method depend largely upon the statements of the patient, that
is to say, they are largely subjective. A number of instruments have been
devised, however, by means of which the refraction of the eye may be studied

* For discussion and literature, see Henderson and Starling, ' Proceed-
ings Royal Society," 1906, B. Ixxvii.

DIOPTRICS OF THE EYE.

311

in a purely objective way, so far as the patient is concerned. The most
important of these instruments are the ophthalmoscope, the retinoscope or
skiascope, and the ophthalmometer. A brief description is given of each
of these instruments, but for the numerous practical details necessary to
their successful use reference must be made to special manuals.

The Ophthalmoscope.— The light that falls into the eye is partly ab-
sorbed by the black pigment of the choroid coat and is partly reflected back
to the exterior. This latter portion is reflected back in the direction in which
it entered. Merely holding a light near
the eye does not, therefore, enatpe us to
see the interior more clearly, since in order
to catch the returning rays in our own
eye it would be necessary to interpose the
head between the source of light and the
observed eye. If, however, we could ar-
range the light to enter the observed eye
as though it proceeded from our own eye,
then the returning rays would be per-
ceived, and with sufficient illumination
the bottom or fundus of the observed eye
might be seen. Arguing in this way,
Helmholtz constructed his first form of
the ophthalmoscope in 1851. The value
of the ophthalmoscope is twofold: It en-
ables the observer to examine the interior
of the eye and thus recognize diseased
conditions of the retina; it is also useful
in detecting abnormalities in the refrac-
tive surfaces of the eye. The principle of
the instrument is well represented in the
original form devised by Helmholtz, as
shown schematically in Fig. 131, A. I
represents the observed eye and II the
eye of the observer. Between the two
eyes is placed a piece of glass inclined at
an angle. Light from the candle falling
upon this glass is in part reflected from
the surface to enter eye 7, and these rays
on emerging from the eye along the same
line pass through the glass in part and
enter eye II. In place of the plane un-
silvered glass it is now customary to use
a concave mirror with a small hole through
the center, the observer's eye being placed
directly behind this hole. Such an in-
strument is shown in Fig. 130. The in-
strument is used in two ways, known as
the direct and the indirect method. In the direct method the mirror is held
very close to the observed eye and the paths of the rays of light into and out
of the eye are represented schematically in Fig. 131, B. The light from a
lamp caught upon the mirror is thrown into the eye, the rays coming to a
focus and then spreading out so as to give a diffuse illumination of the fundus.
This latter surface may now be considered as a luminous object sending out
rays of light. Taking any three objects on the retina, A, B, C, it is apparent
that if eye 7 is an emmetropic eye these points are at the principal focal dis-
tance and the rays sent 'from each after emerging from the eye are in parallel
bundles. These rays penetrate the hole in the mirror and fall into the ob-
server's eye as though they came from distant objects. If the observer's eye
is also emmetropic, or is made so by suitable glasses, these bundles of rays
will be focused on his retina without an act of accommodation. He must, in
fact, in looking through the mirror, gaze, not at the eye before him, but, re-

Fig. 130. — Loring's ophthalmoscope.

312

THE SPECIAL SENSES.

laxing his accommodation, gaze through the eye, as it were, into the distance.
In this way he will see the portion of the retina illuminated, the image of the
objects seen being inverted on his own retina and therefore projected or seen
erect. If the observed eye is myopic its retina is farther back than the prin-
cipal focus of its refracting surfaces; consequently the rays sent out from the
illuminated retina emerge in converging bundles and cannot be focused on
the retina of the observer's eye. By inserting a concave lens of proper power
between his eye and the mirror the observer can render the rays parallel and
thus bring out the image. From the power of the lens used the degree of my-
opia may be estimated. Just the reverse happens if the observed eye is
hypermetropic. In such an eye the retina is nearer than the principal focal

!\

FIG. 131. — Diagrams to represent the principle of the ophthalmoscope: A, The orig-
inal form of ophthalmoscope, consisting of a piece of glass, M, inclined at a suitable angle.
The rays from the source of light are reflected into the observed eye, /, and thence return
along the same lines passing through M to reach the observer's eye, //. B, the direct
method with the ophthalmoscopic mirror. The rays of light illuminate the fundus of the
observed eye, /, and thence pass out in parallel rays, if the eye is emmetropic, to reach the
observer's eye, //. C, the indirect method with ophthalmoscopic mirror and intercalated
lens. The rays of light-red lines are brought to a focus within the anterior chamber of the
eye and thence diverge to give a general illumination of the interior of the eyeball. The
returning rays of light are indicated for a single point, 6. At a', b', d ', a. real inverted image
of a portion of the retina is formed in the air, which in turn is focused on the retina of the
observer's eye.

distance of the refractive surface; consequently the light emitted from the
retina emerges in bundles of diverging rays which cannot be brought to a
focus on the retina of the observer unless he exerts his own power of accom-
modation or interposes a convex lens between his eye and the mirror.

The indirect method of using the ophthalmoscope is represented in Fig.
131, C. The mirror is held at some distance, at arm's length, from the ob-
served eye, I, while just before this eye a biconvex lens of short focus is
placed. As shown in the diagram by the red lines, the reflected light from
the mirror comes to a focus and then diverging falls upon the biconvex lens.
This lens brings the rays to a focus at or near the eye, whence they again
diverge and light up the retina with a diffuse illumination. The light from

DIOPTRICS OF THE EYE. 313

this retina is in turn sent back toward the mirror, its path being indicated for
the point b by the black lines. If the eye is emmetropic the rays from this
point emerge parallel, and falling upon the biconvex lens are brought to a
focus at b'. Similarly the rays from « will be brought to a focus at a' and
from c at c1 '. Consequently there will be formed in the air an inverted image,
and it is at this image that the eye of the observer gazes through the hole in
the mirror. This image forms its image on the retina of the observer's eye,
as represented in the diagram at a", b", c", and is projected outward or seen
inverted as regards the original position of the points in the retina of eye 7.
The indirect method is the one usually employed in ophthalmoscopic exam-
inations of the retina. It gives a larger field than the direct method, although
the objects seen are of smaller size.

The Retinoscope or Skiascope. — When one reflects a spot of light
upon a wall, any movement of the reflecting (plane) mirror is followed by a
movement of the reflected spot in the same direction. So if the fundus of the
eye is illuminated by a plane mirror provided with a peep-hole, the observer
looking through this hole may see a spot of light reflected from the retina
and can determine whether the spot moves in the same direction as the
mirror or against it. If the eye under observation is normal (emmetropic),
then the rays of light starting from the retina will emerge in parallel bundles,
since the retina lies at the principal focal distance, and as the mirror is tilted
from side to side the illuminated spot moves in the same direction. By placing
a convex lens of suitable focus in front of the observed eye we can cause the
emerging parallel rays to come to a focus and cross before reaching the ob-
server's eye. In such a case the movements of the spot of light upon the retina
will be against those of the mirror. For example, let us suppose that the
observing eye is placed just 1 meter away from the eye observed, then if
we put in front of the latter a convex lens of 1.25 D. the emerging rays will be
focused at a point 25 ctm. in front of the observer's eye and the movements
of the spot of light will be against the mirror. A lens of less than 1 D. placed
in front of the observed eye would not bring the rays to a focus in front of
the observer's retina, consequently the movements of the spot would be with
the mirror. Assuming that we are dealing with an emmetropic eye, it can
be shown that at the distance mentioned (1 meter) any lens of less than
1 D. placed in front of the eye leaves the movements with the mirror,
while any lens of more than 1 D. gives movements against the mirror.
Consequently a lens of just 1 D. would mark the exact "point of rever-
sal." With a lens of this power the focus "would fall theoretically just on the
observer's retina. In such a case any movement of the mirror would be
followed by the appearance or disappearance of the spot, but no direction of
movement would be perceived. The movements of the spot of light formed
upon the retina by the retinoscopic mirror may be used to determine all the
various abnormalities of refraction of the eye according to the following
general schema : The observer sits at a fixed distance, say 1 meter, from
the patient, and determines whether the reflected spot from the illuminated
fundus moves with or against the mirror. If the movement is with the mirror,
then the eye under observation is either normal or hyperopic (or if myopic
the myopia is less than ID.). By placing convex lenses in front of the eye
the observer seeks for the point of reversal. If this point is given by a lens
of + ID., then the eye under examination is emmetropic ; if a stronger lens
is required the eye is hyperopic, that is, the emerging rays are divergent and
require a stronger lens to bring them to a focus before reaching the observer's
eye. In the latter case the amount of hyperopia is obtained by ascertaining
the strength in diopters of the lens required to just reverse the movement
and subtracting 1 D. from it, since the latter amount is required, at a distance
of 1 meter, to get reversal with the normal eye. If the reversal is given by
a convex lens of less than ID., then the eye is myopic to an extent less than
1 D. When the movements of the spot of light are against the mirror
from the beginning, then the observer is dealing with a myopic eye (the myopia
being greater than 1 D.). To reverse the movement it is now necessary to
place concave lenses in front of the observed eye until the point of reversal
is obtained, that is, until the focus of the emerging rays falls behind the

314 THE SPECIAL SENSES.

retina of the observer. The concave lens necessary to give this result, plus 1 D.
for distance, gives the extent of the myopia in diopters. With astigmatic
eyes the point of reversal may be determined for the different meridians
of the eye, the movements of the mirror being in the same meridian. By
the character of the reflected spot and the points of reversal it is possible
with the retinoscope to determine the principal meridians, and the difference
in refraction between them, that is, the degree and the axis of the astigmatism.
The Ophthalmometer. — The ophthalmometer is an instrument for
measuring the curvature of the refracting surfaces of the eye. As actually
applied in practise it is arranged especially for measuring the curvatures
of the cornea along its different meridians. The point for which the instru-
ment is designed is to obtain the size of the image reflected from the convex
surface of the cornea. Any luminous object placed in front of the eye will give
a reflected image from the cornea as from the surface of a convex mirror.
If the size of the object and its distance from the cornea are known and the
size of the corneal image is determined, then the radius of curvature of the

cornea is given by the equation r = ?_, in which p represents the distance of

Fig. 132. — Schema to indicate the general principle of the ophthalmometer: Tf
Telescope to observe the reflected images from the cornea ; A and B, the targets or mires
in the shield at a known distance apart whose images are reflected from the cornea ; a
and 6, the reflected images of A and B on the cornea. The distance a-b has to be determined.

the object from the cornea, i, the size of the corneal image, and o. the size
of the object. For example, let A and B in Fig. 132 be two luminous areas
arranged on the arc of a circle. If placed in front of the cornea C each
will give a reflected image a and 6, which may be observed by means of
the telescope T. The distance between A and B represents the size of
the object and the distance between a and b the size of the image. This
latter factor is determined by means of the telescope. A scale, for in-
stance, might be placed in the eye-piece of the telescope and the distance
a-6 be determined in terms of its graduation. This valuation might then be
converted into millimeters by substituting a scale for the cornea and measuring
off upon it the observed distance in the eye-piece scale. If the arc carrying
AB is arranged so that it may be rotated it is obvious that the size of the
corneal images may be measured for the different meridians and thus enable
one to compare their curvatures. In modern instruments, such as is repre-
sented in Fig. 133, the luminous areas, known as targets or mires, are placed in a
spherical shield which may be rotated around the axis of the telescope. The
shield has a radius of curvature of 0.35 meters and its center of rotation is
approximately coincident with that of the cornea when the eye is in its
proper position. The reflected images of the mires from the surface of the

DIOPTRICS OF THE EYE.

315

cornea are each doubled, when viewed through the telescope, by means of
a double vision prism of Iceland spar and the displacement produced in
this way is a definite amount for the distance chosen. Four images of the
mires are thus seen, and when the mires are properly adjusted for a cornea of
average curvature the two inner images are in contact with each other.
A variation from this average is indicated by an overlapping of the images,

Fig. 133.— Ophthalmometer (Hardy).

the value of which in diopters or in radii of curvature is read off upon the
instrument, The instrument, therefore, when once calibrated enables one
to read off at once the radii of curvature for the different meridians and thus
determine the axis and degree of astigmatism. It should be added that
the instrument gives only the curvatures and degree of astigmatism, if any
exists, of the cornea, and is therefore of no immediate service in determining
the total astigmatism, that is, the astigmatism of cornea and lens acting
together.

CHAPTER XVIII.

THE PROPERTIES OF THE RETINA— VISUAL STIMULI
AND VISUAL SENSATIONS.

The Portion of the Retina Stimulated by Light. — The normal
stimulus to the sensory cells in the retina is found in the vibrations
of the ether, the waves of light. When sunlight is passed through a
prism the waves of different lengths are dispersed, and those capable
of stimulating the retina form the visible spectrum extending from
red to violet. The limits of the spectrum are, on the one hand, the
extreme red rays with a wave length of T winnr mm- and vibrating
at the rate of about 390,000,000,000,000 a second, and, on the other,
the extreme violet, having a wave length of about i oo Sfinnr mm- and
a rate of vibration of 757,000,000,000,000 a second. The part of
the retina stimulated by these vibrations is supposed to be the layer
Of rods and cones. To reach these structures the light must pass

Fig. 134. — To demonstrate the blind spot. Fix the center of the cross with the right
eye, then move the book slowly to or from the face. At a certain distance the image of
the large circle to the right will disappear. At this distance the image of the circle falls
on the optic disc.

through the other layers of the retina. That the rods and cones are
the structures that react to the light stimulation is indicated by
their structure and their connections and by such facts as the follow-
ing: Under certain conditions, which are described below, the
shadows of the retinal vessels and the contained corpuscles may be
seen, a fact which indicates that the perceiving structures lie ex-
ternally to these vessels. In the fovea centralis, in which vision is
most perfect, the layers of the retina are thinned out until practically
only the rods and cones remain to be acted upon. That the optic
nerve fibers themselves are not acted upon by light waves is proved
by the existence of the blind spot. The termination of the optic
nerve within the eyeball, the optic disc, lies about 15 degrees to the
nasal side of the fovea and has a diameter of about 1.5 mms. From

316

PROPERTIES OF THE RETINA. 317

this point the nerve fibers spread out over the rest of the optic cup
to form the internal layer of the retina. But the optic disc itself has
no retinal structure, and light that falls upon it is not perceived.
The presence of this blind spot in our visual field is easily demon-
strated by the experiment illustrated and described in Fig. 134.
In the visual field for each eye, therefore, there is a gap representing
the projection of the area of the optic disc to the exterior, the size
of the gap increasing with the distance from the eye. We do not
notice this deficiency, inasmuch as it exists in our indirect field of
vision (see below), in which our perception of form is poorly de-
veloped; so that any disturbance in outline that might result in the
retinal image of external objects is unperceived. Morever, the
portion of the external world that falls on the blind spot of one eye
falls on the retinal field of the other, and is thus perceived in binoc-
ular vision. It is to be borne in mind, also, that the projection of
the blind spot does not appear in the visual field as a dark area ; it
is simply an absent area, so that no gap exists in our consciousness of
the spatial relations of the visual field; the margins, so to speak, of
the hole come into contact so far as our consciousness is concerned.
The Action Current Caused by Stimulation of the Retina.—
The effect of light waves falling upon the retina is to set up a series
of nerve impulses in the optic nerve fibers. It is interesting to
find that these impulses aroused in a sensory nerve by a normal
stimulus are attended by electrical changes similar to those observed
in motor fibers when stimulated normally or artificially. The fact
strengthens the view that the electrical change is an invariable ac-
companiment of the nerve impulse, if not the nerve impulse itself.
If the eye is excised and connected with a galvanometer or capillary
electrometer by two non-polarizable electrodes, one placed upon the
cut end of the optic nerve and the other on the cornea, the usual
demarcation current is obtained due to the injury to the optic nerve.
If the preparation is kept in the dark and arrangements are made
to throw a light through the pupil upon the retina the galvanometer
indicates an electrical change or current whenever the light is
admitted.* The direction of the current in the eyeball is from the
fundus to the cornea, and as regards the pre-existing demarcation
current it is in the same direction and forms, therefore, a so-called
positive variation. When the electrodes are placed on the longi-
tudinal and the cut surface of the optic nerve, then, according to
Kuhne, the electrical response to light is a negative variation similar
to that described for stimulation of nerves in general (p. 96). Not
only is there a " light response " each time that the retina is stimu-
lated by light, but there is a similar electrical change, a " dark re-

* Dewar and McKendrick, "Transactions, Royal Society, Edinburgh," 27,
1873; Gotch, "Journal of Physiology," 29, 388, 1903, and 31, 1, 1904.

318 THE SPECIAL SENSES.

sponse," when the light is suddenly withdrawn. This last interest-
ing fact would seem to indicate a stimulation process of some kind
in the retina due to darkness, — that is, withdrawal of the objective
stimulus. The reaction is a very sensitive one, lights so weak as to
be near the threshold for the human eye give a distinct electrical
change in the frog's retina, and an eye that has been kept in the
dark for some time (dark-adapted eye) shows an increased sensitive-
ness. It is very interesting, also, to find that the frog's retina
responds to a range of light vibrations that corresponds with the
limits of the visible spectrum as seen by the human eye. If the
electrical response is a true indication of functional activity it
would appear that the frog's vision has about the same extent as
our own as regards the ether waves of different periods of vibration.
The Visual Purple— Rhodopsin. — The change that takes place
in the rods and cones whereby the vibratory energy of the ether
waves is converted into nerve impulses is unknown. It has been
assumed by some observers that the light waves act mechanically,
the wave movements setting into vibration portions of the external
segments of the rods or cones, and that this mechanical movement
forms the direct excitant of the nerve impulses.* The general
view, however, is that the process is photochemical, — that is, the
impact of the ether waves sets up chemical changes in the rods or
cones which in turn give rise to nerve impulses that are transmitted
to the brain. We have an analogy for this action in the known
change produced by light upon sensitized photographic films. In
the retina itself some basis for such a view is found in the existence
of a red pigment which is bleached by light. This interesting dis^
covery was made by Boll,f and the facts were afterward carefully
investigated by Kiihne.J The red pigment, known usually as
visual purple or rhodopsin, is found only in the external segments
of the rods; the cones do not contain it. In the fovea, therefore,
which has only cones, the pigment is entirely absent. The existence
of the visual purple may be demonstrated very easily. A frog is
kept for some time in the dark; it is then killed and an eye removed
and bisected equatorially. If the vitreous is removed from the pos-
terior half the retina may be detached by means of a pair of forceps.
When the operation is performed in red or yellow light, as in photo-
graphic work, the detached retina on examination by daylight is
found to be a deep-red color; but after a short exposure it fades
rapidly, finally becoming colorless. If the frogs before operation
were exposed to strong daylight, the retina is found to be

* Zenker, "Archiv f. mik. Anatomie," 3, 248, 1867.

fBoll, "Archiv f. Physiologic," 1877, 4.

j Kiihne, "Untersuch. a. d. physiol. Inst. d. Univ. Heidelberg," vol. i,
1878. Also "The Photochemistry of the Retina, etc.," translated by Foster,
London, 1878.

PROPERTIES OF THE RETINA. 319

colorless. A similar pigment is found in the eyes of man and
the other mammalia. It has been shown, moreover, that a photo-
graph may be made upon the surface of the retina by means of this
purple. If the head of a rabbit or frog that has been kept in the
dark for some time is exposed with proper precautions to the light
of a window, for instance, the part of the retina on which the image
of the window-lights falls will be bleached, while the parts upon
which the image of the window-bars falls and the surrounding areas
of the retina will retain their red color. A figure of such a retinal
photograph or optogram, as it is called, is represented in the accom-
panying illustration (Fig. 135) . The visual purple has been extracted
from the rods by solutions of bile salts, this substance having the
power to discharge the pigment from its combination in the rods in
the same way as it discharges hemoglobin from its combination in
the red corpuscles. The solutions thus obtained are also bleached
upon exposure to light. We have in the visual purple, therefore,
an unstable substance
readily decomposed or
altered by the me-
chanical effect of the
ether waves, and also,
it may be said, by
gross mechanical re-
actions, such as com-
pression; and there Fig i«._Op*ot*m in eye of rabbit: 1, The nor-
Can be little doubt rna^ appearance of the retina in the rabbit's eye: a, The
entrance of the optic nerve; b, b, a colorless strip of

that the Substance medullated nerve fibers; c, a strip of deeper color sepa-
, . rating the lighter upper from the more heavily pigmented

plaVS an important lower portion. 2 shows the optogram of a window.

part in the functional

response of the rod elements. It has been shown that provision
exists in the retina for the constant regeneration of this red pigment.
It will be remembered that the external segments of the rods im-
pinge upon the heavily pigmented epithelial cells that lie between
the rods and the choroid coat. From experiments upon frogs' eyes
it appears that a portion of the retina detached from the pigment
cells and bleached by the action of light is not able to regenerate its
visual purple until again laid back upon the choroid coat. This
regenerating influence of the black pigmented cells may be con-
nected with another interesting relation that they exhibit. Under
normal conditions delicate processes extend from these cells and
penetrate between the rods and cones. When the eye is exposed
to light the black pigment migrates along these processes as far even
as the external limiting membrane, and it is possible that this ar-
rangement may be useful in obviating diffuse radiation of light
from one rod to another. When the eye is kept in the dark, however,

320 THE SPECIAL SENSES.

the pigment moves outwardly and collects around the external
segments, where the process of regeneration of the visual purple is
taking place. Further evidence that the visual purple is connected
with the irritability of the rods toward light stimulation is shown
by the fact that when it is exposed to the different rays of the spec-
trum the absorption of light is greatest in that part of the spec-
trum (green) which appears the brightest in vision when carried out
under such conditions as may be supposed to involve the activity
chiefly of the rods (see below for these conditions). It is, however,
perfectly obvious that visual purple is not essential to vision. The
fact that it is absent from the fovea centralis is alone sufficient
proof of this statement. Moreover, it seems to be absent entirely
in the eyes of some animals; for instance, the pigeon, hen, some
reptiles, and some bats. The most attractive view of the function
of the visual purple is that it serves to increase the delicacy of re-
sponse or irritability of the rods in dim lights, — a view that is ex-
plained in more detail in the paragraph below, dealing with the sup-
posed difference in function between the rods and cones.

The Extent of the Visual Field— Perimetry.— By the visual field
of each eye is meant the entire extent of the external world which
when the eye is fixed forms an image upon or is projected upon the
retina of that eye. From what has been said previously regarding
the dioptrics of the eye it is obvious that the visual field is inverted
upon the retina, and that, therefore, objects in the upper visual field
fall upon the lower half of the retina, and objects in the right half
of the visual field fall upon the left half of the retina. Since the
retina is sensitive to light up to the ora serrata, it is evident that if.
the eye were protruded sufficiently from its orbit its projected visual
field when represented upon a flat surface would have the form of a
circle the center of which would correspond to the fovea centralis.
As a matter of fact, the configuration of the face is such as to cut
off a considerable part of this field and to give to the field as it
actually exists an irregular outline. The bridge of the nose, the
projecting eyebrows and cheek bones serve to thus limit the field.
To obtain the exact outline and extent of the visual field in any given
case it is only necessary to keep the eye fixed and then to move a
small object in the different meridians and at the same distance
from the eye. The limits of vision may be obtained in this way
along each meridian and the results combined upon an appropriate
chart. An instrument, the perimeter, has been devised to facilitate
the process of charting the visual field. It has been given a number
of different forms, one of which is illustrated in Fig. 136. The shape
of the visual fields in the normal eye is represented in Fig. 137.
The determination of the visual fields is of especial importance in
cases of brain lesions involving the visual area in the occipital lobe.

PROPERTIES OF THE RETINA.

321

The extent and portion of the retina affected may be used to aid in
locating the seat of the lesion. For physiological and for clinical
purposes it is necessary to distinguish between the central (or direct)
and the peripheral (or indirect) fields of vision. The former term
is meant to refer to that portion of the field which falls upon the
fovea centralis; in other words, it is the projection, in any fixed

Fig.
n obj

136. — Perimeter. The semicircular bar may be placed in any meridian. A
gven oject is then moved along the bar from without in until it is just perceived. The
angular distance at which this occurs is marked off on the corresponding meridian on the
chart seen at the left of the figure. The eye examined gazes over the top of the vertical
rod at the right at a fixed point in the middle of the semicircular bar.

position of the eye, of the fovea into the external world. The
peripheral field refers to the rest of the visual field involving the
retina outside the fovea. As a matter of fact, all of our distinct and
most useful vision in the daytime at least is effected through the
fovea. When the eye is kept fixed the small portion of the external
world that falls upon the fovea is seen distinctly. All the rest is
seen more or less indistinctly in proportion to the distance of its

21

322

THE SPECIAL SENSES.

retinal image from the fovea. In using our eyes, therefore, we keep
them continually in motion so as to bring each object, as we pay
especial attention to it, in the field of central vision. The line
from the fovea to the point looked at is designated as the line of
sight. The area of the fovea is quite small. The measurements
given by different observers vary somewhat, especially as in some
cases the measurements are estimated for the bottom of the de-
pression, the fundus, and in others for the diameter from edge to
edge. The average diameter is usually given as lying between 0.3
and 0.4 mm. Lines drawn from the ends of this diameter to the

06L 081

Fig. 137. — Perimeter chart to show the field of vision for a right eye when kept in a fixed

position.

nodal point of the eye subtend an angle of 1 degree to 1 .5 degrees ;
and therefore all objects in the external world around the line of
sight whose visual angle is within this limit are comprised in the
central field of vision, and their retinal images fall upon the fovea.
Unilateral lesions of one occipital lobe cause half-blindness (hemi-
opia) in the retinas on the same side, — that is, lesions in the right
occipital lobe cause blindness of the right halves of the retinas, while
injuries to the left occipital lobes are accompanied by loss of vision
on the left sides of the retinas (see p. 195); but such unilateral
lesions, it is stated, do not involve the central field of vision — only
the peripheral portion of the field is affected. In connection with

PROPERTIES OF THE RETINA. 323

its special functions in vision the fovea centralis possesses a peculiar
structure. It forms a shallow depression in the center of the retina
described by some authors as elliptical, by others as circular in out-
line. In the center of the fovea lies a smaller, very shallow depres-
sion spoken of as the foveola. The diameter of the fovea, as stated
above, is estimated differently by different authors. While meas-
urements on preserved specimens give the diameter as 0.2 to
0.4 mm., ophthalmoscopic examination seems to indicate that in
the fresh state it may be larger. According to Fritsch,* the fundus,
reckoned from the point at which the depression begins, has a diam-
eter of 0.5 to 0.75 mm. Within the fovea cones only are present,
and these cones are longer and more slender (diameter, 0.002 mm.)
than in the rest of the retina. Moreover, the thickness of the retina
is much reduced in the fovea, whence arises the depression. At
this point the cones are practically exposed directly to the light,
whereas in other parts the light must penetrate the other layers
before reaching the rods and cones. Lying around the fovea is an
area about 6 mm. in diameter, of a yellowish color, and hence
known as the macula lutea. According to recent observers f
the yellow color of the macula is due to post-mortem changes.
In a normal retina this area does not show a yellow color and
there is, therefore, no reason why it should be given a special desig-
nation.

Visual Acuity. — The distinctness of vision varies greatly in
different parts of the retina. It is usually measured by bringing
two fine lines closer and closer together until the eye is unable
to see them as two distinct objects. Measured in this way it is
usually stated that when the distance between the lines subtends an
angle of 1 minute (60 seconds) at the eye the limit of visibility is
reached. This angle on the retina comprises an area of about 0.004
mm. in diameter, sufficient to cover two cones in the fovea. A
simpler method to ascertain the size of a just perceptible image
on the retina is to use a black spot upon a white background. At a
sufficient distance this object will be invisible, but if brought closer
to the eye it will be just seen at a certain distance. The diameter
of the spot being known, and its distance from the eye, the size of the
retinal image may be calculated. Using this method, Guillery J
estimated the size of the just perceptible retinal image, or, as it
has been appropriately called, the physiological point, at 0.0035 mm.
These estimates apply only to the fovea, and, indeed, to the central
part of the fovea, the foveola. Numerous authors have called
attention to the fact that the size of the physiological point for the
fovea varies with the intensity of illumination. The estimates

243, 1896.

324

THE SPECIAL SENSES.

given are for ordinary room light. Out of doors, and especially in
the case of persons who live habitually an outdoor life, the physio-
logical point is smaller — less than half the size given above. We
may believe, therefore, that under the most favorable conditions
we can perceive an object whose image on the fovea is less than the
diameter (0.002 mm.) of a single cone. The acuity of vision does
not vary greatly throughout the fovea; any object whose retinal
image falls well within the fovea can be seen quite distinctly in all
of its parts when the eye is fixed for the center of the object. This

30

30

10° 3* 0°

10

40°

fff

Fig. 138. — Curve to show the relative acuity of vision in the central and peripheral
fields and in the light-adapted and the dark-adapted eye. — (Koester.) The full line repre-
sents the relative acuteness of vision in the eye exposed to usual illumination. From the
center of the fovea, 0°, the acuity of vision falls rapidly at first and then more slowly as one
passes outward into the peripheral field. The dotted line represents the acuity of vision in
dim lights. The fovea, it will be noticed, is less sensitive than the parts of the retina at an
angular distance of 10° or even 60°.

is the case, for instance, with the moon. Nevertheless, in looking
at such an object as the moon the eye to make out details will
fixate one point after another, showing that for most distinct
vision we use probably only the center of the fovea. As we pass out
from the fovea in the peripheral field of vision the acuity of vision
diminishes at first very rapidly, so that at 20 degrees, for instance,
from the center of the fovea the physiological point on the retina is

PROPERTIES OF THE RETINA. 325

0.035 mm.; that is, it has a diameter ten times as large as in the
fovea. On this account our vision in the peripheral field is very
indistinct, — details of form cannot be clearly perceived. The
rapidity with which visual acuity diminishes as we pass outward
from the fovea is indicated by the curve given in Fig. 136. In all
<?lose work, therefore, we keep our eyes moving continually so as to
bring one point after another into the center of the fovea, as is well
illustrated by the act of reading. If the eye is kept fixed upon the
central letter of a long word, only one or two letters on each side
oan be made out distinctly in spite of the fact that with such
familiar objects we can guess the letter even when the image is not
entirely distinct. In ophthalmological practice the acuity of vision
(central vision) is measured usually by test letters whose size is
such that at the distance at which they are read — say, 6 meters (20
feet), the practical far point at which no accommodation is needed —
•each subtends at the eye an angle of 5 minutes. An eye that can
distinguish the letters at this distance is said to be normal ; one that
can distinguish them only at a smaller distance or at the given
distance requires letters of larger size has a subnormal acuity of
vision. If, for instance, an individual at 20 feet can read only
those letters that the normal eye can distinguish at 100 feet his
visual acuity, V, is equal to •&$.

Relation between the Amount of Sensation and the Intensity
of the Stimulus — Threshold Stimulus. — With the sensory as with
the motor nerves we may distinguish between various degrees of sub-
maximal stimulation. The stronger the stimulus, the stronger the
reaction, — that is, in the case of the optic nerve, the visual sensation.
The end reaction of the activity of a sensory nerve is a state of con-
sciousness. The variations in magnitude of this state can not be
measured with objective exactness, they must be judged subjectively
by the individual concerned. A stimulus too weak to give a re-
sponse with a motor nerve is usually designated in physiology as
subminimal ; a similar stimulus with sensory nerves is frequently
expressed by the equivalent term subliminal, — that is, below the
threshold. So a stimulus just strong enough to provoke a percep-
tible reaction is the minimal stimulus for efferent nerves and the
threshold stimulus for sensory nerves. Inasmuch as the variations
in the intensity of consciousness can not be adequately measured,
it is customary, in studying the relations of the strength of stimulus
to the conscious response, to pay attention to the strength of stimu-
lus under any given condition which is sufficient to arouse a just
perceptible difference in the conscious reaction. Proceeding upon
this method, it is found in the case of the visual sensations and the
optic nerve, as with other sensations and their corresponding nerves,
that the increase of stimulus necessary to cause a just perceptible
•change in consciousness varies with the amount of stimulus already

326 THE SPECIAL SENSES.

acting. If, for instance, the retina is being stimulated by a light of
1 candle power an increase of illumination to 1.1 candle power may
make a perceptible difference in sensation. But if the retina is-
being illuminated by a light of 10 candle power an increase to 10.1
candle power would probably make no perceptible difference. For
a certain range of stimulation, in fact, it has been stated that the
increase in stimulus must be a constant fractional part of the stimu-
lus already acting. That is, in the hypothetical case given, if, with
1 candle power, an increase to 1.1 candle power makes a just per-
ceptible difference in consciousness, then with 10 candle power an
increase of y^- of the acting stimulus, namely — 1 candle power — will
be necessary to cause a perceptible difference. The relation as
expressed in this form is known as Weber's law ; but it seems prob-
able that, while the general fact is true, this exact expression of it
holds only approximately for an intermediate range of stimulation.
In this matter of a threshold stimulus the sensitiveness .of the
retina shows also certain interesting differences in the foveal a&
compared with the peripheral field. The difference is especially
marked when the reaction of the retina in strong lights is compared
with its reaction in dim lights.

The Light-adapted and the Dark-adapted Eye. — The con-
dition of the retina changes when after exposure to light it is sub-
mitted to darkness, the change being most marked in the peripheral
field. When one passes from daylight into a dark room vision
at first is very imperfect, but after some minutes rapidly im-
proves, "as the eye becomes accustomed to the dark." The
change is known as an adaptation, and in this respect the retina
differs from the sensitive photographic plate. Comparison of the
threshold stimulus for different parts of the retina, in an eye
exposed alternately to darkness and to light, has shown that
in the dark the sensitiveness in the peripheral field increases
greatly during an hour or so, while that of the foveal field is appar-
ently unchanged. With such a dark-adapted eye, therefore,
there will be a certain dim light which will be seen by the per-
ipheral parts of the retina, but perhaps will cause no reaction
upon the fovea. For such a degree of light, therefore, the fovea
would be blind. This general fact has, indeed, long been known.
Anyone may notice in late twilight, when the stars are beginning
to appear, that a very faint star may disappear when looked at, — that
is, when its image is brought upon the fovea ; to see it one must direct
his eyes a little to the side, so as to bring its image into the periph-
eral field. This greater sensitiveness of the dark-adapted eye in
the peripheral field where the rods predominate over the cones seems
to be associated with the movement of the pigment in the pigment
epithelium (see above) and the resulting regeneration of the visual
purple in the external segments of the rods. The increase in the

PROPERTIES OF THE RETINA. 327

visual purple in the dark may, indeed, account for the increased
sensitiveness to light in the rod-region and explain why a similar
increase fails to occur in the fovea, where only cones are present.
The curve given in Fig. 138 shows that in the dark-adapted eye
the acuity of vision in the peripheral field is greater than in the
fovea. In accordance with these facts von Kries* has suggested that
the rods, the peripheral field of the retina, are especially adapted
for vision in dim lights, night4 vision, while the cones are especially
adapted for vision in strong lights, day vision. This general fact
will perhaps accord with the experience of anyone who attempts
to estimate the value of his peripheral vision in dim nightlight as
compared with daylight. Other interesting differences in the reac-
tion of the light-adapted and the dark-adapted eye are referred to
below in connection with color blindness.

CHARACTERISTICS OF THE VISUAL SENSATIONS.

In addition to the spatial attributes connected with our visual
sensations — that is, the perception of form — they are characterized
by two properties which may be described in general as variations
in intensity and in quality.

Luminosity or Brightness. — That characteristic which we
describe as the luminosity or brightness of a visual sensation has
been defined differently by various writers. We may consider it,
however, as the expression of the intensity of the acting stimulus.
Sensations of the same quality are easily compared as regards their
brightness. We can tell as between two whites or two greens which
is the brighter of the two, but when two different qualities — a red
and a green sensation, for instance — are compared our subjective
determination of the relative brightness is, for most persons, difficult
or impossible to make. To a lesser degree the difficulty is similar
to that of the comparison of sight and sound. According to the
conception adopted here, however, that the brightness is an ex-
pression of the intensity of the stimulus, an objective standard of
comparison might be obtained by measuring the resulting action cur-
rents in the optic nerve fibers. When the spectral colors are ex-
amined it is obvious that some of the colors are brighter than others,
the extreme red and extreme violet, for instance, possessing little
luminosity as compared with the yellow. The relative brightness
of the different spectral colors is found to vary with the amount of
illumination, as is shown in the curves given in Fig. 139. With a
brilliant spectrum the maximum brightness is in the yellow, but
with a feeble illumination it shifts to the green. This fact accords
with what is known as the "Purkinje phenomenon," — namely, the

* Von Kries, "Zeitschrift f. Psychologic u. Physiologie d. Sinnesorgane/*
9, 81, 1895.

328

THE SPECIAL SENSES.

changing luminosity and color value of colors in dim lights. As the
light becomes more feeble the colors toward the red end of the
spectrum lose their quality, the blue colors being perceived last of
all, just as in late twilight it may be noticed that the sky remains
distinctly blue after the colors of the landscape become indistin-
guishable. It should be added that the " Purkinje phenomenon "
is true only for the parts of the retina lying outside the fovea,
that is, for the peripheral field. As the light grows dimmer the
perception of blue is lost first in the fovea, so that with a certain

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Fig. 139. — Diagram showing the distribution of the intensity of the spectrum as de-
pendent upon the degree of illumination. The spectrum is represented along the abscissa,
the numerals giving the wave lengths from red, 670, to violet, 430. The ordinates give
the luminosity of the different colors. Eight curves are given to show the changes in
distribution of relative brightness with changes in degree of illumination. With the
greatest illumination the maximum brightness is in the yellow (605-625); with weaker
illumination it shifts to the green (535) . — (Konig. )

feebleness of illumination the central field becomes blue-blind.
With a very feeble illumination the dark-adapted eye becomes
practically totally color blind.

Qualities of Visual Sensations. — The different qualities of our
color sensations may be arranged in two series: an achromatic
series, consisting of white and black and the intermediate grays,
and a chromatic series, comprising the various spectral colors, to-
gether with the purples made by combination of the two ends of
the spectrum, red and blue, and the colors obtained by fusion of

PROPERTIES OF THE RETINA. 329

the spectral colors with white or with black, such, for instance, as
the olives and browns.

The Achromatic Series. — Our standard white sensation is that
caused by sunlight. Objects reflecting to our eye all the visible
rays of the sunlight give us a white sensation. This sensation,
therefore, is due primarily to the combined action of all the visible
rays of the spectrum, each of which, taken separately, would give
us a color sensation. White 'or gray may be produced also by the
combined action of certain pairs of colors, — complementary colors, —
as is described below. Black, on the contrary, is the sensation
caused by withdrawal of light. It must be emphasized that in
order to see black a retina must be present. It is probable that
a person with both eyes enucleated has no sensation of darkness.
That black is a sensation referable to a condition of the retina is
made probable also by the interesting observations recorded by
Gotch,* — namely, that when an eye that has been exposed to light
is suddenly cut off from the light there is an electrical change in the
retina, a dark response, similar to that caused by throwing light on
a retina previously kept in the dark. Blackness, therefore, is a
sensation produced by withdrawing light from the retina, and a
black object is one that reflects no light to the eye. Black may be
combined with white to produce the series of grays, and when com-
bined with the spectral colors it gives a series of modified color tones,
thus the olives of different shades may be considered as combina-
tions of green and black in varying proportions.

The chromatic series consists of those qualities to which we give
the name of colors, and, as stated above, they comprse the spectral
colors, and the extraspectral color, purple, together with the light-
weak and light-strong hues obtained by combining the colors with
white or black. In the spectrum many different colors may be.
detected, — some observers record as many as one hundred and
sixty, — but in general we give specific names only to those that
stand sufficiently far apart to represent quite distinct sensations, —
namely, the red, orange, yellow, green, blue, and violet. When
light is taken from a definite limited portion of the spectrum we
have a monochromatic light that gives us a distinct color sensation
varying with the wave length of the portion chosen.

Color Saturation and Color Fusion. — The term saturation as
applied to colors is meant to define their freedom from accompany-
ing white sensation. A perfectly saturated color would be one
entirely free from mixture with white. On the objective side it is
easy to select a monochromatic bundle of rays from the spectrum
without admixture of white light, but on the physiological side it is
not probable that the color sensation thus produced is entirely free
* Gotch, "Journal of Physiology," 29, 388, 1903.

330 THE SPECIAL SENSES.

from white sensation, since the monochromatic rays may initiate
in the retina not only the specific processes underlying the pro-
duction of its special color, but at the same time give rise in some
degree to the processes causing white sensations. Even the spectral
colors are therefore not entirely saturated, but they come as near
to giving us this condition as we can get without changing the state
of the retina itself by previous stimulation.

Color Fusion. — By color fusion we mean the combination of two
or more color processes in the retina, this end being obtained by
superposing upon the same portion of the retina the rays giving
rise to these color processes. It must be borne in mind that color
fusion upon the retina is quite a different thing from color mixture
as practised by the artist. A blue pigment, such as Prussian blue,
for instance, owes its blue color to the fact that when sunlight falls
upon it the red-yellow rays are absorbed and only the blue, with
some of the green, rays are reflected to the eye. So a yellow pig-
ment, chrome yellow, absorbs the blue, violet, and red rays and
reflects to the eye only the yellow with some of the green rays. A
mixture of the two upon the palette will absorb all the rays except
the green and will therefore appear green to the eye. If, however,
by means of a suitable device, we throw simultaneously upon the
retina a blue and a yellow light, the result of the retinal fusion is
a sensation of white. Many different methods have been employed
to throw colors simultaneously upon the retina, the most perfect
being a system of lenses or mirrors by which different portions of
a spectrum can be superposed. The usual device employed in
laboratory experiments is that of rotation of discs of colored paper.
Each disc has a slit in it from center to periphery so that two discs
can be fitted together to expose more or less of each color. If a
combination of this kind is attached to a small electrical motor it
can be rotated so rapidly that the impressions of the two colors
upon the retina follow at such a short interval of time as to be prac-
tically simultaneous.

The Fundamental Colors. — By the methods of color fusion
it can be shown that three colors may be selected from the spec-
trum whose combinations in different proportions will give white,
or any of the intermediate color shades, or purple Considered
purely objectively, a set of three such colors may be designated
as the fundamental colors, and red, yellow, and blue, or red,
green, and violet have been the three colors selected. On the
physiological side, however, it has been assumed that there are
certain more or less independent color processes — photochemical
processes — in the retina which give us our fundamental color sen-
sations, and that all other color sensations are combinations of these
processes in varying proportions with each other or with the proc-

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PROPERTIES OF THE RETINA. 331

esses causing white and black. Referring only to the colors proper,
the fundamental color sensations according to some views are red,
green, and blue or violet; according to others, they are red, yellow,
green, and blue. (See paragraph on Theories of Color Vision.)

Helmholtz calls attention to the fact that the names used for these funda-
mental color sensations are obviously of ancient origin, thus indicating that
the difference in quality of the sensations has been long recognized. Red is
from the Sanskrit rudhira, blood; blue from the same root as blow, and re-
fers to the color of the air ; green from the same root as grow, referring to the
color of vegetation. Yellow seems to be derived from the same root as gold,
which typified the color. The other less distinct qualities have names of
recent application, such as orange, violet, indigo blue, etc.

Complementary Colors. — It has been found by the methods of
color fusion that certain pairs of colors when combined give a white
(gray) sensation. It may be said, in fact, that for any given color
there exists a complement such that the fusion of the two in suitable
proportions gives white. If we confine ourselves to the spectral
colors we recognize such complementary pairs as the following:

Red and greenish blue.

Orange and cyan blue.

Yellow and indigo blue.

Greenish yellow and violet.

The complementary color for green is the extraspectral purple.
Colors that are closer together in the spectral series than the
complementaries give on fusion some intermediate color which is
more saturated — that is, less mixed with white sensation — the nearer
the colors are together. Thus, red and yellow, when fused, give
orange. Colors farther apart than the distance of the comple-
mentaries give some shade of purple. On the physical side, there-
fore, we can produce a sensation of white in two ways : Either by the
combined action of all the visible rays of the spectrum (sunlight)
or by the combined action of pairs of colors whose wave lengths vary
by a certain interval. It is probable that in the retina the processes
induced by these two methods are qualitatively the same, the
wave-lengths represented by the complementary colors setting up
by their combined action the same photochemical processes that
normally are induced by the sunlight.

After-images. — As the name implies, this term refers to images
that remain in consciousness after the objective stimulus has ceased
to act upon the retina. They are due doubtless to the fact that the
changes set up in the retina by the visual stimulus continue, with
or without modification, after the stimulus is withdrawn. After-
images are of two kinds: positive and negative. In the positive
after-images the visual sensation retains its normal colors. If one
looks at an incandescent electric light for a few seconds and then

THE SPECIAL SENSES.

closes his eyes he continues to see the luminous object for a con-
siderable time in its normal colors. Objects of much less intensity
of illumination give positive after-images, especially when the
eyes have been kept closed for some time, as, for instance, upon
waking in the morning. In negative after-images the colors are all
reversed, — that is, they take on the complementary qualities (see
Fig. 140). White becomes black, red a bluish green, and vice versa.
Negative after images are produced very easily by fixing the eyes
steadily upon a given object for an interval of twenty seconds or
more and then closing them. In the case of colored objects the
after-image is shown better, perhaps, by turning the eyes upon a
white surface after the period of fixation is over. After-images
produced in this way often appear and disappear a number of
times before ceasing entirely, and, although the color at first is the
complementary of that of the object looked at, it may change before
its final disappearance. Anyone who has gazed for even a brief
interval at the setting sun will remember the number of colored and
changing after-images seen for a time when the eye is turned to
another portion of the sky. That several different after-images
are seen in this case is due to the fact that the eyes are not kept
fixed under the dazzling light of the sun, and a number of different
images are formed, therefore, upon the retina.

After-images may be used in a very instructive way to show that
our estimates of the size of a retinal image vary with the distance to
which we project it, — that is, with the distance at which we suppose
we see it. Once the image is, so to speak, branded on the retina,
its actual size, of course, does not vary, but our judgment of its size
may be made to vary rapidly by projecting the image upon screens at
different distances. If, for instance, in obtaining the after-image
of the strips shown in Fig. 140 one moves the white paper used
to catch the image toward and away from the eye, the apparent size
varies proportionally to its distance.

Color Contrasts. — By color contrast is meant the influence
that one color field has upon a contiguous one. If, for instance, a
piece of blue paper is laid upon a larger yellow square, the color
of each of them is heightened by contrast. A piece of blue
paper on a blue background does not appear so saturated as when
placed against a yellow background. The influences of contrast
may be shown in a great variety of ways.* For instance, if a disc
like that in the illustration, Fig. 142A , is rotated rapidly, it should
give circles of gray, the darkest at the middle; but each circle should
be uniform as it is made by the fusion of a definite amount of white
and black. On the contrary, the appearance obtained is that repre
sented in Fig. 1425. Each circle appears darker on its outer edge

*Rood, "Modern Chromatics/' " International Scientific Series."

PROPERTIES OF THE RETINA. 333

where it borders on a lighter circle, and lighter on its inner edge where
it borders on a darker circle. Similar contrasts may be obtained from
comparing shadows cast by yellow and white light. If a rod be
arranged in a dark room so as to cast a shadow from an opening
admitting daylight and one also from a lighted candle, either shadow
taken separately appears black, but if the two are cast side by side
one will appear blue, the other yellow. The shadow cast by the
daylight, being illuminated by the j-ellow candle-light, will appear
yellow, and the other shadow, that from the candle-light, will by
contrast seem quite blue. A striking instance of the effect of con-
trast is given, also, by the simple experiment of Mayer, illustrated
in Fig. 141. The gray square on the green background suffers no
apparent change from contrast, but if the figure is covered by a
sheet of white tissue paper the gray square at once takes on a red-
dish hue. It is evident that in all artistic and ornamental employ-
ment of colors this influence must be considered, and empirical
rules are established which indicate for the normal eye the bene-

Fig. 142^.— Black and white disc for ex- Fig. 142B.— Showing the result when the
penment on contrast.— (Rood.) disc --i is set into rapid rotation.— (Rood.)

ficial or the killing effect of different colors when brought into
juxtaposition.

Color Blindness. — The fact that some eyes do not possess
normal color vision does not seem to have attracted the attention
of scientific observers until it was studied with some care by Dalton,
the distinguished English chemist, at the end of the eighteenth
century. Dalton himself suffered from color blindness, and the
particular variety exhibited by him was for some time described
as Daltonism, but is now usually designated as red blindness. The
subject was given practical importance by later observers, espe-
cially by the Swedish physiologist Holmgren,* who emphasized its
relations to possible accidents by rail or at sea in connection with

* Holmgren, "Color Blindness in its Relations to Accidents by Rail and
Sea," " Smithsonian Institution Reports," Washington, 1878. See also Jeffries,
"Color Blindness, its Dangers and its Detection," Boston.

334 THE SPECIAL SENSES.

colored signals. It is now the practice in all civilized countries to
require tests for color blindness in the case of those who in railways
or upon vessels may be responsible for the interpretation of signals.
The numerous statistics that have been gathered show that the
defect is fairly prevalent, especially among men. It is said that
on the average from 2 to 4 per cent, are color blind among males,
while among women the proportion is much smaller, — 0.01 to 1 per
cent. Among the poorly educated classes the defect is said to be
more common than among educated persons. Color blindness
may exist in different degrees of completeness, from a total loss to
a simple imperfection or feebleness of the color sense, and it is
usually congenital. Those who are completely color blind as re-
gards some or all of the fundamental colors fall into two groups:
the dichromatic, whose color vision may be represented by two
fundamental colors and their combinations with white or black,
and the monochromatic or totally color blind, who see only the
white-gray-black series.

Dichromatic Vision. — The color-blind who belong to this class
fall into two or three groups, which have been designated, under
the influence of the Young- He Imholtz theory of color vision, the
red-blind, the green-blind, and the violet-blind. As the terms
red-blind and green-blind imply a more specific condition of
vision than is found to be the case on careful examination, von
Kries has suggested as a substitute the names protanopia and
deuteranopia, as indicating a defect in a first or second constit-
uent necessary for color vision. According to the same nomen-
clature so-called violet-blindness would be designated as tritanopia.
The most common by far of these groups is that of so-called red-
blindness (protanopia); it constitutes the usual form of color
blindness. As a matter of fact, persons so affected are in reality
red-green blind. In what may be called the most typical cases
they distinguish in the spectrum only yellows and blues. The
red, orange, yellow, and green appear as yellow of different shades,
the green-blue as gray, and the blue-violet and purple as blue.
The red end of the spectrum is distinctly shortened, especially
if the illumination is poor, and the maximum luminosity, instead
of being in the yellow, as in normal eyes, is in the green. When
the spectrum is examined by such persons a neutral gray band is
seen at the junction of the blue and green. In some cases, how-
ever, this neutral band is not seen, the yellow passing with but
little change into the blue. As a matter of fact, in red-blindness
the most characteristic defect is a failure to see or to appreciate
the green. This color is confused with the grays and with dull
shades of red. When such persons are examined for their negative
after-images for different colors, it will be noted that they de-

PROPERTIES OF THE RETINA. 335

scribe some of their after-images as red, the after-image of' indigo-
blue, for example, but that they describe none as green. The
after-image of purple, for instance, which to the normal eye is
bright green, is described by them as gray blue or pale blue.
From the descriptions given it is probable that the color vision
of the so-called red-blind is not by any means the same in all cases,
but exhibits many individual differences. The green-blind are
also, according to recent descriptions, red-green blind; they also
confuse reds and greens and in the spectrum are conscious of only
two color qualities, namely, yellow and blue. They differ from
the red-blind in that the red end of the spectrum is not shortened,
and the maximum luminosity, as with the normal eye, is placed
in the yellow. In the matching and combination of colors they
show distinct differences from the red-blind, so that though re-
sembling the latter in general features, they differ obviously in
some details. Violet blindness (tritanopia) seems to be so rare
as a congenital and permanent condition that no very exact study
of it has been made. In cases of acquired tritanopia resulting
from pathological changes it is reported that the violet end of
the spectrum is colorless (neutral) and that a neutral band appears
also in the yellow-green region of the spectrum.* By the ingestion
of santonin it is said that a condition of this kind may be produced
temporarily. The violet end of the spectrum is shortened and
white objects take on a yellowish hue. The conditions produced
by santonin are evidently more complex than can be explained
by simply assuming that the violet color sense is lost. Recent
observers f state that the drug produces a condition of yellow
vision, outside the fovea, in the daylight, and a condition of
violet vision with yellow-blindness, but no red- or green-blindness,
in dim lights.

Tests for Color Blindness. — Although the vision of the red and
the green blind is deficient as regards green and red colors, it will
be found in many cases that they recognize these colors and name
them correctly, having adopted the usual nomenclature and adapted
it to their own standards. In order to detect the deficiency they
must be examined by some test which will compel them to match
•certain colors. Under these circumstances it will be found that
along with correct matches they will make others which to the nor-
mal eye are entirely erroneous. A great number of methods have
been proposed and used to detect color blindness. The simplest
perhaps is that of Holmgren. :j: A number of skeins of wool are used

* Collins and Nagel, " Zeitschrift f. Psychol. u. Physiol. d. Sinnesorgane,"
1906, xli., 74.

fSiven and Wendt, " Skandinavisches Archiv f. Physiologie," 14, 196,
1903, and 1905, 17, 306.

J For details see the works of Holmgren and of Jeffries, already quoted.

336 THE SPECIAL SENSES.

and three test colors are chosen, — namely, (I) a pale pure green
skein, which must not incline toward yellow green; (II) a medium
purple (magenta) skein; and (III) a vivid red skein. The person
under investigation is given skein I and is asked to select from the
pile of assorted colored skeins those that have a similar color value.
He is not to make an exact match, but to select those that appear
to have the same color. Those who are red or green blind will see
the test skein as a gray with some yellow or blue shade and will
select, therefore, not only the green skeins, but the grays or grayish
yellow and blue skeins. To ascertain whether the individual is red
or green blind tests II and III may then be employed.

With test II, medium purple, the red blind will select, in addition
to other purples, only blues or violets; the green blind will select as
"confusion colors" only greens and grays.

With test III, red, the red blind will select as confusion colors
greens, grays, or browns less luminous than the test color, while the
green blind will select greens, grays, or browns of a greater brightness
than the test.

Monochromatic Vision. — A number of cases of total color
blindness have been carefully examined.* It would seem that in
such individuals there is an entire loss of color sense, — they possess
only achromatic vision. The external world appears to them only
iji shades of gray. In the majority of these cases (-f) there
is a region of blindness in the fovea (central scotoma), and an
unusual sensitiveness to light and nystagmus (rolling movement of
the eyeballs) are also characteristic. Since the peripheral field of
vision is nearly normal as regards sensitiveness to light, while the.
central field is frequently blind or amblyopic, it has been assumea
that this condition is one of loss of function in the cones.

Distribution of the Color Sense in the Retina. — What has
been said above in regard to color blindness refers especially to the
central field of vision. When we examine the peripheral field in
the normal eye it is found that on the extreme periphery the retina
is totally color blind, perceiving only light and darkness, — that is,
the shades of gray. As we pass in toward the center the color
sense develops gradually, the blue colors being perceived first and
the greens last, — that is, nearest to the center, — so that in a cer-
tain zone the normal eye is red-green blind. The distribution of
the color sense may be studied conveniently by means of the pe-
rimeter (see p. 321). It will be found to vary with each individual,
so much so that it is possible that a test of this character might be
used for the identification of individuals. Exceptionally it is found
that the entire retina possesses a nearly normal color sense. Usu-
*Grunert, "Archiv fur Ophthalmologie," 56, 132, 1903.

PROPERTIES OF THE RETINA.

337

ally, for the colors red, green, and blue, the blue has the most exten-
sive field and the green the least, as is indicated in the perimeter
chart given in Fig. 143. If the green chosen is blue green (490 ////)—
that is, the complementary of the red— it is stated that their fields
are co-extensive.* From this standpoint the retina presents three
concentric zones: an extreme peripheral zone devoid of color
vision, an intermediate zone in which yellow and blue are perceived,
and a central zone sensitive 'to red and green. The outlines of

Fig. 143. — Perimeter chart indicating the average fields of vision for blue, red, and
green compared with white (gray). Right eye: The outlines of the color fields are repre-
sented as smooth since the chart is an average from many determinations. As a matter of
fact, in each individual the outline is highly irregular. Normally green (bright green) is the
smallest field, green objects outside the limit appearing yellow and farther out colorless
(gray).

the different fields usually show many irregularities, and in some
cases it will be found that bright green is perceived over a larger area
than the red. The fields are not identical in the two eyes, and in
each eye it is, as a rule, more extensive upon the nasal than
upon the temporal side of the retina. In the red-green blind the
peripheral fields of color vision, judged by the individual's own
standards, may be markedly constricted as compared with the nor-
mal retina (see Fig. 144).

Functions of the Rods and Cones. — Many facts unite in mak-
ing it probable that the rods and cones are different in function.

* Baird, "The Color Sensitivity of the Peripheral Retina," Carnegie Pub-
lication, No. 29, 1905.
22

338

THE SPECIAL SENSES.

They differ in structure and especially in their connections. As is
shown in the diagram given in Fig. 145, the cones terminate in the
external nuclear layer in arborizations which connect with the
bipolar ganglion cells, and in the fovea at least this connection is such
that each cone connects with a single nerve cell and eventually per-
haps with a single optic nerve fiber. The rods, on the contrary,
end in a single knob-like swelling, and a number of them make con-
nections with the same nerve cell. Histologically, therefore, the

06t 081

Fig. 144. — Perimeter chart showing the highly restricted color fields in the left eye
of a typical case of so-called red-green color blindness. The ability to distinguish red and
green, by whatever characteristics of intensity 9r color they possessed extended for a very
short distance outside the fovea. It is interesting that the ability to distinguish blue was
in this case limited as compared with a normal eye.

conduction paths for the cones seem to be more direct than in
the case of the rods. These latter elements, moreover, possess the
visual purple, which is lacking in the cones. Lastly, in the eye of
the totally color blind, in the dark-adapted eye in dim lights, in the
color-blind peripheral area of the normal eye, and in the eyes of
most distinctly night-seeing animals, such as the mole and the owl,
vision seems to be effected solely by the rods. These facts find
their simplest explanation perhaps in the view advocated by Pari-
naud, Franklin, von Kries,* and others, according to which the
perception of color is a function of the cones alone, while the rods
* Von Kries, " Zeitschrift f. Psychologic u. Physiol. d. Sinnesorgane," 9,
81, 1895.

PROPERTIES OF THE RETINA.

339

are sensitive only to light and darkness, and by virtue of their power
of adaptation in the dark through the regeneration of their visual
purple they form also the special apparatus for vision in dim
lights (night vision). Color blindness, therefore, whether total or
partial, may be regarded as an affection or lack of normal develop-
ment of the cones. On the other hand, those interesting cases in

Fig. 145. — Schema of the structure of the human retina (Greeff): I, Pigment layer;

layer; 6, fiber of Miille'r.

which the vision, while good in daylight, is faulty or lacking in dim
lights (night blindness, hemeralopia) may be referred to a defective
functional activity of the rods, probably from lack of formation of
visual purple.

340 THE SPECIAL SENSES.

Theories of Color Vision. — A number of theories have been
proposed to explain the facts of color vision. None of them has
been entirely successful in the sense that the explanations it affords
have been submitted to satisfactory experimental verification. The
immediate stimuli that give rise to the visual impulses are assumed
to be of a chemical nature, and it seems probable that in this
case as in that of many other problems of physiology, we must
await the development of a more complete knowledge of the
chemical processes involved. The theories proposed at present,
while all tested by experimental inquiries, are in a large measure
hypotheses constructed to fit more or less completely the facts that
are known. Three of these theories may be described briefly as
examples of the modes of reasoning employed:

I. The Young-Helmholtz Theory. — This theory, proposed essen-
tially by Thomas Young (1807) and afterward modified and ex-
panded by Helmholtz,* rests upon the assumption that there are
three fundamental color sensations, — red, green, and violet — and
corresponding with these there are three photochemical substances
in the retina. By the decomposition of each of these substances cor-
responding nerve fibers are stimulated and impulses are conducted
to a special system of nerve cells in the visual center of the cerebrum.
The theory, therefore, assumes special nerve fibers and nerve centers
corresponding respectively to the red, green, and violet photo-
chemical substances, and the peculiar quality of the resulting sensa-
tions are referred, in the original theory, to the different reactions
in consciousness in the three corresponding centers in the brain.
When these three substances are equally excited a sensation of
white results, of greater or less intensity according to the extent of
the excitation. White, therefore, on this theory, is a compound
sensation produced by the combination or fusion in consciousness
of the three equal fundamental color sensations. The sensation of
black, on the other hand, results from the absence of stimulation,
from the condition of rest in the retina and in the corresponding
nerve fibers and nerve centers. All other color sensations — yellow,
for instance — are compound sensations produced by the combined
stimulation of the three photochemical substances in different propor-
tions. It is assumed, furthermore, that each of the photochemical
substances is acted upon more or less by all of the visible rays of the
spectrum, but that the rays of long wave lengths at the red end
of the spectrum affect chiefly the red substance, those corresponding
to the green of the spectrum chiefly the green substance, and the
rays of shortest wave length chiefly the violet substance. These rela-
tionships are expressed in the diagram given in Fig. 146. The figure
also indicates that it is impossible to stimulate any one of these sub-

* Helmholtz, " Handbuch der physiologischen Optik ," second edition
1896, I, 344.

PROPERTIES OF THE RETINA.

341

stances entirely alone, — that is, we cannot obtain a perfectly satu-
rated color sensation. Even the extreme red or the extreme violet
rays act more or less on all of the substances, and the resulting red
or violet sensation, is, therefore, mixed to some extent with white,—
that is, is not entirely saturated. The theory, as stated by Helm-
holtz, held strictly to the doctrine of specific nerve energy, in assuming
that each photochemical substance serves simply as a means for the
excitation of a nerve fiber, and that the quality of the sensation
aroused depends on the ending of this fiber in the brain. The phe-
nomenon of negative after-images finds a simple explanation in terms
of this theory. If we look fixedly at a green object, for example,
the corresponding photochemical substance is chiefly acted upon, and
if subsequently the same part of the retina is exposed to white light,
the red and violet substances, having been previously less acted
upon, now respond in greater proportions to the white light, and

R 0

B

V

Fig. 146. — Schema to illustrate the Young-Helmholtz theory of color vision. — (Helm-
holtz.) The spectral colors are arranged in their natural order, — red to violet. The curves
represent the intensity of stimulation of the three color substances: 1, The red perceiving
substance; 2, the green perceiving; 3, the violet perceiving. Verticals drawn at any
point of the spectrum indicate the relative amount of stimulation of the three substances
for that wave length of the spectrum.

the after-image takes a red- violet — that is, purple — color. Many
objections have been raised to the Young-Helmholtz theory. It
has been urged, for instance, that we are not conscious that white
or yellow sensations are blends or compounded color sensations;
we perceive in them none of the supposed component elements as
we do in such undoubted mixtures as the blue-greens or the purples.
The theory explains poorly or not at all the fact that on the periphery
of the retina we are color blind and yet can perceive white or gray,
and it breaks down also in the face of the facts of partial and com-
plete color blindness. The explanation given for black is also
unsatisfactory in that it assumes an active state of consciousness
associated with a condition of rest in the visual mechanism.

II. Bering's Theory of Color Vision. — This theory also assumes
the existence in the retina of three photochemical substances, but

342

THE SPECIAL SENSES.

of such a nature as to give us six different qualities of sensation.
There is a white-black substance which when acted upon by the
visible rays of light undergoes disassimilation and sets up nerve
impulses that arouse in the brain the sensation of white. On the
other hand, when not acted upon by light this same substance under-
goes assimilatory processes that in turn set up nerve impulses which
in the brain give us a sensation of black. There are in the retina also
a red-green and a yellow-blue substance. The former when acted
upon by the longer rays undergoes disassimilation and gives a
sensation of red, while the shorter waves cause- assimilation and
produce a sensation of green. A similar assumption is made for
the yellow-blue substance. The essence of the theory may be stated,
therefore, in tabular form, as follows *:

PHOTOCHEMICAL SUBSTANCE.

Red-green ,

Yellow-blue.
White-black.

RETINAL PROCESS.
f Disassimilation
\ Assimilation
f Disassimilation
\ Assimilation
f Disassimilation
\ Assimilation

SENSATION.
red
green
yellow
blue
white
black

It will be observed that the theory gives an independent ob-
jective cause for the sensations of white, black, and yellow, and in

0 Y 6 B V

Fig. 147.— Schema to illustrate the Hering theory of color vision.— (Foster.} The
curves indicate the relative intensities of stimulation of the three color substances by dif-
ferent parts of the spectrum. Ordinates above the axis, X-X, indicate catabolic .changes
(disassimilation), those below anabolic changes (assimilation). Curve a represents the
conditions for the black-white substance. It is stimulated by all the rays of the visible
spectrum with maximum intensity in the yellow. Curve c represents the red-green sub-
stance, the longer wave lengths causing disassimilation (red), the shorter ones assimilation
(green). Curve 6 gives the conditions for the yellow-blue substance.

this respect satisfies the objections made on this score to the Young-
Helmholtz theory. It fits better, also, the facts of partial and total
color blindness. In the latter condition one may assume, in terms of

* For discussion of color theories see Calkins, " Archiv f. Physiologic,"
1902, suppl. volume, p. 244.

PROPERTIES OF THE RETINA.

343

this theory, that only the white-black substance is present, wliile
red and green blindness — both of them, it will be recalled, really
forms of red-green blindness — are explained on the view that in such
persons the red-green substance is deficient or lacking. On this
theory, complementary colors — red and blue-green, yellow and
blue — are, in reality, antagonistic colors. When thrown on the
retina simultaneously their
effects neutralize each other,11 w

and there remains over only
the disassimilatory effect on
the white substance which is
exerted by all the visible
rays. The effect of the vari-
ous visible rays of the spec-
trum on the three photo-
chemical substances is illus-
trated by the chart given in
Fig. 147. Ordinates above
the abscissa representing dis-
assimilatory effects ; those
below, assimilatory.

///. The Franklin Theory
of Color Vision (Molecular
Dissociation Theory} . — This
theory, proposed by Mrs. C.
L. Franklin,* takes into ac-
count the fact of a gradual
evolution of the color sense
of the retina from a primitive
condition of colorless vision
such as still exists in the
periphery of the retina and
in the eyes of the totally
color blind. It assumes that
the colorless sensations —
white, gray, black — are occa-
sioned by the reactions of a
photochemical material
which for convenience may
be designated as the gray

substance. This substance in the normal eye exists in both rods
and cones; in the latter, however, in a differentiated condition
capable of giving color sensations. When the molecules of this
substance are completely dissociated by the action of light, gray

* Franklin, " Zeitschrift f. Psychologic und Phys. d. Sinnesorgane," 1892,
iv; also "Mind," 2, 473, 1893, and " Psychological Review," 1894, 1896, 1899.

Fig. 148.— Schema to illustrate the Frank-
lin theory of color vision (Franklin) : W, The
molecule of the primitive visual (gray-perceiv-
ing) substance; Y and B, the first step hi the
differentiation into a yellow- and a blue-per-
ceiving substance, whose combined dissociation
gives the same effect as that of the original sub-
stance, W; G and R, the second step in the
differentiation of the yellow-perceiving sub-
stance, the combined dissociation of the two
giving the same effect as that of the yellow-per-
ceiving substance alone. The complete devel-
opment of color vision as it exists in the central
part of the retina consists in the existence of
three substances, which, taken separately, give
red, green, and blue color sensations.

344 THE SPECIAL SENSES.

sensations result, and as this is the only reaction possible in the
rods these elements can furnish us only sensations of this quality.
The molecules of gray substance in the cones, on the other
hand, have undergone a development such that certain portions
only of the molecule may become dissociated by the action of light
of certain periods of vibration. This development may be sup-
posed to have taken place in two stages: first, the formation of
two groupings within the molecule, one of which is dissociated by
the slower waves and gives a sensation of yellow, and one of which
is dissociated by the more rapid waves and gives the sensation of
blue. This stage remains still on portions of the periphery of the
retina, and is the condition present in the fovea also in the eyes
of the red-green blind. The second stage consists in the division
of the yellow component into two additional groupings in one
of which the atomic movements are of such a period as to be
affected by the longest visible waves, the red of the spectrum,
while the other is dissociated by rays corresponding to the green
of the spectrum and gives rise to the sensation of green. If
the red and green groupings are dissociated together the resulting
effect is the same as follows from the dissociation of the entire yellow
component, while the complete dissociation of the red, green, and
blue groupings gives the stimulus obtained originally from the disso-
ciation of the whole molecule, and causes gray sensations. The idea
of this subdivision or differentiation in structure of the original gray
substance is indicated diagrammatically in Fig. 148. The theory
accounts admirably for many phenomena in vision, and is perhaps
especially adapted to explain the facts of color blindness and the
variations in quality of our visual sensations in the peripheral areas
of the retina.

The two latter theories seem to imply that a number of different kinds
of impulses may be transmitted along the optic fibers. Hering's theory re-
quires apparently the possibility of six qualitatively different impulses, —
namely, white, black, red, green, yellow, and blue, — while the Franklin theory
assumes impulses corresponding to white (gray), red, green, yellow, and blue.
Black is not specifically accounted for except as a part of the gray series. At
present in physiology there is no proof that nerve impulses can differ quali-
tatively from each other, although it may be urged, perhaps with equal force,
that there is no proof that they can not so differ. The doctrine of specific
nerve energy assumes that nerve impulses are, as regards quality, always
the same, and differ from one another only in intensity, the qualitative differ-
ences that exist among sensations being referred to a difference in reaction
in the end-organ in the brain.

Entoptic Phenomena. — Under the term entoptic phenomena
is included a number of visual sensations due to the shadows of
various objects within the eyeball itself. Ordinarily these shadows
are imperceptible, owing to the diffuse illumination of the interior
of the eye through the relatively wide opening of the pupil. By
means of various devices the illumination of the eye may be so
controlled as to make these shadows more distinct and thus bring

PROPERTIES OF THE RETIXA.

345

the retinal images into consciousness. Some of these entopic ap-
pearances are described briefly, but for a detailed description the
reader is referred to the classical work of Helmholtz.*

The Blood-corpuscles. — The entoptic images that are most easily
recognized perhaps are those of the moving corpuscles in the capil-
laries of the retina. If one looks off into the blue sky he will have
no difficulty in recognizing a number of minute clear and dark specks
that move in front of the eye in definite paths. The character of
the movement leaves no doubt that these sensations are due to the
shadows of the blood-corpuscles. In fact, the shadows often show
a rhythmic acceleration in velocity synchronous with the heart-
beats, a pulse movement. By projecting the moving images upon
a screen at a known distance from the eye the velocity of the capil-
lary circulation has been estimated in man.

The Retinal Blood-vessels. — The blood-vessels of the retina lie
in front of the rods and cones and must necessarily throw their
shadows upon these sensitive end-organs. The shadows may be
made more distinct and a visual picture of the vessels obtained by
a number of methods. For instance, if a card with a pin hole
through it is moved slowly in front of the eye the images of the
blood-vessels stand out in the field of vision with more or less
distinctness. The card should be given a circular movement. If it
is kept in one position the images quickly disappear, since the
retina apparently fatigues very quickly for such faint impressions.
A more impressive picture may be obtained by the method of
Purkinje. In a dark room one holds a candle toward the side of the
head in such a position as
to give the sensation of a
glare in the correspond-
ing eye. If the eye is di-
rected toward the opposite
side of the room and the
candle is kept in continual
circular movement the
blood-vessels appear in
the field of vision magni-
fied in proportion to the
distance of projection; the
picture makes the impres-
sion of a thicket of inter-
lacing branches. In this experiment the light from the candle
strikes the nasal side of the retina at an oblique angle and is re-
flected toward the other side of the globe. The blood-vessels are
in this way illuminated from an unusual direction and their

* Helmholtz, " Handbuch der physiologischen Optik," second edition,
I, 184.

a

Fig. 149. — Helmholtz's method of showing en-
toptic phenomena due to imperfections in the lens
and vitreous (Helmholtz) : c, a screen with pinhole ;
a, lens with short focus.

346 THE SPECIAL SENSES.

shadows are thrown upon a portion of the retina not usually affec-
ted and for that reason perhaps more sensitive to the impression.
Imperfections in the Vitreous Humor and the Lens. — Small frag-
ments of the cells from which the vitreous humor was constructed
in the embryo and similar relatively opaque objects in the lens may
throw shadows on the retinal bottom. These shadows take
different forms, but usually are described as small spheres or beads,
single or in groups, that move with the eyes and are designated,
therefore, as the muscae volitantes (flitting flies or floating flies). To
bring out these shadows it is convenient to make the source of illu-
mination small and to bring it at or nearer than the anterior focal
distance of the eye (15 to 16 mms.). The method employed for this
purpose by Helmholtz is illustrated in Fig. 149. In this figure b
is a candle flame, and a a lens of short focus which makes an image
of the flame at the small opening shown in the dark screen, c. The
eye is placed just behind this opening and is illuminated by the rays
from the small, bright image of the flame at that spot. The shadows
are seen projected upon the illuminated surface of the glass lens.

CHAPTER XIX.
BINOCULAR VISION.

Vision with two eyes differs from monocular vision chiefly in
the varied combinations of movements of the two eyeballs and the
aid thereby afforded in the determination of distance and size,
in the enlarged field of vision, and, above all, in the more exact per-
ception of solidity or perspective, especially for near objects.

The Movements of the Eyeballs. — Each eyeball is moved
by six extrinsic muscles which are innervated through three
cranial nerves. The third or oculomotor nerve controls the internal
rectus, the superior rectus, the inferior rectus, and the inferior
oblique; the fourth cranial nerve (n. patheticus) innervates the
superior oblique alone; and the sixth cranial (n. abducens) the
external rectus alone. By means of these muscles the eyeballs may
be given various movements, all of which may be considered as
rotations of the ball around various axes. The common point of
intersection of these axes is designated as the rotation point or
center of rotation of the eyeball; it lies about 13.5 mms. back of the
cornea in the emme tropic eye. The various axes of rotation all
pass through this point, and we may classify them under four
heads: (1) The horizontal or sagittal axis, which is the line passing
through the rotation point and the object looked at, — the fixation
point. This axis corresponds practically with the line of sight, —
that is, the line drawn from the object looked at to the middle of the
fovea, and it may therefore, without serious error, be spoken of as
the visual axis. Rotations around this axis give a wheel movement
or torsion to the eyeballs. (2) The transverse axis, the line passing
through the rotation points of the two eyes and perpendicular
to 1. Rotations around this axis move the eyeballs straight up
or down. (3) The vertical axis, the vertical line passing through
the rotation point and perpendicular at this point to the horizontal
and transverse axes. Rotations around this axis move the eyeball
to the right or the left. (4) The oblique axes, under which are in-
cluded all the axes of rotation passing through the rotation point at
oblique angles to the horizontal axis. These axes all lie in the
equatorial plane of the eye, and rotations around any of them move
the eyeball obliquely upward or downward. These definitions all
have reference to what is known as the primary position of the

347

348 BINOCULAR VISION.

eyes, — that is, that position taken by the eyes when we look straight
before us toward the horizon, — a position, therefore, in which the
plane of the horizontal axes is parallel to the ground; all other
positions of the eyes are spoken of as secondary.

With regard to the movements of the eyes about its axes of
rotation the following general statements are made : Starting from
the primary position, rotations of the eyes about the vertical axis —
that is, movements directly to right or left — may be made by the
contraction of the internal or the external rectus as the case may be.
Rotations around the transverse axis — that is, movements directly
up or down — require in each case the co-operation of two muscles.
In movements upward the superior rectus, acting alone, would in

-Hi

Fig. 150. — " Diagram showing for the left eye the paths of the line of sight caused by the
action of the different eye-muscles (Hering). The horizontal line indicates movements out or
in to various degrees as caused by the contraction of the internal or external rectus. The
curved lines show the amount of torsion given the eyeball by the superior and inferior
rectus and the superior and inferior oblique when contracting separately. Tne short
heavier line at the end of the paths indicates the position of the horizontal meridian at
the end of the movement." R. e., the external rectus; R, i., the internal rectus; /,'. N.,
the superior rectus; R. inf., the inferior rectus; O. i., the inferior oblique; O. S., the superior
oblique.

rotating the eyeball upward also give it a slight torsion so as to
turn the upper part of the vertical meridian inward. To obtain a
movement directly upward (rotation around the transverse axis)
the superior rectus and inferior oblique must act together. For
a similar reason rotation directly downward requires the com-
bined action of the inferior rectus and superior oblique. These
facts are expressed clearly in Hering' s diagram, reproduced in
Fig. 150, which indicates the paths traversed by the line of sight
when the eyeball is moved by the different muscles acting sepa-
rately. Rotation of the eyeballs around oblique axes require
the co-operation of three of the muscles : movements upward
and outward — the superior rectus, inferior oblique, and external
rectus; movements upward and inward — superior rectus, inferior

BINOCULAR VISION. 349

oblique, and internal rectus; movements downward and outward-
inferior rectus, superior oblique, and external rectus; movements
downward and inward — inferior rectus, superior oblique, and
internal rectus. Most of the movements of the eyes are of the
latter kind, — namely, rotations around an oblique axis, — and
the position of the axis for each definite movement of this character
may be determined by Listing's law, which may be stated as
follows : When the eye passes from a primary to a secondary
position it may be considered as having rotated around an axis
perpendicular to the lines of sight in the two positions. It will
be noted readily from observations upon the movements of one's
own eyes that they ordinarily make only such movements as will
keep the lines of sight of the two eyes parallel or will converge
them upon a common point. In movements of convergence the
internal recti of the two eyes are associated, while in symmetrical
lateral movements the internal rectus of one eye acts with the
external rectus of the other. Under normal conditions it is
impossible for us to diverge the visual axes, — that is, to associate
the action of the external recti. A movement of this kind would
produce useless double vision (diplopia), and it is therefore a
kind of movement which all of our experience has trained us to
avoid.

The Co-ordination of the Eye Muscles — Muscular Insuf-
ficiency— Strabismus. — In order that the eyeballs may move with
the minute accuracy necessary in binocular vision, a beautifully
balanced or co-ordinated action of the opposing muscles is neces-
sary. The object of these movements is to bring the point looked
at in the fovea of each eye and thus prevent double vision, diplopia
(see following paragraphs). This object is attained when the eye-
balls are so moved that the lines of sight unite upon the object or
point looked at. In viewing an object or in reading we keep
readjusting the eyes continually to bring point after point at the
junction of the lines of sight. If the eye is perfectly normal the
contractions of the muscles for objects in a symmetrical position are
equal in the two eyes; if, however, one or more of the muscles in the
eyes are weaker than normal, then to adjust the eyes properly
requires a greater contraction of these muscles to overcome the op-
posing action of their stronger antagonists. If the disproportion
in strength is not great, then by a stronger innervation, made under
the desire to prevent double vision, the visual axes may be properly,
adjusted; but the strain that results from this continual overcon-
traction may be injurious. A condition of lack of balance of this
kind in the muscles is spoken of as heterophoria, and, according to
the direction in which the visual axis tends to deviate the condition
is described specifically as esophoria, deviation inward; exophoria,

350 THE SPECIAL SENSES.

deviation outward; hyperphoria, deviation up or down. The
condition may be obviated by prismatic glasses so placed as to
aid the weaker muscle. When the lack of balance between the
opposing muscles is so great that the visual axes can not be brought
to bear upon the same points we have the condition of squint or
strabismus. Such a condition may result from a deficiency in
strength or in actual paralysis of one or more of the muscles, or from
an overaction in some of the muscles as contrasted with their
antagonists.

The Binocular Field of Vision. — When the two eyes are fixed
upon a given point, placed, let us say, in front of us in the median
plane, each eye has its own visual field that may be charted
by means of the perimeter. But the two fields overlap for a
portion of their extent, and this overlapping area constitutes
the field of binocular vision (see Fig. 151). Every point in the bin-
ocular field forms an image upon the two retinas. The most
interesting fact about the binocular field is that some of the objects
contained in it are seen single in spite of the fact that there are two
retinal images, while others are seen or may be seen double when
one's attention is directed to the fact. Whether any given object
is seen single or double depends upon whether its image does or does
not fall upon corresponding points in the two retinas.

Corresponding or Identical Points. — By definition corre-
sponding or identical points in the twc retinas are those which when
simultaneously stimulated by the same luminous object give us a
single sensation, while non-corresponding points are those which
when so stimulated give us two visual sensations. It is evident;
from our experience, that the' fovese form corresponding points or
areas. When we look at any object we so move our eyes that the
image of the point observed shall fall upon symmetrical parts of the
f ovea ; the lines of sight of the two eyes converge upon and meet in
the point looked at. If while observing an object we press gently
upon one eyeball with the end of the finger, two images are seen
at once, and they diverge farther and farther from each other
as the pressure upon the eyeball is increased. Experiment shows,
also, that, in a general way, portions of the retina symmetrically
placed to the right side of the foveae in the two eyes are cor-
responding, and the same is true for the two left halves and the two
upper and lower halves. The right half of the retina in one eye is
non-corresponding to the left half of the other retina, and vice
versa; and the same relation is true of the upper and lower halves,
respectively. If we imagine one retina to be lifted without turning
and laid over the other so that the fovese and vertical and horizontal
meridians coincide, then the corresponding points will be superposed
throughout those portions of the retina that represent the binocular
field. This statement, however, is theoretical only; an exact point

BINOCULAR VISION.

351

to point correspondence has not been determined experimentally.
Experiments have shown, however, that the corresponding points
in the upper halves of the retinas along the vertical mid-line do
not cover each other, that is, they do not lie in the actual anatom-
ical vertical meridian, but form two meridians which diverge
symmetrically from the mid-line so as to make an angle of about
2 degrees (physiological incongruence of the retinas). Within the
limits of our powers of observation for ordinary objects we may
adopt Tscherning's rule, — namely, that when the images of
an object on the two retinas are projected to the same side of the

Fig. 151.— Perimeter chart to show the extent of the binocular visual field (shaded area)
when the eyes are fixed upon a median point in the horizontal plane.

point of fixation they are seen single, their retinal images in this
case falling on the retina to the same side of the lines of sight ; when,
however, the retinal images fall on opposite sides of the lines of
sight and are projected to opposite sides of the point of fixation,
they are seen double. The doubling of objects that do not fall on
corresponding points (physiological diplopia) is most readily
demonstrated for objects that lie between the lines of sight, either
closer or farther away than the object looked at. If, for instance,
one holds the two forefingers in front of the face, in the median
plane, one hand being at about the near point of distinct vision
and the other as far away as possible, it will be noticed that when

352

THE SPECIAL SENSES.

the eyes are fixed on the far finger the near one is seen double
and vice versa. In this, as in other experiments in which the eyes
are accommodated for one object while the attention is directed
to another, some difficulty may be experienced at first in disso-
ciating these two acts which normally go together, but a little
practice will soon enable one to distinguish clearly the doubling
of the point upon which the lines of sight are not converged.
If a long stick is held horizontally in front of the eyes the end
near the face will be doubled when the eyes are directed to the
far end and vice versa. Moreover, by a simple experiment it
may be shown that objects nearer the eyes than the point looked at
are doubled heteronymously, — that is, the right-hand image be-
longs to the left eye and the left-hand one to the right eye. This is
easily demonstrated by closing the eyes alternately and noting

Fig. 152. — Diagrams to show homonymous and heteronymous diplopia: In / the eyes
are focused on A; the images of B fall on non-corresponding points, — that is, to different
sides of the fovese, — and are seen double, being projected to the plane of A, giving heter-.
onymous diplopia. In II the eyes are focused on the nearer point, A, and the farther point,
JB, forms images on non-corresponding points and is seen double, — homonymous diplopia,
— the images being projected to the focal plane A.

which of the images disappears. The reason for the cross-projec-
tion of the images is made apparent by the construction in Fig. 152,
/, bearing in mind the essential fact that in projecting our retinal
images we always project to the plane of the object upon which the
eyes are focused. In the figure the eyes are converged on A ; the
images of point B fall to opposite sides of the line of sight and are
seen double and are projected to the plane of A, the image on the
right eye-being projected to b' on the left of A and that on the left eye
to 6 on the right of A. In a similar way it may be shown that ob-
jects farther away from the eye than the point looked at are doubled
homonymously, — that is, the right-hand image belongs to the right
eye, and the left-hand one to the left eye. The fact is explained by
the construction in Fig. 152, II, in which A is the point converged
upon and B the more distant object. In all binocular vision, there-
fore, the series of objects between the eye and the point looked at are

BINOCULAR VISION. 353

doubled heteronymously, and those extending beyond the point in
the same line are doubled homonymously. Normally we take no
conscious notice of this fact, our attention being absorbed by the
object upon which the lines of sight are directed. Some physi-
ologists, however, have assumed that the knowledge plays an im-
portant part subconsciously in giving us an idea of depth or per-
spective,— an immediate perception, as it were, of the distinction
between foreground an background. It is usually assumed that the
explanation of corresponding points is to be found in the anatomical
arrangement of the optic nerve fibers. Those from the right halves
of the two retinas, which are corresponding halves, unite in the
right optic tract and are distributed to the right side of the brain,
while the fibers from the left halves go to the left side of the brain.
The basis of the single sensation from two visual images is to be
found probably in the fact that the cerebral terminations through
which the final psychical act is mediated lie close together or possibly
unite.

The Horopter. — In every fixed position of the eyes there are
a certain number of points in the binocular field which fall
upon corresponding points in the two retinas and are therefore
seen single. The sum of these points is designated as the horopter
for that position of the eyes. It may be a straight or curved line,
or a plane or curved surface. Helmholtz calls attention to the fact
that, when standing with our eyes in the primary position, — that
is, directed toward the horizon, — the horopter is a plane coinciding
with the ground, and this fact may possibly be of service to us in
walking.

Suppression of Visual Images. — It happens not infrequently
that when an image of an object falls upon non-corresponding
points in the two retinas the mind ignores or suppresses one of the
images. This peculiarity is exhibited especially in the case of per-
sons suffering from "squint" (strabismus). In this condition the
individual, for one reason or another, is unable to adjust the contrac-
tions of his eye muscles so as to unite his lines of sight upon the
object looked at. The image of the object falls upon non-corre-
sponding points and should give double vision, diplopia. This
would undoubtedly be the case if the condition came on suddenly ;
just as double vision results when we dislocate one eyeball by
pressing slightly upon it. But in cases of long standing one of the
images, that from the abnormal eye, is usually suppressed. The
act of suppression seems to be a case of a stronger stimulus prevail-
ing over a weaker one in consciousness, just as a painful sensation
from stimulation of one part of the skin may be suppressed by a
stronger pain from some other region.

Struggle of the Visual Fields. — When the images of two dis-
similar objects are thrown, one on each retina, the mind is presented,

23

354 THE SPECIAL SENSES.

so to speak, simultaneously with two different sensations. Under
such circumstances what is known as the struggle of the visual
fields ensues. If the image on one eye consists of vertical lines
and on the other of horizontal lines we see only one field at a time,
first one then the other, or the field is broken, vertical lines in part
and horizontal lines in part ; there is no genuine fusion into a con-
tinuous, constant picture. The struggle of the two fields is better
illustrated when different colors are thrown on the two retinas.
When red and yellow are superposed on one retina we obtain a com-
pound sensation of orange; if they are thrown one on one retina,
one on the other, no such fusion takes place. We see the field
alternately red or yellow or a mixture of part red and part yellow,
or at times one color, as it were, through the other. If, however,
one field is white and the other black a peculiar sensation of glitter
is obtained, quite unlike the uniform gray that would result if the
two fields were superposed on one retina.

Judgments of Solidity. — Our vision gives us knowledge not
only of the surface area of objects, but also of their depth or solidity,
— that is, from our visual sensations we obtain conceptions of the
three dimensions of space. The visual sensations upon which this
conception is built are of several different kinds, partly monocular, — •
that is, such as are perceived by one eye alone, — partly binocular.
If we close one eye and look at a bit of landscape or a solid object
we are conscious of the perspective, of the right relations of fore-
ground and background, and those individuals who have the
misfortune to lose one eye are still capable, under most circum-
stances, of correct visual judgments concerning three dimen-
sional space. Nevertheless it is true that with binocular vision
our judgments of perspective are more perfect, and that under
certain circumstances data are obtained from vision with two eyes
which give us an idea of solidity far more real than can be obtained
with one eye alone. This difference is shown especially in the
combination of stereoscopic pictures, and in ordinary vision when
the light is dim, as in twilight, or in exact judgments of perspective
in the case of objects close at hand. If, for example, we close one
eye and attempt to thread a needle, light a pipe, or make any similar
co-ordinated movement that depends upon an exact judgment of
the distance of the object away from us, it will be found that the
resulting movement is far less perfectly performed than when two
eyes are used. The sensation elements upon which our judgments
of depth or perspective are founded may be classified as follows :*

The Monocular Elements, — That is, those that are experienced
in vision with one eye. (a) Aerial perspective. The air is not en-
tirely transparent, and, therefore, in viewing landscapes the more
distant objects are less distinctly seen, as is illustrated, for instance,
* See Le Conte, "Sight," vol. 31 of "The International Scientific Series," 1881

BINOCULAR VISION. 355

by the haze covering distant mountains. This experience leads us
sometimes to make erroneous judgments when the conditions are
unusual. An object seen suddenly in a fog looms large, as the
expression goes, since the feeling that hazy objects are at a great
distance leads us to give a proportional overvaluation to the rela-
tively large visual image made by the near object.

(b) Mathematical perspective. The outlines of objects before
us are projected upon the surface of the eye in two dimensions only,
just as they are represented in a drawing. The lines that indicate
depth are therefore foreshortened, and lines really parallel tend to
converge more and more to a vanishing point in proportion to their
distance away from us. When one stands between the tracks of a
railway, for instance, this convergence of the parallel lines is dis-
tinctly apparent. We have learned to interpret this mathematical
perspective correctly and with great accuracy. The use of this
perspective in drawings is, in fact, one of the chief means employed
by the artist to produce an impression of depth or solidity. For
distant objects at least this factor is probably the most potent of
those that can be appreciated by monocular vision.

The importance of the mathematical perspective for our visual judgments
may be illustrated very strikingly by a simple experiment. If one takes a
biconvex lens of short focus and standing at a window that looks out upon a
long street holds the lens in front of the eyes at arm's length he will be able
to see, by focusing on the inverted image formed by the lens, that not only
are objects inverted as regards their surface features, but, for mcst persons
at least, the perspective is also inverted. Objects actually in the foreground
will appear in the background, and one may have the curious sensations of
watching persons who, as they walk, seem to recede farther and farther into
the distance in spite of the fact that they continue to increase in size. The
inverted or pseudoscopic vision thus produced is due undoubtedly to the in-
version of the lines of perspective. Parallel lines which, without the lens,
would have on the retina a projection of this kind /\ are with the lens projected
inverted \/, and our visual judgments are controlled by this factor in spite
of the opposing evidence from the size of the retinal images. In order for
the experiment to succeed it is necessary that the objects viewed shall be far
enough away so that a iiat picture may be given by the lens, — that is, a pic-
ture in which the foci for the near points shall not differ practically from those
of more distant points, otherwise the muscular movements of accommodation
interfere with the delusion. The relative importance of this last factor
(see succeeding paragraph) is well illustrated by varying the experiment in
this way: Place two objects upon a well-lighted table, one at the near end
and one at the far end. Then standing close to the table view these objects
through the lens as before. Tney will be seen in their right relations to each
other. If, however, one backs away from the table while watching the images
there will come a distance at which the near object will be seen to shift around
to the rear of the far object.

(c) The Muscle Sense (Focal Adjustment). — For objects near
enough to require accommodation it is obvious that the nearer
object will need a stronger contraction of the ciliary muscle, and
also of the internal rectus in order to bring the line of sight to bear
correctly. By means of the fibers of muscle sense we have a verv

356

THE SPECIAL SENSES.

exact conception of the degree of contraction of these muscles, and
this sensation is perhaps the most important factor used in making
our monocular judgments of depth for objects at a short distance.
In binocular vision the same factor is doubtless of increased effi-
ciency byreason of the sensations obtained from the two eyes.

(d) The disposition of lights and shades and the size of familiar
objects. It may be assumed that in distant vision of complex
fields the varying lights and shades exhibited by objects according
as they stand in front of or behind each other also aid our judg-
ment. The actual size also of the retinal images of familiar objects —
such as animals, trees, etc. — gives us an accessory fact which con-
tributes to the impression derived from the sources mentioned
above. These factors are employed with effect by the artist in
strengthening the general impression which he wishes to give of
the difference between the foreground and the background.

The Binocular Perspective. — In binocular vision there is an
additional element which contributes greatly to our judgment of
depth. This element consists in the fact that the retinal images
of external objects, particularly near objects, are different in the two
eyes. Inasmuch as the eyes are separated by some distance the
projection of any solid object upon one retina is different from
the projection on the other. If a truncated pyramid is held in
front of the eyes, the right eye sees more of the right side, the left
more of the left side. The projection of the same object upon the
two retinas may, in fact, be represented by the drawings given in
Fig. 153. Whenever this condition prevails, whenever what we
may call a right-eyed image of an object is thrown on the right eye '
and simultaneously a left-eyed image on the left eye, whether in
nature or by an artifice, we at once perceive depth or solidity in the
object. This fact is made use of in all devices employed to produce
stereoscopic vision.

Stereoscopic Vision. — Stereoscopic pictures may be obtained

by photographing the
same object or collec-
tion of objects from
slightly different
points so as to get a
right-eyed and a left-
eyed picture ; or for
simple outline pic-
tures, such as geo-
metrical figures, they
may be made by draw-
ings of the object as seen by the two eyes, respectively (see Figs.
153 and 155). Any optical device that will enable us to throw the

Fig. 153. — Right- and left-eyed images of truncated
pyramid. May be combined to produce solid image by
relaxing the accommodation, — that is, gazing to a dis-
tance through the book.

BINOCULAR VISION.

357

right- eyed picture on the right eye and the left-eyed picture on
the left eye constitutes a stereoscope. Many different forms of
stereoscope have been devised;

the one that is most frequently A

used is the Brewster stereoscope ' ;\ \ /

represented in principle in Fig. • \ y'B

154. Each eye views its cprre- / \ /\

spending picture through a
curved prism. The sight of the
left-eyed picture is cut off from
the right eye, and vice versa, by
a partition extending for some
distance in the median plane.
The prisms are placed with their
bases outward and the rays of
light from the pictures are re-
fracted, as shown in the diagram,
so as to aid the eyes in converg-
ing their lines of sight upon the
same object. The prisms also
magnify the pictures somewhat.
Stereoscopic pictures are mounted
usually for this instrument so that
the distance between the same

Fig. 154. — Diagram to illustrate the
ciple of the Brewster stereoscope

^Landois) : P and P', the prisms, a, 6,
and a, 0, the left- and ri^ht-eyed pictures,
respectively, 6, 0, being a point in the
foreground and a, a, a point in the back-
ground. The eyes are converged and
focused separately for each point as in
viewing naturally an object of three di-
mensions.

object in the two pictures is about 80 mms. — greater, therefore, than
the interocular distance. A simple form of stereoscope that is very
effective and interesting is sold under the name of the anaglyph.
The two pictures in this case are approximately superposed, but the
outlines of one are in blue and the other in red. When looked at,
therefore, the picture gives an ordinary flat view with confused
red-blue outlines. If, however, one holds a piece of red glass in
front of the left eye and a piece of blue glass in front of the right eye,
or more conveniently uses the pair of spectacles provided which
have blue glass on one side, red on the other, then the picture stands
out at once in solid relief with surprising distinctness — and as a
black and white object only. The red and blue glasses in this case
simply serve to throw the right-eyed image on the right eye and the
left-eyed image on the left eye. Assuming that the right-eyed
image is outlined in red, then the blue glass should be in front of the
right eye. This glass will absorb the red rays completely so that
the red outlines in the picture will seem black and a distinct right-
eyed picture is thrown on the right eye, distinct enough to make us
overlook the much fainter image in blue, which is also trans-
mitted through the blue glass. The red glass before the left

358

THE SPECIAL SENSES.

eye cuts out, in the same way, the right-eyed image and presents
in dark outline the left-eyed image. By simply reversing the
spectacles the right-eyed image may be thrown upon the left eye
and vice versa. Under these conditions the picture for most per-
sons may be seen in inverted
relief (pseudoscopic vision),
objects in the foreground re-
ceding into the background.
This inversion of the relief
when the projection upon the
retinas is reversed is a strik-
ing indication of the potency
of the normal projection as a

Fig. 155. — Stereoscopic picture of an octahe- /. -, r

dral crystal. May be combined stereoscopically lactor in OUr judgments OI

by relaxing the accommodation by the method _i; i i • 4. TJ. '11 1 ^1

of heteronymous diplopia. Hold the object at a Solid objects. It Will be ob-

distance of a foot or more and gaze beyond. served, moreover, that those

pictures that show least

mathematical perspective are the most readily inverted, and that
the ability to invert the picture varies in different individuals; in
some, what we have called the binocular perspective, founded upon
the dissimilar images, prevails over the mathematical perspective
more readily than in others.

Stereoscopic pictures may also be combined very successfully
without the use of a stereoscope by virtue of the phenomenon of
physiological diplopia. If, for instance, two stereoscopic drawings,
such as are represented in Fig. 155, are held before the eyes and one
relaxes his accommodation so as to look through the pictures, as it
were, to a point beyond, then, in accordance with what was stated
on p. 352, each picture gives a double image, since it falls on
non-corresponding parts of the two retinas. Four pictures, there-
fore will be seen, all out of focus. With a little practice one can so
converge his eyes as to make the two middle images come together,
and since one of these is an image of the right-eyed picture and is
falling on the right eye, and the other is a left-eyed picture falling
on the left eye, the combination of the two fulfills the necessary
conditions for binocular perspective. The figure stands out in
bold relief.

Explanation of Binocular Perspective. — Our perception of
solidity or relief is a secondary psychical act, and, so far as the binoc-
ular element is concerned, it is based upon the fact that the images
are slightly different on the two retinas; but why this dissimilarity
should produce an inference of this kind is not entirely understood.
Certain facts have been pointed out as having a probable bearing
upon the mental process. In the first place, in stereoscopic pictures,

BINOCULAR VISION. 359

as in nature, we do not see the whole field at once. To see the ob-
jects in the foreground the eyeballs must be converged by the eye
muscles so that the lines of sight may meet in the object regarded.
When attention is paid to objects in the background less convergence
is necessary (see Fig. 152). The point of fixation for the lines of
sight is kept continually moving to and fro, and the sensation of
this muscular movement undoubtedly plays an important part in
giving us the idea of depth or solidity. For persons not practised
in the matter of observing stereoscopic pictures the full idea of relief
comes out only after this muscular activity has been called upon.
But for the practised eye this play of the muscles is not absolutely
necessary. The stereoscopic picture stands out in relief even when
illuminated momentarily by the light of an electric spark. The per-
ception of solidity in this case is instantaneous, and it has been sug-
gested that this result may depend upon the immediate recognition
of physiological diplopia, — that is, the fact that objects nearer than
the point of fixation are doubled heteronymously, while those
farther away are doubled homonymously (see p. 352). Such an
effect can only be produced distinctly by objects having depth
and possibly in the case of the trained eye it alone is sufficient to
give the immediate inference of solidity or relief, while the un-
trained eye requires the accessory sensations aroused by focal
adjustment, mathematical perspective, etc.

Judgments of Distance and Size. — Judgments of distance
and size are closely related. Our judgments regarding size are
based primarily upon the size of the retinal image, the amount of
the visual angle. This datum, however, is sufficient in itself only
for objects at the same distance from us. If they are at different
distances or we suppose that such is the case, our judgment of the
distance controls our judgment of size. This fact is beautifully
shown in the case of after-images (see p. 332). When an after-
image of any object is obtained on the retina our judgment of its
size depends altogether on the distance to which we project it.
If we look at a surface near at hand, it seems small ; if we gaze at a
wall many feet away it is at once greatly enlarged. The familiar
instance of the variation in the size of the full moon according as it
is seen at the horizon or at the zenith depends upon the same fact.
The distance to the horizon as viewed along the surface of the earth
seems greater than to the zenith; we picture the heavens above us
as an arched dome flattened at the top, and hence the same size of
retinal image is interpreted as larger when we suppose that we see
it at a greater distance. Our judgments of distance, on the other
hand, depend primarily upon the data already enumerated in
speaking of the perception of solidity or depth in the visual field.

360 THE SPECIAL SENSES.

For objects within the limit of accommodation we depend chietiy
on the muscle sense aroused by the act of focusing the eyes, — that
is, the contractions of the ciliary and of the extrinsic muscles. For
objects outside the limit of accommodation we are influenced by
binocular perspective, mathematical perspective, aerial perspective,

B

Fig. 156. — Miiller-Lyer figures to show illusion in space perception. The lines A and B

are of the same length.

etc. But here again our judgment of distance is greatly influenced
in the case of familiar objects by the size of the retinal image. A
striking instance of the latter fact is obtained by the use of field
glasses or opera glasses. When we look through them properly
the size of the retinal image is enlarged, and the objects, therefore,
seem to be nearer to us. If we reverse the glasses and look through
the large end the size of the retinal image is reduced and the objects,
therefore, seem to be much farther away, since under normal condi-
tions such small images of familiar objects are formed only when
they are at a great distance from us.

Optical Deceptions. — Wrong judgments as regards distance
and size are frequently made and the fact may be illustrated in a
number of interesting ways. Thus, in Fig. 156 the lines A and B
are of the same length, but B seems to be distinctly the longer. So
in Fig. 157 the vertical lines, although exactly parallel, seem, on
the contrary, to run obliquely with reference to one another. Both
of these deceptions depend apparently upon our inability to estimate
angles exactly ; we undervalue the acute angles and overvalue those
that are obtuse. A very remarkable delusion is given by Fig. 158.
If the book is held flat at the level of the chin and six or eight
inches from the face and the eyes are focused on the point of inter-
section of any two of the lines, a third line will be seen perpen-
dicular to the plane of the other two, and projecting vertically
from the surface of the page. A row of these vertical lines will
be seen if the distance is properly chosen. As one bends the
head from side to side the lines sway in the same direction. It
forms a very striking instance of the fact that we may see most
distinctly a thing that has no real existence, — a case, therefore,
in which we can not trust our senses. The delusion seems to be
due to the fact that the two lines, in the position indicated, form
a projection on the retina such as would be made by an actual
vertical rod placed at the point at which we see one. Fig. 159
gives an interesting illustration of the way in which our judg-

BINOCULAR VISION.

361

ment of solidity may vary with our interpretation of mathe-
matical perspective and shading when these factors are arranged

/

//

//

//
//
//
//
//
//

Fig. 157.— Zollner's lines.

to give more than one choice. If the figure is looked at steadily
it may assume several different appearances; two are especially

Fig. 158. — Optical illusion in projection. — (Franklin.')

prominent. We may see two cubes resting upon a third one,
each with the black side undermost, or we may see one cube rest-
ing on two under ones, each with its black side uppermost. Our

362 THE SPECIAL SENSES.

judgment in the matter changes from one interpretation to the
other without any apparent cause. That the act of accommoda-
tion plays a part in the changes is shown by the fact that if one

a

Fig. 159. — Figure to illustrate binocular deceptions depending upon different inter-
pretations of the mathematical perspective and the lights and shades. On gazing fixedly
the image will change from a single cube with black top resting on two others with black
tops, to one of two cubes with black bottoms resting upon a single cube with black
bottom. Still other figures may appear from time to time.

focuses for the point a, this point may be held in the foreground
and the second of the above appearances be seen. While if the
eyes are accommodated strongly for point b, it will be brought
forward and the first of the two appearances described is brought
into view.

PHYSIOLOGY OF THE EAR.

CHAPTER XX.
THE EAR AS AN ORGAN FOR SOUND SENSATIONS.

In discussing the physiology of the ear it is necessary to consider
the functional importance of its various parts, the external ear
consisting of the lobe or pinna, the external auditory meatus, and
the tympanic membrane ; the middle ear, with its chain of ossicles,
its muscles and ligaments, and the Eustachian tube ; and the internal
ear, with its cochlea, vestibule (utriculus and sacculus), and semi-
circular canals. The eighth cranial or so-called auditory nerve is

Fig. 160. — Semidiagrammatic section through the right ear (Czermak): G, External
auditory meatus; T, membrana tympani; P, tympanic cavity; o, fenestra ovalis; r, fen-
estra rotunda; B, semicircular canal; S, cochlea; Vt, scala vestibuli; Pt, scala tympam;

distributed entirely within the internal ear; the fibers of the coch-
lear branch, which alone perhaps are concerned with hearing, end
among the sensory nerve cells of the cochlea, while the vestibular
branch supplies similar sense cells situated in the utriculus, sacculus,
and the ampullae of the semicircular canals. We may consider
first the functions of the ear in respect to the sensations of sound.

363

364

THE SPECIAL SENSES.

The somewhat complicated anatomy of the parts concerned should
be obtained from the special works on anatomy or histology. For
the purposes of a physiological presentation the schematic figure
employed by Czermak and reproduced in Fig. 160 will suffice to
exhibit the general anatomical relations of the parts concerned in
the transmission of the sound waves from the exterior to the cochlea.
The Pinna or Auricle. — The pinna opens into the external mea-
tus by means of a cone-shaped depression, the concha. The whole
organ, and especially the concha, may be considered as fulfilling
more or less perfectly the function of collecting the sound waves
and reflecting them into the meatus. In the lower animals the con-
cave shape of the ear and its motility probably make it much more
useful in this respect than in the case of the human ear. But even
in man the pinna is valuable to some extent in intensifying the

appreciation of sounds and
also in enabling us to deter-
mine their direction. The ex-
ternal auditory meatus has a
length of about 21 to 26 mms.,
and a capacity of something
over one cubic centimeter.
Its course is not straight, but
passes first somewhat back-
ward and upward, and then
turns forward and inward to
end against the tympanic
membrane. All sound waves
that affect the drum of the ear
must, of course, pass through
this canal.

The Tympanic Mem-
brane.— The tympanic mem-
brane closes the inner end of
the meatus and lies obliquely to the axis of the canal, its plane
making an angle, opening downward, of 150 degrees. The mem-
brane, although not more than 0.1 mm. thick, consists of three
coats : a layer of skin on the external surface, a layer of mucous
membrane on the side toward the middle ear, and in between a
layer of fibrous connective tissue. The middle layer gives to the
membrane its peculiar structure and properties. In form the
membrane has the shape of a shallow funnel with the apex, or
umbo, as it is called, somewhat below the center. The fibers of
the fibrous layer are arranged partly circularly and partly in lines
radiating from the umbo to the peripheral margin (Fig. 161).
The walls of the funnel are slightly convex outwardly; so that

Fig. 161.— To show the structure of the
tympanic membrane, looked at from the side
of the meatus (Henseri) : ax, The axis of rota-
tion of the ear bones; d, the incus; a, the
head of the malleus.

EAR AS AN ORGAN FOR SOUND SENSATIONS. 365

each radiating fiber forms an arch. On the inner side of the mem-
brane the chain of ear ossicles is attached, so that the vibrations
of the membrane are transmitted directly to these bones. The
peculiar form of the membrane, its funnel shape, its arched sides,
and its unsymmetrical division by the umbo are supposed to con-
tribute to its value as a transmitter of the sound vibrations of the
air. In the first place, the membrane shows little tendency to
after-vibrations, — that is, wh'en set in motion by an air wave it
shows little or no tendency to continue vibrating after the acting

Fig. 162. — Tympanum of right side with ossicles in place, viewed from within (after
Morris): 1, Body of incus; 2, suspensory ligament of malleus; 3, ligament of incus; 4,
head of malleus; 5, epitym panic cavity; 6, chorda tympani nerve; 7, tendon of tensor
tympani muscle; 8, foot-piece of stirrup; 9, os orbiculare; 10, manubrium; 11, tensor
tympani muscle; 12, membrana tympani; 13, Eustachian tube.

force has ceased. It is obvious that such a property is valuable in
rendering hearing more distinct, and the peculiarity of the mem-
brane in this respect is attributed partly to its special form and
partly to the damping action of the bones attached to it. In the
second place, the arched sides of the funnel act as a lever, so that
the movements at these parts are transmitted to the umbo with a
diminution in amplitude, but an intensification in force. It is at
the umbo that the movement is communicated to the ear bones.

The Ear Bones. — The three ear bones — the malleus, the incus,
and the stapes — taken together form a chain connecting the tym-

366

THE SPECIAL SENSES.

M

panic membrane with the membrane of the fenestra ovalis. By
this means the vibrations of the tympanic membrane are com-
municated to the membrane of the fenestra ovalis and thus to the
perilymph filling the cavity of the internal ear. The bones consist
of spongy material with a compact surface layer. Their general
shape and connections are illustrated in Figs. 162 and 163. To
understand the manner in which the chain of bones acts in con-
veying the vibrations from one membrane to the other some points
in their structure and connections may be recalled. The malleus
is about 18 to 19 mms. long, and has an average weight of 23 milli-
grams. Its long handle is imbedded in the tympanic membrane,
the tip reaching to the umbo. The large, rounded head projects
above the upper edge of the tympanic membrane and forms a true

joint of a peculiar nature with the
incus. It has two processes in ad-
dition to the manubrium : a short
one, processus brevis, that presses
against the upper edge of the tym-
panic membrane, and a longer one,

<^^SWjj ^11 the processus gracilis or processus

Ml II ; jfScjb s Folianus, which projects forward

^_ \\ ^r^^l^ii anc^ *s continued by a ligament, the
J\ ^^^jJ^ anterior ligament, through which

(J the malleus is attached to the bony

wall of the tympanic cavity. Three
other ligaments are attached to the
malleus, the external ligament, bind-
ing it to the external face of the
cavity, the posterior ligament, and
the superior ligament, the latter at-
taching the upper part of the head
to the roof of the tympanic cavity. By means of these ligaments
the bone is held steadily in position even after its connections
with the incus are loosened. The incus is somewhat more mas-
sive than the malleus, weighing about 25 milligrams. Its thicker
portion articulates with the head of the malleus, and it has two
processes nearly at right angles to each other. The shorter process
extends posteriorly and is attached by a ligament to the posterior
wall of the tympanic cavity; the long process passes downward
parallel with the handle of the malleus, but turns in at the tip
to form the rounded os orbiculare, which articulates with the
head of the stapes. This latter bone is extremely light, weighing
about 3 milligrams, its oval base being attached to the margins
of the fenestra ovalis by a short, stiff membrane.

The Mode of Action of the Ear Bones. — The movements of

Mm.

Fig. 163.— The bones of .the
middle ear in natural connections
(Helmholtz): M, The malleus; Mcp,
the head; Me, the neck; Ml, the
processus gracilis; Mm, the manu-
brium; Ic, body of the incus; 76.
short process; II, long process; S,
the stapes.

EAR AS AN ORGAN FOR SOUND SENSATIONS.

367

the tympanic membrane are communicated to the tip of the handle
of the manubrium. As the handle moves in, the chain of bones
makes a rotary movement around an axis which may be defined as
the line passing through the attachment of the short process of the
incus and the anterior ligament of the malleus. The general posi-
tion of this axis is represented by the line a-b in Fig. 164. This line
passes through the neck of the malleus ; so that as the handle moves
in the head of the malleus and the upper part of the incus move in
the opposite direction, — while the long process of the incus together
with the stapes, being below the axis, move in the same direction aa
the handle, (see Fig. 164A). The chain of bones, therefore, acts
like a bent lever whose fulcrum is at a, the power arm being repre-

Fig. 164. — To illustrate the lever
action of the ear bones (McKendrick) :
M, The malleus; e, the incus; a-b, the
axis of rotation: a, short process of
incus abutting against the tympanic
wall ; a-p, the power arm ; a-r, the
load arm of the lever.

Fig. 164 A. — Schema to illustrate the
way in which the ear ossicles act to-
gether as a bent lever in transmitting the
movements of the tympanic membrane
to the membrane of the fenestra ovalis.
1, The handle of the malleus; 2, the long
process of the incus; 3, the stapes ; a-b,
the axis of rotation. 'Ihe arrows indi-
cate a movement inward of the tympanic
membrane.

sen ted by the line p-a and the load arm by the line r-a. According
to Helmholtz,* the distance p-a is equal to 9.5 mms., while r-a
is 6.3 mms. The movement at r, therefore, or the movement
of the stapes, will have only two-thirds of the amplitude of the
movement at p, but will have a correspondingly greater force
(one and one-half times). The mechanisms of the tympanic
membrane and the ear bones combine, therefore, to convert the
vibratory movements of the tympanic membrane into smaller
but more intense movements of the membrane of the fenestra
ovalis. It should be borne in mind, however, that the amplitude

* Helmholtz, "Die Lehre von den Tonempfindungen, etc.," fifth edition,
1896. See also English translation by Ellis.

368 THE SPECIAL SENSES.

of these movements under normal conditions is very minute.
That of the base of the stirrup is estimated at about 0.04
mm., while the amplitude at the tip of the manubrium, though
relatively much larger, is still less than a millimeter (0.2 to
0.7 mm.). The minute but relatively intense movements of the
stapes set into vibration the perilymph in the internal ear, and
through these movements the sensory nerve cells in the cochlea
are stimulated, and nerve impulses are thereby aroused in the
fibers of the cochlear nerve. Ankylosis of the ear bones impedes
their movements and impairs the delicacy of hearing, and if the an-
kylosis affects the base of the stapes at its insertion into the fenestra
ovalis practically complete deafness ensues. The articulation of
the head of the malleus with the body of the incus is a peculiar
saddle-shaped joint, which, according to the description given by
Helmholtz, acts like a cogged or ratchet movement. When the
tympanic membrane moves in and the head of the malleus, there-
fore, moves outward, the joint locks, so that the incus follows the
malleus. If, however, from any unusual cause the tympanic mem-
brane is moved outward from its resting position, as may result, for
instance, from a marked fall in air pressure, then the malleus-incus
joint unlocks and the incus fails to follow completely the movement
of the malleus, thereby protecting the structures in the internal ear.
Muscles of the Middle Ear. — Two small muscles are present in
the middle ear : the tensor tympani and the stapedius. The former
arises in a groove just above the Eustachian tube and its long tendon
is inserted into the neck of the malleus just below the axis of rotation.
The muscle is innervated by a branch of the fifth nerve. It is
obvious that when this muscle contracts it must pull the tympanic
membrane inward and put it under greater tension. The stapedius
muscle arises from the inner wall of the tympanic cavity and its
tendon is inserted into the neck of the stapes. This muscle is
innervated through a branch of the facial. When it contracts it
tends to pull the stapes laterally, and thus probably places the mem-
brane attached to its base under greater tension. The functions
fulfilled by these muscles have been the subject of much controversy.
According to a view first proposed by Johannes Miiller, they act as
a protective mechanism to the membranes of the middle ear. By
increasing the tension of the membranes they limit the amplitude of
their vibrations and thus protect the membranes from injury or
possible rupture in the case of the violent movements resulting from
loud, explosive noises. Or possibly by their reflex contraction
they protect us from intense, disagreeable noises, by limiting the
responsiveness of the vibrating membranes. A more probable view,
however, and one supported to some extent by experimental evi-
dence, was suggested by Mach. According to this observer, the

EAR AS AN ORGAN FOR SOUND SENSATIONS. 369

contractions of the muscles adjust the membranes to the better
reception of sound vibrations and are used, therefore, in attentive
listening. They form, in fact, a mechanism of accommodation simi-
lar in its general functions to the ciliary muscle of the eye. Hensen*
has shown that both muscles contract reflexly to sounds, and that the
contractions of the tensor tympani are stronger, the higher the
pitch of the sound. This contraction seems to take place at the
beginning of the sound, but' is not maintained for a long period.
The reaction is apparently a reflex movement the sensory path of
which lies in the acoustic nerve and the reflex center in the medulla
oblongata. That a similar reflex adjustment takes place in man is
indicated by the following experiment described by Hensen. If
while listening to a tuning-fork (400 to 1000 v. d.) a metronome is set
going at a rate of 40 to 60 beats per minute, the tone of the tuning-
fork becomes obviously strengthened. The stimulus of the noise
caused by the metronome may be supposed to excite the reflex con-
tractions of the muscles of the ear and thus increase its responsive-
ness to the vibrations of the tuning-fork. According to this view,
therefore, the ear muscles are kept constantly in play by sounds or
sudden variations in the intensity of sounds, and perhaps the obvious
effort experienced in listening intently to a sound is also due to a con-
traction of these muscles.

The Eustachian Tube. — Through the Eustachian tube a com-
munication is established between the tympanic cavity and the
pharynx, and through this latter with the exterior. The obvious
advantage of this arrangement is that it keeps the air within the
tympanum Under the same pressure as the outside air, — that is, the
pressure on the two sides of the tympanic membrane is kept the
same. The pharyngeal opening of the tube is normally closed, but it
may be opened by raising or lowering the pressure in the pharynx.
This happens, for instance, in the act of swallowing, and we perform
this act, therefore, whenever our sensations from the tympanic mem-
brane warn us of an inequality in pressure upon the two sides. When,
for instance, one enters a caisson in which the external pressure is
increased over the normal atmospheric pressure the tympanic
membrane would be driven inward by the excess of external pres-
sure were it not for the existence of the Eustachian tube. Under
these conditions swallowing movements will open the pharyngeal end
of the tube and thus bring the tympanic cavity under a barometric
pressure equal to that on the outside. In nasal catarrh the tube
may be occluded so as to prevent this equalization, and under such
conditions, as is well known, the delicacy of hearing is much im-
paired, until by raising the pressure in the pharynx or by other
means the tube is opened.

* Hensen, "Archiv f. d. gesammte Physiologic," 87, 355, 1901.
24

370 .THE SPECIAL SENSES.

The Projection of the Auditory Sensations. — Auditory sen-
sations are projected to the exterior and, indeed, to the supposed
origin of the sound. The projection, however, is nothing like so
perfect as in the case of visual stimuli. Our judgments of the dis-
tance and direction of sounds are manifestly less exact than in the
case of objects seen by the eye. As an example, one may refer to
the difficulty of locating exactly such sounds as the note of a cricket.
In the ear the sensitive elements in the cochlea are not arranged so
that sounds coming from different directions can affect different
nerve fibers. All sound stimuli come to this part of the ear by one
path, — namely, the tympanic membrane and its accessory struc-
tures. In judging the direction and distance of sounds we must
rely, therefore, upon the relative distinctness of the sounds in the
two ears, the variations in distinctness observed by varying the
position of the head, the accessory information obtained from
vision, etc. The general sensibility of the tympanic membrane
also plays a part. When a vibrating body — a tuning-fork, for
example — is held between the teeth, the vibrations are transmitted
to the internal ear in part at least through the bones of the head,
and the sound in this case is referred or projected into the head
itself instead of to the tuning-fork. So that in hearing by the usual
method the sensations of the vibrating tympanic membrane must
form part of the data by means of which we project the sensation
to the exterior.

The Sensory Epithelium of the Cochlea. — The fibers of the
cochlear branch of the auditory nerve arise in the nerve cells of the
spiral ganglion situated in the central pillar, the modiolus, of the
cochlea. This ganglion resembles in structure the posterior root
ganglion of the spinal nerves. Each cell is bipolar, sending one
fiber toward the brain in the acoustic nerve, and one fiber to end in
terminal arborizations around the sensory cells or hair cells of the
organ of Corti in the cochlea. We have every reason to believe,
therefore, that these hair cells form the apparatus which is affected
by sound and by means of which nerve impulses are generated
and transmitted to the acoustic fibers. The general arrangement
and the relations of these cells are indicated in Fig. 165. They
consist of short more or less cylindrical cells (E, 6, 6', 6", Fig. 165),
whose lower portion does not reach to the basilar membrane, but
is supported by the intervening Deiters cells. The upper ends of
the cells project through the openings in the reticulate membrane
and end in a number — according to Retzius,* about twenty — short,
stiff hairs. The hair cells are arranged in four to six rows, one

* The most complete details of the structure of the ear will be found in
the great work of Retzius, "Das Gehororgan der Wirbelthiere," vol. ii, 1884,
Stockholm.

EAR AS AN ORGAN FOR SOUND SENSATIONS.

371

row on the inner side of the inner rods of Corti and three to five
rows, according to the part of the cochlea examined, on the outer
side of the rods of Corti. Their total number has been estimated
differently by different observers; but, accepting the lower figures
given, it may be said that there are at least 3500 inner hair cells
and 13,000 outer ones, giving a total of 16,500 or more. The theory
usually proposed to account *f or the mechanism by which the vibra-
tions of the perilymph affect these cells, and especially the expla-
nation of the means by which different sounds affect different cells,
is that there is contained in the cochlea a mechanism which acts
by sympathetic resonance. To make this theory clear a short

Fig. 165. — Diagrammatic view of the organ of Corti, the sense cells, and the accessory
structures of the membranous cochlea (Testut): A, Inner rods of Corti ; B, outer rods
of Corti ; C, tunnel of Corti ; D, basilar membrane; E, single row of inner hair (sense)
cells; 6, 6', 6", rows of outer hair (sense) cells; 7, 7', supporting cells of Deiters. The
are seen projecting through the openings of the reticulate
arborizations of the cochle

ends of the inner hair cells are
membrane. The terminal
inner and outer hair cells.

lear nerve fibers end around the

description must be given of the nature of sound waves and the
physical facts in regard to sympathetic resonance.

The Nature and Action of Sound Waves. — Sound waves in
air consist of longitudinal vibrations of the air molecules, alternate
phases of rarefaction and condensation. For convenience' sake,
these waves are usually represented graphically after the manner of
water waves, by a curved line rising above and falling below a
median zero line, the ordinates above the zero line representing
the phase of condensation, and those below the phase of rarefaction.
These waves are produced by the vibrations of the sounding body,
and may vary greatly in length, in 'amplitude, and in form. For

372 THE SPECIAL SENSES.

musical sounds within the range of hearing the length of the waves
may vary from forty to seventy feet, at the one extreme, to a frac-
tion of an inch at the other. They travel through the air with an
average velocity of 1100 to 1200 feet per second, the exact rate vary-
ing with the temperature. When these waves, whatever may be
their form, follow each other with regularity — that is, with a definite
period or rhythm — a musical sound is perceived provided the
rhythm is maintained for a number of vibrations. So that regular-
ity or periodicity of the sound waves may be considered as the un-
derlying physical cause of musical sounds. Non-musical sounds or
noises, which constitute the vast majority of our auditory sensa-
tions, are referred, on the contrary, to non-periodical vibrations.
Waves of this kind may be due to the nature of the impulse given
to the air by the sounding body, — single pulses, for instance, or a
series of such pulses or shocks following at a slow or irregular
rhythm, or as is more frequently the case, they may result from a
mixture of very short and different rhythmical vibrations. As
the case of musical sounds is far the simpler, the theory of the
action of the cochlea has been based chiefly upon the results
obtained from a study of these forms of waves.

Classification and Properties of Musical Sounds. — Musical
sounds exhibit three fundamental properties, each of which may be
referred to a difference in the physical stimulus. They vary, in
the first place, in pitch, and this difference finds its explanation in
the rapidity of vibration of the sounding body and the sound waves
produced by it. The more rapid the rate, the shorter will be the
waves and the higher will be the pitch of the musical note. Notes
of the same pitch may, however, vary in loudness or intensity, and
this difference is referable to the amplitude of the vibrations. A
given tuning fork emits always a note of the same pitch, but the
loudness of the note may vary according to the amplitude of the
vibrations. The vibrations of the tympanic membrane and of
the perilymph in the internal ear vary in rate and intensity with
the sounding body; so that we may say that the stimulation of
the hair cells in the cochlea gives us auditory sensations that vary
in pitch with the rate of excitation and in intensity with the ampli-
tude of the vibratory movement. A third property of musical
sounds is their variations in quality or timbre. The same note of
the same amplitude when given by different musical instruments
varies in quality, so that we have no difficulty in recognizing the
note of a piano from the same note when given by a violin or the
human voice. The underlying physical cause of variations in timbre
is found in the form of the sound waves produced, and immediately,
therefore, in the form of vibratory movement communicated to
the perilymph. Examination of the forms of sound waves produced

EAR AS AN ORGAN FOR SOUND SENSATIONS. 373

by different musical instruments shows that they may be divided
into two great groups: (1) The simple or pendular form; (2) the
compound or non-pendular form. The simple or pendular form
of wave is given, for instance, by tuning forks. A graphic repre-
sentation of this wave form may be obtained by attaching a bristle
to the end of the fork and allowing it to write upon a piece of black-
ened paper moving with uniform velocity, — the blackened surface,
for instance, of a kymograpnion. The form of the wave obtained
is represented in Fig. 166. The vibrating body swings symmetrically
to each side of the line of rest, and, inasmuch as this is also the form
of movement that would be traced by a swinging pendulum, this
form of wave is designated frequently as pendular. It is sometimes
called also the sinusoidal wave, since the distance of the vibrating
point to each side of the line of rest is equal to the sine of an arc
increasing proportionally for the time of the phase. A compound
(or non-pendular or non-sinusoidal) wave may have a very great
variety of forms. The different phases follow periodically, but the
movement of the vibrating body to each side of the line of rest is not

Fig. 166. — Form of wave made by tuning fork.

perfectly symmetrical . Fourier has shown that any periodical vibra-
tory movement, whatever may be its form, may be considered as
being composed of a series of simple or pendular movements whose
periods of vibrations are 1, 2, 3, 4, etc., times as great as the vibra-
tion period of the given movement. That is, every so-called com-
pound wave form may be considered as being caused by the fusion
of a number of simple waves. Representing the wave movement
of the air graphically as water waves, this composition of simple
waves into compound ones is illustrated by the curves given in Fig.
167. In this figure A and B represent two simple vibrations such
as would be given by two tuning-forks, the vibrations in B being
double those of A. If these two waves are communicated to the air
at the same time the actual movement of the molecules will be a
resultant of the forces acting upon them at any given instant, and
the actual movement will be indicated, therefore, by the algebraical
sum of the ordinates above and below the lines of rest. If the
movements are so timed that e in curve B is synchronous with d° in
curve A , then the resulting compound wave form is illustrated by C.
If, however, curve B is supposed to be in a different phase, so that e
is synchronous with d' , then a form of wave illustrated by D will be

374

THE SPECIAL SENSES.

obtained. In this way a great variety of forms of compound waves
may be supposed to be produced by the union of a series of simple
waves of different periods of vibration. That compound waves dif-
fer from simple ones in being composed of several series of vibrations
is indicated directly by our sensations. When we listen to the note
of a tuning-fork we hear only a single tone; when two or more
tuning-forks are sounded together the trained ear can detect the tone
due to each fork, and similarly when a single note is sounded by
the human voice, a violin, or any other instrument that has a char-
acteristic quality the trained ear can detect a series of higher tones,

Fig. 167. — Schema by Helmholtz to illustrate the formation of a compound wave
from two pendular waves: A and B, pendular vibrations, B being the octave of A. If
superposed so that e coincides with d° and the ordinates are added algebraically, the non-
pendular curve C is produced. If superposed so that e coincides with d' the non-pendular
curve D is produced.

the upper partial tones, or harmonics, or overtones, which indicate
that the note is really compound, and not simple. The formation
of these overtones is due to the fact that the sounding body vibrates
not only as a whole, but also in its aliquot parts, as may be repre-
sented in Fig. 168, illustrating the vibrations of a string. When
the string is plucked it vibrates as a whole (a), giving large waves
which produce what is called the fundamental tone, but at the same
time each half (b), third (c), fourth (d), etc., may vibrate, giving
each its own simple tone. The combination of all of these simple
waves forms a compound wave whose form or at least whose

EAR AS AN ORGAN FOR SOUND SENSATIONS.

375

composition determines the quality of the tone heard. As
many as ten or sixteen of these overtones may be detected from the
vibrating strings of a violin or guitar. When the period of vibra-
tion of these overtones bears a simple ratio to that of the funda-
mental, a ratio that can be expressed by the simple numbers, 1, 2,
3, 4, 5, they harmonize with it and form the harmonic overtones.
It should be borne in mind that, so far as the tympanic membrane
is concerned, it does not respond separately to the single tones
which constitute the compound wave, but swings in unison with
the movement of the compound wave. Nevertheless the internal

Fig. 168 — To illustrate the mechanism of the formation of overtones. — (Helmholtz.)
In a the string vibrates as a whole, giving its fundamental tone; in b, c, and d, its halves,
thirds, and fourths are vibrating independently. When a string is struck, plucked, or bowed
these movements may happen simultaneously and the fundamental note due to the vibra-
tions of the whole string is combined with the notes due to the vibrations of aliquot parts,
the overtones. The combination gives a compound wave whose form and musical quality
vary with the number and relative strength of the overtones.

ear, according to the law of Ohm, is capable of analyzing the com-
pound wave form into the series of simple or pendular wave forms
of which it is composed and of distinguishing the series of corre-
sponding tones. While this analysis cannot be made consciously
except by the trained musician, it is made unconsciously, as it
were, by every normal ear, and in consequence of this analysis we
recognize the variations in quality of different compound tones.
The principle upon which the cochlea acts in thus separating the
compound tones into their elements is not explained with entire
satisfaction. According to the view so admirably presented by

376 THE SPECIAL SENSES.

Helmholtz,* the analysis depends upon the existence in the ear of
a mechanism for sympathetic vibrations or resonance.

Sympathetic Vibrations or Resonance. — By sympathetic
vibration is meant the fact that an elastic body is easily set into
vibration by movements of the surrounding medium when these
movements correspond with its own period of vibration. A string
whose period of vibration is 128 per second will be little affected
by vibrations of the surrounding air unless they have the same
periodicity. If, however, a note of this period is sounded by the
voice, for instance, the string will be set into vibration with rela-
tive ease. By means of this principle the untrained ear can readily
pick out the more prominent of the upper harmonics of any given
note of a musical instrument. It is only necessary to select a series of
resonators corresponding to the series of overtones. Each reso-
nator is set into vibration by its corresponding overtone and so
emphasizes this particular tone that it may be easily recognized.
If one stands in front of a piano with the strings exposed and
sings a given note it may be shown that a series of the piano strings
is set into vibration corresponding, in the first place, to the rate
of. vibration of the fundamental tone, and secondly to the more
prominent of the harmonic overtones. In this case the com-
pound wave strikes upon the collection of strings of the piano,
and is analyzed into its component simple tones by the sympa-
thetic vibrations of the corresponding strings. Helmholtz assumes
that the cochlea analyzes compound musical waves by an essentially
similar method.

The Functions of the Cochlea. — The vibratory movement,
whatever may be its form, in the air of the external meatus im-
parts to the tympanic membrane a similar form of movement, and
this, in turn, through the ear bones and the membrane of the fenes-
tra ovalis sets the perilymph into vibrations of the same form. That
the perilymph can swing or vibrate under the influence of the move-
ments of the stapes is explained by the existence of the second
opening, the fenestra rotunda, between the middle and the inter-
nal ear (see Fig. 160). As the membrane of the fenestra ovalis is
pushed in, that of the fenestra rotunda is pushed out, and vice
versa. These vibratory movements of the perilymph affect the
membranous cochlea, which may be regarded as being suspended
in the perilymph, and according to the resonance theory certain
structures within the membranous cochlea are set into sympa-
thetic vibrations corresponding to the simple waves of which the
compound wave is constituted. Helmholtz first suggested -that
the peculiar rods of Corti form the resonating apparatus and
by sympathetic vibrations are capable of analyzing the compound

* Helmholtz, loc. tit.

EAR AS AN ORGAN FOR SOUND SENSATIONS. 377

movement. Later, however, this suggestion was abandoned,
since the number of the rods is not sufficiently great perhaps to
answer the requirements of this theory. According to Retzius,
the inner rods number 5600 and the outer ones 3850. Moreover,
these structures are absent from the bird's cochlea, and we must
assume that these animals are capable of appreciating musical
sounds. Helmholtz then adopted a suggestion of Hensen's, that
the basilar membrane constitutes the resonating apparatus. This
membrane forms the floor of the membranous cochlea, stretching
from the limbus to the opposite side of the bony cochlea (Fig.
165). Its middle layer consists of fibers, running radially, which,
though united to one another, are sufficiently independent to be
regarded as separate strings. These fibers in the portion covered
by the rods of Corti, the inner zone or zona tecta, are finer and
more difficult to separate than in the portion exterior to the outer
rods, the outer zone or zona pectinata. From the base to the apex
of the cochlea the membrane increases in width, the length of the
strings in the outer zone varying, according to Retzius, from 135 /^ in
the basal portion to 220 fi in the middle spiral and to 234 p. at the
apex. The whole structure is estimated to contain about 24,000
strings varying gradually in length, as stated, and resembling in
general arrangement the strings of the piano. Assuming that each
of these fibers has its own period of vibration, we may imagine that
the entire collection forms an apparatus for sympathetic vibration
which is capable of analyzing each compound wave motion into
its constituent simple waves, each string being set into strong-
est vibrations by the wave of the corresponding period. More-
over, it is implied or assumed in this theory that the vibrations of
each string are communicated to a corresponding nerve fiber of
the cochlear nerve, through which the stimulus is conveyed to
the brain as a nerve impulse. We should be capable of perceiv-
ing, theoretically, as many distinct musical tones as there are
fibers in the basilar membrane, while a compound wave, by setting
a number of these mechanisms into action, gives a series
of sensations which are more or less fused in consciousness. The
peculiar quality or timbre of the tone of each instrument is refer-
able, therefore, immediately to the number and relative intensities
of the simple tone sensations that it arouses. The fusion of these
elementary tone sensations into compound ones of different qual-
ities is comparable, in a general way, to the fusion of simple color
sensations, with this exception, however, that in the compound
tone sensations we are capable of distinguishing more clearly the
fact that they are composed of simpler elements ; the constituent
tones may be recognized by the trained ear at least. The mechan-
ism by which the vibrations of the strings of the basilar mem-

378 THE SPECIAL SENSES.

brane are conveyed to the hair cells and through them to the nerve
fibers is a matter of speculation only, as are also the functions of the
remaining parts of the organ of Corti. It may be suggested,
perhaps, that the rods of Corti and Deiters's cells, together with
the reticulate membrane, with which they are both connected,
form not only a supporting apparatus for the hair cells, but also
a mechanism by which the vibrations of the strings are commu-
nicated to the hairs of the hair cells ; but the suggestion is unsatis-
factory, as the anatomical arrangement does not suffice to explain
how the vibrations of individual strings are transmitted to the
separate hair cells. The assumption has also been made that
the tectorial membrane acts as a damper to the vibrating hair cells
or the reticulate membrane. Its position as a pad lying over the
rods of Corti and the reticulate membrane justifies perhaps such an
assumption. Many physiologists, while accepting the general
principle that the cochlea analyzes the sound waves by a mechan-
ism for sympathetic vibrations, have been unwilling to admit
that the basilar membrane constitutes such a mechanism. They
point to the improbability or impossibility of fibers of only 0.36
mm. (or 0.5 mm. at the best) in length acting as efficient reso-
nators, especially as they are not entirely free and are surrounded
by liquid. Attempts have been made, therefore, to select other
structures in the cochlea as more likely to be affected by sympa-
thetic vibrations. Attention has been directed mainly to the
tectorial membrane or membrane of Corti. Thus, Ayers* believes
that this structure as seen in the usual microscopical prepara-
tions, is simply an artefact. Under normal conditions he believes
that it is a band of very long and delicate hairs projecting from the
hair cells and lying free in the endolymph. According to his
view, it is these hairs that take up the vibrations and transmit their
impulses directly to the hair cells. The histological statement upon
which this view is based has not, however, been verified. More
recently v. Ebner,f reviving an older view of Hasse, has suggested
that the tectorial membrane, especially its free end, serves as the
mechanism for sympathetic vibration. This membrane increases
in width from the base to the apex of the cochlea and varies in
thickness in its radial diameter, so that it might be conceived to
respond to different periods of vibrations in its different parts,
its movements being communicated directly to the hair cells upon
which it rests. Unfortunately we have no direct experimental
evidence in favor of any of these views. Several observers, how-
ever, have demonstrated apparently that, whatever may be the

* Ayers, " Journal of Morphology," 6, 1, 1892.

f Kolliker, " Handbuch d. Gewebelehre," sixth edition, vol. iii, pt. 11,
p. 958, 1902.

EAR AS AN ORGAN FOR SOUND SENSATIONS.

379

mechanism for sympathetic vibration, it is so arranged that at the
base of the cochlea the higher notes are received and at the apex
the notes of the lowest pitch. Thus, Munk, in experiments upon
dogs, in which by an operation through the fenestra rotunda he had
destroyed the basal portion of the cochlea, found that the animals,
after a temporary deafness of some days, could hear apparently
only low tones and noises. Baginsky,* in a later series of experi-
ments, opened the bulla ossea on each side, destroyed the cochlea
on one side entirely so as to render that ear deaf, while on the other
he injured it in certain areas only. He found
that when the apex of the cochlea was des-
troyed the animal appeared to perceive only
the high tones, c'" ', c"", c'"".

The fundamental principle of the theory of the
function of the cochlea as developed by Helmholtz
has been subjected to some criticism. The theory of a
series of resonators each responding to a definite note
does not explain with entire satisfaction some of the
known acoustic phenomena. Thus, it is known that
when two notes are sounded together combinational
tones may be heard, either a low difference tone whose
pitch is equal to that of the difference between the
rates of the two notes, or a summation tone whose
pitch is equal to the sum of the vibrations of the two
notes. It is difficult to conceive that these combina-
tional tones have an objective existence, as vibrations,
and the means by which they are perceived by the
cochlea is not explained satisfactorily by the theory
of resonators. Other theories of the function of the
cochlea have been proposed to avoid such difficulties.
Thus, Ewald f suggests a view according to which the
basilar membrane vibrates throughout its length for
each note. He has shown that a rubber membrane of
the dimensions of the basilar membrane will be set
into such vibrations throughout its length and when
examined under the microscope presents such a pic-
ture as is represented in Fig. 169, in which the crests
of the waves are at a fixed interval for each tone. If
at these intervals the corresponding hair cells and
nerve fibers are supposed to be stimulated, then our
consciousness would recognize each note by its appro-
priate interval. For the application of this theory to
combinational tones and beats — reference must be made

Fig. 169.— To il-
lustrate the idea of
a fixed sound wave. —
(Ewald.) The illus-
tration shows a fun-
damental note and its
first overtone.

musical harmony —
to the original.

Sensations of Harmony and Discord. — The combination of
notes to produce various harmonies or intentional discords is a part
of the theory of music, but attention may be called briefly to the
physiological explanation offered by Helmholtz to account for the
fact that certain notes when combined give us a disagreeable sen-
sation, appear rough and unpleasant ; while others, on the contrary,
produce pleasant sensations. Discord or dissonance is due, accord-

* Baginsky, "Virchow's Archiv f. pathol. Anat.," 94, 65, 1883.
t Ewald. "Archiv f. d. gesammte Physiologic," 76, 147, 1899.

380 THE SPECIAL SENSES.

ing to Helmholtz, to the beats produced when two dissonant notes
are sounded together. On the physical side the beat, — that is, a
rhythmical variation in the intensity of the sound, — is due to the
phenomenon of interference. If the rates of vibration of two notes
are such that at certain intervals the crests of the waves fall to-
gether and again the crest of one coincides with the hollow of the
other, the sound sensations will be periodically increased and
decreased. While there is no fundamental explanation for the
fact that a regularly varying intensity of sound is disagreeable, it
is a well-known phenomenon and it finds analogies in the other
sensations, — for instance, in the very disagreeable effect of a flick-
ering light. When two notes are sounded together the number of
beats varies with the difference between the rates of vibration;
thus, two notes, one of 128 vibrations and the other of 136 vibra-
tions, give 8 beats per second. When the number of beats
rises to 33 per second the discord is most disagreeable; if, however,
the rate of interference is more rapid, the unpleasant sensation
becomes less perceptible, and beyond 132 per second is not notice-
able. When the rates of vibrations of two tones are such that
neither the fundamentals nor any of the overtones give beats, the
effect is that of harmony, the vibrations of one note strengthening
those of the other. The most perfect harmony is that of a note
sounded simultaneously with another of the same rate, ratio 1:1,
or with its octave, ratio 1:2. The various intervals which in
music have been found to be perfectly consonant or which vary so
little from it as to be usable in harmonies are those whose vibra-
tions bear a simple ratio to each other. Thus, the octave of any
note has the ratio of 1:2, the double octave 1 : 4, the twelfth 1:3.
These three intervals give absolutely consonant sounds. Other
intervals — such as the fifth, 2:3, or the major third, 4: 5 — give
a less perfect consonance. Three or more notes bearing such rela-
tions to each other constitute a chord, the vibrations in the
major chord being, for instance, in the ratios 4:5:6, — c' (128),
e' (160), g' (192).

The Limits of Hearing. — The rates of vibration that can be
perceived by the ear as musical tones lie between fairly well-
defined limits, although in this organ, as in the case of the eye,
there are individual variations, — variations, indeed, which are
more marked in the case of the ear, since its range of appreciation
is larger. The lowest rate of vibration that can cause a musical
sensation is usually placed at 28 to 30 per second, although some
ears can still respond to an octave lower, about 16 per second. To
most ears vibrations below 30 per second are felt, if perceived at all,
as single pulses that stimulate the sensory nerves of the tympanic
membrane itself. The cochlea does not respond. It may happen,

EAR AS AN ORGAN FOR SOUND SENSATIONS. 381

however, that a vibration too slow to be perceived by the ear will
give overtones of sufficient strength to be recognized. An inter-
esting example in physiology of this fact is furnished by the tone
of the contracting muscle. As heard, this tone corresponds to a
vibration of 40 per second; but other data lead us to believe that
the vibrations of the contracting muscle, due to the single con-
tractions of which the compound contraction is composed, occur
at the rate of only 10 per second; so that what is heard is, in reality,
the second octave of the fundamental. The high limit of audibility,
on the other hand, is usually placed at 40,000 double vibrations
per second, although the various estimates published vary so
widely that in this respect there must be great individual differences.
The shrill notes of insects are said to be inaudible to some ears.
Konig, making use of Kundt's method of light powders, succeeded
in tuning a series of forks to an estimated rate of 90,000 double
vibrations per second. It was found that those between c7and c9
(8192 to 32,768) were generally audible, while the c10 (65,536) was
inaudible. The limit, therefore, lay between c9 and c10. Notes
near this high limit are not, however, usable in ordinary music;
the sensations produced have a disagreeable, if not actually painful
shrillness. The range of vibrations employed in music is illustrated
by the seven octaves of the piano, the notes varying from the lowest
c of 32 vibrations to ce of 4096 vibrations. The intervening series
is divided into tones whose serial relations to each other are ex-
pressed by the ratios f or V° and semitones of the ratio yf or ff ;
thus, c"= 256 vibrations and the d" of the same octave corresponds
to 256 X f = 288 vibrations.*

"See Helmholtz, Popular Scientific Lectures, "Ueberdie physiologischen
Ursachen des musikalischen Harmonic," Bonn, 1857.

CHAPTER XXI.

THE FUNCTIONS OF THE SEMICIRCULAR CANALS AND
THE VESTIBULE.

Position and Structure. — The membranous semicircular canals
lie within the bony semicircular canals, the space between being
filled with perilymph which communicates freely with that in the
rest of the labyrinth. Within the membranous canals is the endo-
lymph, which communicates through the five openings with the
endolymph in the utriculus. The canals lie in three planes that are,
approximately at least, at right angles to one another (Fig. 170).
The horizontal or external canals lie in a horizontal plane at right

angles to the mesial or sagittal
plane of the body, the vertical
canals on each side make an angle
of about 45 degrees with this
mesial plane. The plane of each
of the anterior canals is parallel to
that of the posterior or inferior
vertical canal of the opposite side,
as represented in the figure. At
one end of each canal near its
junction with the utriculus is the'
swelling known as the ampulla
and within the ampulla lies the
crista acustica containing the hair
cells with which the nerve fibers
communicate, and which, there-
fore, are considered as the sense
cells of the organ. The hair
cells are cylindrical and each
gives off a long hair, consisting
perhaps of a bundle of finer
hairs, which projects into the
interior of the canal for a distance
of at least 28 /i. The nerve fibers
distributed to these hair cells are given off by the vestibular branch
of the eighth nerve, or more properly the vestibular nerve, one
branch of which (ramus utriculo-ampullaris) supplies the utriculus
and the ampulla of the superior and horizontal canals, while the
other (ramus sacculo-ampullaris) furnishes fibers to the sacculus.
and the posterior ampulla.

382

FIG. 170. — Diagram to show the posi-
tion of the semicircular canals in the head
of the bird. On each side it will be seen
that the three canals lie in planes at right
angles to one another. The external or
horizontal canals (E) of the two sides lie
in the same plane. The anterior canal of
one side (A) lies in a plane parallel to that
of the posterior canal (P) of the other side
(Ewald).

SEMICIRCULAR CANALS AND THE VESTIBULE. 383

Flourens's Experiments upon the Semicircular Canals. —

Modern experiments and theories concerning the functions of the
semicircular canals date from the classical researches of Flourens*
(1824). This investigator laid bare the canals in birds and mam-
mals and studied the effects of sections of one or more of them.
The experiments have since been repeated by numerous observers,
and the results obtained have,, been described in great detail, for an
account of which reference must be made to original sources.f In
general, it may be said that injuries to the canals are followed by
certain more or less definite movements of the head, eyes, and body,
and by a disturbance in the power of the animal to co-ordinate nor-
mally the muscles used in standing, locomotion, or flying. The
character and extent of these results vary with the number of
canals injured, and, indeed, show a more or less definite relationship
to the several canals. When the horizontal canal is cut on one side
in pigeons the animal makes movements of the head in the plane of
that canal, and if the similar canal on the other side is also sec-
tioned these movements are more pronounced. The animal may
also in moving show an inability to walk normally and a tendency,
especially when excited, to make abnormal forced movements of
rotation of the whole body. After such an operation the pigeon will
not fly voluntarily and if thrown into the air is not able to guide
its flight with accuracy and soon descends. Similar operations
on the anterior or the posterior canals cause movements of the head
in the corresponding planes and a tendency in walking or flying
to make forced movements — somersaults — forward or backward.
When all three canals are cut on one or both sides the animal shows
a distressing inability to maintain a normal position. The head is
twisted, it is not able to stand unless supported, and any attempt
at walking or flying results in violent forced and inco-ordinated
movements. The animal makes continual somersaults at each
attempt to stand or walk and the head is kept in spasmodic, forceful
movements, which may produce injury or death. To preserve the
animal from injury after such an extensive operation it is necessary
to keep it wrapped in bandages. It should be added that results
of this character are obtained only when the membranous canals
are injured. If the bony canal alone is cut and even if the peri-
lymph is removed by suction no such effects are obtained. At
most slight and relatively transient movements of the head are
observed. If the exposed membranous canal is pricked with a

* Flourens, " Recherches experimentales sur les proprietes et les fonctions
du systeme nerveux," second edition, 1842.

f The literature of the semicircular canals and the vestibule is very ex-
tensive. The complete bibliography may be obtained from the following
sources : " Die Lehren von den Funktionen der einzelnen Theile des Ohrlaby-
rinths," by von Stein, 1894; Richet's " Dictionnaire de Physiologic," article
by Cyon, on "Espace," 1900. Ewald, ''Physiolog. Untersuchungen u. d.
Endorgan des nervus octavus, " 1892.

384 THE SPECIAL SENSES.

needle more violent movements result, and if sectioned these move-
ments are maintained for a longer period and are accompanied by
the other results described. Similar effects have been obtained
from operations on mammals and other animals, but the results
are more pronounced in some animals than in others, varying
apparently with the delicacy of the co-ordination necessary to the
movements (Ewald). Thus, the movements of walking or flying
in the pigeon may be assumed to require a nicer adjustment of the
muscles used than is necessary in the swimming movements of the
fish, and in correspondence with this idea it is found that opera-
tions on the canals of fishes are not followed by conspicuous effects
upon the movements of the animals.

Temporary and Permanent Effects of the Operation. — The
general effects of operations on the semicircular canals, so far as
disturbances of equilibrium and occurrence of forced movements
are concerned, resemble those resulting from operations upon the
cerebellum, and, as in the case of the last mentioned organ, it is
found by most observers that if the animal is properly cared
for the severity of the first effects passes off to a greater or less
extent. Flourens states that his pigeons, with two or more canals
cut, continued to show the effects of the operation almost with the
same intensity for nearly a year. Some unpublished experiments
made in the author's laboratory have given different results.*
Pigeons with only one canal cut recover practically completely
within ten or more days. Those with two canals cut recover nearly
completely within a month, so far as walking is concerned, although
they exhibit an unwillingness to fly. Those with three or more
canals cut never recover completely, but their final condition is very
different from that exhibited shortly after the operation. Even
when all six canals have been cut the animal, if well cared for in the
beginning, is able finally to stand and walk and feed itself. It
is not able, however, to fly, and in walking its progress is uncertain;
there is a tendency to walk zigzag or in circles, first to one side, then
to the other. If hurried or excited some return of the violent
movements of the head and inco-ordination of the movements of
locomotion may be seen. The partial recovery from the operations
upon the canals may be due, however, to a more or less complete
restoration of the canals to their former functional activity, owing
to a regeneration, partial or complete, since a new section of the
canals, after a year or more, again brings on the violent and dis-
orderly movements of the head and the body.

Effect of Direct Stimulation of the Canals. — The mem-
branous canals or their ampullary enlargements have been stimu-
lated by many observers and by many different methods — electrical,
chemical, and mechanical. The results of electrical stimulation are
* Experiments lasting over two years made by Dr. E. Rosencraiitz.

SEMICIRCULAR CANALS AND THE VESTIBULE. 385

not constant nor striking, but chemical and especially mechanical
stimulation in the hands of many observers has called forth definite
movements of head or eyes similar in a general way to those caused
by section of the canal, but lasting, of course, for a short time only.
In the dog-fish Lee* finds that pressure upon an ampulla causes
movements of the eyes and fins such as would occur normally if
the animal's body were rotated in the plane of the canal stimulated.

Effect of Section of the Ampullary or the Acoustic Nerve.—
Many of the older and newer observers have 'cut one or both of the
acoustic nerves or destroyed the entire labyrinth on one or both
sides. The effects described vary somewhat with the animals used,
but, in general, section of the nerve on one side is followed by
forced movements, especially by rolling movements around the
long axis of the body. When the nerves are cut on both sides
disturbances in the power to maintain equilibrium perfectly are
more or less distinctly marked. In fishes (dog-fish) the animal may
swim or come to rest in unusual positions, — on the back or side, for
instance.

Is the Effect of Section of the Canals Due to Stimulation?—
The movements that result from section of one or more of the canals
have been attributed by some authors to stimulations set up by the
injury caused by the operation, and by others have been considered
as a result of the falling out of the stimuli normally and constantly
proceeding from the canals. This fundamental question has not
been decided. On the one hand, the movements observed are simi-
lar to those caused by excitation, which would indicate that a stimu-
lation is set up by the operation. On the other hand, the effects are
so long lasting as to make it improbable that they are entirely due to
the irritation of the operation. Moreover, Gaglio f states that when
the spot operated upon is cocainized the same effects follow. Indeed,
cocainizing the membranous canals gives the same results as cutting
them. It is possible, of course, that both processes take place, an
irritative stimulation and a falling out of normal impulses, the
effects of the latter being longer lasting.

Theories of the Functions of the Semicircular Canals. — As
indicated briefly above, the facts regarding injury to and stimulation
of the semicircular canals are very numerous and, on the whole, fairly
concordant. Their interpretation, however, has offered great dif-
ficulties, and many views have been proposed; almost every inves-
tigator, in fact, has, to some extent, varied in his interpretation of
the precise functional significance of these organs. t These views
may be classified, although imperfectly, under the following heads :

* Lee, "Journal of Physiology," 15, 328, 1903.

t Gaglio, "Archives ital. de biologic," 31, 377, 1899.

t For a detailed and complete account of these views to 1892 see Stein,
"Die Lehren von den Funktionen der eizelnen Theile des Ohrlabyrinths."
Jena, 1894.

386 THE SPECIAL SENSES.

1. The old view, first proposed by Autenrieth (1802), that the
canals or their sense cells are stimulated by sound waves and give
us the means of determining the direction of sound in accordance
with their position in three planes at right angles to one another.
This view has been revived from time to time by recent writers.

2. Flourens himself believed that the impulses normally proceed-
ing from these organs serve to moderate, or, as we should say now,
to inhibit the movements of the head. As soon as the canals are cut
the movements that have been kept under control by their influence
are unrestrained. On this view the semicircular canals are
organs which inhibit or restrain the voluntary movements, and
thus take an essential part in the proper co-ordination of such
movements. He did not attempt to define the physiology of the
organs in terms of the sensations aroused.

3. The view that the stimulus to the hair-cells is to be found in
the varying pressure of the endolymph. As first proposed by Goltz
(1870), it was assumed that the endolymph exerts a hydrostatic
pressure upon the hair cells which in any given position varies in the
different ampullas and varies with different positions of the head.
The sensory impulses thus aroused give us a knowledge of the posi-
tion of the head and enable us, therefore, to control its movements
and also those of the body. On this view these organs act as sense
organs in maintaining body equilibrium and may be designated as
peripheral sense organs of equilibrium. Later observers (Mach,
Breuer, Brown, et al.) modified this view by the assumption that the
hair cells are stimulated not so much by the hydrostatic pressure of
the endolymph as by the pressure changes developed during move-
ments of the head, making the organs, therefore, a means of
appreciating especially the movements of the head, a dynamic
rather than a hydrostatic organ of equilibrium. It was assumed
that rotation movements of the head in the plane of a canal set up
a movement or pressure of the endolymph in the opposite direc-
tion, just as, to use a rough comparison, when one twirls a pail of
water in one direction the water lags behind and exerts a pressure
in the opposite direction. According to this hypothesis, which
in some form or other is the view usually taught, the hair cells in
each ampulla are stimulated chiefly by movements in the plane of
that canal toward the ampulla, the pressure of the endolymph be-
ing in the opposite direction, — that is, from utriculus toward the
canal. Moreover, the vertical canals act in pairs (see Fig. 170), the
superior or anterior vertical of one side acting with the posterior or
inferior vertical of the other side, the two canals lying in parallel
planes. Movements in this plane forward would stimulate the
anterior ampulla on one side chiefly, movements in the same plane
backward, the posterior ampulla of the opposite side. The horizon-
tal canals also act together, being stimulated chiefly by rotational

SEMICIRCULAR CANALS AND THE VESTIBULE. 387

movements in the horizontal plane, the hair cells in one responding
chiefly to movements in one direction, the other to movements in
the same plane, but in the opposite direction. Rotational
movements in other planes — sagittal, oblique, etc. — would
affect two or more of the pairs of canals in proportion to the
degree that each is involved in the movement on the principle of
the parallelogram of forces.* By a mechanism of this sort it
may be supposed that we are informed regarding the plane, di-
rection, and extent of the movements of the head and are thereby
enabled to control these movements. The canals function es-
pecially as a dynamic organ of equilibrium, but may also give us
guiding sensations when the movements are progressive rather than
rotational, and also when the head is at rest, although, as is ex-
plained below, this last function is by some relegated to the hair
cells of the utriculus and sacculus. According to this view, the
loss of the power of maintaining exact equilibrium after injuries to
the canals or section of the nerves may be explained by supposing
that false sensations are experienced and false compensatory move-
ments are made. So, also, the vertigo experienced after continued
rotation may be attributed to abnormal stimulation of these sense
organs, — a view that finds some support in the fact that many
deaf-mutes, whose internal ear is supposed to be deficient, do not
experience vertigo after rotation, and in animals with the labyrinth
destroyed rotational movements fail to give the symptoms of vertigo.

4. Cyon has advocated the view that the semicircular canals con-
stitute an organ for the perception of space in its three dimensions.
Each canal or pair of canals gives us the sense of direction in its own
plane, and the fact that we have three pairs in planes at right angles
to one another gives the physiological foundation of our conception
of three dimensional space. On this fundamental conception of
space are projected the additional space conceptions derived from
our visual, tactile, and muscle senses. This author is not specific in
stating by what means the sensory cells in the three canals are
stimulated. In addition to the sensations of direction and of space
furnished by the canals, the nerve impulses from them are supposed
to co-ordinate the action of the motor centers concerned in move-
ments of the head and body.

5. Ewald, while accepting the general view that the sense cells
are stimulated by the pressure of the endolymph, lays stress upon
the fact that the nerve impulses thus aroused have, as their main
result, a reflex effect upon the tonicity of the voluntary muscula-
ture. The constant flow of impulses from these organs serves to
maintain the muscles in a normal condition of tone. In animals
with the labyrinth destroyed on both sides the body musculature
is flabby and lacking in tonicity. On this view, therefore, the semi-

* Consult Lee, loc. cit.

388 THE SPECIAL SENSES.

circular canals constitute what might be called a muscle-tone organ,
and the obvious disturbances in motion caused by their injury are
due primarily to a diminution or loss in muscle tone, each canal
possibly being reflexly connected with special muscles.

Summary. — With reference to the kind of sensation mediated
by the nerves of the semicircular canals, it should be borne in mind
that these sensations are not distinctly recognized by consciousness ;
hence the difficulty of designating them by a specific name. Of
the many qualities of sensation or consciousness which we can
distinguish some have characteristics so clear that we recognize
them at once and give them distinctive names, — such, for instance,
as the sensations of sight, hearing, taste, etc. Others, however,
produce a psychical reaction of such an indefinite character that
they escape recognition by mere introspection. The change in con-
sciousness is not sufficiently marked to make itself felt to the un-
trained mind. This condition prevails regarding the sensations,
if any, aroused through the semicircular canals; they are too
indistinct to be recognized and named by an appeal to conscious-
ness, and it would seem to be wiser to designate them after the
analogy of the muscle sensations simply as semicircular canal
sensations. Our perceptions or ideas of space and direction are
possibly founded in part upon these reactions and in part upon
the muscle sense, visual, and tactile sensations. Our reasoning
with regard to the semicircular canal sensations would be more
satisfactory if it could be shown that the vestibular nerve after
ending in the brain was continued forward by sensory paths to
the cortex of the cerebrum. As a matter of fact, such paths have
not been demonstrated, and if we assume that conscious sensations
are mediated only through the cortex of the cerebrum we have
no anatomical proof that the semicircular canals give us any
reaction in consciousness. The vestibular nerve fibers end in the
nucleus of Deiters and the nucleus of Bechterew, through which
reflex connections are established with the motor centers of the
spinal and possibly the cranial nerves. There is a connection
also with the nucleus fastigii of the cerebellum and through
this possibly with the cerebellar cortex, although this latter
connection has not been actually demonstrated. With regard
to the influence of the nerve impulses from the semicircular canals
upon movements, all the facts known seem to indicate that they
play an important part in the regulation or co-ordination of the
movements of equilibrium and locomotion. Inasmuch, as this gen-
eral co-ordination or control seems to rest normally in the nervous
mechanisms of the cerebellum and inasmuch as the vestibular
nerves make possible end connections with the cerebellum, to-
gether with the fibers of muscle sense, we may assume that the

SEMICIRCULAR CANALS AND THE VESTIBULE. 389

cerebellum forms the brain center in which the semicircular canal
impulses exert their influence upon co-ordinated muscular con-
tractions,— the cerebellum forms the nerve center for the semi-
circular canals or the semicircular canals form a peripheral sense
organ to the cerebellum. Some such hypothesis seems to be
necessary to account for the general similarity between the effects
of lesions of the canals a/id of the cerebellum. Whether the
impulses from the canals are excitatory or inhibitory or both, as
regards their effect upon muscular contractions, is not clearly
apparent from the experimental evidence so far furnished, but
Ewald's suggestion that they serve to maintain reflexly the tonus
of the body musculature is perhaps the most acceptable view.
In regard to the means by which these nerves are normally stim-
ulated there is also much room for conjecture, but provisionally
at least it seems permissible to adopt the view that variations
in the pressure of the endolymph upon the hairs of the hair cells,
especially in movements of rotation, constitute the immediate
cause of their excitation. Granting that changes in position or
movement of the head may cause such variations in pressure the
theory offers a simple and satisfactory explanation of the mode
of excitation and the means by which the excitation may vary
appropriately under different conditions. While the endolymph
theory may be criticized easily, no other equally satisfactory theory
has been suggested to take its place.

Functions of the Utriculus and Sacculus. — These small sacs
contain sensory hair cells similar in general structure to those found
in the crista of the ampullary sacs. The collection of hair cells with
their supporting cells is designated as the macula, the macula utriculi
and the macula sacculi. Lying among the hairs of the hair cell are
found masses of small crystals of calcium carbonate, the otoliths or
otoconia. In this respect the structure of the macula differs strik-
ingly from that of the crista. The position and connections of the
utriculus and sacculus lead at first naturally to the supposition that
they are stimulated by the sound waves of the perilymph and are,
therefore, concerned in the function of hearing. The accepted
views regarding the functions of the cochlea in hearing make this
organ sufficient for all auditory purposes and there is no specific
part of this process that need be attributed to the vestibular sacs.
It was, indeed, at one time suggested that their structure adapts
them to respond especially to short and irregular vibrations, but
no cogent reasons or facts have been advanced to support this
view. The fact that the sacs are so closely connected with the
semicircular canals suggests rather that the functions of these organs
are similar and that like the canals, therefore, they influence the
contractions of the muscles and function as organs of equilibrium.

390 THE SPECIAL SENSES.

In recent years the view that has been most discussed is that ad-
vanced by Breuer, — namely, that these organs give us information
regarding the position of the head when at rest and when mak-
ing progressive — that is, non-rotary — movements, supplementing,
therefore, the functions of the semicircular canals on the supposition
that these latter act especially in movements of rotation. Or, as it
is sometimes expressed, the sacs form a static and the canals a dy-
namic organ of equilibrium. According to this view, the otoliths
act as a means of mechanical stimulation of the hairs. Being
heavier than the endolymph, they press upon the hairs with a force
varying with the position of the head and thus give rise to sensations
or reflexes which are adapted to the maintenance of equilibrium.
Since the planes of the two sacs are different, they may be differ-
ently affected by the same position or movement. So also in pro-
gressive movements forward the weight of the otoliths may be im-
agined to exercise a stress of some sort upon the hairs. This theory
has been the subject of much investigation, numerous experiments
having been made chiefly upon fishes and invertebrates.* Accord-
ing to some observers destruction of these sacs or section of their
nerves is accompanied by a distinct interference with the fish's nor-
mal equilibrium: the animal swims at times upon its back or side
and apparently loses its normal means of judging correctly its posi-
tion. In many invertebrates there is present a sac, known as the
otocyst, containing hair cells and otoliths. Its structure resembles
that of the vestibular sacs of the mammalian ear, and it has been
assumed that it has a similar function. Experiments by numerous
observers have indicated that when the otoliths are removed the
animal shows disturbances in equilibrium, particularly in the matter
of the compensatory movements exhibited during rotation. Others,
however, deny these facts and state that invertebrates without oto-
cysts make compensatory movements when rotated and that in
those with otocysts compensatory movements and maintenance of
normal equilibrium persist after destruction of the sacs. A very
ingenious experiment reported by Kreidl seems to show that the oto-
liths may affect the hairs by their weight. When the palsemon, a
crustacean, molts it casts off the inner lining of the otocyst, together
with the otoliths. The otocysts in these animals lie at the base of
the antennules and open freely to the exterior. After molting the
animal by means of its claws places fine grains of sand in the otocyst
to act as otoliths. Taking advantage of this peculiarity, Kreidl
placed the animal, after molting, upon finely powdered iron, with
the result that some of the iron granules were deposited in the oto-

* Consult the following papers: Sewall, "Journal of Physiology/' 4, 339,
1884; Lee, ibid., 15, 311, 1893, and "American Journal of Physiology," 1,
128, 1898; Lyon, 'American Journal of Physiology/' 3, 86, 1900.

SEMICIRCULAR CANALS AND THE VESTIBULE. 391

cyst in place of the usual grains of sand. When now a magnet was
brought near to the animal reactions were obtained which showed
that the pressure of the iron upon the hairs influenced its position.
The position taken by the animal under these conditions was such
as would be expected as a resultant of the forces of magnetism and
gravity, and the experiment, therefore, justifies the hypothesis that
under normal conditions gravity affects the otoliths and through
them the muscular co-ordination of the animal. These experiments
have been confirmed by Prentiss.* This author has shown,
moreover, that if larval lobsters (4th stage) are prevented from
obtaining otoliths after moulting by placing them in filtered sea-
water, their movements, like those of larvae deprived of their
otocysts, show a distinct instability and lack of normal orientation.

* Prentiss, 'Bulletin of Museum of Comparative Zoology," Harvard,
1901, xxxvi., No. 7.

SECTION IV.
BLOOD AND LYMPH.

CHAPTER XXII.

GENERAL PROPERTIES: PHYSIOLOGY OF THE
CORPUSCLES.

The blood of the body is contained in a practically closed system
of tubes, the blood-vessels, within which it is kept circulating by the
force of the heart beat. It is usually spoken of as the nutritive
liquid of the body, but its functions may be stated more explicitly, al-
though still in quite general terms, by saying that it carries to the tis-
sues foodstuffs after they have been properly prepared by the diges-
tive organs; that it transports to the tissues oxygen absorbed from
the air in the lungs; that it carries off from the tissues various waste
products formed in the processes of disassimilation ; that it is the
medium for the transmission of the internal secretion of certain
glands; and that it aids in equalizing the temperature and water
contents of the body. It is quite obvious, from these statements,
.that a complete consideration of the physiological relations of the
blood would involve substantially a treatment of the whole subject
of physiology. It is proposed, therefore, in this section to treat the
blood in a restricted way, — to consider it, in fact, as a tissue in itself,
and to study its composition and properties without special reference
to its nutritive relationship to other parts of the body.

Histological Structure. — The blood is composed of a liquid part,
the plasma, in which float a vast number of microscopical bodies, the
blood corpuscles. There are at least three different kinds of cor-
puscles, known respectively as the red corpuscles or erythrocytes;
the white corpuscles or leucocytes, of which in turn there are a
number of different kinds; and the blood plates. Blood-plasma,
when obtained free from corpuscles, is perfectly colorless in thin
layers, — for example, in microscopical preparations; when seen in
large quantities it shows a slightly yellowish tint, the depth of
color varying with different animals. The red color of blood is
not due, therefore, to coloration of the blood-plasma, but is caused

392

GENERAL PROPERTIES: THE CORPUSCLES. 393

by the mass of red corpuscles held in suspension in this liquid.
The proportion by bulk of plasma to corpuscles is usually given,
roughly, as two to one.

Blood-serum and Defibrinated Blood. — In connection with the
explanation of the term "blood-plasma " just given it will be con-
venient to define briefly the terms " blood-serum " and " defibrin-
ated blood." Blood, after it escapes from the vessels, usually clots
or coagulates; the nature of this process is discussed in detail on
page 426. The clot, as it forms, gradually shrinks and squeezes out
a clear liquid to which the name blood-serum is given. Serum re-
sembles the plasma of normal blood in general appearance, but dif-
fers from it in composition, as will be explained later. At present
we may say, by way of a preliminary definition, that blood-serum is
the liquid part of blood after coagulation has taken place, as blood-
plasma is the liquid part of blood before coagulation has taken place.
If shed blood is whipped vigorously with a rod or some similar object
while it is clotting, the essential part of the clot — namely, the fibrin
— forms differently from what it does when the blood is allowed to
coagulate quietly ; it is deposited in shreds on the whipper. Blood
that has been treated in this way is known as defibrinated blood. It
consists of blood-serum plus the red and white corpuscles, and as far
as appearances go it resembles exactly normal blood; it has lost,
however, the power of clotting. A more complete definition of
these terms will be given after the subject of coagulation has been
treated.

Reaction of the Blood. — When tested with litmus or lakmoid
paper blood gives an alkaline reaction. This reaction is attributed
to the sodium carbonate in solution in the plasma, and the amount
of the alkalinity has been determined, therefore, by ti-tra&ion with
a weak acid, such as tartaric acid. The acid is employed in
a known strength — one two-hundredth or one four-hundredth
normal solution, — ^ or ~^t that is the solution contains in each
liter ,^0 or — - of the number of grams represented by the molecular
weight of tartaric acid (C4H6O6= 150). A solution of this strength
is added to a known quantity of blood until the sodium carbonate
is all neutralized, the end of the reaction being determined usually
by one of the recognized indicators, such as litmus or lakmoid.
Tested in this way, it has been found that the alkalinity of the blood
corresponds to that of an aqueous solution containing from 0.2 to
0.3 per cent, of sodium carbonate. Much attention has been paid
to the variations in the alkalinity of the blood in different diseases,
as also under varying conditions of normal life, and in consequence
many methods for determining this alkalinity have been suggested
with reference to their clinical application, these methods being
characterized by the fact that but little blood is employed. The

394 BLOOD AND LYMPH.

methods differ among themselves chiefly in the means used to
determine the point of neutralization of the blood by the acid
added. In some methods litmus is employed, in others lakmoid,
and in one (Dare's) the end-reaction is determined spectroscopically
on the belief that the characteristic absorption spectrum of oxy-
hemoglobin (p. 408) disappears at the point of neutralization.*

In reference to this subject of the reaction of the blood and of the
tissues of the body generally a difference in terminology prevails
at present which tends to confuse the beginner. Some writers use
the term alkalinity in the sense of titration alkalinity to indicate
that the blood will neutralize a certain amount of weak acid added
to it. Others, however, employ the term in its strict sense, as
developed by modern physical chemistry, to indicate an excess of
hydroxyl ions (OH — ). From the latter standpoint a solution is
alkaline when it contains a substance" or substances which upon
dissociation yield an excess of hydroxyl ions, — sodium hydroxid,
for example, which on dissociation gives Na-h and OH — , or sub-
stances, such as sodium carbonate, which give rise to hydroxyl ions
by reaction with water.

In a solution of sodium carbonate we may assume that some of the
molecules dissociate into the ions Na -j-, Na -(-, and CO3 =, and that the anion,
CO3 =, reacts with the dissociated molecules of water, H -)-, HO — , giving
HCO3 — and OH — . There will be present in the solution, therefore, the
following ions, Na -f, OH — , and Na -f-, HCO3 — ; and the presence of the
hydroxyl ion confers upon the solution its alkaline reaction and properties.
In such a solution of a strong base with a weak acid the alkalinity, that is,
excess of OH — , cannot be determined by titration with an acid stronger
than carbonic acid. If tartaric acid is added, for instance, the acid will not
only give its H 4- to combine with the OH — , but its own anion will combine
with all of the dissociated Na -f ', consequently more Na2COs will be dissociated,
and this reaction goes on, if sufficient acid is used, until all of the sodium
carbonate is destroyed. To determine the excess of hydroxyl ions in such
a solution as blood it is necessary to make use of the methods of physical
chemistry. Those who have employed these methods f report that olood
contains no greater quantity of hydroxyl ions than pure water, and must,
therefore, be reckoned as a neutral liquid. This conclusion is corroborated
further by the fact that with some indicators — e. g., phenolphthalein — the
blood does not give an alkaline reaction. In fact, the sodium in the blood
behaves substantially as if it were present as the bicarbonate, NaHCO3,
whose dissociation would be represented by the two ions Na +» HCO3 —
The many observations, therefore, which have been made by titration of the
blood must be considered as not giving its variations in alkalinity, but rather
the variations in the amount of alkali, Na, in combination with weak acids,
such as carbonic or phosphoric acid or with the blood-proteins. The results
represent what has been called the "titration alkalinity" of the blood and
are useful in the information they furnish regarding the capacity of the blood
to carry carbon dioxid (see Respiration), or to neutralize the acid products
formed during normal metabolism and especially during the abnormal metab-
olism of many diseased conditions.

Specific Gravity. — The specific gravity of human blood in the
adult male may vary from 1.041 to 1.067, the average being about

* For an account of these methods see Simon, "A Manual of Clinical Diag-
nosis," 1904.

fFraenckel, "Archiv f. d. gesammte Physiologic," 96, 601, 1903; and
Hober, ibid., 99, 572.

GENERAL PROPERTIES: THE CORPUSCLES. 395

1.055. The most satisfactory method of determining this factor is,
of course, to compare the weight of a known volume of blood with
that of an equal volume of water, but for observations upon human
beings such small quantities of blood must be used that recourse must
be had usually to a more indirect method. Perhaps the simplest of
the methods suggested is that devised by Hammerschlag.* In this
method a mixture is made of 4. chloroform (sp. gr., 1.526) and benzol
(sp. gr., 0.889). The mixture is made in such proportions as to
have a specific gravity of about 1.055. A drop of blood from the
finger is shaken into this mixture; if the drop sinks to the bottom
it is evident that the specific gravity of the blood is higher than that
of the mixture, and the reverse is true if the drop rises. By adding
more of the chloroform or of the benzol, as the case may be, the
specific gravity of the mixture may be quickly altered so as to be
equal to that of the drop of blood, which will then float in the liquid
without a distinct tendency to rise or fall. The specific gravity of
the mixture, which is also that of the blood, is then determined by a
suitable hydrometer. By the use of such methods it has been found f
that the specific gravity varies with age and with sex; that it is
diminished after eating and is increased after exercise ; that it has a
diurnal variation, falling gradually during the day and rising slowly
during the night; and that it varies greatly in individuals, so that
a specific gravity which is normal for one may be a sign of disease
in another. The specific gravity of the corpuscles is slightly greater
than that of the plasma. For this reason the corpuscles in shed
blood, when its coagulation is prevented or retarded, tend to settle
to the bottom of the containing utensil, leaving a more or less clear
layer of supernatant plasma. Among themselves, also, the cor-
puscles differ slightly in specific gravity, the red corpuscles being
heaviest.

Red Corpuscles. — The reel corpuscles in man and in all the
mammalia, with the exception of the camel and other members of
the group Camelidse, are biconcave circular discs or, according to
some authors, bell-shaped corpuscles without nuclei; in the Cam-
elidae they have an elliptical form. Their average diameter in
man is given as 7.7 // (1 /* -- 0.001 mm.); their number, which
is usually reckoned as so many in a cubic millimeter, varies greatly
under different conditions of health and disease. The average
number is given as 5,000,000 per c.mm. for males and 4,500,000 for
females. The red color of the corpuscles is due to the presence in
them of a pigment known as "hemto^lofcin." Owing to the minute
size of the corpuscles, their color when seen singly under the micro-
scope is a faint yellowish red, but when seen in mass they exhibit
the well-known blood-red color, which varies from scarlet in arterial

* Hammerschlag, " Zeitschrift f. klin. Med.," 20, 444, 1892.
f See Jones, " Journal of Physiology," 12, 299, 1891.

396 BLOOD AND LYMPH.

blood to purplish red in venous blood, this variation in color being
dependent upon the amount of oxygen contained in the blood in
combination with the hemoglobin. Speaking generally, the func-
tion of the red corpuscles is to carry oxygen from the lungs to the
tissues. This function is entirely dependent upon the presence of
hemoglobin, which has the power of combining easily with oxygen
gas. The physiology of the red corpuscles, therefore, is largely con-
tained in a description of the properties of hemoglobin.

Condition of the Hemoglobin in the Corpuscle. — The finer structure
of the red corpuscle is not completely known. It is usually stated
that the corpuscle is composed of two substances, stroma and hem-
oglobin, together with a certain amount of water and salts and
also a certain amount of lecithin and cholesterin. The stroma is a
delicate, extensible, colorless substance that gives shape to the
corpuscles; it forms a mesh work or spongy mass in which the
hemoglobin is deposited. This latter substance forms the chief
constituent of the corpuscle, since it makes about 32 per cent, of the
weight of the normal corpuscle, and when dry from 90 to 95 per
cent, of the total solid material. According to another view the
corpuscles are vesicles with an external envelope or pellicle in
which lecithin and cholesterin are found, while the hemoglobin is
contained within.* Whichever view may be correct great interest
attaches to the presence of the lecithin and cholesterin, whether
these substances are found in an external membrane or in a stroma
permeating the corpuscle. According to Pascucci the lecithin and
cholesterin constitute as much as 30 per cent, of the dry weight of
the stroma, that is, of the portion of the corpuscle left after re-
moval of the hemoglobin. Such a large proportion of these two
substances is not found elsewhere in the body except in the myelin
sheath of the nerve fibers. It is believed that they play an impor-
tant role in maintaining the integrity of the corpuscles. Another
point that remains uncertain is the condition in which the hemo-
globin exists within the corpuscle. It is evidently not in solution,
since the amount present is too great to be held in solution in the
corpuscle, and, moreover, even a thin layer of corpuscles is far
from being transparent. Nor is it deposited in the form of crystals.
It is assumed, therefore, that it is present in a peculiar, amorphous
form, and Gamgee has shown that from its aqueous solutions the
hemoglobin can be obtained in an amorphous state by the action
of an electrical current. It is protected from the action of the
water within and without the corpuscle. In various ways, how-
ever, the relations of the hemoglobin within the corpuscle may be

* For recent discussions upon the histological structure of the corpuscles,
see Weidenreich, "Anatom. Anzeiger," 1905, xxvii., 583; Ruzicka, ibid.,
xxviii., 453; Schiifer, ibid., 1905, xxvi., 589.

GENERAL PROPERTIES: THE CORPUSCLES. 397

disturbed; so that it escapes and enters into solution in the plasma.
Blood in which this has happened suffers a change in color, be-
coming a dark crimson, and is therefore known as "laked blood."
Laked blood in thin layers is quite transparent compared with
the normal, blood with its opaque corpuscles.

HetootySis. — The act of discharging the hemoglobin from the
corpuscles so that it becomes dissolved in the plasma is designated
as hemolysis, and substances1 that cause this action are spoken of
as herrttrtytic agents. A number of such agents are known; but,
although the results of their action are the same, so far as the hemo-
globin is concerned, the way in which they bring about this result
must vary greatly. Some of the known methods of producing
hemolysis, or rendering the blood "laky," are as follows: (1)
By the addition of water to the blood or by diminishing in any way
the concentration or osmotic pressure of the plasma. (2) By add-
ing ether or chloroform. (3) By adding bile or solutions of the bile
salts. (4) By adding amyl-alcohol. (5) By adding the serum
from the blood of certain animals. (6) By adding saponin or
sapo toxin. (7) By the addition of an excess of alkali. (8)
By various toxins found in snake venom or in the serum of other
animal^ or among the products of bacterial activity (natural
hdmolysins) or by similar organic substances produced within the
body by the process of immunizing. Two of these methods de-
mand especial mention, as they involve the consideration of proc-
esses of great physiological importance.

Hemolysis Caused by Lowering the Osmotic Pressure of the Plasma.
— The blood corpuscles contain a certain amount of water ( 57 to
64 per cent.), an amount insufficient to discharge the hemoglobin.
We may imagine that the osmotic pressure within the corpuscle is
such, compared with the osmotic pressure exerted by the salts in
the plasma, that a water equilibrium is established, and that,
although water molecules diffuse into and out of the corpuscle,
the exchange is equal in the two directions. If, however, the
outside plasma is diluted by the addition of water to any consider-
able extent, then the osmotic pressure outside the corpuscles is
correspondingly reduced, while that within the corpuscles is
unchanged. Consequently an increased amount of water will
pass into the corpuscles, sufficient, in fact, to discharge and dissolve
the hemoglobin. It is evident, therefore, that, in injecting liquids
into the circulation, or in diluting blood outside the body, care
must be taken not to use solutions whose osmotic pressure is
markedly less than that of blood-plasma, otherwise many of the
red corpuscles may be destroyed. Solutions whose osmotic pressure
is the same as that of the plasma are said to be isosmotic or iso'toriic
with the blood, those whose pressure is lower are designated as

398 BLOOD AND LYMPH.

hypotonic, and those whose pressure is higher as hypertonic.*
The salt that is contained in the plasma in largest amounts is
sodium chlorid. In making isotonic solutions this salt is there-
fore generally employed. A solution containing nine-tenths of
1 per cent, of sodium chlorid (NaCl, 0.9 per cent.) gives the
same osmotic pressure as plasma as determined by the effect of
each on the lowering of the freezing point (see appendix, Diffusion,
Osmosis, and Osmotic Pressure). Such a solution mixed with blood
should not and does not alter the water contents of the corpuscles.
One may, in fact, use a 0.7 per cent, solution of sodium chlorid with-
out causing any noticeable hemolysis/and this strength of solution
is generally employed in infusions and experimental work; it con-
stitutes what is known in the laboratories as normal saline or physio-
logical saline. If, however, one uses a lower concentration some of
the corpuscles are hemolyzed, and the number of corpuscles
destroyed and the rapidity of the hemolysis increase rapidly with
the lowering of the osmotic pressure. While a 0.7 per cent, solution
of sodium chlorid suffices in most cases for infusions and for diluting
blood, it does not entirely replace the normal plasma or serum, since
these liquids, in addition to the sodium salts, contain salts of
calcium, potassium, magnesium, etc., each of which has doubtless
a certain specific importance. In diluting blood outside the body,
when the dilution is large, better results are obtained by using what
is known as Ringer's mixture, which consists of the physiological
saline solution plus small amounts of potassium and calcium
chlorid. One formula for Ringer's solution is:

Sodium chlorid 0.7 per cent.

Calcium chlorid 0.026 " "

Potassium chlorid 0.03 " "

Hemolysis Caused by the Action of Hdmolysins. — It has long been
known that the serum of one animal may destroy the red corpuscles
of another animal. Thus, rabbits' blood corpuscles added to the
clear serum of a dog, cat, or man are quickly destroyed, with the
liberation of their hemoglobin. This action was formerly described
under the term " globulicidal action of serum," and was compared
to the similar destruction, bactericidal action, exhibited by serum
toward some bacteria. In more recent literature the term hemol-
ysis has replaced that of "globulicidal action," and the hemolytic
effect that a serum may exert upon foreign corpuscles is attributed
to the presence in it of certain substances which in general are classed
as hemolysins. This hemolytic action is not due to a simple differ-
ence in osmotic pressure. The serums of the different mammalia

* For a full consideration of osmotic pressure in its relations to physio-
logical processes, see Hamburger, "Osmotischer Druck und lonenlehre.7'"
Wiesbaden, 1902.

GENERAL PROPERTIES! THE CORPUSCLES. 399

have all approximately the same osmotic pressure; the differences
are too slight to explain the effects observed. Moreover, if the
serum used is heated to 55° C. its hemolytic action is destroyed,
although no noticeable change occurs in the osmotic pressure. In
addition to the hemolysins found normally in the blood of different
animals it was shown first by Bordet * that they may be produced
artificially. The serum of guinea pigs has little or no effect normally
on the red corpuscles of rabbits' blood. If, however, one injects
some rabbits' blood beneath the skin of a guinea pig and, if neces-
sary, repeats the process it will be found that the blood of this
particular guinea pig has now a strong hemolytic action toward the
red- corpuscles of rabbits. This method of producing specific
hemolysins by means of subcutaneous or intraperitoneal injections
of foreign red corpuscles is designated as a process of immunizing,
and the serum of the animal in which a specific hemolysin has been
thus produced is frequently called, for convenience, an immune
serum. These terms are employed on account of the essential
similarity of the processes involved to those underlying the devel-
opment of immunity toward special diseases. When the body is in-
vaded by pathogenic bacteria the toxic substances produced by these
organisms stimulate the tissues to form specific antitoxins which
are capable of neutralizing the action of the bacterial toxins. The
body is thus rendered immune toward special bacteria, and that the
blood of the immunized animal actually contains a definite anti-
toxin may be shown in some cases by the fact that when injected
into another individual the latter also acquires the specific immun-
ity. So in regard to the hemolysins. The presence of the foreign
red corpuscles causes the development of a specific antisubstance
capable of destroying the special form of red corpuscle injected. This
interesting reaction may be obtained with other cells than the red
corpuscles and bacteria. By injecting spermatozoa a toxin or lysin
may be produced in the blood which destroys this particular form
of cell, and the same fact holds good for epithelial cells, etc. More-
over, solutions of foreign proteins injected in the same way give rise
to the formation of definite antisubstances capable of coagulating or
precipitating the special proteins used. In this last case the anti-
substance is designated as a precipitin on account of its precipita-
ting effect on the solution of protein (see Appendix, p. 909). This
wonderful protective adaptation of the body toward the invasion
of foreign cells or proteins is at bottom doubtless a chemical reaction
dependent upon the properties of the living cells, but the nature of
the processes involved is not at all understood, and the phenomenon
is, therefore, designated provisionally as a biological reaction. The
specific hemolysins produced by immunization have been studied
* Bordet, " Annales de 1'Inst. Pasteur," 1895.

400 BLOOD AND LYMPH.

by Bordet, Ehrlich, and others.* It has been shown that they
are in reality composed of two substances whose combined action
is necessary for the hemolysis. There is, first, a new and specific
substance that is produced by the body as a consequence of the
injection of the foreign blood corpuscles. This substance has been
given different names, but is known most frequently (Ehrlich)
as the immune body (or amboceptor). It is not destroyed by mod-
erate heating. The immune body is enabled to act upon the
corpuscles by the co-operation of certain substances which are
normally present in the serum and are therefore not produced by
the process of immunization. These substances are known usually
as complements, and it is they that are destroyed by heating to
55° C. If the immune serum of a guinea pig is heated to 55° C.
its hemolytic action upon rabbits' corpuscles is destroyed. The
action may be restored, however, by adding a little of the rabbit's
own serum, since in terms of the above hypothesis the complements
are present in normal serum. That is to say, an experiment of
the following kind may be performed. Washed blood corpuscles
of a rabbit plus immune serum from a guinea pig show hemolysis.
Washed blood corpuscles of a rabbit plus immune serum which has
been made inactive by heating show no hemolysis. Addition of
normal rabbits' serum to this latter mixture again activates the
immune serum and causes hemolysis. The rabbits' serum in this
case supplies the needed complement.

These facts, it should be stated, are interpreted somewhat differently
by Bordet. The immune substance he designates as a "substance sensibila-
trice" and the complement as alexin. The latter forms the protective sub-
tance of the blood, but is unable to act upon the foreign cells until these
latter have been changed in some way, that is, sensitized by the specific
immune substance developed during the process of immunizing.

In the case of some of the natural hemolysins referred to above
it has also been shown that they are composed in reality of two
bodies, each necessary to the reaction, — one the complement, de-
stroyed by heating, and one comparable to the immune body,
but in this case designated as the interbod}/ or intermediary body,
since it is not produced by immunization.

Speaking in general terms, the serum of any animal is more or
less hemolytic in relation to the blood corpuscles of an animal of
another species; but great differences are shown in this respect. The
blood-serum of the horse shows but little hemolytic action upon the
red corpuscles of the 'rabbit when compared with the effect of the
serum of the dog or cat. Eels' serum has a remarkably strong

* For a brief statement of the development of the subject, see Wasser-
mann, "Immune Sera, Hemolysins, Cytotoxins, and Precipitins, " trans-
lated by Bolduan, New York, 1904. For a more extended review, see Aschoff,
"Zeitschirft f. alhremeine Physiologic," 1, 69, 1902, or Ehrlich, " Collected
Studies on Immunity/' translated by Bolduan, New York, 1906.

GENERAL PROPERTIES: THE CORPUSCLES. 401

hemoly tic action upon the red corpuscles of most mammals ; a very
minute quantity of this serum (0.04 c.c.) injected into the veins of a
rabbit will cause hemoly sis of the corpuscles and, as a consequence,
the appearance of bloody urine (hemoglobinuria). It should be
added that this curious toxic or lytic effect of foreign serums is not
confined to the red corpuscles. They contain cytotoxins that affect
also other tissue elements, especially those of the central nervous
system, and may therefore cause death. As little as 0.04 c.c. of
eels' serum injected into a small rabbit will cause the death of the
animal, the fatal effect being due apparently to an action on the
vasomotor and respiratory centers in the medulla. The hemolytic
and generally toxic effect of foreign sera has been known for a long
time. It was discovered practically in the numerous attempts made
in former years to transfuse the blood of one animal into the veins
of another. It has been found that this process of transfusion as a
means of combatting severe hemorrhage is dangerous unless the
blood is taken from an animal of the same or a nearly related species.
Nature and Amount of Hemoglobin. — Hemoglobin is a very
complex substance belonging to the group of combined proteins.
Under the influence of heat, acids, alkalies, etc., it may be broken
up, with the formation of a simple protein, globin, belonging to the
group of histons (see appendix) and a pigment, hem<a'tin/. The
gldbin forms, according to different estimates, from 86 to 94 per cent,
of the molecule, and the hematin about 4 per cent. Other sub-
stances of an undetermined character result from the decomposition.*
When the decomposition takes place in the absence of oxygen, the
products formed are globin and hemochromogen, instead of globin
and hematin. Hemochromogen in the presence of oxygen quickly
undergoes oxidation to the more stable hematin. Hoppe-Seyler
has shown that hemochromogen possesses the chemical grouping
which gives to hemoglobin its power of combining readily with oxy-
gen and its distinctive absorption spectrum. On the basis of facts
such as these, hemoglobin may be defined as a compound of a protein
body with hematin. It seems, then, that, although the hemochro-
mogen or hematin portion is the essential constituent, giving to the
molecule of hemoglobin its valuable physiological properties as a
respiratory pigment, yet in the blood corpuscles this substance is
incorporated into the much larger and more unstable molecule of
hemoglobin, whose behavior toward oxygen is different from that
of the hematin itself, the difference lying mainly in the fact that
the hemoglobin as it exists in the corpuscles forms with oxygen a
comparatively feeble combination that may be broken up readily,
with liberation of the gas.

* Schulz, 'Zeitschrift f. physiologische Chemie, " 24; also Lauraw, ibid., 26.
26

402 BLOOD AND LYMPH.

Hemoglobin is widely distributed throughout the animal king-
dom, being found in the blood corpuscles of mammalia, birds,
reptiles, amphibia, and fishes, and in the blood or blood corpuscles
of many of the invertebrates. The composition of its molecule is
found to vary somewhat in different animals; so that, strictly
speaking, there are probably a number of different forms of hemo-
globin— all, however, closely related in chemical and physiological
properties. Elementary analysis of dogs' hemoglobin shows the
following percentage composition (Jaquet): C, 53.91; H, 6.62; N,
15.98; S, 0.542; Fe, 0.333; O, 22.62. Its molecular formula is
given as C758H1203N195S3FeO218, which would make the molec-
ular weight 16,669. Other estimates are given of the molecular
formula, but they agree at least in showing that the molecule is of
enormous size. The hematin that is split off from the hemoglobin
is a pigment whose constitution is relatively simple, as is indicated
by its percentage formula, C34H34N4FeO5 (Kuster). It contains
all of the iron of the original hemoglobin molecule. Gamgee has
called attention to two facts which seem to indicate that the globin
and hematin do not exist as such in the hemoglobin molecule.
Thus, hematin is magnetic, — that is, is attracted by a magnet, — while
hemoglobin, on the contrary, is diamagnetic. Globin alone rotates
the plane of polarized light to the left, levorotatory, while hemo-
globin solutions are dextrorotatory. The exact amount of hemo-
globin in human blood varies naturally with the individual and with
different conditions of life. According to Preyer,* the average
amount for the adult male is 14 grams of hemoglobin to each 100
grams of blood. It is estimated that in the blood of a man weighing
68 kilograms there are contained about 750 grams of hemoglobin,
which is distributed among some 25,000,000,000,000 of corpuscles,
giving a total superficial area of about 3200 square meters. Practi-
cally all of this large surface of hemoglobin is available for the
absorption of oxygen from the air in the lungs, for, owing to the
great number and the minute size of the capillaries, the blood, in
passing through a capillary area, becomes subdivided to such an
extent that the red corpuscles stream through the capillaries, one
may say, in single file. In circulating through the lungs, therefore,
each corpuscle becomes exposed more or less completely to the action
of the air, and the utilization of the entire quantity of hemoglobin
must be nearly perfect. It may be worth while to call attention to
the fact that the biconcave form of the red corpuscle increases
the superficies of the corpuscle and tends to make the surface
exposure of the hemoglobin more complete. Instruments known
as hemometers or hemoglobinometers have been devised for clinical
use in determining the amount of hemoglobin in the blood of
* "Die Blutkrystalle." Jena, 1871.

GENERAL PROPERTIES! THE CORPUSCLES. 403

patients. A number of different forms of this instrument are in
use. In all of them, however, the determination is made with a
drop or two of blood, such as can be obtained without difficulty
by pricking the skin. The amount of hemoglobin in the withdrawn
blood is determined usually by a colorimetric method, — that is, its
color, which is due to the hemoglobin, is compared with a series of
standard solutions containing known amounts of hemoglobin, or
with a wedge of colored glass whose color value in terms of hemo-
globin has been determined beforehand. For details of the structure
of the several instruments employed and the precautions to be
observed in their use reference must be made to the laboratory-
guides.*

Compounds with Oxygen and other Gases. — Hemoglobin has
the property of uniting with oxygen gas in certain definite propor-
tions, forming a true chemical compound. This compound is known
as oxyhemoglobin', it is formed whenever blood or hemoglobin
solutions are exposed to air or otherwise brought into contact with
oxygen. Each molecule of hemoglobin is supposed to combine with
one molecule of oxygen. According to a determination by Hiifner,t
the O capacity of the Hb of ox's blood is 1.34 c.c. 0 to each gram of
Hb. It should be stated that some observers I find that the maxi-
mum oxygen capacity of the blood may show individual variations
within narrow limits, and that, therefore, what we designate as
hemoglobin may not be a single chemical substance, but a mixture
of closely related compounds. Oxyhemoglobin is not a very firm
compound. If placed in an atmosphere containing no oxygen
it is dissociated, giving off free oxygen and leaving behind hemo-
globin or, as it is often called by way of distinction, "reduced
hemoglobin" This power of combining with oxygen to form a
loose chemical compound, which in turn can be dissociated easily
when the oxygen pressure is lowered, makes possible the function
of hemoglobin in the blood as the carrier of oxygen from the lungs
to the tissues. The details of this process are described in the
section on Respiration. Hemoglobin forms with carbon monoxid
gas (CO) a compound, similar to oxyhemoglobin, which is known
as carbon monoxid hemoglobin. In this compound also the union
takes place in the proportion of one molecule of hemoglobin to one
molecule of the gas. The compound formed differs, however,
from oxyhemoglobin in being much more stable, and it is for this
reason that the breathing of carbon monoxid gas is liable to prove
fatal. The CO unites with the hemoglobin, forming a firm com-

* See Simon, "A Manual of Clinical Diagnosis." Philadelphia, 1904.

t 'Archiv f. Physiologic, " 1894, p. 130.

t See Bohr, in Nagel's "Handbuch der Physiologie," vol. I., pt. I., 1905.

404 BLOOD AND LYMPH.

pound; the tissues of the body are thereby prevented from obtain-
ing their necessary oxygen, and death results from suffocation or
asphyxia. Carbon monoxid forms one of the constituents of
coal-gas. The well-known fatal effect of breathing coal-gas for
some time, as in the case of individuals sleeping in a room in which
gas is escaping, is traceable directly to the carbon monoxid. Nitric
oxid (NO) forms also with hemoglobin a definite compound that
is even more stable than the CO hemoglobin; if, therefore, this
gas were brought into contact with the blood, it would cause death
in the same way as the CO.

Oxy hemoglobin, carbon monoxid hemoglobin, and nitric oxid
hemoglobin are similar compounds. Each is formed, apparently,
by a definite combination of the gas with the hematin portion of the
hemoglobin molecule, and a given weight of hemoglobin unites
presumably with an equal volume of each gas. In marked contrast
to these facts, Bohr* has shown that hemoglobin forms a compound
with carbon dioxid gas, carbohemoglobin, in which the quantitative
relationship of the gas to the hemoglobin differs from that shown
by oxygen. In a mixture of 0 and CO2 the latter gas is absorbed by
hemoglobin solutions independently of the oxygen, so that a solu-
tion of hemoglobin nearly saturated with oxygen will take up CO2
as though it held no oxygen in combination. Bohr suggests, there-
fore, that the O and the CO2 must unite with different portions of the
hemoglobin — the oxygen with the pigment portion and the CO2 possi-
bly with the protein portion. Although the amount of CO2 taken up
by the hemoglobin is not influenced by the amount of O already in
combination, the reverse relationship does not hold in all cases. It is
found that the presence of the CO2 loosens, as it were, the combina-
tion between the hemoglobin and the oxygen so that the oxyhemo-
globin dissociates more readily than would otherwise be the case.
This is observed at least when the oxygen is under a low pressure,
such as occurs, for instance, in the capillaries of the tissues. The
importance of this fact in regard to the oxygen supply to the tissues
is referred to more explicitly in the section on Respiration.

Presence of Iron in the Molecule. — It is probable that iron
is quite generally present in the animal tissues in connection with
nuclein compounds, but its existence in hemoglobin is noteworthy
because it has long been known, and because the important property
of combining with oxygen seems to be connected with the presence
of this element. According to the analyses made, the proportion
of iron in hemoglobin varies somewhat in different animals: the
figures given are from 0.333 to 0.47 per cent. The amount of
hemoglobin in blood may be determined, therefore, by making a
* " Skandinavisches Archiv f. Physiologic," 3, 47, 1892, and 16, 402, 1904.

GENERAL PROPERTIES: THE CORPUSCLES.

405

quantitative determination of the iron. The amount of oxygen
with which hemoglobin will combine may be expressed by saying
that one molecule of oxygen will be fixed for each atom of iron in the
hemoglobin molecule. In the decomposition of hemoglobin into
globin and hematin, which has been spoken of above, the iron is
retained in the hematin.

Crystals. — Hemoglobin may be obtained readily in the form of
crystals (Fig. 171). As usually prepared, these crystals are really
oxyhemoglobin, but it has
been shown that reduced
hemoglobin also crystallizes,
although with more diffi-
culty. Hemoglobin from
the blood of different ani-
mals varies to a marked
degree in respect to the
power of crystallization.
From the blood of the rat,
dog, cat, guinea pig, and
horse, crystals are readily
obtained, while hemoglobin
from the blood of man and
of most of the vertebrates
crystallizes much less easily.
Methods for preparing and
purifying these crystals will
be found in works on phys-
iological chemistry. To ob-
tain specimens quickly for
examination under the mi-
croscope, one of the most
certain methods is to take
some blood from one of the
animals whose hemoglobin
crystallizes easily, place it
in a test-tube, add to it a

few drops of ether, shake the tube thoroughly until the blood be-
comes laky,— that is, until the hemoglobin is discharged into the
plasma, — and then place the tube on ice until the crystals are
deposited. Small portions of the crystalline sediment may then be
removed to a glass slide for examination. According to Reichert,
the deposition of the crystals is hastened by adding ammonium
oxalate to the blood in quantities sufficient to make from 1 to
5 per cent, of the mixture. Hemoglobin from different animals
varies not only as to the ease with which it crystallizes, but in some

Fig. 171.— Crystallized hemoglobin (after
Frey) : a, b, Crystals from venous blood of man :
c, from the blood of a cat ; d, from the blood of
a guinea pig; e, from the blood of a hamster;
/, from the blood of a squirrel.

406 BLOOD AND LYMPH.

cases also as to the form that the crystals take. In man and in most
of the mammalia hemoglobin is deposited in the form of rhombic
prisms; in the guinea pig it crystallizes in tetrahedra (d, Fig. 171),
and in the squirrel in hexagonal plates. This difference in crystal-
line form implies some difference in molecular structure, and taken
together with other known variations in property shown by hemo-
globin from different animals lead us to believe that the huge mole-
cule has a labile structure, and that it may differ somewhat in its
molecular composition or atomic arrangement without losing its
physiological property of an oxygen-carrier. In this connection
it is interesting to state that the hemoglobin of horses' blood, which
crystallizes ordinarily in large rhombic prisms, may be made to give
hexagonal crystals by allowing it to undergo putrefaction, and that
the form of the crystals may then be changed from hexagons to
rhombs by varying the temperature of the solutions.* The crystals
are readily soluble in water, and by repeated crystallization the
hemoglobin may be obtained perfectly pure. As in the case of
other soluble protein-like bodies, solutions of hemoglobin are
precipitated by alcohol, by mineral acids, by salts of the heavy
metals, by boiling, etc. Notwithstanding the fact that hemoglobin
crystallizes so readily, it is not easily dialyzable, behaving in this
respect like non-crystallizable colloidal bodies. The compounds
which hemoglobin forms with carbon monoxid (CO) and nitric oxid
(NO) are also crystallizable, the crystals being isomorphous with
those of oxyhemoglobin.

Absorption Spectra. — Solutions of hemoglobin and its deriv-
ative compounds, when examined with a spectroscope, give
distinctive absorption bands.

Light, when made to pass through a glass prism, is broken up into its
constituent rays, giving the play of rainbow colors known as the spectrum.
A spectroscope is an apparatus for producing and observing a spectrum. A
simple form, which illustrates sufficiently well the construction of the appara-
tus, is shown in Fig. 172, P being the glass prism giving the spectrum. Light
falls upon this prism through the tube (A) to the left, known as the "colli-
mator tube." A slit at the end of this tube OS) admits a narrow slice of light —
lamplight or sunlight — which then, by means of a convex lens at the other
end of the tube, is made to fall upon the prism (P) with its rays parallel. In
passing through the prism the rays are dispersed by unequal refraction, giving
a spectrum. The spectrum thus produced is examined by the observer with
the aid of the telescope (£). When the telescope is properly focused for the
rays entering it from the prism (P), a clear picture of the spectrum is seen.
The length of the spectrum 'will depend upon the nature and the number of
the prisms through which the light is made to pass. For ordinary purposes a
short spectrum is preferable for hemoglobin bands, and a spectroscope with one
prism is generally used. If the source of light is a lamp flame of some kind,
the spectrum is continuous, the colors gradually merging one into another
from red to violet. If sunlight is used, the spectrum will be crossed by a
number of narrow dark lines known as the "Fraunhofer lines." The position
of these lines in the solar spectrum is fixed, and the more distinct ones are

* Uhlik, "Archiv f. d. gesammte Physiologic," 104, 64, 1904.

GENERAL PROPERTIES: THE CORPUSCLES. 407

designated by letters of the alphabet, A, B, C, D, E, etc., as shown in the charts
below. If while using solar light or an artificial light a solution of any sub-
stance which gives absorption bands is so placed in front of the slit that the
light is obliged to traverse it, the spectrum as observed through the telescope
will show one or more narrow or broad black bands that are characteristic
of the substance used and constitute its absorption spectrum. The positions
of these bands may be designated by describing their relations to the Fraun-
hofer lines, or more directly by stating the wave lengths of the portions of
the spectrum between which absorption takes place. Some spectroscopes are
provided with a scale of wave lengths superposed on the spectrum, and when
properly adjusted this scale enables one to read off directly the wave lengths
of any part of the spectrum.

When very dilute solutions of oxyhemoglobin are examined with
the spectroscope, two absorption bands appear, both occurring in

Fig. 172. — Spectroscope : P, The glass prism ; A, the collimator tube, showing the slit, S,
through which the light is admitted; B, the telescope for observing the spectrum.

the portion of the spectrum included between the Fraunhofer lines
D and E. The band nearer the red end of the spectrum is known
as the "a-band"; it is narrower, darker, and more clearly defined
than the other, the ",M>and" (Fig. 173). The width and distinct-
ness of the bands vary naturally with the concentration of the solution
used (see Fig. 174) or, if the concentration remains the same,
with the width of the stratum of liquid through which the light
passes. With a certain minimal percentage of oxyhemoglobin
(less than 0.01 per cent.) the ,3-band is lost and the a-band is very
faint in layers 1 centimeter thick. With stronger solutions the
bands become darker and wider and finally fuse, while some of the
extreme red end and a great deal of the violet end of the spectrum

408

BLOOD AND LYMPH.

are also absorbed. The variations in the absorption spectrum,
with differences in concentration, are clearly shown in the accom-
panying illustration from Rollett * (Fig. 174); the thickness of the
layer of liquid is supposed to be one centimeter. The numbers
on the right indicate the percentage strength of the oxyhemoglobin
solutions. It will be noticed that the absorption which takes

E b

6£0

650 640 630 620 610 600 5Jti 580 570 560 550 5W 5J0| 520

5/0 500 MO

,L,I..,,L In

Fig. 173. — Table of absorption spectra (Ziemke and Mutter) : 1, Absorption spectrum
of oxyhemoglobin, dilute solution ; 2, absorption spectrum of reduced hemoglobin ; 3, ab-
sorption spectrum of methemoglobin, neutral solution; 4, absorption spectrum of met-
hemoglobin, alkaline solution ; 5, absorption spectrum of hematin, acid solution; 6, ab-
sorption spectrum of hematin, alkaline solution.

place as the concentration of the solution increases affects the
red-orange end of the spectrum last of all.

Solutions of reduced hemoglobin examined with the spectroscope

show only one absorption band, known sometimes as the "f-band."

This band lies also in the portion of the spectrum included between

the lines D and E; its relations to these lines and the bands of

* Hermann's " Handbuch der Physiologic," vol. iv., 1880

GENERAL PROPERTIES! THE CORPUSCLES.

409

oxy hemoglobin are shown in Fig. 173. The f-band is much more
diffuse than the oxyhemoglobin bands, and its limits, therefore,
especially in weak solutions, are not well denned. The width and
distinctness of this band vary also with the concentration of the
solution. This variation is sufficiently well shown in the accom-
panying illustration (Fig. 175), which is a companion figure to the
one given for oxyhemoglobin (Fig. 174). It will be noticed that
the last light to be ab-
sorbed in this case is
partly in the red end
and partly in the blue,
thus explaining the pur-
plish color of hemoglo-
bin solutions and of
venous blood. Oxy-
hemoglobin soluti o n s
can be converted to
hemoglobin solutions,
writh a corresponding
change in the spectrum
bands, by placing the
former in a vacuum or,
more conveniently, by
adding reducing solu-
tions. The solutions
most commonly used
for this purpose are am-
monium sulphid and
Stokes's reagent.* If
a solution of reduced
hemoglobin is shaken
with air, it quickly
changes to oxyhemo-
globin and gives two
bands instead of one

0.2

o.i

o.

aBC

G

Fig. 174. — Diagram to show the variations in the
absorption spectrum of oxyhemoglobin with varying
concentrations of the solution. — (After Rollelt.) The
numbers to the right give the strength of the oxy-
hemoglobin solution in percentages; the letters give
the positions of the Fraunhofer lines. To ascertain
the amount of absorption for any given concentration
up to 1 per cent., draw a horizontal line across the
diagram at the level corresponding to the concentra-
tion. Where this line passes through the shaded part
of the diagram absorption takes place, and the width
of the absorption bands is seen at once. The diagram
shows clearly that the amount of absorption increases
as the solutions become more concentrated, especially
the absorption of the blue end of the spectrum. It
will be noticed that with concentrations between 0.6
and 0.7 per cent, the two bands between D and E fuse
into one.

when examined by the

spectroscope. Any given solution may be changed in this way from
oxyhemoglobin to hemoglobin, and the reverse, a great number of
times, thus demonstrating the facility with which hemoglobin takes
up and surrenders oxygen.

Solutions of carbon monoxid hemoglobin also give a spec-

* Stokes's reagent is an ammoniacal solution of a ferrous salt. It is made
by dissolving 2 parts (by weight) of ferrous sulphate, adding 3 parts of tar-
taric acid, and then ammonia to distinct alkaline reaction. A permanent
precipitate should not be obtained.

410

BLOOD AND LYMPH.

0.9

0.8

0.6

0.5

0,4

0.3

0,2

JO. I

0.

trum with two absorption bands closely resembling in posi-
tion and appearance those of oxy hemoglobin. They are dis-
tinguished from the
oxyhemoglobin bands
by being slightly
nearer the blue end
of the spectrum, as
may be demonstrated
•0.7 by observing the wave
lengths or, more con-
veniently, by super-
posing the two spectra.
Moreover, solutions of
carbon monoxid hem-
oglobin are not re-
duced to hemoglobin
by adding Stokes's
liquid, two bands be-
ing still seen after such
treatment. A solu-
tion of carbon mon-
oxid hemoglobin suit-
able for spectroscopic
examination may be
prepared easily by
passing ordinary coal-
gas through a dilute oxyhemoglobin solution for a few minutes
and then filtering.

Derivative Compounds of Hemoglobin. — There are a number
of pigmentary bodies which are formed directly from hemoglobin
by decompositions or chemical reactions of various kinds. Some
of these derivative substances occur normally in the body. The
best known are as follows * :

Methemoglobin. — When blood or a solution of oxyhemoglobin
is allowed to stand for a long time exposed to the air it undergoes
a change in color, taking on a brownish tint. This change is due to
the formation of methemoglobin, and it is said that to some extent
the transition occurs very soon after the blood is exposed to the air,
and that, therefore, determinations of the quantity of hemoglobin
by the ordinary colorimetric methods should be made promptly to
avoid a deterioration in color value. Methemoglobin may be
obtained rapidly by the action of various reagents on the blood,

* For more detailed information concerning the chemistry and literature
of these compounds, see Hammarsten, "Physiological Chemistry, " translated
by Mandel, fourth edition, 1904; Abderhalden, " Physiologische Chemie," 1906.

aBC

Fig. 175. — Diagram to show the variations in the ab-
sorption spectrum of reduced hemoglobin with vary-
ing concentrations of the solution (after Rolletf). The
numbers to the right give the strength of the hemo-
globin solution in percentages; the letters give the posi-
tions of the Fraunhofer lines. For further directions
as to the use of the diagram, see the description of Fig.

GENERAL PROPERTIES: THE CORPUSCLES. 411

some of them oxidizing substances, such as permanganate of potash
or ferricyanid of potash, some of them reducing substances. In-
deed, it is known that the change may occur within the blood-vessels
by the action of such bodies as the nitrites, antifebrin, acetanilid,
etc. According to most observers, methemoglobin contains the
same amount of oxygen as hemoglobin; it is combined differently,
however, -forming a more stable compound, which can not be dis-
sociated by * the action of a "vacuum. On this account, therefore,
methemoglobin is not capable of acting as a respiratory pigment,
and to the extent that it is formed in the blood this tissue suffers a
loss of its functional value as a carrier of oxygen. By the stronger
action of reducing solutions — such as ammonium sulphid — the
oxygen may be removed from the methemoglobin and reduced
hemoglobin be obtained. Methemoglobin crystallizes in needles,
and its solutions give an absorption spectrum which varies ac-
cording as the solution is neutral or has an alkaline reaction. In
neutral solutions the characteristic band is one in the orange, as
indicated in Fig. 173. In alkaline solution the absorption spectrum
has three bands, two of which are nearly identical with those of
oxy hemoglobin.

Hemalin (C34H34N4Fe05) is obtained when hemoglobin is de-
composed by the action of acids or alkalies in the presence o$ oxygen.
It may occur in the feces if the diet contains hemoglobin or hematin,
or in case of hemorrhage in the stomach or small intestine, since
both the pancreatic and the gastric secretion break up hemoglobin,
with the formation of hematin. It is an amorphous substance, of a
dark-brown color, easily soluble in alkalies or in acid alcoholic solu-
tions. These solutions give a characteristic absorption spectrum
which is represented in Fig. 173.

Hemin (C34H33O4N4FeCl) is regarded as the hydrochloric acid
ester of hematin and is obtained by the action of HC1 upon blood
previously treated with alcohol. The compound is obtained in the
form of crystals, which under the microscope appear usually as
small, rhombic plates of a dark-brown color. These crystals may
be obtained from small quantities of blood stains, etc., no matter
how old, and they have been relied upon, therefore, as a sure and
easy test for the existence of blood, — that is, hemoglobin. The
test is one that has been much used in medicolegal cases, and may
be carried out as follows : A bit of dried blood is powdered with a
few crystals of NaCl. Some of the powder is placed upon a glass
slide and covered with a cover-slip. By means of a pipette a drop
or two of glacial acetic acid is run under the slip, and then by draw-
ing the slide repeatedly through a flame the acid is evaporated to
dryness, taking care not to heat the acid so high -as to cause it to
boil. After the evaporation of the acid water is run under the slip
and the specimen is ready for examination with the microscope.

412 BLOOD AND LYMPH.

Hemochromogen (C34H3(.N4Fe05 ?) is obtained when hemoglobin
is decomposed by acids or alkalies in the absence of free oxygen. By
oxidation it is converted to hematin. Hemochromogen is crystal-
line, and gives a characteristic absorption spectrum.

Hematoporphyrin (C34H38N4O6) differs from the preceding deriv-
atives of hemoglobin in that it contains no iron. It may be ob-
tained from hematin by the action of strong acids, and is of much
physiological interest because of its relationship to the bile pigments,
which, like it, are iron-free derivatives of the hemoglobin. In old
blood-clots or extravasations it has long been known that a colored
crystalline product may be formed. This product was designated
as hematoi'din by Virchow and later was stated, on the one hand, to
be identical with the bile pigment, bilirubin, and, on the other hand,
to be isomeric with hematoporphyrin. Later observers have
prepared from hematoporphyrin by careful reduction a substance
designated as mesoporphyrin. It contains one less oxygen atom
than the hematoporphyrin, and is claimed to be identical with
hematoi'din. Another fact of great general interest is that from
plant chlorophyl there may be prepared a compound, phylloporphy-
rin, very similar to the mesoporphyrin. It would appear from this
relationship that the red coloring matter of the blood and the
green coloring matter of plants are compounds that have some
similarity in chemical structure.

Histohematins. — This name is a general term that has been given
to the coloring matter found in the tissues, so far as it has the
property of taking up oxygen. The red coloring matter in some
muscles is an example of such a compound and has been designated
specifically as myohematin. According to most observers, myo-
hematin is identical with hemoglobin, — that is, the muscle substance
contains some hemoglobin, — and we may suppose that its presence
in the tissue furnishes a further means for the transportation of
oxygen to the muscle protoplasm.

Bile Pigments and Urinary Pigments. — These pigments are
referred to in the description of the composition of bile and urine.
In this connection the fact may be emphasized that each of them is
supposed to be derived from hemoglobin, and each constitutes, so
to speak, a form of excretion of hemoglobin.

Origin and Fate of the Red Corpuscles. — The mammalian red
corpuscle is a cell that has lost its nucleus. It is not probable, there-
fore, that any given corpuscle lives for a great while in the circulation.
This is made more certain by the fact that hemoglobin is the mother
substance from which the bile pigments are made, and, as these
pigments are being excreted continually, it is fair to suppose that
red corpuscles are as steadily undergoing disintegration in the blood-
stream. Just how long the average life of the corpuscles may be

GENERAL PROPERTIES: THE CORPUSCLES. 413

has not been determined, nor is it certain where and how they go
to pieces. It has been suggested that their destruction takes place
in the spleen, but the observations advanced in support of this
hypothesis are not very numerous or conclusive. Among the rea-
sons given for assuming that the spleen is especially concerned in
the destruction of red corpuscles, the most weighty is the histo-
logical fact that one can sometimes find in teased preparations of
spleen-tissue certain large cells which contain red corpuscles in their
cell-substance in various stages of disintegration. It has been
supposed that the large cells actually ingest the red corpuscles,
selecting those, presumably, that are in a state of physiological de-
cline. Against this idea a number of objections may be raised.
Large leucocytes with red corpuscles in their interior are not found
so frequently nor so constantly in the spleen as we should expect
would be the case if the act of ingestion were constantly going on.
There is some reason for believing, indeed, that the whole act of
ingestion may be a postmortem phenomenon; that is, after the
cessation of the blood-stream the ameboid movements of the large
leucocytes continue, while the red corpuscles lie at rest, — conditions
that are favorable to the act of ingestion. It ma}7 be added also
that the blood of the splenic vein contains no hemoglobin in solu-
tion, indicating that no considerable dissolution of red corpuscles ia
taking place in the spleen. Moreover, complete extirpation of the
spleen does not seem to lessen materially the normal destruction
of red corpuscles, if we may measure the extent of that normal
destruction by the quantity of bile pigment formed in the liver,
remembering that hemoglobin is the mother-substance from which
the bile pigments are derived. It is more probable that there is no
special organ or tissue charged with the function of destroying red
corpuscles, but that they undergo disintegration and dissolution
while in the blood-stream and in any part of the circulation, the
liberated hemoglobin being carried to the liver and excreted in part
as bile pigment. The continual destruction of red corpuscles
implies, of course, a continual formation of new ones. It has been
shown satisfactorily that in the adult the organ for the reproduction
of red corpuscles is the red marrow of bones. In this tissue hema-
topoiesis, as the process of formation of red corpuscles is termed, goee
on continually, the process being much increased after hemorrhages
and in certain pathological conditions. The details of the histo-
logical changes will be found in the text-books of histology. It is
sufficient here to state simply that groups of nucleated, colorless
cells, erythroblasts, are found in the red marrow. These cells
multiply by karyokinesis and the daughter-cells eventually produce
hemoglobin in their cytoplasm, thus forming nucleated red cor-
puscles. The nuclei are subsequently lost, either by disintegration

414 BLOOD AND LYMPH.

or by extrusion, and the newly formed non-nucleated red corpuscles
(erythrocytes) are forced into the blood-stream, owing to a gradual
change in their position during development caused by the growing
hematopoietic tissue. When the process is greatly accelerated, as
after severe hemorrhages or in certain pathological conditions,
red corpuscles still retaining their nuclei (normoblasts) may be
found in the circulating blood, having been forced out prematurely.
Such corpuscles may subsequently lose their nuclei while in the
blood-stream. In the embryo, hematopoietic tissue is found in
parts of the body other than the marrow, notably in the liver and
spleen, which at that time serve as organs for the production of
new red corpuscles. In the blood of the young embryo nucleated
red corpuscles are at first abundant, but they become less numerous
as the fetus grows older.* It is interesting to note that in the
adult after severe anemias — e. g., pernicious anemia — and in rabbits
after the injection of saponin the spleen may again take on its
hematopoietic function. The venous sinuses become crowded with
cells of the marrow type.t

Variations in the Number of Red Corpuscles. — The average
number of red corpuscles for the adult male, as has been stated
already, is usually given as 5,000,000 per c.mm. The number
is found to vary greatly, however. Outside pathological con-
ditions, in which the diminution in number may be extreme, dif-
ferences have been observed in human beings under such conditions
as the following : The number is less in females (4,500,000) ; it varies
in individuals with the constitution, nutrition, and manner of life;
it varies with age, being greatest in the fetus and in the new-born
child; it varies with the time of the day, showing a distinct diminu-
tion after meals; in the female it varies somewhat in menstruation
and in pregnancy, being slightly increased in the former and di-
minished in the latter condition.

Variation with Altitude. — Perhaps the most interesting of the
conditions that may influence the number of the blood corpuscles
is a change in altitude. Attention was first directed to this point
by Bert,J wno believed that the diminished supply of oxygen
in high altitudes may be compensated by an increased amount of
hemoglobin, and subsequently Viault§ demonstrated that living for
a short time at very high altitudes (4000 meters) causes a marked in-
crease in the number of red corpuscles, — an increase, for instance,
from 5,000,000 per c.mm. to 7,000,000 or even 8,000,000. This fact

* Howell, "Life History of the Blood Corpuscles," etc., " Journal of
Morphology," 1890, vol. iv.; Bunting, "Univ. of Pennsylvania Medical Bulle-
tin," 1903, xvi., 200.

t See Bunting, "The Journal of Experimental Medicine," 1906, viii., 625.

t Bert, "La pression barometrique, " 1878, p. 1108.

§ Viault, "Comptes rendus de 1'acade'mie des sciences," 1890 and 1891.

GENERAL PROPERTIES.' THE CORPUSCLES. 415

has since been investigated with great care by a large number of
observers and under a great variety of conditions. The observation
has been abundantly confirmed, and indeed it would seem that the
reaction takes place very quickly. Within twenty-four hours,
according to some observers, and in less time, according to others
who have experimented during balloon ascensions (Gaule, Hallion,
and Tissot), the increase in* the number of corpuscles may be de-
tected, although the maximum increase comes on more gradually.
According to Kemp,* the number of blood plates is also greatly
increased by high altitudes, while the leucocytes are not affected.
There has, however, been much difference of opinion as to whether
this increase in number of the red corpuscles is relative or absolute,
— that is, whether the total number of red corpuscles in the blood,
and therefore probably the total amount of hemoglobin, is increased,
or whether it is simply an apparent increase due, for instance, to a
diminution in the water of the blood and a consequent concentration
as regards the number of corpuscles, or to a variation in the distri-
bution of the corpuscles between the vessels of the skin and those
of the internal organs. The results published upon these questions
have been conflicting. One may, however, believe that the in-
creased number or concentration of red corpuscles is an adaptation
by means of which the oxygen-carrying capacity of the blood
is raised to compensate for the diminished amount of oxygen in the
air. According to one set of observers, this adaptation is brought
about by an absolute increase in the total number of red corpuscles,
and therefore in the total amount of hemoglobin. There seems
to be little doubt that such a change occurs in cases of long residence
in high altitudes, and we may assume that the diminished amount
of oxygen in the air or some other condition peculiar to these
altitudes acts as a stimulus to the blood-forming tissues (red mar-
row) and augments the output of corpuscles and hemoglobin.
Zuntz and his co-workers have shown in experiments upon dogs
that there is a visible increase in the red marrow of the bones as
a result of living for some months at a high altitude. According
to another set of observers, the adaptation is brought about by a
concentration of the blood. The blood-plasma is reduced in
quantity, perhaps by transudation of water into the tissues, and
therefore the number of red corpuscles and the amount of hemo-
globin become greater for each cubic millimeter. If we assume
that this smaller bulk of blood, more concentrated in corpuscles
and hemoglobin, circulates more rapidly, then also the oxygen-
carrying capacity of the blood is increased. In favor of this view,
Abderhalden, for instance, has claimed that, if animals of the
same species and same litter are bled to death and the total quan-
* Kemp, " American Journal of Physiology," 10, 34, 1904.

416 BLOOD AND LYMPH.

tity of hemoglobin is estimated, the average figures obtained for
the animals at low levels are the same as for those at the high
altitudes. Zuntz has, however, called attention to the fact that
when Abderhalden's figures are estimated per kilogram of weight
they show an increase in total hemoglobin in the high altitudes,
and he and other observers have obtained similar results. It
seems certain, therefore, that high altitudes cause eventually a
marked increase in the production of red corpuscles, but that the
very sudden changes of this kind reported by some authors as
happening within a few hours must be considered as apparent
rather than real, and are to be explained by some change in the
water contents or in the distribution of the blood.*

Physiology of the Blood Leucocytes. — The function of the
blood leucocytes has been the subject of numerous investigations,
particularly in connection with the pathology of blood diseases.
Although many hypotheses have been made as the result of this
work, it cannot be said that we possess much positive information as
to the normal function of these cells in the body. It must be borne
in mind, in the first place, that the blood leucocytes are not all the
same histologically, and it may be that their functions are as diverse
as their morphology. Various classifications have been made,
based upon one or another difference in microscopical structure and
reaction, but at present the system most used is that adopted
by Ehrlich-t According to this nomenclature, the white cor-
puscles fall into two main groups, — the lymphocytes and the
leucocytes, — and each of these into two or more subgroups. Thus:

I. LYMPHOCYTES. No granules in the cell substance, and, though capable of
ameboid changes of form, this property is not characteristic and prob-
ably not sufficient to cause locomotion.

(a) Small lymphocytes are about the size of the red corpuscles; the nu-
cleus is large, symmetrically placed, stains homogeneously, and the
cytoplasm is reduced to a very small amount. They form from 20
to 25 per cent, of all the white corpuscles.

(6) Large lymphocytes. Two to three times as large as the preceding.
Nucleus somewhat eccentric; the cytoplasm is relatively more
abundant than in a, but non-granular. These forms exist only in
small numbers, forming 1 per cent, or less of the white corpuscles.
II. LEUCOCYTES. Granules of different sorts found in the cytoplasm. Cells
characteristically ameboid.

(a) Transition forms (uninuclear leucocytes). Single large nucleus, more
or less lobulated; cytoplasm abundant and faintly granulated. The
granules stain with neutral dyes and are therefore designated as
neutrophile granules. The name, transition form, implies that these
leucocytes represent an intermediate stage between the large lympho-
cytes and the following variety. This form exists in small numbers,
— 2 to 10 per cent, of the total number of white corpuscles.

* For the extensive literature see Van Voornveld, "Das Blut im Hoch-
gebirge," "Pfliiger's Archiv," 92, 1, 1902; Zuntz et al., "Hohenklima und
Bergwanderungen in ihrer Wirkung auf den Menschen," 1906.

t Ehrlich, "Die Anaemic," 1898; see also Seemann, "Ergebnisse der
Physiologic," 3, part i., 1904.

GENERAL PROPERTIES: THE CORPUSCLES. 417

(6) Polynuclear or polymorphonuclear leucocytes. The nucleus is seg-
mented into lobes connected by narrow strands. The cytoplasm
is especially ameboid and is granular. The granules in most cases
are neutrophilic and small in size. The typical cells of this kind
form the bulk of the white corpuscles of the blood, — 60 to 75 per
cent. Eosinophilic leucocytes form a subgroup of this variety. They
have a similar segmented nucleus, but the cytoplasm contains nu-
merous coarse granules that stain in acid dyes, such as eosin, whence
the name.

(c) Mast cells. These peculiar cells exist in very small numbers under
normal conditions, — less than 1 per cent, of the total number of
white corpuscles. They have a polymorphic nucleus like the pre-
ceding group, but differ in the fact that the granules in the cyto-
plasm are strongly basophilic, — that is, will stain only with basic
dyes, such as thionin.

According to some authors the small lymphocytes are cells
that have an origin and function different from those of the granular
leucocytes. While the latter are supposed to originate from cells
(leucoblasts, myeloblasts) in the bone marrow, the lymphocytes
are produced in the nodules of the lymph glands and lymphoid
tissue, and enter the blood through the lymph circulation. Others,
however, lay stress on the fact that lymphocytes occur in the bone-
marrow and hold that it is possible or probable that the lympho-
cytes of the blood may be derived from the marrow tissue as well
as from the lymphoid tissue. The subject is one that at present is
discussed chiefly in connection with the pathology of blood dis-
eases.*

Variations in Number.— Under normal conditions the total
number of leucocytes may show considerable variation; the aver-
age number in health varies usually between 5000 and 7000
per cubic millimeter. A distinct increase in number is designated
as a condition of leucocytosis, a marked diminution as a condition of
leucopenia. Leucocytosis occurs under various normal conditions,
such as digestion, exercise or cold baths, pregnancy, etc. The
variations, relative or absolute, under pathological conditions, have
been studied with exhaustive care as an aid to diagnosis and classi-
fication.

Functions of the Leucocytes. — Perhaps the most striking
property of the leucocytes as a class is their power of making
ameboid movements, — a characteristic which has gained for them
the sobriquet of "wandering" cells. By virtue of this property
some of them are able to migrate through the walls of blood capil-
laries into the surrounding tissues. This process of migration takes
place normally, but is vastly accelerated under pathological con-
ditions. As to the function or functions fulfilled by the leucocytes,
numerous suggestions have been made, some of which may be
stated in brief form as follows: (1) They protect the body from
*See Emerson, 'Clinical Diagnosis," 1906, p. 483.

418 BLOOD AND LYMPH.

pathogenic bacteria and other foreign cells or organisms. In
explanation of this action it has been suggested that they may
either ingest bacteria, and thus destroy them directly, or they
may form certain substances, bacteriolysins, that destroy the
bacteria. The wonderful protective adaptation of the body des-
ignated by the term "biological reaction" has already been referred
to (p. 399). The formation of immune substances in the blood is
attributed, in part at least, to the leucocytes. Leucocytes that
act by ingesting the bacteria are spoken of as " phagocytes " (y-dfeev,
to eat; proc, cell). This theory of their function is usually
designated as the "phagocytosis theory of Metchnikoff " ; it is
founded upon the fact that the ameboid leucocytes are known to
ingest foreign particles, including bacteria, with which they come
in contact. One of the most interesting recent developments in
pathology in this connection is the discovery (Wright) that this
power of the leucocytes to ingest bacteria depends upon the presence
in the plasma of certain substances designated as opsonins (from
oyovsev, to prepare food for). While the nature of the opso-
nins is not known, their amount can be determined relatively
for different bacteria by the degree of phagocyting activity of the
leucocytes. Whether . or not there is a specific opsonin for each
pathogenic organism is a subject still under discussion. (2) They
aid in the absorption of fats from the intestine. (3) They aid in
the absorption of peptones from the intestine. It may be noticed
here that these theories apply to the leucocytes found so abundantly
in the lymphoid tissue of the alimentary canal, rather than to those
contained in the blood itself. (4) They take part in the process
of blood coagulation. A complete statement with reference to
this function must be reserved until the phenomenon of coagula-
tion is described. (5) They help to maintain the normal composi-
tion of the blood-plasma in proteins. It may be said for this view
that there is considerable evidence to show that the leucocytes
normally undergo disintegration and dissolution in the circulating
blood, to some extent at least. The blood proteins are peculiar,
and they are not formed directly from the digested food. It is
possible that the leucocytes, which are the only typical cells in
the blood, aid in keeping up the normal supply of proteins. From
this standpoint they might be regarded in fact as unicellular glands,
the products of their metabolism serving to maintain the normal
composition of the blood-plasma. The formation of granules
within the substance of the eosinophiles offers a suggestive analogy
to the accumulation of zymogen granules in glandular cells.

Physiology of the Blood Plates. — The blood plates are small,
circular or elliptical bodies, nearly homogeneous in structure and
variable in size (0.5 to 5.5 //), but they are always smaller than the
red corpuscles. Less is known of their origin, fate, and functions

GENERAL PROPERTIES! THE CORPUSCLES. 419

than in the case of the leucocytes.* When removed from the circu-
lating blood they are known to disintegrate very rapidly. This
peculiarity, in fact, prevented them from being discovered for a long
time after the blood had been studied microscopically. It has been
shown that they are formed elements, and not simply precipitates
from the plasma, as was suggested at one time. The theory of
Hay em, their real discoverer, that they develop into red corpuscles
may also be considered as ' erroneous. There is considerable evi-
dence to show that in shed blood they take part in the process of
coagulation. The nature of this evidence will be described later.
On account of their small size and somewhat indefinite form the
structure of the blood plates is not satisfactorily known. Deetjenf
has demonstrated that they are capable of ameboid movements.
When removed from the blood vessels to a glass slide they usually
agglutinate into larger or smaller masses, swell, and disintegrate,
but if received upon a surface of agar-agar which has been made up
with physiological saline, together with some sodium metaphos-
phate (NaPO3), they flatten out, show a central granular portion
and a peripheral clear layer, and may make quite active ameboid
movements. Deetjen claims also that they possess a distinct
nucleus. This latter statement is perhaps doubtful, as other
observers report that the material which stains like a nucleus is
present as separate granules in the interior of the plate. These
granules, though doubtless of nuclear material, do not have the
morphological appearance of a cell nucleus. It remains, therefore,
uncertain whether the blood plates are to be considered as inde-
pendent cells or as fragments of disintegrated cells. On account
of their tendency to agglutinate and dissolve when the blood is shed
it is difficult to obtain reliable data as to their numbers under
normal and pathological conditions.! The results obtained by
later observers using special methods to prevent known sources of
error indicate that the average number may be 500,000 per cubic
millimeter. The extremes reported vary from 200,000 or 250,000
to 778,000. Under certain pathological conditions, especially in
pernicious anemia and lymphatic leukemia, their number is greatly
reduced. Outside the part that they take in the formation of
thrombi and in the initiation of coagulation, nothing is known
of their function under normal conditions.

* Wright ("Boston Medical and Surgical Journal," June 7, 1906)
calls attention to a relationship between the blood plates and the giant cells
of the marrow (megalokaryocytes), and ventures the opinion that the
plates are detached pieces of the cytoplasm of the giant cells.

t "Virchow's Archiv f. path. Anat. u. Physiol.," 164, 239, 1901.

J For a summary of the literature and methods consult Kemp, "Journal
of the American Medical Association, " April 7 and 14, 1906, and Pratt, ibid.l
Dec. 30, 1905. The preservative solution recommended by Pratt consists
of sodium metaphosphate, 2 grams; sodium chlorid, 0.9 gram; water, 100 c.c.
That preferred by Kemp is, formalin (40 per cent., aqueous solution of for-
maldehyd), 10 c.c.; sodium chlorid (1 per cent, solution), 150 c.c.

CHAPTER XXIII.

CHEMICAL COMPOSITION OF THE BLOOD-PLASMA; CO-
AGULATION; QUANTITY OF BLOOD; REGENERA-
TION AFTER HEMORRHAGE.

Composition of the Plasma and Corpuscles. — Blood (plasma
and corpuscles) contains a great variety of substances, as might be
inferred from its double relations to the tissues as a source of
nutrition and as a means of removing the waste products of their
functional activity. The constituents that may be present in
normal blood-plasma are in part definitely known and in part
entirely unknown from a chemical standpoint. Some idea of the
complexity of the composition may be obtained from the following
table:

COMPOSITION OF THE BLOOD-PLASMA.
WATER, OXYGEN, CARBON DIOXID, NITROGEN.

Proteins

Extractives, — that is, substances other
than proteins that may be ex-
tracted from the dried residue by
water, alcohol, or ether.

Salts

Enzymes and unknowns.

Fibrinogen.
Paraglobulin |

Serum-albumin.

Nucleo-protein.

Fats.

Sugar.

Urea.

Jecorin.

Glucuronic acid.

Lecithin.

Cholesterin

Lactic acid.

Chlorids
Carbonates
Sulphates
Phosphates

Internal secretions.

of

(Sodium.
Potassium.
Calcium.
Magnesium.
Iron.

{

e, etc

Immune bodies (Amboceptors) .
Complements.
Opsonins.

A number of detailed chemical analyses of the blood of different
animals, so far as its constituents can be determined by analytical
methods, have been reported at different times. The following

420

CHEMICAL COMPOSITION OF BLOOD-PLASMA. 421

table, taken from Abderhalden,* and showing the composition of
dogs' blood, may serve as an example:

1000 PARTS, BY

1000 PARTS, BY

1000 PARTS, BY

WEIGHT, OF BLOOD

WEIGHT, OF SE-

WEIGHT, OF CORPUS-

CONTAIN

RUM CONTAIN

CLES CONTAIN

Water .

810.05

923.98

644.26

Solids

189.95

76.02

355.75

Hemoglobin

133.4

327.52

Protein

39.68

60.14

9.918

Sugar

, 1.09

1.82

Cholesterin

1.298

0.709

2.155

Lecithin

2.052

1.699

2.568

Fat

0.631

1.051

Fatty acids ,

0.759

1.221

0.088

Phosphoric acid:

as nuclein . . .

0.054

0.016

0.110

Na,0
K20

3.675
0.251

4.263
0.226

2.821
0.289

FejOo

0.641

1.573

CaO

0.062

0.113

MgO

0.052

0.040

0.071

Cl

2.935

4.023

1.352

PA

0.809

0.242

1.635

Inorganic :

PA

0.576

0.080

1.298

The same constituents in much the same proportions are found
in the blood of all the mammalia examined. The amount of protein
in the serum is greater in some cases than in others, — in the dog,
for instance, according to Abderhalden's analyses, the protein
amounts to only 6 per cent., while in the horse it may be 7 or 8 per
cent. So also there are small variations in the amount of choles-
terin, sugar, and other constituents, but, on the whole, the composi-
tion of the liquid part of the blood, blood-serum or blood-plasma,
is remarkably uniform so far as chemical analyses go. We know,
however, that the physiological properties of mammalian serum may
be very different indeed; that the serum of a dog, for instance, will
kill a rabbit when injected into its vessel. Such physiological dif-
ferences as this, however, depend upon constituents which can not
be denned or determined by chemical means. The chemical com-
position of the blood-serum differs from that of the red corpuscles in
a number of respects in addition to the presence of hemoglobin in
the latter. The corpuscles contain no sugar nor fat, a larger amount
of cholesterin, lecithin, phosphoric acid, and potassium, and less
sodium and chlorin. The red corpuscles of different mammalia
show a remarkable variation in the amount of potassium salts
contained. Thus, according to Brandenburg, 1000 parts by weight
of the red corpuscles contain the following amounts of K2O in
different mammalia: Cat, 0.258: dog, 0.257; man, 4.294; horse,
4.957; rabbit, 5.229.

* "Zeitschrift f. physiologische Chemie," 25, 88, 1898.

422 BLOOD AND LYMPH.

Proteins of the Blood-plasma; — The general properties and
reactions of proteins and the related compounds, as well as a classi-
fication of those occurring in the animal body, are described briefly
in the Appendix. This description should be read before attempt-
ing to study the proteins of the plasma and the part they take in
coagulation. Three proteins are usually described as existing in the
plasma of circulating blood, — namely, fibrinogen, paraglobulin,
or, as it is sometimes called, "serum-globulin," and serum-albumin.
The first two of these proteins, fibrinogen and paraglobulin, belong
to the group of globulins, and hence have many properties in com-
mon. Serum-albumin belongs to the group of so-called "native
albumins," of which egg-albumin constitutes another member.

Serum-albumin. — This substance is a typical protein. It can be
obtained readily in crystalline form from the horse's blood. Its
percentage composition, according to Michel, is as follows: 0,53.08;
H, 7.10; N, 15.93; S, 1.90; O, 21.96.

Its molecular composition, according to Schmiedeberg,* may be
represented by C78H122N20SO24 or some multiple of this formula.
Serum-albumin shows the general reactions of the native albumins.
One of its most useful reactions is its behavior toward magnesium
sulphate and ammonium sulphate. Serum-albumin usually occurs in
the body-liquids together with the globulins, as is the case in blood.
If such a liquid is thoroughly saturated with solid magnesium sul-
phate or half saturated with ammonium sulphate, the globulins
are precipitated completely, while the albumin is not affected.
So far as the blood and similar liquids are concerned, a definition
of serum-albumin might be given by saying that it comprises all
the proteins not precipitated by saturation with magnesium sul-
phate or by half saturation with ammonium sulphate. When its
solutions have a neutral or an acid reaction, serum-albumin is
precipitated in an insoluble form by heating the solution above a
certain degrea. Precipitates produced in this way by heating
solutions of proteins are spoken of as coagulations — heat coagula-
tions— and the exact temperature at which coagulation occurs
is to a certain extent characteristic for each protein. The tem-
perature of coagulation of serum-albumin is usually given at from
70° to 75° C., but it varies greatly with the conditions, — for in-
stance, with the reaction of the solution, its concentration in salts,
or with the nature of the salts present. It has been asserted,
in fact, that careful heating under proper conditions gives separate
coagulations at three different temperatures, — namely, 73°, 77°,
and 84° C., — indicating the possibility that what is called "serum-
albumin" may be a mixture of three proteins. Serum-albumin
occurs in blood-plasma and blood-serum, in lymph, and in the
different normal and pathological exudations found in the body,
* "Archiv f. exper. Pathol. u. Pharmakol.," 39, 1, 1897.

CHEMICAL COMPOSITION OF BLOOD-PLASMA. 423

such as pericardial liquid, hydrocele fluid, etc. The amount of
serum-albumin in the blood varies in different animals, ranging
among the mammalia from 2.67 per cent, in the horse to 4.52 per
cent, in man. In some of the cold-blooded animals it occurs in
surprisingly small quantities, — 0.36 to 0.69 per cent. As to the
source or origin of serum-albumin, it is frequently stated that it
comes from the digested proteins of the food. It is known that
protein material in the food Is not changed at once to serum-albumin
during the act of digestion; indeed, it is known that the final products
of digestion are a group of proteins of an entirely different char-
acter,— namely, peptones and proteoses, — or, indeed, a series of
much simpler split products; but during the act of absorption
into the blood these latter bodies have been supposed to undergo
transformation into serum-albumin. From a physiological stand-
point serum-albumin is often considered to be the main source of
protein nourishment for the tissues generally. As will be explained
in the section on Nutrition, one of the most important requisites
in the nutrition of the cells of the body is an adequate supply of
protein material to replace that used up in the chemical changes,
the metabolism, of the tissues. Serum-albumin has been supposed
to furnish a part, at least, of this supply, although, as a matter of
fact, there is no substantial proof that this view is correct. As
long as the serum-albumin is in the blood-vessels it is, of course,
cut off from the tissues. The cells, however, are bathed directly
in lymph, and this in turn is formed from the plasma of the blood
which is transuded or, according to some physiologists, secreted
through the vessel walls.

Paraglobulin, which belongs to the group of globulins, exhibits
the general reactions characteristic of the group. As stated above,
it is completely precipitated from its solutions by saturation with
magnesium sulphate or by half saturation with ammonium sulphate.
It is incompletely precipitated by saturation with common salt
(NaCl). In neutral or feebly acid solutions it coagulates upon
heating to 75° C. Hammarsten gives its percentage composition
as: C, 52.71; H, 7.01; N, 15.85; S, 1.11; O, 23'.32. Schmiedeberg
gives it a molecular composition corresponding to the formula
Cii7H182N30S038 + JH2O. According to Faust, the precipitate of
paraglobulin usually obtained with magnesium sulphate contains a
certain amount of an albuminoid body, glutolin, which he believes
to be a constant constituent of blood-plasma. Paraglobulin occurs
in blood, in lymph, and in the normal and pathological exudations.
The amount of paraglobulin present in blood varies in different
animals. Among the mammalia the amount ranges from 1.78 per
cent, in rabbits to 4.56 per cent, in the horse. In human blood it is
given at 3.10 per cent., being less in amount, therefore, than the
serum-albumin. It is usually stated that more of this protein is

424 BLOOD AND LYMPH.

found in the serum than in the plasma. This fact is explained by
supposing that during coagulation some of the leucocytes disinte-
grate and part of their substance passes into solution as a globulin
identical with or closely resembling paraglobulin. Paraglobulin as
obtained from blood-serum by half saturation with ammonium
sulphate or full saturation with magnesium sulphate does not behave
like a chemical individual. Portions of it, for instance, are precipi-
tated by C02 or by dialysis, and portions are not so precipitated.
Recently, therefore, it has been assumed that paraglobulin is in
reality a mixture of two or possibly three different, although re-
lated, proteins. The separation usually given is into euglobulin
and pseudoglobulin, euglobulin being the portion precipitated by
ammonium sulphate when added to one- third saturation (28 to 33
per cent.), and pseudoglobulin the portion precipitated only by
one-half saturation (34 to 50 per cent.). The latter portion shows
properties more nearly related to the albumins.* The whole basis
of classification is, however, unsatisfactory and provisional (see
appendix). It is even stated that under certain conditions of
temperature and reaction serum-albumin may be converted to a
globulin body that precipitates upon one-half saturation with
ammonium sulpha te.f The origin of paraglobulin remains unde-
termined. It may arise from the digested proteins absorbed from
the alimentary canal, but there is no evidence to support such a
view. Another suggestion is that it comes from the disintegration
of the leucocytes (and other formed elements) of the blood. These
bodies are known to contain a small quantity of a globulin resem-
bling paraglobulin, and it is possible that this globulin may be liber-
ated after the dissolution of the leucocytes in the plasma, and thus go
to make up the normal supply of paraglobulin. Several observers!
have claimed that during starvation the proportion of globulins
in the blood is increased relatively or absolutely. A possible
explanation is that the increase is due to cell globulins received from
the tissues which must undergo destruction and dissolution in pro-
longed fasting. The fact remains, however, that our knowledge is
too incomplete at present to venture any positive statements
regarding the origin and specific functions of the paraglobulin.

Fibrinogen is a protein belonging to the globulin class and exhibit-
ing all the general reactions of this group. It is distinguished from
paraglobulin by a number of special reactions; for example, its
temperature of heat coagulation is much lower (56° to 60° C.), and

* Forges and Spiro, "Beitrage zur chem. Physiol. u. Pathol.," 3, 277,
1903; and Freund and Joachim, "Zeitschrift f. physiologische Chemie," 36,
407, 1902.

t Moll, "Beitrage zur chem. Physiol. u. Pathol. " 4, 561, 1903.

t See St. Githens, "Beitrage zur chem. Physiol. u. Pathol./' 5, 515, 1904;
also Lewinski, "Pfliiger's Archiv f. d.

gesammte Physiol.," 100, 611, 1903-

CHEMICAL COMPOSITION OF BLOOD-PLASMA. 425

it is completely thrown down from its solutions by saturation with
sodium chlorid as well as with magnesium sulphate. Its most
important and distinctive reaction is, however, that under proper
conditions it gives rise to an insoluble protein, fibrin, whose forma-
tion is the essential phenomenon in the coagulation of blood.
Fibrinogen has a percentage composition, according to Hammar-
sten, of: C, 52.93; H, 6.90; N, 16.66; S, 1.25; O, 22.26; while its
molecular composition, according to Schmiedeberg, is indicated by
the formula C108H162N30S034.

Fibrinogen is found in blood-plasma, lymph, and in some cases,
though not always, in the normal and pathological exudations. It
is absent from blood-serum, being used up during the process of*
clotting. It occurs in very small quantities in blood, compared
with the other proteins. There is no good method of determining
quantitatively the amount of fibrinogen, but estimates of the
amount of fibrin, which cannot differ very much from the fibrinogen,
show that in human blood it varies from 0.22 to 0.4 per cent. In
horse's blood it may be more abundant, — 0.65 per cent. As to the
origin and the special physiological value of this protein we are, if
possible, more in the dark than in the case of paraglobulin, with the
exception that fibrinogen is known to be the source of the fibrin of
clotted blood. But clotting is an occasional phenomenon only.
What nutritive function, if any, is possessed by fibrinogen under
normal conditions is unknown. No satisfactory account has been
given of its origin. It has been suggested by different investigators
that it may come from the nuclei of disintegrating leucocytes (and
blood plates) or from the dissolution of the extruded nuclei of newly
made red corpuscles, but here again we have only speculations, that
can not be accepted until some experimental proof is advanced to
support them. It may be added that there is some evidence to
indicate that the fibrinogen is produced in the liver. Thus Doyon
and his co-workers * have shown that when the fibrinogen is re-
moved from blood by defibrinating and the blood is then returned
to the animal, new fibrinogen is produced within a few hours.
In frogs, at least, the new fibrinogen is not manufactured if the
liver is removed, and in dogs it is also stated that after removal
of the liver the blood may become incoagulable owing to a disap-
pearance of fibrinogen.

The following table t gives some recent results of analyses of
blood which indicate the average amounts of the different proteins
in the blood-plasma of several animal's. The figures give the weight
of the protein in grams for 100 c.c. of plasma.

* Doyon et al., "C. R. Soc. de Biol.," lx., 606, 681, 860. See also Nolf.
"Archives internat. de Physiol.," 1905, iii., 1.
f Lewinski, he. cit.

426 BLOOD AND LYMPH.

SERUM-
TOTAL PROTEINS. ALBUMIN. PARAGLOBULIN. FIBRINOGEN.

Man 7.26 4.01 2.83 0.42

Dog 6.03 3.17 2.26 0.60

Sheep 7.29 3.83 3.00 0.46

Horse 8.04 2.80 4.79 0.45

Pig 8.05 4.42 2.98 0.65

Other Proteins of the Blood-serum or Blood-plasma. — From time to time
other protein bodies have been described in the serum or plasma of the blood.
In the serum after coagulation Hammarsten has obtained a globulin body,
fibrin-globulin, which he supposes may be split off from the fibrinogen during
the act of clotting. Faust, as was mentioned above, describes an albuminoid
substance, glutolin, which is present in the blood and is usually precipitated
together with the paraglobulin. A number of observers have noted the ex-
istence in blood of a protein not coagulated by heat. By some authors this
has been described as a peptone or an albumose (Langstein), by others as an
ovomucoid (Zanetti), and by others still (Chabrie) as a peculiar protein for
which the name albumon has been proposed. By others still this non-coagu-
lable protein obtained from serum or plasma has been explained as an artificial
product arising from the globulins of the blood during the process of remov-
ing the coagulable proteins by heating. So, too, nucleoprotein substances
have been described in the blood-serum by several observers, most recently by
Freund and Joachim. It is quite possible, however, that the substance de-
scribed as nucleoprotein is in reality a mixture or combination of lecithin and
protein. Most of the protein when precipitated from the blood carries down
with it some lecithin, and will therefore show a reaction for phosphorus. It
can be shown that the phosphorus present is, in most cases at least, remov-
able by boiling with alcohol, and there is at present no entirely satisfactory
proof that nucleoprotein exists in the blood.

Coagulation of Blood. — One of the most striking properties of
blood is its power of clotting or coagulating shortly after it escapes
from the blood-vessels. The general changes in the blood during
this process are easily followed. At first perfectly fluid, in a few
minutes it becomes viscous and then sets into a soft jelly which
quickly becomes firmer, so that the vessel containing it may be
inverted without spilling the blood. The clot continues to grow
more compact and gradually shrinks in volume, pressing out a
smaller or larger quantity of a clear, faintly yellow liquid to which
the name blood-serum is given. The essential part of the clot is the
fibrin. Fibrin is an insoluble protein not found in normal blood.
In shed blood, and under certain conditions in blood while still in the
blood-vessels, this fibrin is formed from the soluble fibrinogen.
The deposition of the fibrin is peculiar. It is precipitated, if the
word may be used, in the form of an exceedingly fine network of
delicate threads that permeate the whole mass of the blood and give
the clot its jelly-like character. The shrinking of the threads
causes the subsequent contraction of the clot. If the blood has not
been disturbed during the act of clotting, the red corpuscles are
caught in the fine fibrin meshwork, and as the clot shrinks these
corpuscles are held more firmly, only the clear liquid of the blood
being squeezed out, so that it is possible to get specimens of serum
containing few or no red corpuscles. The leucocytes, on the con-

COAGULATIOX. 427

trary, although they are also caught at first in the forming
meshwork of fibrin, may readily pass out into the serum in the later
stages of clotting, on account of their power of making ameboid
movements. If the blood has been agitated during the process of
clotting, the delicate network will be broken in places and the serum
will be more or less bloody — that is, it will contain numerous red
corpuscles. If during the time of clotting the blood is vigorously
whipped with a bundle of fine rods, all the fibrin is deposited
as a stringy mass upon the whip, and the remaining liquid part
consists of serum plus the blood corpuscles. Blood that has been
whipped in this way is known as " defibrinated blood." It resembles
normal blood in appearance, but is different in its composition; it
can not clot again. The way in which the fibrin is normally de-
posited may be demonstrated very easily under the microscope by
placing a good-sized drop of blood on a slide, covering it with a
cover-slip, and allowing it to stand for several minutes until coagu-
lation is completed. If the drop is now examined, it is possible by
careful focusing to discover in the spaces between the masses of
corpuscles many examples of the delicate fibrin network. The
physiological value of clotting is that it stops hemorrhages by
closing the openings of the wounded blood-vessels.

Time of Clotting. — The time necessary for the clot to form varies
slightly in different individuals, or in the blood of the same in-
dividual varies with the conditions. It may be said in general that
under normal conditions the blood passes into the jelly stage in
from three to ten minutes. The separation of clot and serum takes
place gradually, but is usually completed in from ten to forty-eight
hours. The time of clotting shows marked variations in different
animals; the process is especially slow in the blood of the horse,
terrapin, and birds, so that coagulation of shed blood is more easily
prevented in these animals. In the human being also the time
of clotting may be much prolonged under certain conditions — in
fevers, for example. This fact was noticed in the days when blood-
letting was a common practice. The slow clotting of the blood
permitted the red corpuscles to sink somewhat, so that the upper
part of the clot in such cases was of a lighter color, forming what
was called the " buffy coat." The time of clotting may be shortened
or prolonged, or the clotting may be prevented altogether, in
various ways, and much use has been made of this fact in studying
the composition and the coagulation of blood as well as in con-
trolling hemorrhages.

Theories of Coagulation. — The clotting of blood is such a
prominent phenomenon that it has attracted attention at all
times, and as a result numerous theories to account for it have been

428 BLOOD AND LYMPH.

advanced. Most of these theories have now simply an historical
interest. In recent years much experimental work has been done
upon the subject, the result of which has been to increase greatly
our knowledge of the process ; but no complete explanation has yet
been reached. It is generally admitted that the essential constit-
uent of the clot — namely, the fibrin — is formed from the fibrinogen
normally present in the plasma, and that without this fibrin-
ogen clotting is impossible. If, for instance, blood is heated to
60° C., a temperature sufficient to precipitate the fibrinogen as a
heat coagulum, its power of clotting is lost. Clotting, therefore, is
essentially a process of the blood-plasma, as was shown indeed by
the old experimenters (Hewson). Moreover it is also admitted that
the conversion of the soluble fibrinogen to the insoluble fibrin is
accomplished by the agency of an unorganized ferment or enzyme,
which is not present, in its active form at least, in the blood while in
the blood-vessels, but is formed after the blood is shed or under
certain abnormal conditions within the blood-vessels. These two
important facts — in the definite form in which they are stated —
we owe mainly to the investigations of Alexander Schmidt,* whose
work completed the older observations of Hewson, Buchanan,
Denis, and Briicke.

Fibrinogen is readily prepared by the method of Hammarsten
from the plasma of horses' blood that has been kept from clotting
by cooling. By several successive precipitations with sodium
chlorid it can be obtained free from the other proteins of blood, and
upon the addition of a solution of fibrin ferment it gives a typical
clot. Fibrin ferment solutions are prepared by the method first
suggested by Schmidt. Blood-serum is precipitated by the addi-
tion of fifteen to twenty times its volume of alcohol, and the precipi-
tate is allowed to stand under the alcohol for at least fourteen days
in order to render the proteins insoluble. The precipitate is then
dried over sulphuric acid and extracted with water. The aqueous
solutions thus obtained cause solutions of fibrinogen to clot, and
induce coagulation in certain pathological exudates, such as
hydrocele liquid, which contain fibrinogen, but are not spontane-
ously coagulable. The fibrin ferment solutions are destroyed by
moderate heat, 50° to 60° C. As is seen from the method of prep-
aration, the ferment is contained in fresh blood-serum. Schmidt
was able to show, however, that it is not present, in detectible
amounts at least, in normal blood. That is, if blood flowing im-
mediately from an artery is caught under alcohol and is treated as
described above for the serum it yields no ferment. The conclu-

* " Archiv f. Anat., Physiologie, u. Wiss. Medicin," Reichert u. du Bois-
Reymond, 1861, pp. 545, 675, and 1862, pp. 428, 533; "Pfliiger's Archiv. f.
d. gesammte Physiol.," 6, 413, 1872; " Zur Blutlehre," Leipzig,. 1892 and 1895.

COAGULATION. 429

sion, therefore, is justified that the active ferment is formed after
the blood is shed. Schmidt subsequently designated this ferment
as thrombin. A third fact of essential importance in theories of coag-
ulation is that soluble calcium salts are necessary to the process.
This discovery was made definitively by Arthus and Pages,* who
showed that blood received into an oxalate solution, so as to
precipitate the calcium, does not clot. Subsequent addition of a
solution of a calcium salt induces clotting promptly.

We may say, therefore, that there are three fibrin factors which
are undoubtedly concerned in the production of fibrin, — namely,
fibrinogen, calcium salts, and thrombin. Two of these exist in the
circulating blood, one of them, the ferment, is formed after the blood
is shed. Obviously, therefore, we may conclude that the main
reason for the clotting of the blood when shed is the formation of
thrombin. The difficulties in the way of an adequate explanation
of the formation of the thrombin and its mode of action are very
great.

The theories that have been proposed in recent years are numer-
ous and conflicting.* It has long been believed that the for-
mation of the thrombin is initiated by the breaking down of the
formed elements in the blood, — the leucocytes and the blood plates.
Concerning the amount of destruction of leucocytes in shed blood
opinions still differ. While some observers report that they dis-
integrate in large numbers when the blood escapes from the ves-
sels, others deny that they show any marked immediate effect of
such a change in environment. Concerning the blood plates there
can be no doubt. Immediately after the shedding of blood and
within the time that precedes normal coagulation these structures
agglutinate and then dissolve or disintegrate. There is much
evidence to show that the fibrin is deposited first in the neighbor-
hood of these agglutinated masses of blood plates, and moreover
that any reagent or condition that prevents or retards the breaking
down of the plates prevents or delays the clotting of the blood.
We may believe, therefore, that the blood plates (and leucocytes)
give rise to some substance or substances necessary in the forma-
tion of the thrombin.

According to a theory proposed by Pekelharing and formerly
much quoted, it was suggested that the dissolution of the formed
elements liberates a nucleoprotein which then combines with the
calcium present to form a calcium nucleoprotein compound which

* "Archives de physiologic normale et pathologique," fifth series, 2, 739,
1890.

f For recent theories and literature see Morawitz, 'Beitriige zur chem.
Physiol. u. Pathol.," 4, 381, 1904, and "Deutsches Archiv f. klin. Med.,"
1904, Ixxix., 1 and 215; Fuld, ' Zentralblatt f. Physiol.," 17, 529, 1903; Nolf,
"Arch, internat. de Physiol.," 1906, iv., 165; Loeb, ''The Medical News,"
April 1, 1905.

430 ^ BLOOD AND LYMPH.

I

constitutes the thrombin. This compound reacts with the fibrin-
ogen to form an insoluble calcium compound, the fibrin. This
theory may be expressed in simple form by an equation of this
kind:

Ca nucleoprotein + fibrinogen = Ca fibrinogen.
(Thrombin.) (Fibrin.)

Hammarsten has shown that the latter part of this theory is not
correct. Fibrin as ordinarily formed does contain much calcium,
but when a calcium-free solution of fibrinogen is brought into reac-
tion with a calcium-free ferment solution (blood-serum) a typical
clot is formed the fibrin of which is practically free from calcium.
This result also enables us to draw the important conclusion that
the calcium is not essential to the process of clotting after the
thrombin is once formed, and that therefore its role probably comes
in in the production of the thrombin.

Some recent observers hold to the view that the active throm-
bin is formed from an inactive antecedent substance which is
designated usually as prothrombin. Schmidt and others believe
that the prothrombin exists preformed in blood-plasma and that
it may be converted into active thrombin by certain substances
arising from the blood corpuscles or indeed from many tissue cells.
These substances are described as zymoplastic substances (also
cytozyms, coagulins, or thrombokinases) . Others have considered
that the calcium salts constitute the efficient zymoplastic substance
that converts the prothrombin to thrombin, — a view that is con-
tained in the first part of Pekelharing's theory, given above.
At present it would seem that the view advocated by Morawitz
explains best the numerous observations that are on record.
According to this author fibrin ferment results from the interaction
of three substances. One of these, corresponding in a general
way to a proferment, is found chiefly in the blood plates. When
these elements disintegrate, this substance, which the author desig-
nates as thrombogen, is liberated. Thrombogen alone cannot
convert the fibrinogen to fibrin. In order for it to produce this
effect it must be activated by the combined influence of calcium
salts and a thrombokinase. The latter substance, presumably
of an enzyme-nature, can be extracted from the tissue-elements
in general and in the blood may be obtained from the white or the
red corpuscles or the blood plates. The activated thrombogen
constitutes the fibrin ferment or thrombin which is capable of
converting the fibrinogen to fibrin. It would seem that in ordinary
clotting only a portion of the thrombogen is activated, so that
in the serum we find some thrombin and some thrombogen. This
belief is justified by the results of experiments made with the

COAGULATION. 431

serum. When serum is added to a solution of fibrinogen clotting
takes place, but the process is much accelerated if at the same time
one adds some tissue-extract and calcium chlorid. The efficacy
of these two latter substances, which in themselves are incapable
of changing the fibrinogen to fibrin, is explained on the assumption
that they activate some of the remaining thrombogen in the blood-
serum. Delezenne has shown that if the blood of birds is with-
drawn carefully, by means* of a cannula inserted into an artery,
it clots very slowly, and if centrifugalized at once the supernatant
plasma when removed may remain unclotted for some days. This
result seems to be due to the fact that the corpuscular elements
in the blood of these animals disintegrate less readily. A similar
result holds good for the blood of terrapins, as was pointed out
long ago by the present author. If, however, in withdrawing the
blood it comes into contact with the tissues, — at the wound, for
instance, — it will clot quickly, and it would appear that a zymo-
plastic substance is furnished by the tissues. In the bird the
normal clotting of the blood to stop wounded vessels must depend
upon this co-operation from the outside tissues. In the mammal
the blood itself contains all the sources necessary for prompt coagu-
lation, but it is quite possible that here also the clotting in ordinary
hemorrhages from wounds may be normally accelerated by zymo-
plastic substances supplied from the vessel walls or the surrounding
tissues.

After the active thrombin is formed its manner of action upon the
fibrinogen is also a matter concerning which we have little positive
knowledge. Hammarsten has supposed that the thrombin causes
a splitting of the fibrinogen molecule, with the formation of the
insoluble fibrin and a soluble globulin, fibrin globulin,

which can be found in small quantities in the serum after coagula-
tion. This conclusion has not, however, been demonstrated to be
correct. Some observers have suggested that the enzyme causes a
rearrangement in the structure of the fibrinogen molecule, while
others have given some reasons for believing that the action of the
thrombin is hydrolytic, as is the case with most of the enzymes of
digestion. Thus, Fuld* states, from experiments upon the blood-
plasma of birds, that the rapidity of clotting varies, not directly
with the amount of enzyme (thrombin) present, but rather in pro-
portion to the square root of the amount, thus following the law of
Schiitz for hydrolytic enzymes.

Summary. — By way of summary the following statements may

* Fuld, "Beitrage zur chem. Physiol. u. Pathol.," 2, 514.

432 BLOOD AND LYMPH.

be made: The immediate factors necessary in coagulation are fibrin
ferment (thrombin) and fibrinogen. Calcium salts are necessary
to the process of clotting as it occurs in the blood, but it is probable
that they play some part in preparing the thrombin. It is probable,
also, that the formed elements of the blood, the blood plates and
leucocytes, furnish the chief preliminary material from which
the thrombin is formed. We may provisionally adopt the view
that thrombin is produced from an antecedent thrombogen or
prothrombin which is derived from the blood plates. This is
converted into an active form by the influence of the calcium salts
present in the plasma and a thrombokinase which is furnished
by the plates or the leucocytes and can be obtained from the tissues
generally. The process may be represented schematically as
follows:

Thrombogen + calcium salts + zymoplastic substance (thrombokinase) =

thrombin.
Thrombin + fibrinogen = fibrin.

In this last reaction the fibrinogen disappears entirely, so that none
is found in the serum after clotting. The thrombin, on the con-
trary, like other enzymes, is not destroyed in the reaction and is
found, therefore, in the serum of the clot, together with some throm-
bogen which has not been activated. The indefinite form in which
it is necessary to state this theory is in itself sufficient indication
of the amount of additional investigation which will have to be
made before we shall be in a position to explain satisfactorily
the entire history of the act of clotting.

Why Blood Does Not Clot Within the Blood-vessels— An-
tithrombin. — The reason that blood remains fluid within the blood-
vessels and coagulates in a few minutes after being shed would seem
to be contained in the theories of coagulation just described. We
may assume that in the living blood-vessels the formed elements —
leucocytes and blood plates — do not disintegrate in great numbers
at a time, and therefore do not give rise to any noticeable quantity
of the antecedents of thrombin. It seems most probable that little,
if any, thrombin is actually present in the blood under normal
circumstances, and this in itself may be regarded as the main reason
for the fact that the blood remains unclotted. It is quite possible,
however, that other safeguards may exist in a matter" of such
prime importance. It has been shown, for instance, that, when
solutions of fibrin ferment (thrombin) are injected into the circu-
lation, clotting is not produced with the certainty that one might
expect. Delezenne has described experiments which indicate
that the liver exercises a defensive power in this respect.* He
states that when blood-serum — containing, as it normally does,
* "Travaux de Physiologic/' Universite de Montpellier, 1898.

COAGULATION. 433

some active thrombin — is circulated through a living liver it loses
its power of inducing coagulation in solutions containing fibrinogen.
Its thrombin has been destroyed or made inactive by some effect
of the liver, and it is possible, although not demonstrated as yet,
that the liver may exercise such a protective action under special
circumstances during life. That this supposed action of the liver
is not always essential is shown by the fact that in animals from
whom the liver has been Removed experimentally the blood does
not clot within the vessels. The older observers were impressed
writh the fact that blood remains uncoagulatcd for long periods if
kept in contact with w7hat may be called its normal surface, — that
is, the interior of the heart or blood-vessels. In an excised heart
or blood-vessel the blood, although at rest, remains fluid for a long
time. It was thought possible, therefore, that the normal en-
dothelial walls of the vessels exercise a restraining influence of
some kind upon the coagulation of the blood. In recent times
this view has taken the form, corresponding to the knowledge of
the day, of a suggestion that an antibody — namely, an anti-
thrombin — exists in the blood and actively retards or prevents co-
agulation. While some authors (Morawitz) believe that such an
antithrombin exists normally in circulating blood and is essential
in maintaining its fluidity, others (Schmidt) hold to the view that
substances retarding coagulation are liberated only from the dis-
integration of the cellular elements and are present practically,
therefore, only in the shed blood. Loeb* has not been able to
detect the existence of an antithrombin in extracts of the inner wall
of the blood-vessels. It would seem to be premature to accept
the view that under normal conditions there exists in the blood any
substance that retards or prevents coagulation, although under
artificial or unusual conditions, as stated in the next paragraph,
such substances may be produced.

Intravascular Clotting. — As is well known, clots may form
within the blood-vessels in consequence of the introduction of for-
eign material of any kind. Air, for instance, that has gotten into
the veins, if not absorbed, may act as a foreign substance and
cause the same chain of events as when the blood is shed, — namely,
the disintegration of formed elements, formation of thrombin, and
clotting. So also when the internal coat of a blood-vessel is in-
jured as, for instance, by a ligature — the altered endothelial cells
act as a foreign substance. If the circulatory conditions are favor-
able— for instance, if the ligated artery causes a stasis of blood at
that point — there may be an agglutination of the blood plates,
starting at the injured surface, and the subsequent formation of a
clot. Intravascular clotting may also be produced by the injection

* Leo Loeb, u Virchow's Archiv," 176, 10, 1904; also " Hofmeister's Bei-
trage," 5, 534, 1904.
28

434 BLOOD AND LYMPH.

of other substances. Calcium solutions added in quantity sufficient
to notably raise the calcium percentage of the plasma distinctly
favor the process of clotting and may lead to the formation of
intra vascular clots. So, too, injections of thrombin or of leucocytes
as obtained from macerated lymph glands cause clotting. In
this latter case, however, it has been noticed that if the quantity
injected is not sufficient the coagulability of the blood may be
distinctly retarded instead of being accelerated. This fact has been
accounted for on the hypothesis that in the disintegration of the
foreign leucocytes two products are formed, one tending to acceler-
ate coagulation (positive phase of the injection) and one tending to
retard it (negative phase). Lilienfeld* has made this hypothesis
more specific by showing that lymphocytes (and blood plates)
yield a nucleoprotein which in turn on decomposition furnishes a
second nucleoprotein, leuconuclein, whose presence favors coagula-
tion, and a simple protein, histon, whose action retards clotting.
Delezenne f has still further added to the hypothesis by experiments
which indicate that the element favoring coagulation (leuconuclein)
is removed or destroyed by the liver. When an insufficient quan-
tity of leucocytes is injected into the circulation the histon action
may predominate, and thus retard coagulation, while with larger
quantities and a more extensive decomposition the leuconuclein
may bring about clotting before it is completely destroyed by the
liver.

Means of Hastening or of Retarding Coagulation. — Blood
coagulates normally within a few minutes, but the process may be
hastened by increasing the extent of foreign surface with which it
comes in contact. Thus, agitating the liquid when in quantity, or
the application of a sponge or a handkerchief to a wound, hastens
the onset of clotting. This is easily understood when it is remem-
bered that the breaking down of leucocytes and blood-plates is
hastened by contact with foreign surfaces. It has been proposed
also to hasten clotting in case of hemorrhage by the use of ferment
solutions or of tissue-extracts containing some thrombokinase.
Hot sponges or cloths applied to a wound hasten clotting, probably
by accelerating the formation of ferment and the chemical changes
of clotting. Coagulation may be retarded or be prevented alto-
gether by a variety of means, of which the following are the most
important :

1. By Cooling. — This method succeeds well only in blood that
clots slowly — for example, the blood of the horse, bird, or terrapin.
Blood from these animals received into narrow vessels surrounded
by crushed ice may be kept fluid for an indefinite time. The blood
corpuscles soon sink, so that by this means one may readily obtain
* Lilienfeld, " Zeitschrift f. physiol. Chemie," 18, 473. }Loc. cit.

COAGULATION. 435

pure blood-plasma. The cooling probably prevents clotting by
keeping the corpuscles intact.

2. By the Action of Neutral Salts. — Blood received at once from
the blood-vessels into a solution of such neutral salts as sodium
sulphate or magnesium sulphate, and well mixed, does not clot. In
this case also the corpuscles settle slowly, or they may be centri-
fugalized, and specimens of plasma be obtained. For this purpose
horses' or cats' blood is to be preferred. Such plasma is known
as " salted plasma "; it is frequently used in experiments in coag-
ulation,— for example, in testing the efficacy of a given ferment
solution. The best salt to use is magnesium sulphate in solutions
of 27 per cent. : 1 part by volume of this solution is usually mixed
with 4 parts of blood; if cats' blood is used a smaller amount may
be taken — 1 part of the solution to 9 of blood. Salted plasma
or salted blood again clots when diluted sufficiently with water or
when ferment solutions are added to it. How the salts prevent
coagulation is not definitely known — possibly by preventing the
disintegration of corpuscles and the formation of ferment, possibly
by altering some later stage in the process.

3. By the Action of Oxalate Solutions. — If blood as it flows from
the vessels is mixed with solutions of potassium or sodium oxalate
in proportion sufficient to make a total strength of 0.1 per cent,
or more of these salts, coagulation is prevented entirely. Ad-
dition of an excess of water does not produce clotting in this case,
but solutions of some soluble calcium salt quickly start the process.
The explanation of the action of the oxalate solutions is simple:
they are supposed to precipitate the calcium as insoluble calcium
oxalate.

4. By the Action of Sodium Fluorid. — Blood drawn directly into
a solution of sodium fluorid (1 part of a 3 per cent, solution of
sodium fluorid to 9 parts of blood) does not clot. Addition of
calcium salts alone to such a mixture fails to provoke clotting, but
addition of solutions of thrombin, or of calcium and zymoplastic
substance, will provoke coagulation. The plasma obtained by
centrifugalizing a mixture of blood and sodium fluorid gives,
therefore, a means of testing for the presence of thrombin (Arthus) .

5. By the Injection of Certain Organic Substances. — There are a
number of substances which when injected into the blood retard
or prevent its coagulation. For instance, solutions of ordinary
preparations of pepsin, trypsin, peptone, snake venom, leech
extracts, etc. Snake venom may be wonderfully potent in this
particular; it is stated that so little as 0.00001 gm. to each kilogram
of animal suffices to destroy the coagulability of the blood. Of
these various bodies solutions of peptone have received the most
attention from investigators. Peptone, as usually obtained by

436 BLOOD AND LYMPH.

digestion experiments, is in reality a mixture of prot:oses and
peptones. When injected into the circulation in the proportion of
0.3 gm. to each kilogram of animal the coagulability of the blood is
very greatly diminished. When, however, such solutions are added
to freshly drawn blood they exercise no influence upon the coagu-
lation. Evidently, therefore, when injected into the blood they
provoke a reaction of some sort the products of which prevent
coagulation. Delezenne's work given above offers a simple ex-
planation. Such solutions cause a rapid destruction of leucocytes
(and blood plates) with the production of leuconuclein and histon ;
the former substance is destroyed or removed by the liver and the
histon remaining in the blood is the cause of the non-coagulation.
Pick and Spiro * have shown that this action of peptone solutions is
not due to the peptone or the albumoses contained in it. When
obtained in purified form these substances have no such effect.
They attribute the action to a substance, derived probably from
the tissues used in the preparation of the peptone, and for which
they suggest the name of peptozym. Leech extracts differ from
solutions containing peptozym in that they prevent the clotting
of the blood when added to it outside the body. They evidently
contain already formed a substance whose action prevents coagula-
tion. This substance is secreted by the salivary glands of the leech.
It has been extracted from the glands in a more or less pure form,
and is designated as hirudin. Nothing is definitely known regarding
its chemical structure or its mode of action in preventing clotting.

Total Quantity of Blood in the Body. — The total quantity of
blood in the body has been determined approximately for man and
a number of the lower animals. The method (Welcker) used in
such determinations consists essentially in first bleeding the animal
as thoroughly as possible and weighing the quantity of blood thus
obtained, and afterward washing out the blood-vessels with water
and estimating the amount of hemoglobin in the washings.

Grehant ("Journal de 1'Anat. et de Physiol.," 1882, 564) has devised an-
other method which may be used upon the living animal, as follows : A
specimen of blood is taken from the animal and the volume per cent, of
oxygen is determined by extraction with a gas-pump. The animal is then
made to breathe a known volume of carbon monoxid for a certain time, and
the total amount of this carbon monoxid that is absorbed is ascertained by
analysis. A second specimen of blood is then taken and its volume per cent,
in oxygen is again determined. The difference between this volume per cent,
of oxygen and that obtained before the administration of the carbon monoxid
gives the volume per cent, of carbon monoxid in the blood, since the latter
gas displaces an equal volume of oxygen. If the total amount of carbon
monoxid absorbed by the blood is indicated by V and the volume per cent.,
that is, the number of c.c. to each 100 c.c. of blood, is indicated by v, then the

total quantity of the blood will be given by the formula — X 100.
*" Zeitschrift f. physiol. Chemie," 31, 235, 1900.

REGENERATION AFTER HEMORRHAGE. 437

The average results obtained from numerous experiments are as
follows: The ratio of weight of blood to weight of body is, in the
dog, 7.7 per cent.; rabbit and cat, 5 per cent.; birds, 10 per cent.
On man we have upon record twro determinations on guillotined
criminals made by Bischoff, which gave 7.7 and 7.2 per cent.
Haldane and Smith,* however, have devised a modification of
Grehant's carbon monoxid method, which they have applied to
living men. The results of some 74 experiments gave them an
average value of only 5 per cent, for man. The distribution of
this blood in the tissues of the body at any time has been esti-
mated by Rankest from experiments on freshly killed rabbits, as
follows :

Spleen 0.23 per cent.

Brain and cord 1.24 "

Kidneys 1.63 "

Skin 2.10 "

Intestines 6.30 "

Bones 8.24 "

Heart, lungs, and great blood-vessels 22.76 "

Resting muscles 29.20 "

Liver 29.30 "

It will be seen from inspection of this table that in the rabbit the
blood of the body is distributed at any one time about as follows:
One-fourth to the heart, lungs, and great blood-vessels; one-fourth
to the liver; one-fourth to the resting muscles; and one-fourth to the
remaining organs.

Regeneration of the Blood after Hemorrhage. — A large
portion of the entire quantity of blood in the body may be lost
suddenly by hemorrhage without producing a fatal result. The
extent of hemorrhage that may be recovered from safely has been
investigated upon a number of animals. Although the results
show more or less individual variation, it may be said that in dogs
a hemorrhage of from 2 to 3 per cent, of the body-weight J is re-
covered from easily, while a loss of 4.5 per cent., more than half
the entire blood, will probably prove fatal. In cats a hemorrhage
of from 2 to 3 per cent, of the body-weight is not usually followed
by a fatal result. Just what percentage of loss may be borne by the
human being has not been determined, but it is probable that a
healthy individual may recover without serious difficulty from the
loss of a quantity of blood amounting to as much as 3 per cent, of
the body-weight. It is known that if liquids that are isotonic to
the blood, such as physiological saline (NaCl, 0.7 to 0.9 per cent.)

* Haldane and Smith, " Journal of Physiology," 1900, xxv., 331.

f Taken from Vierordt's " Anatomische, physiologische, und physikalische
Daten und Tabellen," Jena, 1893.

J Fredericq: "Travaux du Laboratoire " (Universite de Liege), 1, 189,
1885.

438

BLOOD AND LYMPH.

or Ringer's solution, are injected into the veins immediately after
a severe hemorrhage, recovery is more certain; in fact, it is
possible by this means to restore persons after a hemorrhage that
would otherwise have been fatal. By an infusion of this kind,
particularly if at or somewhat above the body temperature, the
heart beat is increased, the volume of the circulating liquid is
brought to an amount sufficient to maintain approximately normal
conditions of pressure and velocity, and the red corpuscles that still
remain are kept in more rapid circulation and are thus utilized more
completely as oxygen carriers. If a hemorrhage has not been fatal,
experiments on lower animals show that the plasma of the blood is
regenerated with some rapidity, the blood regaining its normal vol-

HaaioglobUL

Fig. 176. — To show the effect of hemorrhage upon the number of red and white cor-
puscles and the amount of hemoglobin. — (Dawson.) The ordinates express the numbers
of corpuscles and also the percentages of hemoglobin as stated in the figures to the left.
The abscissas give the days after hemorrhage. The experiment was made upon a dog of
8.1 kgms. The hemorrhage, which lasted 2.3 minutes, was equal to 4.3 per cent, of the
body-weight. An equal amount of physiological saline (NaCl, 0.8 per cent.) was injected
immediately.

ume within a few hours in slight hemorrhages, and in from twenty-
four to forty-eight hours if the loss of blood has been severe; but
the number of red corpuscles and the hemoglobin are regenerated
more slowly, getting back to normal only after a number of days or
after several weeks. The accompanying curves illustrate the results
of a severe hemorrhage (4.3 per cent, of the body-weight) followed
by transfusion of an equal volume of physiological saline. So far
as the red corpuscles and the amount of hemoglobin are concerned,

BLOOD-TRANSFUSION. 439

it will be noticed that the large sudden fall from the hemorrhage,
first day, is followed by a slower drop in both factors during the
second and third days. This latter phenomenon constitutes what
is known as the posthemorrhagic fall.*

Blood-transfusion. — Shortly after the discovery of the circu-
lation of the blood (Harvey, 1628), the operation was introduced
of transfusing blood from., one individual to another or from some
of the lower animals to man. Extravagant hopes were held as to
the value of such transfusion not only as a means of replacing the
blood lost by hemorrhage, but also as a cure for various infirmities
and diseases. Then and subsequently fatal as well as successful
results followed the operation. It is now known to be a dangerous
undertaking, mainly for two reasons: first, the strange blood,
whether transfused directly or after defibrination, is liable to contain
a quantity of fibrin ferment sufficient, perhaps, to cause intra vas-
cular clotting; second, the serum of one animal may be toxic to
another or cause a destruction of its blood corpuscles. Owing to
this hemolytic and toxic action, which has previously been referred
to (p. 398), the injection of foreign blood is likely to be directly
injurious instead of beneficial. In cases of loss of blood from severe
hemorrhage, therefore, it is far safer to inject a neutral liquid,
such as the so-called "physiological salt solution" — a solution of
sodium chlorid of such a strength (0.7 to 0.9) as will suffice to pre-
vent hemolysis of the red corpuscles.

*Dawson, " American Journal of Physiology," 4, 1, 1900.

CHAPTER XXIV.
COMPOSITION AND FORMATION OF LYMPH.

Lymph is a colorless liquid found in the lymph- vessels as well
as in the extravascular spaces of the body. All the tissue elements,
in fact, may be regarded as being bathed in lymph. To understand
its occurrence in the body one has only to bear in mind its method
of origin from the blood. Throughout the entire body there is a
rich supply of blood-vessels penetrating every tissue with the ex-
ception of the epidermis and some epidermal structures, as the nails
and the hair. The plasma of the blood, by the action of physical or
chemical processes, the details of which are not yet entirely under-
stood, makes its way through the thin walls of the capillaries, and is
thus brought into immediate contact with the tissues, to which it
brings the nourishment and oxygen of the blood and from which it
removes the waste products of metabolism. This extravascular
lymph is collected into small capillary spaces which in turn open into
definite lymphatic vessels. It is still a question among the his-
tologists whether the lymph- vessels form a closed system or are in
direct anatomical connection with the tissue spaces. Recent work*
supports the view that the lymph capillaries are closed vessels simi-
lar in structure to the blood capillaries. They end in the tissues
generally, but are not in open communication with the spaces
between the cellular elements or with the larger serous cavities
between the folds of the peritoneum, pleura, etc. From the phys-
iological standpoint, however, the liquid in these latter cavities,
the cerebrospinal liquid, and the liquid bathing the tissue elements
must be regarded as a part of the general supply of lymph and as
being in communication with the liquid contained in the lymph-
vessels. That is to say, the water and the dissolved substances
contained in the tissue spaces interchange more or less freely with
the lymph proper found in the formed lymph- vessels. The lymph-
vessels unite to form larger and larger trunks, making eventually
one main trunk, the thoracic or left lymphatic duct, and a second
smaller right lymphatic duct, which open into the blood-vessels,
each on its own side, at the junction of the subclavian and internal
jugular veins. While the supply of lymph in the lymph- vessels may

* See MaCallum, "Bulletin of the Johns Hopkins Hospital," 14, 1, 1903;
also Sabin, "American Journal of Anatomy," 1, 367, 1902, and 3, 183, 1904.

440

COMPOSITION AND FORMATION OF LYMPH. 441

be considered as being derived ultimately entirely from the blood-
plasma, it is well to bear in mind that at any given moment this
supply may be altered by direct interchange with the plasma on one
side and the extravascular lymph permeating the tissue elements on
the other. The intravascular lymph may be augmented, for ex-
ample, by a flow of water from the blood-plasma into the lymph
spaces, or by a flow from the tissue elements into the lymph spaces
that surround them. The lymph movement is from the tissues
to the veins, and the flow is maintained chiefly by the difference
in pressure between the lymph at its origin in the tissues and in the
large lymphatic vessels. The continual formation of lymph in the
tissues leads to the development of a relatively high pressure in the
lymph capillaries, and as a result of this the lymph is forced toward
the point of lowest pressure, — namely, the points of junction of the
large lymph ducts with the venous system. A brief discussion of
the factors concerned in the movement of lymph will be found in
the section on Circulation. As would be inferred from its origin,
the composition of lymph is essentially the same as that of blood-
plasma. It contains the three blood proteins, the extractives (urea,
fat, lecithin, cholesterin, sugar), and inorganic salts. The salts
are found in the same proportions as in the plasma ; the proteins are
less in amount, especially the fibrinogen. Lymph coagulates, but
does so more slowly and less firmly than the blood. Histologically ,
lymph consists of a colorless liquid containing a number of leuco-
cytes, and after meals a number of minute fat droplets; red blood
corpuscles occur only accidentally, and blood plates, according to
most accounts, are likewise normally absent.

Formation of Lymph. — The careful researches of Ludwig and
his pupils were formerly believed to prove that the lymph is derived
directly from the plasma of the blood mainly by filtration through
the capillary walls. Emphasis was laid on the undoubted fact that
the blood within the capillaries is under a pressure higher than that
prevailing in the tissues outside, and it was supposed that this excess
of pressure is sufficient to squeeze the plasma of the blood through
the very thin capillary walls. Various conditions that alter the
pressure of the blood were shown to influence the amount of lymph
formed in accordance with the demands of a theory of filtration.
Moreover, the composition of lymph as usually given seems to sup-
port such a theory, inasmuch as the inorganic salts contained in it
are in the same concentration, approximately, as in blood-plasma,
while the proteins are in less concentration, following the well-
known law that in the filtration of colloids through animal mem-
branes the filtrate is more dilute than the original solution. This
simple and apparently satisfactory theory has been subjected to
critical examination within recent years, and it has been shown that

442 BLOOD AND LYMPH.

filtration alone does not suffice to explain the composition of the
lymph under all circumstances. At present two divergent views
are held upon the subject. According to some physiologists, all
the facts known with regard to the composition of lymph may be
satisfactorily explained if we suppose that this liquid is formed
from blood-plasma by the combined action of the physical processes
of filtration, diffusion, and osmosis. According to others, it is
believed that, in addition to filtration and diffusion, it is necessary
to assume an active secretory process on the part of the endothe-
lial cells composing the capillary walls. The actual condition of our
knowledge of the subject can be presented most easily by briefly
stating some of the objections that have been raised by Heidenhain*
to a pure filtration-and-diffusion theory, and indicating how these
objections have been met.

1. Heidenhain shows by simple calculations that an impossible
formation of lymph would be required, upon the filtration theory,
to supply the chemical needs of the organs in various organic and in-
organic constituents. Thus, to take an illustration that has been
much discussed, one kilogram of cows' milk contains 1.7 gms. CaO
and the entire milk of twenty-four hours would contain, in round
numbers, 42.5 gms. CaO. Since the lymph contains normally
about 0.18 part of CaO per thousand, it would require 236 liters of
lymph per day to supply the necessary CaO to the mammary glands.
Heidenhain himself suggests that the difficulty in this case may be
met by assuming active diffusion processes in connection with
filtration. If, for instance, in the case cited, we suppose that the
calcium of the lymph is quickly combined by the tissues of the mam-
mary gland, then the tension of calcium salts in the lymph will be
kept at zero, and an active diffusion of calcium into the lymph will
occur so long as the gland is secreting. In other words, the gland
will receive its calcium by much the same process as it receives its
oxygen, and will get its daily supply from a comparatively small
bulk of lymph. Strictly speaking, therefore, the difficulty we are
dealing with here shows only the insufficiency of a pure filtration
theory. It seems possible that filtration and diffusion together
would suffice to supply the organs, so far at least as the diffusible
substances are concerned.

2. Heidenhain found that occlusion of the inferior vena cava
causes not only an increase in the flow of lymph — as might be ex-
pected, on the filtration theory, from the consequent rise of pressure
in the capillary regions — but also an increased concentration in the
percentage of protein in the lymph. This latter fact has been
satisfactorily explained by the experiments of Starling.f Accord-

* "Archiv f. die gesammte Physiologic," 49, 209, 1891.
t "Journal of Physiology," 16, 234, 1894.

COMPOSITION AND FORMATION OF LYMPH. 443

ing to this observer, the lymph formed in the liver is normally more
concentrated than that of the rest of the body. The occlusion of
the vena cava causes a marked rise in the capillary pressure in the
liver, and most of the increased lymph-flow under these circum-
stances conies from the liver; hence the greater concentration.
The results of this experiment, therefore, do not antagonize the
filtration-and-diffusion theory.

3. Heidenhain discovered that extracts of various substances,
which he designated as " lymphagogues of the first class," cause a
marked increase in the flow of lymph from the thoracic duct, the
lymph being more concentrated than normal, and the increased flow
continuing for a long period. Nevertheless, these substances cause
little, if any, increase in general arterial pressure; in fact, if injected
in sufficient quantity they produce usually a fall of arterial pressure.
The substances belonging to this class comprise such things as pep-
tone, egg-albumin, extracts of liver and intestine, and especially
extracts of the muscles of crabs, crayfish, mussels, and leeches.
Heidenhain supposed that these extracts contain an organic
substance which acts as a specific stimulus to the endothelial cells
of the capillaries and increases their secretory action. The results
of the action of these substances has been differently explained by
those who are unwilling to believe in the secretion theory. Starling *
finds experimentally that the increased flow of lymph in this case, as
after obstruction of the vena cava, comes mainly from the liver.
There is at the same time in the portal area an increased pressure
that may account in part for the greater flow of lymph; but, since
this effect upon the portal pressure lasts but a short time, while
the greater flow of lymph may continue for one or two, hours, it is
obvious that this factor alone does not suffice to explain the result
of the injections. Starling suggests, therefore, that these extracts
act pathologically upon the blood capillaries, particularly those of
the liver, and render them more permeable, so that a greater
quantity of concentrated lymph flows through them. Starling's
explanation is supported by the experiments of Popoff .f According
to this observer, if the lymph is collected simultaneously from the
lower portion of the thoracic duct, which conveys the lymph from
the abdominal organs, and from the upper part, which contains the
lymph from the head, neck, etc., it is found that injection of
peptone increases the flow only from the abdominal organs. Popoff
finds also that the peptone causes a dilatation in the intestinal
circulation and a marked rise in the portal pressure. At the same
time there is some evidence of injury to the walls of the blood-
vessels from the occurrence of extravasations in the intestine. As

* "Journal of Physiology," 17, 30, 1894.
t "Centralblatt f. Physiologic," 9, No. 2,

1895.

444 BLOOD AND LYMPH.

far, therefore, as the action of the lymphagogues of the first class is
concerned, it may be said that the advocates of the filtration-and-
diffusion theory have suggested a plausible explanation in accord
with their theory. The facts emphasized by Heidenhain with
regard to this class of substances do not compel us to assume a
secretory function for the endothelial cells.

4. Injection of certain crystalline substances — such as sugar,
sodium chlorid, and other neutral salts — causes a marked increase
in the flow of lymph from the thoracic duct. The lymph in these
cases is more dilute than normal, and the blood-plasma also becomes
more watery, thus indicating that the increase in water comes from
the tissues themselves. Heidenhain designated these bodies as
"lymphagogues of the second class." His explanation of their
action is that the crystalloid materials introduced into the blood are
eliminated by the secretory activity of the endothelial cells, and that
they then attract water from the tissue elements, thus augmenting
the flow of lymph. These substances cause but little change in
arterial blood-pressure; hence Heidenhain thought that the greater
flow of lymph can not be explained by an increased filtration.
Starling * has shown, however, that, although these bodies may not
seriously alter general arterial pressure, they may greatly augment
intracapillary pressure, particularly in the abdominal organs. His
explanation of the greater flow of lymph in these cases is as follows :
" On their injection into the blood the osmotic pressure of the circu-
lating fluid is largely increase^. In consequence of this increase
water is attracted from lymph and tissues into the blood by a process
of osmosis, until the osmotic pressure of the circulating fluid is
restored to normal. A condition of hydremic plethora is thereby
produced, attended with a rise of pressure in the capillaries generally,
especially in those of the abdominal viscera. This rise of pressure
will be proportional to the increase in the volume of the blood, and
therefore to the osmotic pressure of the solutions injected. The
rise of capillary pressure causes great increase in the transudation
of fluid from the capillaries, and therefore in the lymph-flow from
the thoracic duct." This explanation is well supported by experi-
ments, and seems to obviate the necessity of assuming a secretory
action on the part of the capillary walls.

5. Numerous other experiments have been devised by Heidenhain
and his followers to show that the physical laws of filtration, diffu-
sion, and osmosis do not suffice to explain the production of lymph ;
but in all cases possible explanations have been suggested in terms
of the physical laws, so that it may be said that the facts do not
compel us to assume a secretory activity on the part of the endo-
thelial cells of the capillaries. In recent years Asherf and his

* Loc. cit. t "Zeitschrift f. Biologie," vols. xxxvi-xl, 1897 to 1900.

COMPOSITION AND FORMATION OF LYMPH. 445

co-workers have brought forward many facts to show that the lymph
is controlled as to its amount by the activity of the tissue elements
and may be considered as a product of the activity of the tissues, as
a secretion, in fact, of the working cells. When the salivary glands,
the liver, etc., are in greater functional activity the flow of lymph
from them is increased beyond doubt, so that the activity of the
organs does influence most markedly the production of lymph.
Most physiologists, however, prefer to explain this relationship on
the view suggested by Koranyi, Starling, and others, — namely, that
in the metabolic changes of functional activity the large molecules
of protein, fat, etc., are broken down to a number of simpler ones,
the number of particles in solution is increased and therefore the
osmotic pressure is increased. By this means it may be supposed
that the flow of lymph toward the tissue elements is increased in
proportion to their activity.

The lymph in the tissue spaces between the cells is subjected
to many influences wrhich, taken together, regulate its amount.
It is continually augmented by a flow of water and dissolved
substances from the blood in the capillaries and from the liquid
in the interior of the cells, and it is continually depleted by
the excess passing off into the -lymphatics, on the one hand,
through which it eventually reaches the blood, and also by direct
absorption into the blood capillaries. In regard to this last factor,
there is abundant evidence that solutions injected into the tissue
spaces so as to increase the amount or concentration of the tissue
liquid are promptly absorbed into the blood. The play of these
opposing forces maintains the tissue lymph within normal limits,
and, although the movement of the water and dissolved sub-
stances can not be shown in all cases to be governed solely by
the physical processes of diffusion, osmosis, and nitration, there
is at present no conclusive evidence that these factors are in-
sufficient to account for the regulation.

Summary of the Factors Controlling the Flow of Lymph. —
We may adopt, provisionally at least, the so-called mechanical theory
of the origin of lymph. Upon this theory the forces in activity are,
first, the intracapillary pressure tending to filter the plasma through
the endothelial cells composing the walls of the capillaries; second,
the force of diffusion depending upon the inequality in chemical
composition of the blood-plasma and the liquid outside the capil-
laries, or, on the other side, between this liquid and the contents of
the tissue elements; third, the force of osmotic pressure. These
three forces acting everywhere control primarily the amount and
composition of the lymph; but still another factor must be con-
sidered ; for when we come to examine the flow of lymph in different
parts of the body striking differences are found. It has been shown,

446 BLOOD AND LYMPH.

for instance, that in the limbs, under normal conditions, the flow is
extremely scanty, while from the liver and the intestinal area it is
relatively abundant. In fact, the lymph of the thoracic duct may
be considered as being derived almost entirely from the latter two
regions. Moreover, the lymph from the liver is characterized by
a greater percentage of proteins. To account for these differences
Starling suggests the plausible explanation of a variation in permea-
bility in the capillary walls. The capillaries seem to have a similar
structure all over the body so far as this is revealed to us by the
microscope, but the fact that the lymph-flow varies so much in
quantity and composition indicates that the similarity is only
superficial, and that in different organs the capillary walls may
have different internal structures, and therefore different permea-
bilities. This factor is evidently one of great importance. The
idea that the permeability of the capillaries may vary under dif-
ferent conditions has long been used in pathology to explain the
production of that excess of lymph which gives rise to the condition
of dropsy or edema. The theories and experiments made in con-
nection with this pathological condition have, in fact, a direct bearing
upon the theories of lymph formation.* Under normal conditions
the lymph is drained off as it is formed, while under pathological
conditions it may accumulate in the tissues owing either to an
excessive formation of lymph or to some interruption in its circu-
lation. From the foregoing considerations it is evident that changes
in capillary pressure, however produced, may alter the flow of
lymph from the blood-vessels to the tissues, by increasing or
decreasing, as the case may be, the amount of filtration ; changes in
the composition of the blood, such as follow periods of digestion,
will cause diffusion and osmotic streams tending to equalize the
composition of blood and lymph; and changes in the tissues them-
selves following upon physiological or pathological activity will
also disturb the equilibrium of composition, and, therefore, set up
diffusion and osmotic currents. In this way a continual interchange
is taking place by means of which the nutrition of the tissues is
effected, each according to its needs. The details of this interchange
must of necessity be very complex when we consider the possibilities
of local effects in different parts of the body. The total effects of
general changes, such as may be produced experimentally, are
simpler, and, as we have seen, are explained satisfactorily by the
physical and chemical factors enumerated.

* Consult Meltzer, "Edema" ("Harrington Lectures"), "American
Medicine," 8, Nos. 1, 2, 4, and 5, 1904.

SECTION V.

PHYSIOLOGY OF THE ORGANS OF CIRCULA-
TION OF THE BLOOD AND LYMPH.

The heart and the blood-vessels form a closed vascular system
containing a certain amount of blood. This blood is kept in endless
circulation mainly by the force of the muscular contractions of the
heart. But the bed through which it flows varies greatly in width
at different parts of the circuit, and the resistance offered to the
moving blood is very much greater in the capillaries than in the
large vessels. It follows from the irregularities in size of the chan-
nels through which it flows that the blood-stream is not uniform in
character throughout the entire circuit; indeed, just the opposite is
true. From point to point in the branching system of vessels the
blood varies in regard to its velocity, its head of pressure, etc.
These variations are connected in part with the fixed structure of the
system and in part are dependent upon the changing properties of
the living matter of which the system is composed. It is con-
venient to consider the subject under three general heads: (1)
The purely physical factors of the circulation, — that is, the me-
chanics and hydrodynamics of the flow of a definite quantity of
blood through a set of fixed tubes of varying caliber under certain
fixed conditions. (2) The general physiology of the heart and the
blood-vessels, — that is, mainly the special properties of the heart
muscle and the plain muscle of the blood-vessels. (3) The innerva-
tion of the heart and the blood-vessels, — that is, the variations in
the circulation produced by the action of the nervous system.

CHAPTER XXV.
THE VELOCITY AND PRESSURE OF THE BLOOD-FLOW.

The Circulation as Seen Under the Microscope.— It is a

comparatively easy matter to arrange a thin membrane in a living
animal so that the flowing blood may be observed with the aid of a
microscope. For such a purpose one generally employs the web
between the toes of a frog, or better still the mesentery, lungs, or

447

448 CIRCULATION OF BLOOD AND LYMPH.

bladder of the same animal. With a good preparation many
important peculiarities in the blood-flow may be observed directly.
If the field is properly chosen one may see at the same time the flow
in arteries, capillaries, and veins. It will be noticed that in the
arteries the flow is very rapid and somewhat intermittent, — that is,
there is a slight acceleration of velocity, a pulse, with each heart
beat. In the capillaries, on the contrary, the flow is relatively very
slow; the change from the rushing arterial stream to the deliber-
ate current in the capillaries takes place, indeed, with some
suddenness. The capillary flow, as a rule, shows no pulses corre-
sponding with the heart beats, but it may be more or less irregular,
— that is, the flow may nearly cease at times in some capillaries,
while again it maintains a constant flow. In the veins the flow
increases markedly in rapidity, and indeed it may be observed
that, the larger the vein, the more rapid is the flow. There is not,
however, as a rule, any indication of an intermittence or pulse in
this flow, — the velocity is entirely uniform. In both arteries and
veins it will be noticed that the red corpuscles form a solid column
or core in the middle of the vessel, and that between them and the
inner wall there is a layer of plasma containing only, under normal
conditions, an occasional leucocyte. The accumulation of cor-
puscles in the middle of the stream makes what is known as the
axial stream, while the clear layer of plasma is designated as the
inert layer. The phenomenon is readily explained by physical
causes. As the blood flows rapidly through the small vessels the
layers nearer the wall are slowed by adhesion, so that the greatest
velocity is attained in the middle or axis of the vessel. The cor-
puscles, being heavier than the plasma, are drawn into this rapid
part of the current. It has been shown by physical experiments
that, when particles of different specific gravities are present in a.
liquid flowing rapidly through tubes, the heavier particles will be
found in the axis and the lighter ones toward the periphery. In
accordance with this fact, leucocytes, which are lighter than the
red corpuscles, may be found in the inert layer. When the con-
ditions become slightly abnormal (incipient inflammation) the
leucocytes increase in number in the inert layer sometimes to a
very great extent, owing apparently to some alteration in the
endothelial walls whereby the leucocytes are rendered more ad-
hesive. The agglutination of the leucocytes and their migration
through the walls into the surrounding tissues are described in
works on Pathology.

The Velocity of the Blood-flow. — The microscopical observa-
tions described above show that the velocity of the blood-current
varies widely, being rapid in the arteries and veins and slow in the
capillaries. To ascertain the actual velocity in the larger vessels

VELOCITY AND PRESSURE OF BLOOD-FLOW.

449

and the variations in vessels of different sizes experimental de-
terminations are necessary. While the general principle involved
in these determinations is simple, their actual execution in an
experiment is attended with
some difficulties, and various
devices have been adopted.
The most direct method .per-
haps is that used in the in-
strument devised by Ludwig, — •
namely, the stromuhr. The prin-
ciple used is to cut an artery
or vein of a known size and de-
termine how much blood flows
out in a given time. We may
define the velocity of the blood
at any point as the length of
the column of blood flowing by
that point in a second. If we
cut the artery there a cylindri-
cal column of blood of a defi-
nite length and with a cross-area
equal to that of the lumen of
the artery will flow out in a
second. The volume of the
outflow can be determined di-
rectly by catching the blood.
Knowing this volume and the
cross-area of the artery, we can
determine the length of the
column — that is, the velocity
of the flow — since in a cylinder
the volume, V, is equal to the
product of the length into the
cross-area.

V = length X cross-area, or
croJarea

We cannot, of course, make
the experiment in this simple
way upon a living animal; the
loss of so much blood would at
once change the physical and physiological conditions of the circula-
tion, and would give us a set of conditions at the end of the experi-

Fig. 177. — Ludwig's stromuhr: a and 6,
The glass bulbs; a is filled with oil to the
mark (5 c.c.), while b and the neck are filled
with salt solution or defibrinated blood; p,
the movable plate by means of which the
bulbs may be turned through 180 degrees,
c, c, for the cannulas inserted into the artery ;
«, the thumb screw for turning the bulbs;
h, the holder. When in place the clamps
on the arteries are removed, blood flows
through c into a, driving out the oil and
forcing the salt solution in b into the head
end of the artery through c'. When the
blood entering a reaches the mark, the bulbs
are turned through 180 degrees so that 6 lies
over c. The blood flows into b and drives
the oil back into a. When it just fills this
bulb, they are again rotated through 180
degrees, and so on. The oil is driven out of
and into a a given number of times, each
movement being equal to an outflow of 5 c.c.
of blood. When the instrument has been
turned, say, ten times, 50 c.c. of blood have
flowed out. Knowing the time and the
caliber of the artery, the calculation is made
as described in the text. A modification of
the form of this instrument has been de-
vised by Tigerstedt.*

29

*"Skandinavisches Archiv f. Physiol.," 3, 152, 1891.

450

CIRCULATION OF BLOOD AND LYMPH.

v

merit different from those at the beginning. By means of the
stromuhr, however, this experiment can be made, with this important
variation, that the blood that flows from the central end of the cut
artery is returned to the peripheral end of the same artery, so that
the circulation is not blocked nor deprived of its normal volume of
liquid. The instrument, as is explained in the legend of Fig. 177,
measures the volume of blood that flows out of the cut end of an
artery in a definite time. The calculation for velocity is made as

follows: Suppose that the capacity
of the bulb is 5 c.c., and that in the
experiment it has been filled 10
times in 50 seconds, — i. e., the bulbs
have been reversed 10 times; then
obviously 10 X 5 or 50 c.c. have
flowed out of the artery in this
time, or 1 c.c. in 1 second. The
diameter of the vessel can be meas-
ured, and if found equal, say, to 2
mms., then its cross-area is Trr2 =
3.15 X 1 = 3.15. Since 1 c.c. equals
1000 c.mm., the length of our cyl-
inder of blood would be given by
the quotient of |^ = 317 mms.
So that the blood in this case was
moving with the velocity of 317
mms. per second. Another instru-
ment that has been employed for
the same purpose is the dromograph
or hemodromograph of Chauveau.
This instrument is represented in
the accompanying figure (Fig. 178).
A rigid tube (p-c) is placed in the
course of the artery to be examined.
This tube is provided with an offset
(a) the opening of which is closed
with rubber dam (m). The rubber
dam is pierced by a needle the lower
end of which terminates in a small

plate lying in the tube (pi}. When the instrument is in place and
the blood is allowed to stream through the tube, it deflects the
needle, which turns on its insertion through the rubber as a ful-
crum. The angle of -deflection of the free end of the needle may
be measured directly upon a scale or it may be transmitted
through tambours and recorded upon a kymographion. The in-
strument must, of course, be graduated by passing through it cur-

Pi

Y

Fig. 178. — Chauveau's hemodromo-
graph (after Langendorff). The tube,
p-c, is placed in the course of an ar-
tery, the blood after removal of clamps
flowing in the direction shown by the
arrow. The current strikes the plate,
pi, and forces it to an angle varying
with the velocity. The movement or
pi is transmitted through the stem, n,
which moves in a rubber membrane
as a fulcrum, m. The angular move-
ment of the projecting end of n may
be measured directly or may be made
to act upon a tambour, as shown in
the figure, and thus be transmitted to
a recording drum.

VELOCITY AND PRESSURE OF BLOOD-FLOW. 451

rents of known velocity, so that the angle of deflection may be
expressed in terms of absolute velocities. It possesses the great
advantage over the stromuhr that it gives not simply the average
velocity during a given time, but also the variations in velocity
coincident with the heart beat or other changes that may occur
during the period of observation.

Efforts have been made to Revise a method for the determination of the
velocity of the blood-flow in the arteries of man. The method used, however,
depends upon certain assumptions that are not entirely certain and the re-
sults obtained, therefore, can not be used with confidence. The principle of
the method consists * in determining the volume of the arm by placing it in
a plethysmograph. Assuming that the outflow from the veins is constant in
the part of the arm inclosed, then the variations in volume of the arm may
be referred to the greater inflow of blood into this part through the arteries.
The curve showing the variations in volume may, therefore, under proper
conditions, be interpreted in terms of velocity changes.

Mean Velocity of the Blood-flow in the Arteries, Veins, and
Capillaries. — Actual determinations of the average velocity in the
large arteries and veins give such results as the following: Carotid
of horse (Volkmann), 300 nuns, per second; (Chauveau) 297 mms.
Carotid of the dog (Vierordt), 260 mms.

The flow in the carotid, as in the other large arteries, is not,
however, uniform; there is a marked acceleration or pulse at each
systole of the heart during which the velocity is greatly augmented.
Thus, in the carotid of the horse it has been shown by the hemo-
dromograph that during the systole the velocity may reach 520
mms. and may fall to 150 mms. during the diastole. It is found, also,
that this difference between the systolic velocity and the diastolic
velocity tends to disappear as the arteries become smaller, and, as
was said above, disappears altogether in the capillaries, in which
the pulse caused by the heart beat is lacking. The smaller the artery,
therefore, the more uniform is the movement of the blood.

The flow in the large veins is approximately equal to that in
arteries of the same size. In the jugular vein of the dog, for
instance, Vierordt found a velocity of 225 mms., while in the
carotid of the same animal the average velocity was 260 mms.
In the capillaries, however, the velocity is relatively very small.
From direct observations made by means of the microscope and
from indirect observations in the case of man the capillary velocity
is estimated as lying between 0.5 mm. and 0.9 mm. per sec.

Vierordt reports some interesting calculations upon the velocity of the
blood, in the capillaries of his own eye. Under suitable conditions,! the
movements of the corpuscles in the retina may be perceived in consequence
of the shadows that they throw upon the rods and cones. The visual images

* Von Kries, "Archiv f. Physiologic," 1887, 279; also Abeles, ibid., 1892,
22.

t "Archiv f. physiologische Heilkunde," 15, 255, 1856.

452

CIRCULATION OF BLOOD AND LYMPH.

thus produced may be projected upon a surface at a known distance from the
eye and the space traversed in a given time may be observed. The distance
actually covered upon the retina may then be calculated by the following con-
struction, in which A-B = the distance traveled by the projected image;
A-n, the distance of the surface from the eye; and a-n, the distance of the
retina from the nodal point
of the eye. We have then
the proportion ab : an ::

AB : An, or ab =

AB

An

According to this method,
Vierordt calculated that the
velocity of the blood in the
human capillaries is equal to
about 0.6 to 0.9 mm. per
second.

In the arteries, more-

•, , , Fig. 179. — Diagram of the eye to show the con-

OVer, It may DC Observed struction used to determine the size of the retinal

ji j X-LXV i •*. image when the size of the external object is known:

that the average Velocity „, The nodal point of the eye. See text.

diminishes the farther

one goes from the heart, — that is, the smaller the artery, — and
reaches its minimum when the arteries pass into the capillaries.
Thus, Volkmann reports for the horse the following figures: Ca-
rotid, 300 mms.; maxillary, 232; metatarsal, 56 mms. In the veins
also the same fact holds. The smaller the vein — that is, the nearer
it is to the capillary region — the smaller is its velocity, the maxi-
mum velocity being found in the vena cava. The general relations
of the velocity of the blood in the arteries, capillaries, and veins

Fig. 180. — Schematic representation of the relative velocities of the blood-current in
different parts of the vascular system: a, The arterial side, indicating the changes with
each heart beat and the fall of mean velocity as the arterial bed widens ; c, the capillary
region — the great diminution in velocity corresponds with the great widening of the bed ;
v, the venous side, showing the gradual increase toward the heart.

may be expressed, therefore, by a curve such as is shown in Fig.
180.

Explanation of the Variations in Velocity. — The general rela-
tionship between the velocities in the different parts of the vascular
system is explained by the difference in the width of the bed in
which the blood flows. In the systemic circulation the main stem,
the aorta, branches into arteries which, taken individually, are smaller

VELOCITY AND PRESSURE OF BLOOD-FLOW. 453

and smaller as we approach the capillaries. But each time that
an artery branches the sum of the areas of the two branches is
greater than that of the main stem. The arterial system may be
compared, in fact, to a tree, the sum of the cross-areas of all the
twigs is greater than that of the main trunk. It follows, there-
fore, that the blood as it passes to the capillaries flows in a bed
or is distributed in a bed which becomes wider and wider, and as it
returns to the heart in the veins it is collected into a bed that be-
comes smaller as we approach the heart. Vierordt estimates that
the combined calibers of all the capillaries in the systemic circula-
tion would make a tube with a cross-area about 800 times as large as
the aorta. If the circulation is proceeding uniformly it follows
that for any given unit of time the same volume of blood must
pass through any given cross-section of the system, — that is, at
a given point in the aorta or vena cava as much blood must flow
by in a second as passes through the capillary region, and that
consequently where the cross-section or bed is widest the velocity
is correspondingly diminished. If the capillary bed is 800 times
that of the aorta, then the velocity in the capillaries is -g^^- of that
in the aorta, — say, -g-J-g- of 320 mms. or 0.4 mm. Just as a stream
of water flowing under a constant head reaches its greatest velocity
where its bed is narrowest and flows more slowly where the bed
widens to the dimensions of a pool or lake.

Variations in Velocity with Changes in the Heart-beat or
the Size of the Vessels. — While the above statement holds true as
an explanation of the general relationship between the velocities in
the arteries, veins, and capillaries at any given moment, the absolute
velocities in the different parts of the system will, of course, vary
whenever any of the conditions acting upon the blood-flow vary.
In the large arteries, as has been said, there are extreme fluctuations
in velocity at each heart beat; but if we consider only the average
velocities it may be said that these will vary throughout the system
with the force and rate of the heart beat, or with the variations in
size of the caliber of the small arteries and the resulting changes in
blood-pressure in the arteries. Marey* gives the two following
laws: (1) Whatever increases or diminishes the force with which
the blood is driven from the heart toward the periphery will cause
the velocity of the blood and the pressure in the arteries to vary in
the same sense. (2) Whatever increases or diminishes the resis-
tance offered to the blood in passing from the arteries (to the veins)
will cause the velocity and the arterial pressure to vary in an inverse
sense as regards each other. That is, an increased resistance
diminishes the velocity in the arteries while increasing the pressure,
and vice versa.

* "La Circulation du Sang," Paris, 1881, p. 321.

454 CIRCULATION OF BLOOD AND LYMPH.

The Time Necessary for a Complete Circulation of the
Blood. — It is a matter of interest in connection with many physio-
logical questions to have an approximate idea of the time necessary
for the blood to make a complete circuit of the vascular system, —
that is, starting from any one point to determine how long it will
take for a particle of blood to arrive again at the same spot. In
considering such a question it must be borne in mind that many
different paths are open to the blood, and that the time for a
complete circulation will vary somewhat with the circuit actually
followed. For example, blood leaving the left ventricle may pass
through the coronary system to the right heart and thence through
the pulmonary system to the left heart again, or it may pass to the
extremities of the toes before getting to the right heart, or it may pass
through the intestines, in which case it will have to traverse three
capillary areas before completing the circuit. It is obvious, there-
fore, that any figures obtained can only be regarded as averages
more or less exact. The experiments that have been made, however,
are valuable in indicating how very rapidly any substance that
enters the blood may be distributed over the body. The method
first employed by Hering (1829) was to inject into the jugular vein
of one side a solution of potassium ferrocyanid, and then from time
to time specimens of blood were taken from the jugular vein of the
opposite side. The first specimen in which the ferrocyanid could be
detected by its reaction with iron salts gave the least time necessary
for a complete circuit. The method was subsequently improved in
its technical details by Vierordt, and such results as the following
were obtained: Dog, 16.32 seconds; horse, 28.8 seconds; rabbit, 7.46
seconds ; man (calculated), 23 seconds. The time required is less in
the small than in the large animals, and Hering and Vierordt con-
cluded that in general it requires from 26 to 28 beats of the heart to
effect a complete circulation. Stewart has devised a simpler and
better method,* based upon the electrical conductivity of the blood.
If a solution of a neutral salt, such as sodium chlorid, more concen-
trated than the blood, is injected into the circulation, the con-
ductivity of the blood is increased. If the injection is made at a
given moment and a portion of the vessel to be examined is properly
connected with a galvanometer so as to measure the electrical
conductivity through it, then the instant that the solution of salt
reaches this latter vessel the fact will be indicated by a deflection
of the galvanometer. Using this method, Stewart was able to
show that in the lesser circulation (the pulmonary circuit) the
velocity is very great compared with that of the systemic circulation
• — only about one-fifth of the time required for a complete circuit is
spent in the lesser circulation. Attention may also be called to
* "Journal of Physiology," 15, 1, 1894.

VELOCITY AND PRESSURE OF BLOOD-FLOW. 455

the fact that the important part of the circulation, as regards the
nutritive activity of the blood, is the capillary path. It is while
flowing through the capillaries that the chief exchange of gases
and food material takes place. The average length of a capillary
is estimated at 0.5 mm.; so that with a velocity of 0.5 mm. per
second the average duration of the flow of any particle of blood
through the capillary area is only about 1 sec.

The Pressure Relations in the Vascular System. — That the
blood is under different pressures in the several parts of the vascu-
lar system has long been known and is easily demonstrated. When
an artery is cut the blood flows out in a forcible stream and with
spurts corresponding to the heart beats. When a large vein is
wounded, on the contrary, although the blood flows out rapidly,
the stream has little force. Exact measurements of the hydrostatic
pressure under which the blood exists in the large arteries and veins
were first published by Rev. Dr. Stephen Hales, an English clergy-
man, in his famous book entitled "Statical Essays, containing
Haemostaticks," 1733.* This observer measured the static pressure
of the blood in the arteries and veins by the simplest direct method
possible. After tying the femoral artery in a horse he connected
it to a glass tube 9 feet in length. On opening the vessel the blood
mounted in the tube to a height of 8 feet 3 inches, showing that
normally in the closed artery the blood is under a tension or pressure
sufficient to support the weight of a column of blood of this height.
A similar experiment made upon the vein showed a rise of only 12
inches.

Methods of Recording Blood-pressure. — Since Hales's work
the chief improvements in method which have marked and caused
the development of this part of the subject have been the application
of the mercury manometer by Poiseuillef (1828), the invention of
the recording manometer and kymographion by LudwigJ (1847),
and the later numerous improvements by many physiologists, and
latterly the development of methods for measuring blood-pressures
directly in man. The Hales method of measuring arterial pressure
directly in terms of a column of blood is inconvenient on account
of the great height, large fluctuations, and rapid clotting. The
two former disadvantages are overcome by using a column of mer-
cury. Since this metal is 13.5 times as heavy as blood, the column
which will be supported by the blood will be correspondingly shorter
and all the fluctuations will be similarly reduced. Poiseuille
placed the mercury in a U tube of the general form shown in Fig.
181, M. One leg was connected with the interior of an artery by

456

CIRCULATION OF BLOOD AND LYMPH.

appropriate tubing filled with liquid and when the clamp was
removed from the vessel its pressure displaced the mercury in the
limbs by a certain amount. The difference in height between the
levels of the mercury in the two limbs in each experiment gives the
blood pressure, which is therefore usually expressed as being equal
to so many millimeters of mercury. By this expression it is meant
that the pressure within the artery is able to support a column

Fig. 181. — A, Schema to show the recording mercury manometer and its connection
with the artery: M, The manometer with the position of the mercury represented in black
(the pressure is given by the distance in millimeters between the levels 1 and 2 ; one-half of
this distance is recorded on the kymographion by the pen, P) ; F, the float resting upon the
surface of the mercury; G, the cap through which the stem carrying the pen moves; E, offset
for driving air out of the manometer and for filling or washing out the tube to the artery ;
R, the receptacle containing the solution of sodium carbonate; c. the cannula for insertion
into the artery; w, the washout arrangement shown in detail in B.

B, The washout cannula : c, the glass cannula inserted into the artery ; r, the stem
connected with the reservoir of carbonate solution; o, the stem connected with the manom-
eter. The arrows show the current of carbonate solution during the process of washing
out, the artery at that time being closed by a clamp.

of mercury that many millimeters in height, and by multiplying
this value by 13.5 the pressure can be obtained, when desirable,
in terms of a column of blood or water. For continuous obser-
vations and permanent records the height of the column of mercury
and its variations during an experiment are recorded by the device
represented in Fig. 181.

The distal limb of the U tube in which the mercury rises carries afloat
of hard rubber, aluminum, or some other substance lighter than the mercury.

VELOCITY AND PRESSURE OF BLOOD-FLOW. 457

The float in turn bears an upright steel wire which at the end of the glass tube
plays through a small opening in a metal or glass cap. At its free end it bears
a pen to trace the record. If smoked paper is used the pen is simply a smooth-
pointed glass or metal arm, while if white paper is employed the wire carries
a small glass pen with a capillary tube, which writes the record in ink. The
tube connecting the proximal end of the manometer to the artery of the ani-
mal must be filled with a solution that retards the coagulation of blood. For
this purpose one employs ordinarily a saturated solution of sodium carbonate
and bicarbonate. This tube is connected also by a T piece to a reservoir con-
taining the carbonate solution, and by varying the height of this latter the
pressure in the tube and the mafnometer may be adjusted beforehand to the

g-essure that is supposed or known to exist in the artery under experiment,
y this means the blood, when connections are made with the .manometer,
does not penetrate far into the tube, and clotting is thereby delayed. In
long observations it is most convenient to use what is known as a washout
cannula, — the structure of which is represented in Fig. 181, B. When this
instrument is attached to the cannula inserted into the blood-vessel one can,
after first clamping off the artery, wash out the connections between the artery
and the manometer with fresh carbonate solution as often as desired. By
such means continuous records of arterial pressure may be obtained during
many hours. Determinations of the pressure in the veins may be made with a
similar apparatus, but owing to the low values that prevail on this side of
the circulation it is more convenient to use some form of water manometer
and thus record the venous pressures in terms of the height of the water column-
supported. It should be added also that when it is necessary to know the
pressure in any special artery or vein the connections of the manometer are
made usually to a side branch opening more or less at right angles into the
vessel under investigation, or if this is not possible then a T tube is inserted
and the manometer is connected with the side branch. The reason for this
procedure is that if the artery ifsell is ligated and the manometer is con-
nected with its central stump, the flow in it and its dependent system of capil-
laries and veins is cut off; the stump of the artery constitutes simply a con-
tinuation of the tube from the manometer and serves as a side connection
to the intact artery from which it arises. Thus, when a manometer is inserted
into the carotid artery the pressure that is measured is the side-pressure in
the innominate or aorta from which it arises, while a cannula in the central
stump of a femoral artery measures the pressure in the iliac. A specimen of
what is known as a blood-pressure record is shown in Fig. 182. The exact
pressure at any instant, in millimeters of mercury, is obtained by measuring
the distance between the base line and the record and multiplying by 2.
The base line represents the position of the recording pen when it is at ita
zero position for the conditions of the experiment. It is necessary to mul-
tiply the distance between the base line and the record by 2 because, as
is seen in Fig. 181, the recording apparatus measures only the rise of the
mercury in one limb of the manometer; there is, of course, an equal fall in the
other limb.

The blood-pressure record (Fig. 182) shows usually large rhyth-
mical variations corresponding to the respiratory movements and in
addition smaller waves caused by the heart beat. The causes of the
respiratory waves of pressure are discussed in the section on respi-
ration. Regarding the heart waves or pulse waves the usual record
obtained by means of a mercury manometer gives an entirely false
picture of the extent of the variations in pressure caused by the heart
beat. The mass of mercury possesses considerable weight and iner-
tia, which unfits it for following accurately very rapid changes in
pressure. When the pressure changes are slow, as in the case of
the long, respiratory waves seen in the record, the manometer un-

458 CIRCULATION OF BLOOD AND LYMPH.

doubtedly indicates their extent with entire accuracy. But when
these changes are very rapid, as in the beat of a dog's or rabbit's
heart, the mercury does not register either extreme in the variation,
but tends to record the mean or average pressure. The full extent
of the variations in arterial pressure caused by the heart beat can be

Fig. 182. — Typical blood pressure record with mercury manometer: Bp, The record
showing the heart beats and the larger curves due to the respirations (respiratory waves
of blbod-pressure) and still longer waves due to vasomotor changes; T, the time line, giving
the time in seconds. The actual arterial pressure at any moment is the distance from the
base line — that is, the line of zero pressure — to the blood-pressure line, multiplied by two.
These values are indicated in the vertical line drawn to the right, which shows that the
average pressure at the time of the experiment was 100 mms. Hg. The small size of the
variations in pressure due to each heart beat is altogether a false picture due to the inertia
of the mercury, its inability to follow completely the quick change. Each heart beat,
instead of being smaller, should be larger than the respiratory waves.

determined by other means (see below), and, if the knowledge thus
obtained is applied to the correction of the record of the mercury
manometer, the tracing given in Fig. 182 should have, so far as the
heart beats are concerned, somewhat the appearance shown in Fig.
183. This latter figure gives a more accurate mental picture of
the actual conditions of pressure in the large arteries, as influenced by

VELOCITY AND PRESSURE OF BLOOD-FLOW. 459

the heart beat. These arteries are, in fact, subject to very rapid and
very extensive changes in pressure at each beat of the heart, and
these changes are naturally more pronounced when the force of the
heart beat is increased, — for instance, by muscular exercise.

Systolic, Diastolic, and Mean Arterial Pressure. — As stated
in the last paragraph, the arterial pressure in the larger arteries
undergoes extensive variations with each heart beat. The maxi-
mum pressure caused by the systole of the heart, the apex of the
pulse wave, is spoken of as systolic pressure; the minimum pressure
in the artery — that is, the pressure at the end of the diastole of the
heart, or the bottom of the pulse-wave, is known as the diastolic
pressure. In a dog under ordinary conditions of experimentation
the systolic (lateral) pressure in the aorta may be as much as 168
nuns., while the diastolic pressure is only 100 mms. In man the

or meyumum-

1 10 mm.

A A

or

£ase line

SOJnm.

Fig. 183. — Schematic representation of the pressure change caused by each heart
beat. The schema represents three heart beats supposed to be recorded on a rapidly moving
surface by a manometer delicate enough to follow the pressure changes accurately. The
top of the pulse wave measures the systolic pressure; the bottom the diastolic pressure.

systolic pressure as measured in the brachial artery may be taken
in round numbers as equal to 110 mms., while the diastolic pressure
is only 65 mms. The difference between the systolic and the
diastolic pressure has been designated conveniently as the pulse
pressure. It measures, of course, the variation in pressure in any
given artery caused by the heart beat, and so far as that artery is
concerned it gives the force of the heart beat except for the small
component used to accelerate the movement of the blood. From
the figures given above it will be seen that the pulse pressure in
the brachial artery of man averages 45 mms. Hg. Each systole
of the heart distends this artery, therefore, by a sudden increase
in pressure equal to the weight of a column of mercury 45 mms.
high. As we go outward in the arterial tree the pulse pressure
becomes less and less, the oscillations in pressure with each heart
beat are less marked, until finally in the smallest arteries and

460

CIRCULATION OF BLOOD AND LYMPH.

capillaries and in the veins there is no pulse wave, and no difference
between systolic and diastolic pressure. In speaking of the pressure
in the blood-vessels we refer usually to what is called the mean
pressure. It is obvious that, so far as the larger arteries are con-
cerned, the mean pressure is only a convenient expression for the
average pressure during a certain period. If, by the methods
described below, we determine the systolic and diastolic pressures
in the artery of a man, and assume that there has been no general
variation between the two observations, we can estimate the mean
pressure with approximate accuracy by taking the arithmetical
mean of the two figures.

The arithmetical mean of systolic and diastolic pressures during any given
heart-beat does not give the true mean pressure, owing to the form of the
pulse wave (see Fig. 202). If the rise from diastolic to systolic pressure and
the succeeding fall took place uniformly, so that the pulse curve constituted

Fig. 184. — Schema to indicate the general relations of systolic, mean, and diastolic
pressures throughout the arterial system: «, Systolic; m, mean; d, diastolic; c, pressure
at beginning of the capillaries. The distance from « to d represents the pulse pressure at
different parts of the arterial system.

a true triangle, the true mean pressure would be given by the arithmetical
mean of the two pressures. As a matter of fact, the descending limb
of the pulse curve is not a straight but a curved line, and it is broken,
moreover, by secondary waves. The position of the mean pressure during
any given heart-beat will vary, therefore, with the form of the pulse curve.
Generally speaking, it lies nearer to the diastolic than to the systolic level.*

In physiological observations, as a rule, no attempt is made to
estimate the mean pressure for any given time with mathematical
accuracy. In the ordinaiy tracing as given by the mercury man-
ometer (Fig. 182) the mean pressure for any given period during
which the variations have been symmetrical and not extreme is
estimated as the arithmetical mean of the highest and lowest
points reached. When desirable, the mean pressure may be
recorded by introducing a resistance (narrowing the tube by means
of a stopcock) between the artery and the manometer. The latter
* See Dawson, " British Medical Journal," 1906, 996.

VELOCITY AND PRESSURE OF BLOOD-FLOW.

461

will then record mean pressure and show no variations with the
heart beat. A general idea of the variations in systolic, diastolic,
and mean pressures, throughout the arterial system, may be ob-
tained from the schema given in Fig. 184.

Method of Measuring Systolic and Diastolic Pressure in
Animals. — In animals a manometer may be connected directly
with the artery and systolic and diastolic pressures may be obtained
in one of two general ways: (1) By using some form of pressure
recorder or manometer sufficiently mobile to follow very quick
changes of pressure. (2) By using a mercuiy manometer pro-
vided with maximum and minimum valves. Of the manometers
that have been divised to register accurately the quick changes in
pressure due to the heart beat, the two that are most frequently

Fig. 185. — The spring manometer of Fick (after Langendorff) : f, The flat metal
tube filled with liquid; r, the lead tube connecting with the artery; h, h, h, the lever
mechanism of light wood communicating the movements of / to the writing point, s; p, a
small disc immersed in a vessel of oil to still further dampen the inertia swings.

referred to in physiological literature are the spring manometer of
Tick* and the membrane manometer of Hiirthle.t

The Fick manometer is shown in Fig. 185. It consists of a flat, hollow
metallic spring bent into the form of a C. The interior is filled with liquid
and is connected by rigid tubing also filled with liquid, with the interior of
the artery. The variations of pressure in the artery are transmitted to the
interior of the spring and tend to straighten it, thus causing corresponding
movements of the free end. Before or after using this instrument it mnst be
calibrated, — that is, the variations in movement must be given absolute values
in terms of millimeters of mercury by ascertaining directly the extent of move-
ment caused by known pressures. The Hurthle manometer is more frequently
used at present. The principle made use of in this instrument is illustrated
by the diagram in Fig. 186. The instrument consists essentially of a small
box or tambour of very limited capacity; the top of the tambour is covered

* Fick, "Archiv f. Physiologic/' 1864, p. 583.

t "Archiv f. d. gesammte Physiologic," 49, 45, 1891.

462

CIRCULATION OF BLOOD AND LYMPH.

Fig. 186. — Diagram showing construction of Hurthle's manometer. — (After Curtis.)
The interior 9f the heart or the artery is connected by rigid tubing to a very small tambour,
T. The tubing and the tambour are filled with liquid. The movements of the rubber dam
covering the tambour are greatly magnified by a compound lever, S. The tendency of this
lever to "fling" may be prevented by an arrangement not shown in the diagram. The
essential principles of the recorder are, first, liquid conduction from heart to tambour;
second, a very small tambour and membrane so that a minimal volume of liquid escapes
from the heart into the tambour.

To the artery-

Fig. 187. — Schema to illustrate the use of valves in determining maximum (systolic)
and minimum (diastolic) blood-pressure. When stopcock a is open the heart beats are
transmitted through the maximum valve and the mercury in the manometer is prevented
from falling between beats. The manometer will record the highest pressure reached during
the period of observation. The reverse occurs when valve 6 alone is open.

VELOCITY AND PRESSURE OF BLOOD-FLOW.

463

with thin rubber dam and the cavity is filled with liquid and connected by
rigid tubing, also filled with liquid, with the interior of the artery or heart.
Variations in pressure in the artery are transmitted through the column of
liquid to the rubber membrane of the tambour, and the movements of this
latter are greatly magnified by a sensitive lever attached to it. The liquid
conduction and the small size of the tambour, which prevents any notice-
able outflow of liquid, combine to give a sensitive and very prompt record of
pressure changes. It is also necessary to calibrate this instrument whenever
used in order to give absolute values to the records obtained. A specimen
of a blood-pressure record obtained with this instrument is shown in Fig. 188.
It will be noticed that the size of the heart beat, relative to the distance from
the base line is much greater than in the record obtained with the mercury
manometer, Fig. 182.

Fig. 188. — Blood-pressure record from a dog with a Hiirthle manometer. The size-
of the heart beats is relatively much greater than with a mercury manometer. In this case
the systolic pressure is about 150 mms. Hg; the diastolic, 100 mms. ; and the heart beat or
pulse pressure, 50 mms.

The method that depends upon the use of maximum and minimum valves
may be understood by reference to Fig. 187. On the path between the artery
and the manometer one may place a maximum and a minimum valve so ar-
ranged that the blood-pressure and heart beat may be transmitted through
either valve. As is shown by the figure, if the connection is maintained
through the maximum valve for a certain time the highest pressure reached
during that period will be recorded, while, when the minimum valve is used
the lowest pressure reached will be indicated.

Such valves, of course, act slowly and can not be used to determine the
maximum and minimum pressure in the artery during a single heart beat;
they record the highest and lowest point reached during a certain given
interval.

Actual Data as to the Mean Pressure in Arteries, Veins,
and Capillaries. — The mean value of the pressure in the aorta
has been determined for many mammals. It is found that the actual
figures vary with the conditions under which the results have been
obtained. Such values as the following may be quoted:*

Horse 321 mms. to 150 mms. Hg.

Dog 172

Sheep 206

Cat 150

Rabbit 108

Man (probable, Tigerstedt) 150

104
156

90

*See Volkmann, "Die Haemodynamik," 1850.

464

CIRCULATION OF BLOOD AND LYMPH.

It appears from these figures that there is no proportion between
the size of an animal and the amount of mean arterial pressure. It
is probable that there may be a general relationship between the
size of the animal — that is, the size of the heart — and the amount

C-M

ISO

I'm

LOO

JVL

Fig. 189. — Curve showing the results of actual measurement of systolic, diastolic, and
mean pressure (lateral pressures) along the a9rta and femoral of the dog. The branches
through which the lateral pressures were obtained are indicated as follows: Sb, Left sub-
clavian; C-M, celiac and superior mesenteric; R, left renal; F, left femoral (Ellenberger
and Baum), external iliac; P, profunda branch of femoral; S, saphena. The pressure in
millimeters is given along the ordinates to the left. It will be noted that the mean and
the diastolic pressures remain practically the same throughout the descending aorta and
in-to the femoral. The systolic pressure shows a marked increase at the lower end of
the aorta and then falls off rapidly. The pulse pressure at the inferior end of the descend-
ing aorta is much larger than at the arch. — (Dawson.)

of pulse pressure or the oscillation of pressure with each heart beat,
but sufficient data are not at hand to determine this point. As
we pass from the aorta to the smaller arteries the mean pressure
decreases somewhat, although not very rapidly, while the pulse
pressure decreases also and to a more noticeable extent.

VELOCITY AND PRESSURE OF BLOOD-FLOW. 465

This fact is illustrated in Fig. 189, which gives a graphic repre-
sentation of a number of experimental determinations * of systolic
and diastolic pressures in the large arteries of the dog.

If we turn to the other end of the vascular system, the veins,
we find that the lowest pressure is in the jugular and that it increases
gradually as we go toward the capillary area. According to one
observer,! the fall in pressure from periphery toward the heart is
at the rate of 1 mm. Hg fof every 35 mms. of distance. We have
such figures as the following:

DOG. SHEEP.

Superior vena cava Jugular vein 0.2 mm. Hg.

(near auricle) = — 2.96 mms. Hg. Facial vein 3.0 mms. "

Superior vena cava Branch of brachial 9.0 '

more distal = —1.38 " " Crural 11.4 "

External jugular (left) == 0.52 mm.

Right brachial = 3.90 mms. "

Left facial = 5.12 "

Fig. 190. — Schematic representation of the general relations of blood-pressure (side
pressure) in different parts of the vascular system : a, The arteries ; c, the capillaries ; v,
the veins. The mean and diastolic pressures remain nearly constant in the arterial system ,
as far as they can be measured accurately.

At the heart, therefore, the pressure of the blood upon the walls
of the veins is nearly nil, and, indeed, owing to the circumstance
that the large veins lie in the thoracic cavity, in which the pressure
is below that of the atmosphere, the tension of the blood in them
may be slightly negative. To complete the general conception of
the pressure relations in the vascular system it is necessary to know
the pressure of the blood in the smallest arteries and veins and in the
capillaries. It is not possible — in the case of the capillaries, for
instance — to connect a manometer directly with the vessels, and
recourse has been had to a less direct and certain method. The
capillary pressure in different regions of the skin has been estimated
by determining the pressure necessary to obliterate them — that
is, to blanch the skin. A glass plate is laid upon the skin or
mucous membrane and weights are added until a distinct change

* Dawson, "American Journal of Physiology," 15, 244, 1906.
f Burton-Opitz, "American Journal of Physiology," 9, 198, 1903.
30

466 CIRCULATION OF BLOOD AND LYMPH.

in the color of the skin is noted.* Knowing the necessary weight to
produce this effect and the area submitted to compression, the
pressure may be expressed in terms of millimeters of mercury or
blood.

The following example may be used to illustrate this method: Suppose
that the glass plate has an area of 4 sq.mms., and that to blanch the skin under
it a weight of 1 gm. is necessary; 1 gm. of water = 1 c.c. or 1000 c mms.
Therefore to blanch this area would require a column of water contain-
ing 1000 c.mms. with a cross-area of 4 sq.mms. The height of this column
would therefore be equal to J--0^ or 250 mms. of water, — that is, 18.5 mms.
Hg.

The results obtained by this method are not very constant and
can only be considered as approximate. It would appear, how-
ever, that the pressure lies somewhere between 20 and 40 mms.
of mercury. Thus, upon the gums of a rabbit von Kries found a
capillary pressure of 33 mms. Hg.

The general relations of the pressures in arteries, veins, and
capillaries may be expressed in a curve such as is shown in Fig.
190.

The Method of Determining Blood-pressure in the Large
Arteries of Man. — It is a matter of interest and practical impor-
tance to ascertain even approximately the arterial pressure in man
and its variations in health and disease. The first practical method
for determining this point upon man was suggested by von Basch
(1887), who devised an instrument for this purpose, the sphygmo-
manometer. Since that time a number of different instruments
have been described, but attention may be called to two only, which
are among the most recent and convenient. In the first place, it
must be clearly recognized that the arterial pressure in the large
arteries of man shows marked variations with the heart beat; the
pressure during the beat of the heart rises suddenly to a much higher
level than during the diastole. The relation of the systolic (or
maximum) and diastolic (or minimum) pressures is indicated by the
diagram in Fig. 184. The instruments that have been invented for
determining human blood-pressure are in reality adapted, more or
less accurately, to determine one or the other or both of these pres-
sures. No instrument has been devised for determining the mean
pressure, and, indeed, from a physiological standpoint such an
instrument would not be so valuable as one that gives us the
figures corresponding to the systolic and the diastolic pressures
and thus allows us to calculate an approximate mean. For it is
evident that in the latter case we should be in possession of more
data with which to analyze the causes for any given variation in
pressure. The principle of determining the systolic pressure alone

* V. Kries, "Berechte d. Sachs. Gesellschaft d. Wiss. Math.-phys. Classe,"
1875, p. 148.

VELOCITY AND PRESSURE OF BLOOD-FLOW. 467

is very simple: it consists in determining the amount of pressure
necessary to completely obliterate the artery, — that is, to prevent
a pulse from passing through the region under compression. This
principle was used originally by von Basch, but its application has
been made perhaps most' successfully in the simple apparatus
suggested by Riva-Rocci, which is adapted especially for measure-
ments of pressure in the brachial artery. One form of this instru-
ment is represented in Fig. 191.

Fig. 191 —Figure of the Riva-Rocci apparatus (Sahlf) : a, The leather collar with
inside rubber bag to go on the arm ; c, the bulb for blowing up the rubber bag and thus
compressing the artery; d, the manometer dipping into the reservoir of mercury, 6, to meas-
sure the amount of pressure.

The leather or canvas band, a, is buckled snugly around the arm. On
the inner surface of this band there is a rubber bag which communicates with
the mercury manometer, d, and the pressure bulb, c. When the band is in
place rhythmical compressions of c will force air into the rubber bag surround-
ing the arm. This bag is blown up and exerts pressure upon the arm and
through the arm tissue upon the brachial artery. The amount of pressure
that is being exerted upon the arm is indicated at any moment by the mer-

Fig. 192. — Schema to illustrate the fact that when the pressure upon the outside of the
artery is equal to the diastolic pressure the pulse wave will cause a maximal expansion of
the artery : a represents the normal artery distended by diastolic blood-pressure ; the dotted
lines indicate the additional expansion caused by the pulse wave; b represents the artery
when compressed by an outside pressure equal to the diastolic pressure within; the artery
then takes the size of an empty artery kept patent by the rigidity of its walls. The pulse
wave, on reaching this section, finds a relaxed wall and causes, therefore, a maximum
extension.

cury manometer. The moment of obliteration of the artery is determined
by feeling (or recording) the pulse in the radial artery. The moment that
this pulse disappears, as the pressure upon the brachial is raised, indicates the
maximum or systolic pressure in the brachial artery. As the pressure is low-

468 CIRCULATION OF BLOOD AND LYMPH.

ered again the pulse reappears. Among other sources of error involved in
this method it is to be remembered that the tactile sensibility is not sufficiently
delicate to detect a minimal pulse in the artery. Other methods of determin-
ing the systolic pressure (see below) indicate, as a matter of fact, that the
pulse continues some time after an individual of average tactile sensibility is
unable to detect it. .

To determine the diastolic pressure is more difficult and requires some-
what more apparatus. The principle employed was first suggested by Marey
and first practically applied by Mosso.* The method consists in recording
by some means the pulsations of the artery under different pressures and de-
termining under what pressure the maximal pulsations are given. This pres-
sure should be equal to the diastolic pressure within the artery. The prin-
ciple involved may be illustrated by the accompanying figure (Fig. 192).

Let a represent a longitudinal section of an artery distended by normal
diastolic arterial pressure. At each heart beat the force of the pulse will dis-
tend the artery still more, as represented by the dotted lines, and this in-
crease in size may be measured by proper transmitting apparatus. If now
pressure is brought to bear upon the outside of the artery its lumen
will be diminished as the outside pressure is increased, and when this pres-
sure is equal to the diastolic blood-pressure within the artery one will neu-
tralize the other, and the diameter of the artery will be equal to that assumed
when the vessel contains blood under no pressure and is kept patent only by
the stiffness of its walls (6). Under this condition the pulse wave when it
traverses this portion of the vessel finds its walls completely relaxed, as it
were, and the force of the heart wave will consequently cause a greater dis-
tension of the arterial walls and a larger pulse wave in the recording ap-
paratus. If the outside pressure is increased beyond the amount of diastolic
pressure it will not only neutralize this latter, but will tend to overcome the
stiffness of the arterial wall. When the pulse wave passes through this stretch
it will be forced not only to distend the walls, but also to overcome the excess

Fig. 193. — Record (Erlanger) to show the maximum size of the recorded pulse
wave when the outside or extravascular pressure is equal to the internal diastolic pressure.
The artery is compressed first with a pressure above systolic, sufficient to obliterate the
lumen. As this pressure is lowered in steps of 5 mms. the recorded pulse wave increases in
size to a maximum and then again becomes smaller. The outside pressure with which the
maximum pulse is obtained measures the amount of the internal diastolic pressure (Marey's
principle) .

of pressure on the outside. The movement of the walls with the pulse wave
will be less extensive in proportion to the excess of pressure on the outside.
If, therefore, one starts with an outside pressure sufficient to obliterate the
artery completely the recorded pulse wave will be small. As this pressure
is diminished, the pulse waves become larger up to a certain point and then
decrease again in size (see Fig. 193). The outside pressure at which this
maximum pulse is obtained measures, according to the principle stated above,
the diastolic pressure within the artery. That the principle is correct has
been shown by direct experiments upon the exposed artery of a dog, in which
the pressure was measured by the method outlined above and also directly

* "Archives italiennes de biologic," 23, 177, 1895.

VELOCITY AND PRESSURE OF BLOOD-FLOW.

469

by a manometer connected with the interior of the artery.* In such experi-
ments upon man, however, one condition is present which detracts from the
absolute value of the results obtained, although, since it is substantially
a constant factor, it does not seriously interfere with relative results, that
is, with observations upon the variations of pressure under different condi-
tions. This source of error lies in the fact that in the living person the out-
side pressure can not be applied directly to the arteries, but only indirectly
through the intervening tissues. These tissues interpose a certain resistance
to the pressure exerted from without, and some of this pressure must be spent

Fig. 194. — Schema showing the construction of the Erlanger apparatus: a, Rubber
bag of the arm piece ; c, bulb for blowing up this bag and putting pressure on the arm ; 6,
the manometer for measuring the pressure ; i, two-way stopcock (when turned so as to
communicate with the capillary opening, k, it allows the pressure in a to fall slowly); e,
a rubber bag in a glass chamber, /; e communicates with a when stopcock d is open and
the pulse waves from a are transmitted to e; the pulsations of e in turn are transmitted
to the delicate tambour, h, and are thus recorded.

in overcoming this resistance. The amount of the resistance offered by the
tissues has been estimated differently by various authors, but probably lies
between 6 and 10 mms. of mercury, — that is, the pressure as measured exceeds
the real diastolic pressure by this amount. Several instruments have been
devised, according to this principle, to measure diastolic pressures, but the
sphygmomano meter described by Erlanger f is probably the most complete
and the most convenient for actual use. This instrument is illustrated in
Figs. 194 and 195.

It may be used to determine both systolic and diastolic pressures.

The way in which the apparatus is used may be understood from the sche-
matic Fig. 194. a is the rubber bag which is buckled upon the arm by a leather
strap. This bag communicates with the mercury manometer, b, with a pres-
sure bag, c, through the two-way stopcock, i, and through the stopcock d with
a rubber bag, e, contained in a glass chamber, /. This glass chamber com-
municates above with a sensitive tambour, h, and by means of the stopcock
g can be placed in communication with the outside air. The systolic pressure
may be determined in two ways: By one method only the mercury manom-

* Howell and Brush. " Proceedings of the Massachusetts Medical Society,"
1901.

t" American Journal of Physiology," "Proceedings of the American
Physiological Society," 6, xxii., 1902; and "Johns Hopkins Hospital Reports,"
12, 53, 1904.

470

CIRCULATION OF BLOOD AND LYMPH.

eter is necessary, the instrument corresponding with the Riva-Rocci appa-
ratus described above. By means of the pressure bag, c, the bag, a, upon the
arm is blown up until the pressure is above the systolic pressure and the radial
pulse below disappears. By turning stopcock i properly the system is allowed
to communicate with the air through a capillary opening, k. Consequently
the pressure upon the artery in the arm falls slowly, and by palpating the
radial artery one can determine the pressure, as measured by the mercury
manometer, at which the pulse just gets through. This pressure will measure
approximately the systolic pressure. The second method gives higher and
doubtless more accurate results. In this method the pressure is at first raised
above systolic pressure with stopcocks d and g open, a, e, and b are under

Fig. 195. — Erlanger apparatus. The collar for the arm is not shown. The parts may be
understood by reference to the schema given in Fig. 194.

the same pressure. If stopcock g is now turned off, the pulsations in a are
transmitted to e and through it to the tambour, h, and the lever of the tam-
bour writes these pulsations on a kymographion. It should be explained that
pulsations are obtained even when the pressure on the arm is much more than
sufficient to completely obliterate the brachial artery. The reason for this
is that the pulsations of the central stump of the closed artery will be communi-
cated to bag a. When the pressure is suprasystolic these pulsations are small.
If now the pressure in the system is diminished slowly by turning stopcock i
so as to communicate with the capillary opening, k, it will be found that at
a certain point the pulsations suddenly increase in height. This point marks

VELOCITY AND PRESSURE OF BLOOD-FLOW. 471

the moment when the pulse wave is first able to break through the brachial
artery, and it gives, therefore, the systolic pressure. After finding the sys-
tolic pressure the diastolic pressure is obtained by allowing the pressure to
drop still further. The pulsations increase in height to a maximum size and
then decrease. The pressure at which the maximum pulse wave is obtained
marks the diastolic pressure. It is better perhaps in dropping the pressure
for this last purpose to manipulate stopcock i so as to drop the pressure 5
mms. at a time, recording the pulse wave at each pressure. In this way a
record is obtained such as is given in Fig. 193. It should be added, also, that
in order to keep the lever of the tambour horizontal while the pressure in the
system is being lowered there i» a minute pinhole in the metal bottom of the
tambour. Through this pinhole the pressure in the tambour and chamber,
/, is kept atmospheric throughout, except during the quick changes caused
by the pulse waves. By means of this instrument one can determine within
a minute or so the amount of the systolic and diastolic pressure in the brachial
artery, and also, of course, the difference between the two, the pulse pressure,
which may be taken as a measure of the force of the heart beat.

The Normal Pressure in Man and its Variations. — By means
of one or other of the instruments devised for the purpose numerous
results have been obtained regarding the blood-pressure in man at
different ages and under varying normal and abnormal conditions.
Unfortunately the methods used have not always been complete.
Some authors give only systolic pressures, for example. In such ex-
periments also a troublesome factor is always the psychical element.
The mental interest that the individual experimented upon takes in
the procedure almost always causes a rise of pressure and perhaps
a changed heart rate. Results, as a rule, upon any individual show
lower values after the novelty of the procedure has worn off and
the patient submits to the process as an uninteresting routine.
Under normal conditions Potain * estimated the systolic pressure in
the radial of the adult at about 170 mms. of mercury and the varia-
tions for different ages he expressed in the following figures:

Age 6-10 15 20 25 30 40 50 60 80

Pressure (systolic) 89 135 150 170 180 190 200 210 220

Without the other side of the picture — that is, the diastolic pres-
sure and the force of the heart beat (pulse pressure) — it is difficult
to interpret these figures. The rapid increase up to maturity
probably represents chiefly the larger output of blood from the heart;
the slower and more regular increase from maturity to old age is
due possibly to the gradual hardening of the arteries, since the less
elastic the arteries become, the greater will be the systolic rise with
each heart beat. With his more complete apparatus Erlanger
reports that in the adult (20 to 25), when the psychical factor is
excluded, the average pressure in the brachial is 110 mms., systolic,
and 65 mms., diastolic, — figures much lower than those given by
* "La pression arterielle de 1'homme," Paris, 1902.

472 CIRCULATION OF BLOOD AND LYMPH.

Potain. The same observer reports observations upon the effect
of meals, of baths, of posture, the diurnal rhythm, etc.*

The effect of meals is particularly instructive in that it illustrates
admirably the play of the compensatory mechanisms of the circu-
lation by means of which the heart and the blood-vessels are ad-
justed to each other's activity. During a meal there is a dilatation
of the blood-vessels in the abdominal area, or, as it is frequently
called in physiology, the splanchnic area, since it receives its
vasomotor fibers through the splanchnic nerve. The natural
effect of this dilatation, if the other factors of the circulation
remained constant, would be a fall of pressure in the aorta and a
diminution in blood-flow to other organs, such as the skin and the
brain. This tendency seems to be compensated, however, by an
increased output of blood from the heart. Observations with the
sphygmomanometer show that after full meals there is a marked
increase in the pulse pressure, indicating a more forcible beat of the
heart. So far as the effect on the heart is concerned, the result of a
meal is similar to that of muscular exercise, and this reaction may
account for the fact, not infrequently observed, that in elderly
people whose arteries are rigid an apoplectic stroke may follow a
heavy meal.

* Erlanger and Hooker. "The Johns Hopkins Hospital Reports," voL
xii., 1904.

CHAPTER XXVI.

THE PHYSICAL FACTORS CONCERNED IN THE PRO-
DUCTION OF BLOOD-PRESSURE AND BLOOD-
VELOCITY,

In the preceding pages some of the essential facts have been
stated regarding the pressure and the velocity of the blood in the
different parts of the vascular system. We may now consider the
physical factors that are responsible for the production and mainte-
nance of these peculiarities. The problem as it actually exists in the
circulation, with its elastic vessels varying in size from the aorta,
with an internal diameter of nearly 20 mms., to the capil-
laries, with a diameter of 0.009 mm., is extremely complex, but the
general static and dynamic principles involved are simple and easily
understood.

Side Pressure and Velocity Pressure. — When water flows
through a tube under, let us say, a constant head of pressure it
encounters a resistance due to the friction between the walls of the
vessel and the particles of water. This resistance will be greater,
the narrower the tube. A part of the head of pressure used to drive
the liquid along the tube will be used in overcoming this resistance
to its movement, and the volume of the outflow will be correspond-
ingly diminished. If we use an apparatus such as is represented in
Fig. 196, consisting of a reservoir, H, and a long outflow tube,
1, 2, 3, 4, 5, the outflow from the end and the pressure along the
tube may be measured directly. We must suppose that the head
of pressure — that is, the height of the water in H — is kept constant
by some means. The resistance or tension due to the friction in the
tube may be measured at any point by inserting a side-tube or
gauge (piezometer) at that point. The liquid will rise in this tube
to a level corresponding to the pressure or resistance offered to the
movement of the liquid at that point — that is, the weight of the
column of liquid will measure the pressure at that point upon a
surface corresponding to the cross-area of the tube. The pressure
or tension at any point may be spoken of as the side pressure or
lateral pressure, and it expresses the amount of resistance offered
to the flow of the liquid because of the friction exerted upon the
water by the walls of the tube between that point and the exit.
This side pressure increases in a straight line from the point of exit

473

474

CIRCULATION OF BLOOD AND LYMPH.

to the reservoir, and this in general is the picture presented by
the circulation. The reservoir, the head of pressure, is represented
by the aorta, the exit for the outflow by the opening of the venae
cavae into the right auricle, and the side pressure or internal tension
of the blood due to friction against the walls of the vessels increases
from the vense cavae back to the aorta. If from aorta to vena cava
the vessels were of the same diameter the increase would be in a
straight line, as in the case of the model. In this model it will be
noticed that the straight line showing the side pressure does not
strike the top of the column of liquid in the reservoir, but corre-
sponds to a certain height, hf. This expresses the fact that, of the
total head of pressure in the reservoir, which we may designate as
H, a certain portion only, but a large portion, h', is used in over-

Fig. 196. — Schema to illustrate the side pressure due to resistance, and the velocity pres-
sure (Tigerstedf) : H, A reservoir containing water; 1, 2, 3, 4, 5, the outflow tube with
gauges set at right angles to measure the side pressure; h', the portion of the total pressure
used in overcoming the resistance to the flow ; h, the portion of the total pressure used in
moving the column of liquid — the velocity pressure.

coming the resistance along the tube. What is left — that is, H-h',
represents the force that is employed in driving the liquid through
the tube with a certain velocity ; this portion of the pressure we may
speak of as the velocity pressure, h. If in measuring the side pressure
at any point the gauge were prolonged into the tube and bent so as
to face the stream, this velocity pressure would add itself to the
side pressure at that point and the water would rise to a higher
level in this particular tube. There are two important differences
between the circulation as it exists in the body and that repre-
sented by the model. In the body, in the first place, we have
the area of capillaries, small arteries, and veins, intercalated be-
tween the large arteries on one side and the veins on the other;
and, in the second place, the vessels, especially the arteries, are
extensible and elastic. The effect caused by the first of these

BLOOD-PRESSURE AND BLOOD-VELOCITY.

475

factors — namely, a great resistance placed in the middle of the
course — may be illustrated by the model shown in Fig. 197, which
differs from that in Fig. 196 in having a stopcock in the outflow
tube, which, when partly turned off, makes a narrow opening and a
relatively great resistance. When the stopcock is open the pressure
falls equally throughout the tube, provided the bore of the stopcock
is equal to that of the tube. If, however, it is partially turned the
side pressure is much increased between it and the reservoir on what
we may term the arterial sicie of the schema, and it is correspond-
ingly diminished between the stopcock and the exit, on the venous
side of the schema. Substantially this condition prevails in the body.
The capillary region, including the smallest arterioles and veins,
offers a great resistance to the flow of blood, and this resistance is
spoken of in physiology as the peripheral resistance. Its effect is to

Fig. 197.— Schema like the preceding except that a stopcock is inserted at the middle
of the outflow to imitate the peripheral resistance of the capillary area. The relations of
the internal pressure on the arterial and venous sides of this special resistance is shown by
the height of the water in the gauges.

raise the pressure on the arterial side and lower it on the venous side.
When other conditions in the circulation remain constant it is found
that an increase in peripheral resistance, caused usually by a con-
striction of the arterioles, is followed by a rise of arterial pressures
and a fall of venous pressures. On the contrary, a dilatation of the
arterioles in any organ is followed by a fall of pressure in its artery or
arteries and a rise of pressure in its veins. The effect of the elastic-
ity of the arteries is of importance in connection with the fact that
in reality the circulation is charged with blood not from a constant
reservoir as in the models, Figs. 196 and 197, but by the rhythmical
beats of the heart. If the vascular system were perfectly rigid each
rhythmical charge into the aorta would be followed by an equal dis-
charge from the venae cavse, the pressure throughout the system
would rise to a high point during systole and fall to zero during the

476 CIRCULATION OF BLOOD AND LYMPH.

diastole. The elasticity of the arteries, in connection with the
peripheral resistance, makes an important difference. As the heart
discharges into the aorta the pressure rises, but the walls of the
arterial system are distended by the increased pressure, and during
the following diastole the recoil of these distended walls maintains
a flow of blood through the capillaries into the veins. With a
certain rapidity of heart beat the distension of the arterial walls is
increased to such a point that the outflow through the capillaries
into the veins is as great during diastole as during systole; the
rhythmical flow in the arteries becomes converted by the elastic
tension of the overfilled arterial system into a continuous flow in
the capillaries and veins. This effect may be illustrated by a simple
schema such as is represented in Fig. 198. A syringe bulb (a), rep-
resenting the heart, is connected by a short piece of rubber tubing to a
glass tube (6), and also by a piece of distensible band tubing (e) with

Fig. 198. — Simple schema to illustrate the factors producing a constant head of pres-
sure in the arterial system : a, A syringe bulb with valves, representing the heart ; b, glass
tube with fine point representing a path with resistance alone, but no extensibility (the out-
flow is in spurts synchronous with the strokes of the pump) ; c, outflow with resistance and
also extensible and elastic walls represented by the large rubber bag, e ; the outflow is a
steady stream due to the elastic recoil of the distended bag, e.

a similar glass tube drawn to a fine point (c). In the latter case the
distensible, elastic tubing represents the arterial system, and the
fine pointed glass tube the peripheral resistance of the capillary area.
If the syringe bulb is put into rhythmical play and the flow is directed
through tube b the discharges are in rhythmical spurts, but if
directed through tube c the discharge is a continuous stream,
since the force of the separate beats becomes stored as elastic tension
in the walls of the band tubing, and it is this constant force which
drives a steady stream through the capillary point. In a general
way, this schema gives us a true picture of the conditions in the cir-
culation. The rhythmical force of the heart beat is stored as elastic
tension in the walls of the arteries, and it is the squeeze of these
distended walls which gives the continuous driving force that is
responsible for the constant flow in the capillaries and veins.

Enumeration of the Factors Concerned in Producing Nor-
mal Pressure and Velocity. — In the normal circulation we may

BLOOD-PRESSURE AND BLOOD-VELOCITY. 477

say that four chief factors co-operate in producing the conditions
of pressure and velocity as we find them. These factors are: (1)
The heart beat. (2) The resistance to the flow of blood through the
vessels, and especially the peripheral resistance in the region of the
small arteries, capillaries, and small veins. (3) The elasticity of
the arteries. (4) The quantity of blood in the system. The
way in which these factors act may be pictured as follows : Suppose
the system at rest with the definite quantity of blood distributed
equally throughout the vascular system. The internal or side
pressure throughout the system will be everywhere the same, —
probably zero (atmospheric) pressure, since the capacity of the
vascular system is sufficient to hold the entire quantity of blood
without distension of its walls. If, now, the heart begins to beat
with a definite rhythm and discharges a definite quantity of blood at
each beat the whole mass will be set into motion. The arteries
receive the blood more rapidly than it can escape through the capil-
laries into the veins, and consequently it accumulates upon the
arterial side until an equilibrium is reached, — that is, a point at
which the elastic recoil of the whole arterial tree suffices to force
through the capillaries in a unit of time as much blood as is received
from the heart during the same time. In this condition of equilib-
rium the flow in capillaries and veins is constant, and the side
pressure in the veins increases from the right auricle back to the
capillaries. In the arteries there is a large side pressure throughout,
owing to the resistance between them and the veins and especially
to the great resistance offered by the narrow capillaries. This
pressure rises and falls with each discharge from the heart, and the
pulse waves, both as regards pressure and velocity, are most marked
in the aorta and diminish farther out in the arterial tree, failing
completely in the last small arterioles, since if taken together these
arterioles constitute a large and distensible tube of much greater
capacity than the aorta.

General Conditions Influencing Blood-pressure and Blood-
velocity. — Alterations in any of the four chief factors mentioned
above must, of course, cause a change in pressure and velocity.

I. An increase in the rate or force of the heart beat will increase
the velocity of the flow throughout the system, although, of course,
that general difference in velocity in the arteries, capillaries, and
veins which depends upon the variations in width of bed will remain.
Such a change will also cause a rise of pressures throughout the
system. The whole energy exhibited in the vascular system as
side pressure, velocity pressure, etc., comes, in the long run, from
the force of contraction of the heart muscle. This force is what is
represented in the model, Fig. 196, as the total head of pressure (H).
An increase in rate or force of heart beat is equivalent, therefore,

478 CIRCULATION OF BLOOD AND LYMPH.

to an increase in this head of pressure, and along with the increase
in velocity thus caused there is an increased friction or resistance.

II. An increase or decrease in the width of the vessels will
influence both the resistance to the flow and the velocity. Under
normal conditions it is the small arteries that are constricted or
dilated (vasoconstriction and vasodilatation) . A constriction of
these arteries causes an increase in arterial pressures and a decrease
in venous pressure. The velocity of the blood-flow is decreased.
A dilatation has the opposite effects. Numerous instances of this
relation will be referred to in describing the physiology of the vaso-
motor nerves.

III. A diminution in elasticity of the arteries will tend to
interfere with the constancy of the flow from the arteries into the
capillaries, and in the arteries themselves the swings of pressure
from systolic to diastolic during the heart beat will be more
extensive. This latter fact can be shown upon elderly individuals
whose arteries are becoming rigid, but whether a change of this
character is ever so advanced in human beings as to seriously modify
the capillary circulation does not appear to have been investigated.

IV. A loss of blood, other conditions remaining the same,
will also cause a fall in blood-pressures and velocity. As a matter
of fact, however, a considerable amount of blood may be lost with-
out any marked permanent change in arterial blood-pressure. The
reason for this result is found in the adjustability or adaptability
of the vascular system. It is in such respects that the system differs
greatly from a rigid schema such as we use for our models. When
blood is withdrawn from the vessels the loss may be offset by an
increased action of the heart and by a contraction of the arterioles,
the two effects combining to give a normal or approximately normal
arterial pressure. To carry out the analogy with the model (Fig.
196) if by chance some of the store of water was lost we might sub-
stitute a narrower reservoir, so that with a diminished supply we
could still maintain the same level of pressure. In the body,
moreover, a loss of blood by hemorrhage may be compensated in
part, so far as the bulk of the liquid is concerned, by a flow of
liquid from the tissues into the blood-vessels.

The Hydrostatic Effect. — In the living animal, especially in
those, like ourselves, that walk upright, the actual pressure in the
arteries of the various tissues must vary much also with the position.
For instance, in standing erect the small arteries in the hands or
feet are, in addition to other conditions noted above, exposed to the
weight of the column of arterial blood standing over them. In
the pendent arm the skin of the fingers is congested; if, however,
the arm is raised above the head the skin may become blanched
because now the column of blood from fingers to shoulder exercises

BLOOD-PRESSURE AND BLOOD-VELOCITY. 479

a hydrostatic pressure in the opposite direction. In determinations
of blood-pressure in the brachial artery of man care should be taken
to keep the arm in the same position in a series of observations in
order to equalize the effect of the hydrostatic factor. The impor-
tance of this gravity effect is most evident in the case of the ab-
dominal (splanchnic) circulation. When an animal accustomed
to go on all fours is held in a vertical position the great vascular
area of the abdomen is placed under an increased pressure due to
gravity, and, unless there is a compensatory contraction of the
arterioles or of the abdominal wall, so much blood may accumulate
in this portion of the system that the arterial pressure in the aorta
will fall markedly or the circulation may stop entirely.* In most
cases the compensation takes place and no serious change in the
circulation results. In rabbits, however, which have lax abdominal
walls, it is said that the animal may be killed by simply holding it
in the erect position for some time. For the same reason an erect
posture in man may be dangerous when the compensatory nervous
reflexes controlling the arteries and the tone of the abdominal wall
are thrown out of action, as, for instance, in a faint or in a condition
of anesthesia. In such conditions the recumbent position favors
the maintenance of the normal circulation. Indeed, under ordinary
conditions some individuals are quite sensitive to the effects of a
vertical position, especially if unaccompanied by muscular or mental
activity, and may suffer from giddiness and a sense of faintness
in consequence of a fall in general blood-pressure. It seems prob-
able that in these cases the gravity effect has drafted off an undue
amount of blood into the splanchnic area. Individuals who have
been kept in bed for long periods by sickness, accident, or other
causes suffer from giddiness and unsteadiness when they first
attempt to stand or walk. It seems quite possible that in such
cases also the effect is due to a fall in arterial pressure brought about
by the dilatation in the splanchnic area. The added weight of
blood thrown on these vessels is not compensated by a vasocon-
striction of the arterioles or an increased tone in the abdominal
walls.

Venous Pressures. — While certain general deductions of the
kind given above may be made from our knowledge of the hydro-
dynamics and hydrostatics of the circulation, it is evident that in
particular cases, whether affecting special organs or the organism
as a whole, it is necessary to obtain directly, if possible, the facts,
not only for the arterial pressure and velocity but also for the
venous pressure and velocity, in order to draw safe conclusions
as to the changes in the circulation. The data and methods avail-
able in physiology and clinical medicine at present are more com-
* Hill and Barnard, " Journal of Physiology," 21, 321, 1897.

480 CIRCULATION OF BLOOD AND LYMPH.

plete in regard to the arterial side of the circulation than for the
venous side, and it is important that the latter should be more
thoroughly studied. In animals the venous pressures may be
•determined directly by connecting the vein with a manometer.
In man the same facts may be obtained for the superficial veins
by determining the pressure necessary to obliterate the vein.
A simpler although less exact method (Gaertner), applicable to the
veins of the arm and hand, is to note the level, as regards the heart,
.at which the vein collapses and disappears from view when the
arm is elevated. By means of a special instrument Sewall f has
shown that in muscular exercise the pressure in the veins is in-
creased. External cold lowers venous pressure, while heat increases
it, and during digestion venous pressure in some cases is lowered
and in others raised, depending on the nature of the adjustment of
the heart to the changes in the splanchnic system.

Accessory Factors Aiding the Circulation. — The force of the
heart beat is the main factor concerned in the movement of the
blood, but certain other muscular movements aid more or less in
maintaining the circulation as it actually exists in the living animal.
The most important of these accessory factors are the respiratory
movements and the contractions of the muscles of the limbs and
viscera. At each inspiratory movement the pressure relations are
altered in the thorax and abdomen, and reverse changes occur during
expiration. These effects influence the flow of blood to the heart,
and alter the velocity and pressure of the blood in a way that is
described in the section on Respiration under the title of The
Respiratory Waves of Blood-pressure. Contractions of the skeletal
muscles must also influence the blood-flow. The thickening of the
fibers in contraction squeezes upon the capillaries and small vessels
and tends to empty them. On account of the valves in the veins
the blood is forced mainly toward the venous side of the heart;
so that rhythmical contractions of the muscles may accelerate the
circulation. The contractions of the smooth muscles, especially
in the stomach and intestines during digestion, have a similar effect.
The musculature of the spleen also is supposed to aid the circulation
through that organ by its rhythmical contractions.

The Conditions of Pressure and Velocity in the Pulmonary
Circulation. — The general plan of the smaller circulation from
right ventricle to left auricle is the same as in the major or systemic
circulation, and the same general principles hold. The right
ventricle pumps its blood into the pulmonary artery, and, on ac-
count of the peripheral resistance in the lung capillaries, the side
pressure in the artery is higher than in the capillaries, and higher in
these than in the pulmonary veins. The velocity of movement is
* Sewall, "Journal of the American Medical Association, " 1906, xlvii., 1279.

BLOOD-PRESSURE AND BLOOD-VELOCITY. 481

least, on the other hand, in the extensive capillary area and greatest
in the pulmonary artery and veins, on account of the variations in
width of the bed. So also in the pulmonary artery the pressure and
velocity must fluctuate between a systolic and diastolic level at each
heart beat, while in the pulmonary veins they are more or less uni-
form. An interesting difference between the two circulations
consists in the fact that the peripheral resistance is evidently much
less in the pulmonary circuit, and consequently the pressure in the
pulmonary arteries is much less than in the aortic system. The
velocity of the flow, as already stated (p. 454), is also greater in
the lung capillaries than in the systemic capillaries. Exact deter-
minations of the pressure in the pulmonary artery are made with
difficulty on account of the position of the vessel.* The results
obtained by various observers give such values as the following:

MEAN PRESSURE. EXTREME VARIATIONS.
MMS. HG. MMS. HG.

Dog 20 10 to 33

Cat 18 7.5 " 24.7

Rabbit 12 6 "35

It will be seen, therefore, that the mean pressure is not more
than one-seventh to one-eighth of that prevailing in the aorta.
The thinner walls and smaller muscular power of the right ventricle
as compared with the left are an indication of the fact that less force
is necessary to keep up the circulation through the pulmonary
circuit.

The Variations in Pressure in the Pulmonary Circuit. —
Experimental results indicate that the pressures in the pulmonary
circuit do not undergo as marked changes as in the systemic circu-
lation; the flow is characterized by a greater steadiness. With a
systemic pressure, as taken in the carotid, varying from 144 to 222
mms., that in the pulmonary artery changes correspondingly only
from 20 to 26 mms., and extreme variations of pressure in the
pulmonary artery probably do not exceed, as a rule, 15 to 20 mms.
The regulations of the pressure and flow of blood in the small
circulation do not seem to be so direct or complex as in the aortic
system. The part taken by the vasomotor nerves is referred to
in the chapter upon the innervation of the blood-vessels, and
attention may be called here only to the mechanical factors, which,
indeed, for this circulation are probably the most important. The
output from the right ventricle, and therefore the amount of flow
and the pressure in the pulmonary artery, depends mainly on the
amount of blood received through the venae cavae by the right auricle.

* For a discussion of the special physiology of the pulmonary circulation
and for references to literature see Tigerstedt, " Ergebnisse der Physiologic,"
vol. ii., part ii., p. 528, 1903.
31

482 CIRCULATION OF BLOOD AND LYMPH.

If one of the venae cavse is closed the pulmonary pressure sinks;
pressure upon the abdomen, on the other hand, by squeezing more
blood toward the right heart may raise the pressure in the pulmonary
artery. By such means, therefore, the variations in blood-flow in
the systemic circulation indirectly influence and control the pressure
relations in the pulmonary circuit. But the changes in the systemic
circulation may affect the blood-flow through the lungs in still
another way, — namely, by a back effect through the left auricle.
When for any reason the blood-pressure in the aorta is driven
much above the normal level the left ventricle may not be able to
empty itself sufficiently, and if this happens the pressure in the
left auricle will rise and the flow through the lungs from right
ventricle to left auricle will be more or less impeded. On the whole,
it would seem that the pulmonary circulation is subject to less
changes than in the case of the organs supplied by the aorta. The
mechanical conditions, especially in the capillary region, are such
that the blood is sent through the lungs with a relatively high
velocity, although under small actual pressure. The special effects
of the respiratory movements and of variations in intrathoracic
pressure upon the pulmonary circulation are referred to in con-
nection with respiration.

CHAPTER XXVII.
THE PULSE.

General Statement. — When the ventricular systole discharges
a new quantity of blood into the arteries the pressure within these
vessels is increased temporarily. If the arteries, capillaries, and
veins were perfectly rigid tubes it is evident that this pressure would
be transmitted practically instantaneously throughout the system,
and that a quantity of blood would be displaced from the venae
cavse into the auricles equal to the quantity forced into the aorta by
the ventricle. The flow of blood throughout the vascular system
would take place in a series of spurts or pulses, the pressure rising
suddenly during systole and falling rapidly during diastole. Since
the blood is incompressible and the walls of the vessels if rigid
would be inextensible, the rise of pressure, the pulse, would be
simultaneous in all parts of the system. The fact, however, that
the walls of the vessels are extensible and elastic modifies the trans-
mission of the pulse wave in several important particulars: It
explains why it is that the pulse dies out in or at the beginning of
the capillaries and why it occurs at different times in different
arteries — that is, why the wave of pressure takes a perceptible
time to travel over the arteries. The result that follows from the
elasticity of the arteries may be pictured as follows: Under the
normal conditions of the circulation when the heart contracts and
forces a new quantity of blood into the aorta room must be made
for this blood either by moving the whole mass of the blood forward
— that is, by discharging an equal amount at the other end into the
auricle — or by the enlargement of the arteries. This latter alter-
native is what really happens, as it takes less pressure to distend
the aorta than to move forward' the entire mass of blood under the
conditions that exist in the body. So soon, therefore, as the semi-
lunar valves open and the new column of blood begins to enter the
aorta, the walls of that vessel begin to expand and during the time
that the blood is flowing out of the heart — that is, in round numbers,
about 0.3 sec. — the extension of the walls passes from point to point
along the arterial system. At the end of the outflow from the heart
all the arteries are beginning to enlarge, the maximum extension
being in the aorta, and room is thus made for the new quantity of
blood. The new blood that is actually discharged from the heart

483

484 CIRCULATION OF BLOOD AND LYMPH.

lies somewhere in the aorta, but the pressure that has been trans-
mitted along the system and has caused it to expand has made
room for the blood forced out of the aorta by the new blood.
With the cessation of the heart beat and the closure of the semilunar
valves, the sharp recoil of the distended aorta drives forward the
column of blood, and as the aorta sinks back to its normal diastolic
diameter the more distal portions of the arterial system are at first
distended to a certain point and then return to their diastolic size
as the excess of blood streams through the capillaries into the veins.
At the time that the aorta has reached its diastolic size the walls
of the most distant arterioles have passed their maximum extension
and are beginning to collapse. The distension caused by the pulse,
therefore, spreads through the arterial system in the form of a wave.
At any given point the distension of the walls increases to a maxi-
mum and then declines, and when this change in size is recorded
in the large arteries, by methods described below, it is found that
the expansion of the artery is much more sudden than the subse-
quent collapse. This difference is understood when we remember
that the heart throws its load of blood into the arteries with sud-
denness and force, causing a sharp rise of pressure, while the collapse
of the arteries is due to their own elasticity. The disappearance
of the pulse before reaching the capillary area is readily compre-
hended when one remembers that the arterial tree constantly in-
creases in size as one passes out from the aortic trunk. Many facts,
such as those of pressure and velocity already described, indicate
that the increase in capacity of the arterial system is somewhat
gradual until the region of the smallest arterioles and capillaries is
reached and that at this point there is a sudden widening out or
increase in capacity of the whole system, although the individual
vessels diminish in diameter. It is in this region that the pulse,
under ordinary conditions, becomes imperceptible.* When the
arterioles in any organ are dilated the pulse may spread through
the capillary regions and be visible in the veins.

Velocity of the Pulse Wave. — From the above considerations
it is evident that in a system such as is presented by our blood-
vessels the velocity of the pulse wave must vary with the rigidity
of the tubes. If perfectly rigid the pressure would be transmitted
practically instantaneously; if the walls were very extensible the
propagation would be relatively slow. For our blood-vessels as
they exist at any given moment the velocity of the pulse wave may
be estimated by a simple method : Two arteries may be selected at
different distances from the heart and the pulse wave as it passes by

* For a satisfactory discussion of the pulse and for literature consult von
Frey, "Die Untersuchung des Pulses." Berlin, 1892. For a description of
the variations in disease consult Mackenzie, " The Study of the Pulse, etc."
New York, 1902.

THE PULSE. 485

a given point in each artery may be recorded by some convenient
apparatus, such as can be devised in any laboratory. If the waves
are recorded on a rapidly revolving kymographion whose rate of
movement can be determined, then the difference in time in the
arrival of the pulse wave at the two points is easily ascertained.
That there is a perceptible difference in time one can easily demon-
strate to himself by feeling simultaneously the pulse of the radial
and the carotid arteries, if this difference in time is determined
for two arteries — for instance, the femoral and the tibialis anticus —
and the distance between the two points is recorded, we have
evidently the necessary data for obtaining the velocity of the pulse
wave in the arteries of that region. A record of this kind is shown
in Fig. 199.

Fig. 199. — To illustrate the method of determining the velocity of the pulse wave
in man. Shows record of the pulse at two points on the leg at a known distance apart.
The difference in time is given by the verticals dropped from the beginning of these waves
to the time curve. This last is made by the vibrations of a tuning fork giving 50 vibra-
tions per second. The difference in this case was equal to 0.07 sec.

The results obtained by various authors indicate that the velocity
varies somewhere between 6 and 9 meters per second for adults.
The figures published by recent observers show also that the velocity
is somewhat greater in the upper extremities (7.5 m. for carotid-
radial estimation) than in the descending aorta (6.5 m. for carotid-
femoral estimation).* The average of thirty determinations made
in the author's laboratory upon medical students shows that the
velocity in the leg (femoral-anterior tibial) is 6.1 m. when the
records are made upon the same leg, and 7.4 m. when the record
for the femoral is taken from one leg and that for the anterior tibial

* Edgren, " Skandinavisches Archiv f. Physiol.," 1, 96, 1889.

486 CIRCULATION OF BLOOD AND LYMPH.

from the other. The latter condition would seem to be more nor-
mal, since the blood-flow and normal tension of the walls are
probably less disturbed. An increase in rigidity of the arteries
causes the velocity to rise; in elderly people, therefore, the velocity
is distinctly greater. In arterial sclerosis with hypertrophy of the
heart the velocity may increase to as much as 11 or 13 m. Any
marked dilatation of the arteries — such as occurs, for instance,
in aneurysms, — retards the pulse wave markedly; so that the
existence of an aneurysm may be detected in some cases by this
fact. If we know the velocity of the wave and the time that it takes
to pass any given point the length of the wave is given by the
formula 1= vt. In an adult the duration of the wave (t) at the radial
may be taken as 0.5 to 0.7 sec.; so that if the velocity of the wave
were uniform throughout the arteries the length of the wave would
be from 3.25 to 4.5 m. We can conclude, therefore, that before

Fig. 200. — The Dudgeon sphygmograph in position.

the wave has disappeared at the root of the aorta it has reached the
most distant arteries.

The Form of the Pulse Wave — Sphygmography. — The pulse
wave may be felt upon any superficial artery in consequence of the
distension of the vessel. By the tactile sense alone the experienced
physician may distinguish some of the characters of the wave, its
frequency, its force, etc. The details of the form of the wave,
however, were made evident only when the variations in size of the
artery were recorded graphically by placing a lever upon it. Any
instrument suitable for this purpose is designated as a sphygmo-
graph, and very numerous forms have been devised. The move-
ment of the artery is very small and to obtain a distinct record it is
necessary to magnify this movement greatly by a properly con-
structed lever.

The form of lever that is perhaps most frequently employed is shown in the
accompanying figures. The instrument is strapped upon the arm so that the

THE PULSE.

487

button of the metallic spring rests over the radial artery. The movements
of the artery are transmitted to this spring and this latter in turn acts upon
the bent lever, and the magnified movement is recorded by the writing point,
upon a strip of blackened paper which is moved
under the point by clockwork contained in the
case. To obtain a satisfactory record or sphyg-
mogram, two details are of special importance:
First, the button of the lever must -be pressed
upon the artery with the proper force. Theo-
retically this pressure should be about equal to
the diastolic pressure within'' the artery. All
sphygmographs are provided with means to
regulate the pressure, and practically one must
learn so to place the button and to arrange the
pressure as to obtain the largest tracing. A
second detail of importance is that the weight
of the lever when set suddenly into motion
causes a movement, due to the inertia of the
mass, which may alter the true form of the wave.
To overcome this defect the lever should be as
light as possible, or the spring upon which the
artery plays should have considerable resis-
tance. In those sphygmographs in which the
inertia factor is practically eliminated the diffi-
culty of obtaining a tracing, especially from a
weak pulse, is correspondingly increased, and in
the sphygmographs most commonly employed,
such as the Dudgeon, facility in application is
obtained at the expense of incomplete correction of the error of inertia.

Fig. 201.— The lever of
the Dudgeon sphygmograph :
P, The button of the spring F,
to be placed upon the artery.
The movement is transmitted
to the lever, F\, and thence to
the bent lever, F2, whose
movement is effected through
the weight, g. The writing
point S, of this lever makes
the record on the smoked sur-
face, A.

The pulse wave obtained from the radial artery is represented
in Fig. 202. It will be seen from this figure that the artery dilates
rapidly and then falls more slowly, but it must be borne in mind
that the very pointed apex of the wave recorded by this form of
sphygmograph is due to the instrumental error referred to above,
namely, the "fling" of the lever caused, by the sudden expansion

Fig. 202. — Sphygmogram from the radial artery, Dudgeon sphygmograph: D, The dicrotic
wave; P, the predicrotic wave.

of the artery. The ascending portion of the wave is spoken of as
the anacrotk limb, the descending, as the catacrotic limb. Under
usual conditions the anacrotic limb is smooth, — that is, shows no
secondary waves, — while the catacrotic limb shows one or more
secondary waves, which are spoken of in general as the catacrotic
waves. The most constant of these latter waves occurs usually

488 CIRCULATION OF BLOOD AND LYMPH.

approximately at the middle of the descent (D) and is designated
as the dicrotic wave. A less conspicuous wave between it and the
apex of the pulse wave is known usually as the predicrotic wave, P,
while the wave or waves following the dicrotic are designated as
postdicrotic. These catacrotic waves are too small, under normal
conditions, to be felt by the finger. Under certain abnormal
conditions, however, which cause a low blood-pressure without
marked diminution in the heart beat, the dicrotic wave is empha-
sized and may be detected by the finger. A pulse of this kind is
known as a dicrotic pulse. In each pulse wave we may distinguish
a systolic and a diastolic phase; the former, making due allowance
for transmission, corresponds with the time during which the aortic
valves are open, and blood is streaming from the heart to the aorta,
the latter represents the period during which the aortic valves
are closed and the arteries are shut off from the heart. In Fig. 202
the systolic phase extends from s to d, the diastolic from d to s'.

Explanation of the Catacrotic Waves. — It has been found
difficult to give an entirely satisfactory explanation of the catacrotic
waves or, to speak more accurately, it is difficult to decide between
the different explanations that have been proposed. Concerning
the dicrotic wave, it may be said that tracings from different ar-
teries show that, like the main pulse wave, it has a centrifugal
course, — that is, it starts in the aorta and runs peripherally with the
same velocity as the main wave upon which it is superposed. More-
over, simultaneous tracings of the pressure changes in the heart and
in the aorta show that the closure of the semilunar valves is synchro-
nous with the small depression or negative wave (d, Fig. 202) which
immediately precedes the dicrotic wave. The general belief, there-
fore, is that the dicrotic wave results from the closure of the semi-
lunar valves. When the distended aorta begins to contract by
virtue of the elasticity of its walls, it drives the column of blood in
both directions. Owing to the position of the semilunar valves
the flow to the ventricle is prevented; but the interposition of this
sudden block causes a reflected wave which passes centrifugally
over the arterial system. The dicrotic wave is preceded by a
small negative wave or notch in the curve which marks the time
of closure or just follows the closure of the semilunar valves. The
sequence of events as pictured by Mackenzie* is as follows: "As
soon as the aortic pressure rises above the ventricular the valves
close. At the moment this happens the valves are supported by
the hard, contracted ventricular walls. The withdrawal of the
support by the sudden relaxation of these walls will tend to produce
a negative pressure wave in the arterial system. But this negative

* Mackenzie, "The Study of the Pulse and the Movements of the Heart. "
1902.

THE PULSE.

wave is stopped by the sudden stretching of the aortic valves,
which, on losing their firm support, have now themselves to bear
the resistance of the arterial pressure. This sudden checking of
the negative wave starts a second positive wave, which is prop-
agated through the arterial system as the dicrotic wave." The
smaller waves, such as the predicrotic, have been explained (Lan-
dois)* simply as elasticity waves, — that is, as elastic vibrations of
the arterial walls or as instrumental errors, due to fling of the lever.
According to other authors, f an important — perhaps the chief
factor — in the production of the secondary waves is the reflection
that occurs from the periphery. Where each arterial stem breaks
up into its smaller vessels the main pulse wave suffers a reflection,
a wave running backward toward the heart. It is probable that
such reflected waves from different areas — for instance, from the
coronary system, the subclavian system, the mesenteric system,
etc. — meet in the aorta and may in part summate to larger waves
which again pass peripherally. The catacrotic waves, according to-
this view, probably differ in character in the different arteries,
and tracings indicate that this is the case. The radial pulse differs,
for instance, from the carotid pulse in the character of its waves.
Between these opposite views it is not possible to decide, but it is
perhaps permissible to believe that while the dicrotic wave is due
primarily to the impulse following upon the closure of the semilunar
valves, nevertheless the actual form of this and the other secondary

Fig. 203. — Anacrotic pulse from a case of aortic stenosis (Mackenzie) : b. The anacrotic-

wave.

waves is variously modified in different parts of the system by the
reflected waves from different peripheral regions.

Anacrotic Waves. — As was said above, the anacrotic limb under
normal conditions shows no secondary waves. Under pathological
conditions, however, a secondary wave more or less clearly marked
may appear, as is shown, for instance, in the tracing given in Fig.
203. Such waves are recorded in cases of stiff arteries or stenosis-
of the semilunar valves. In the normal individual an anacrotic
pulse may be obtained, according to von Kries,t by raising the
arm. He believes that in this position the reflection of the pulse
wave from the periphery is favored, and that the anacrotic wave is-
simply a quickly reflected wave. It is possible that the same
explanation will hold for its appearance under pathological con-
ditions.

* Landois, "Die Lehre von Arterienpuls, " 1872.

t See von Frey, loc. cit.

I Von Kries, "Studien zur Pulslehre," 1892.

490 CIRCULATION OF BLOOD AND LYMPH.

Characteristics of the Pulse in Health and in Disease.—

By mere palpation the physician obtains from the pulse valuable
indications concerning the heart and the circulation. The fre-
quency of the heart beat is at once made evident, so far at least as
the ventricle is concerned. One may determine readily whether
the frequency is above or below the normal, whether the rhythm
is regular or irregular. By the same means one can determine
whether the pulse is large (pulsus magnus) or small (pulsus parvus),
whether the wave rises and falls rapidly (pulsus celer) as happens
in the case "of insufficiency of the aortic valves, or whether in one
phase or the other it is more prolonged than normal (pulsus tardus).
It seems obvious, however, that a more satisfactory conclusion may
be reached in all such cases by obtaining a sphygmographic record.
In the works devoted to clinical methods numerous such sphygmo-
grams are described. By mere pressure upon the artery one can
determine also approximately whether the blood-pressure is high

Fig. 204. — Sphygmograms illustrating the effect of variations in blood-pressure, partic-
V upon the position of the dicrotic wave and notch : n, The dicrotic notch ; d, the

ularly upon the position
dicrotic wave. A, Sphy
gram with higher blood-pressure. (Mackenzie.)

dicrotic wave. A, Sphygmogram while blood-pressure was relatively low. B, Sphygmo-
blood-

or low by estimating the force with which the wave presses upon
the fingers, or the pressure necessary to occlude the artery. A
similar inference may be drawn from the character of the sphyg-
mogram, and especially from the relative size and position of the
dicrotic wave. When this latter wave falls at or near the base line
of the curve it indicates a low arterial pressure, since under these
circumstances the artery collapses readily after its first systolic
expansion (see Fig. 204). Since the introduction of the sphyg-
momanometer (p. 466), however, it seems evident that this instru-

THE PULSE. 491

ment must be appealed to whenever the determination of blood-
pressure is a matter of importance.

Venous Pulse. — Under usual conditions the pulse wave is lost
before entering the capillary regions, but as a result of dilatation in
the arteries of an organ the pulse may carry through and appear in
the veins, in which it may be shown, for instance, by the rhythmical
flow of blood from an opened vein. The term venous pulse, how-
ever, as generally used aprj'lies to an entirely different phenomenon,
—namely, to a pulse observed especially in the large veins (jugular)
near the heart. The pulse in this case is not due to a pressure wave
transmitted through the capillaries, but to pressure changes of
both a positive and negative character occurring in the heart and
transmitted backward into the veins. The venous pulse that has
this origin may usually be seen and recorded in the external (or
internal) jugular. Under pathological conditions, especially when
the flow through the right heart is more or less impeded, it may
be plainly apparent at a further distance from the heart and may
cause a noticeable pulsation of the liver, which is designated as a
liver pulse. The venous pulse curve has been much studied in
recent years.* It is somewhat complicated and an explanation
of some of its details has not been agreed upon, but there can be no
doubt that when properly interpreted it will throw much light upon
the pressure changes in the heart, and will afford a valuable means
of diagnosis in cases of valvular lesions and other pathological
conditions of the heart. It is evident also that the venous pulse
gives a ready means of determining the rate of beat of the auricles,
just as the arterial pulse enables us to count the beats of the ven-
tricles.

Fig. 205. — Simultaneous tracings of the carotid and venous pulses. In the venous
tracing (internal jugular) a indicates the auricular wave due to the contraction of the auri-
cle ; c is the carotid wave due to an impulse from the neighboring carotid artery ; v is
the ventricular wave due to the checking or stagnation of the flow into the auricle as this
chamber fills during the period of closure of the auriculo-ventricular valves ; x, dilatation
due to auricular diastole ; y, the period of ventricular diastole. (Mackenzie.)

The venous (jugular) pulse as given by Mackenzie is represented in
Fig. 205. Three positive waves are shown, a, c, and v. The a wave or auric-

* See Mackenzie, "The Study of the Pulse," 1902; also Hirschf elder, "Amer-
ican Journal of the Medical Sciences," Sept., 1906, and Morrow, "British
Med. Journal," 1906 and 1907.

492 CIRCULATION OF BLOOD AND LYMPH.

ular wave is due to the auricular contraction which not only forces blood
into the ventricle, but sends a positive wave backward into the veins. The c
wave is interpreted by Mackenzie as being due to the pulse of the neighboring
artery (carotid); while the v or ventricular wave occurs toward the end of
ventricular systole and is explained as being due to the abrupt checking of
the venous current at the time that the auricles reach their iull distension.
In cases of insufficiency of the tricuspid valves this wave is much increased
in prominence owing probably to back flow during the systole. Another
illustration of the venous pulse (/) is given in Fig. 206, taken from a paper
by Bard.* Simultaneous records are given of the carotid pulse (c) and the apex
beat (v), and the coincident points in the three curves are marked by the

Fig. 206. — Simultaneous tracings of the venous pulse (J), the carotid pulse (C), and
the apex beat of the ventricle (V). The vertical lines mark simultaneous points on the
three curves ; T is a time record, giving ^ sec. In the venous tracing (jugular) the following
waves are marked : p , caused by the contraction of the auricle (presystolic); s, the systolic
wave due to contraction of the ventricle ; t, telesystolic wave ; Ro, the diastole of the
auricle ; Rv, the diastolic expansion of the ventricle. (Bard). (See text for further de-
scription.)

vertical lines. In Bard's curve of the venous pulse (J) three positive waves
are also shown, namely, p, s, and t, corresponding respectively to the a, c, and v
waves of Mackenzie. ' His interpretation, however, differs in some respect
from that of Mackenzie, p is a wave due to the auricular contraction, and
occurs, therefore, in the presystolic interval, so far as the ventricle is concerned,
s corresponds to the c wave of Mackenzie, but on account of the fact that it
occurs, as shown in the figure, before the carotid pulse and while the pressure
in the ventricle is rising, Bard attributes it to the sudden tightening of the
* Bard, "Journal de Physiologic et de Pathologic generate, " 1906, viii.,
454 and 466.

THE PULSE. 493

auriculo- ventricular valves and their protrusion to some extent into the
auricular cavity. This wave occurs, therefore, at the very beginning of the
systole. Wave t, corresponding with Mackenzie's wave v, occurs, on the contrary,
at the end of systole and is therefore designated by Bard as telesystolic. He
attributes this wave to the fact that during ventricular systole the base of the
heart is pulled toward the apex, thus enlarging the auricular cavity and exerting
an aspiratory effect on the venous flow. The cessation of this aspiratory effect
at the end of the systole and when the auricle is already fully distended gives
a sudden check to the flow of venous blood which causes the wave. The
negative wave, Ro, between S and t, corresponds to the diastolic expansion
of the auricles, while the larger depression (Rv) corresponds to the diastolic
expansion of the ventricles. In addition to the three waves described, pre-
systolic (p), systolic (s), and telesystolic (/), Bard describes a small wave
between p ami *, which he designates as intersystolic (?'), and another, occurring
in early diastole (d wave), which follows immediately after the t wave.

CHAPTER XXVIII.
THE HEART BEAT,

General Statement. — We divide the heart into four chambers,
— the two auricles and the two ventricles. What we designate as a
heart beat begins with the simultaneous contraction of the two
auricles, immediately followed by the simultaneous contraction of
the two ventricles; then there is a pause, during which the whole
heart is at rest and is filling with blood. As a matter of fact, the
heart beat is initiated, according to usual belief, not by the auricles
proper, but by a contraction of the mouths of the large veins —
venae cavse — where they open into the auricle. This portion of these
veins corresponds physiologically to u definite chamber, the venous

Fig. 207. — To show the time relations of the auricular systole and diastole, and ven-
tricular systole and diastole (Marey) : Or. D, Tracing from right auricle ; Vent. D, tracing
from nght ventricle ; Vent. G, tracing from left ventricle. Obtained from the heart of the
horse by means of tubes communicating with the cavities.

sinus, in the heart of the lower vertebrates. In the description of
the heart beat the contraction of the veins is usually neglected,
although in a fundamental consideration of the cause of the normal
sequence it is of great importance. The contraction of any part of
the heart is designated as its systole, its relaxation and period of rest
as its diastole. In the heart beat we have, therefore, the auricular
systole, the ventricular systole, and the heart pause during which
both chambers are in diastole. The general relations of systole,
diastole, and pause are represented graphically in the accompanying
figure (Fig. 207). It will be noted that the auricular systole is

494

THE HEART BEAT.

495

H

shorter and its diastole
longer than the similar
conditions in the ventricles.
The Musculature of the
Auricles and Ventricles.
— Embryologically the four-
chambered heart is devel-
oped from a simple tube
and this origin is indicated
in the adult by the fact
that the musculature of the
two auricles is in large part
common to both chambers,
— that is, surrounds them
as though they were a single
chamber, — and the same is
true of the ventricles. In
the auricles there is a super-
ficial layer of fibers which
runs transversely and en-
circles both auricles. The
simultaneous contraction of
the two chambers would
seem to be insured by this
arrangement alone. In addition, each auricle possesses a more or
less independent system of fibers, whose course is at right angles
to that of the preceding layer. These fibers may be considered
as loops arising and ending in the auriculo- ventricular ring. The

IE

Fig. 208. — Musculature of the heart. — (Mac-
Callum.) Heart as seen from the posterior: LAV,
Left auriculo-ventricular opening; RAV, right
auriculo- ventricular opening; PA, opening of pul-
monary artery. 7. The superficial muscle layer
originating in the right and left auriculo-ventric-

ular rings and posterior half of tendon of con us.
//. The superficial layer originating in the anterior
half of the tendon of the conus (fills in the gap of

//. The superficial layer originating in the anterior
half of the tendon of the conus (fills in the ga
Fig. I). ///. The scroll fibers in several Layers

'

forming the deeper strata of the heart's muscu-
lature.

496 CIRCULATION OF BLOOD AND LYMPH.

course of the fibers in the ventricles has been difficult to make
out and several more or less different accounts have been pub-
lished. It is clear from even a casual examination that the super-
ficial fibers are common to both ventricles. They may be considered
as arising from the auriculo-ventricular ring in one ventricle to
pass in a spiral course to the papillary muscles and through their
tendons to the auriculo-ventricular ring of the other ventricle.
Those that begin on the outer surface in one ventricle end on the
inner surface in the other. This arrangement is represented in
Fig. 208, / and //. The contractions of these bands of fibers would
tend not only to diminish the cavities of the ventricles from side
to side, but also to bring the apex and base together and to rotate
the apex from the left to right. Beneath these superficial fibers
lie thicker bands, the fibers of which have a more transverse course.
According to MacCallum,* the fibers form three flat bands which
pass in the form of a scroll from one ventricle through the septum
into the other, as shown in Fig. 208, ///. The band that lies most
superficially in the left ventricle at its origin lies deepest in the right
ventricle. The effect of the contractions of these bands should be
to compress the cavities of the ventricles in the lateral diameters.
In addition to these two main systems of fibers there are other less
prominent bands belonging entirely to one ventricle. A matter
of very great physiological interest in connection with the invariable
sequence of the heart beat has been the question of the existence of
a direct muscular connection between the auricles and ventricles.
While such a connection exists obviously in the lower animals, —
frogs, terrapins, — in the mammalia there is a conspicuous tendinous
ring at the auriculo-ventricular groove which has been believed by
many to make a complete separation between auricles and ventricles.
Several observers, however, have shown recently that there is a
muscular connection in the heart of man and of a number of mam-
malia .f The chief connection is described as a bundle of fibers,
auriculo-ventricular bundle, which springs from the right side of the
interauricular septum, runs obliquely through the connective tissue,
and ends in the muscle of the ventricular septum under the origin
of the aorta.

The Contraction Wave in the Heart. — The muscular contraction
of the heart beat begins, according to the usual description, at the
mouths of the great veins opening into the auricles, and thence
passes to the auricles first and subsequently to the ventricles.

That this sequence is followed in the case of the lower animals may be
demonstrated beautifully in the terrapin. In the slowly beating heart of this

* MacCallum, "Contributions to the Science of Medicine," dedicated to
W. H. Welch, p. 307, Baltimore, 1900; contains also the literature.

t See Retzer, "Archiv f. Anatomic, " 1904, p. 1; and Braeunig, "Archiv
f. Physiologic," 1904, ' suppl. volume, p. 1.

THE HEART BEAT. 497

animal the successive contractions of the veins, auricles, and ventricles may
be followed easily with the eye. According to Fredericq * the sequence is differ-
ent in the mammalian heart ; the cardiac beat begins in the right auricle at
a point lying between the mouths of the two cavse, and thence spreads rapidly
over the auricles and may penetrate for some distance over the veins con-
nected with the auricles. Whether or not this explanation of the sequence of
beat in the mammalian heart is correct will have to be determined by experi-
ment. It is not a fact that can be settled by mere ocular inspection.

The continuity of the muscular tissue enables us to understand
how the contraction passes quickly from cell to cell in the direction
of the muscular fibers. In the mammalian heart when exposed to
view it is evident that the auricular systole is not sufficient to
empty its cavity, so far at least as the atrium is concerned. The
contraction of the auricular appendages is more forcible. The
contraction may be regarded as a rapid peristalsis which sweeps a
portion of the blood before it into the ventricle. The force of the
contraction has been determined in a number of cases. For the
auricle of the dog's heart it may be valued at 20 mms. Hg. The
systole of the ventricle is to the eye a simultaneous contraction of
the whole musculature. Various observers, however, have shown
that the wave of contraction travels over the heart with a certain
velocity, which for the human heart has been estimated at 5 m.
per second ( Waller). f It is probable that this wave starts at
the base of the ventricle and travels along the course of the fibers, —
that is, first toward the apex and then into the interior of the heart,
ending in the papillary muscles. In fact, Roy and Adams have
demonstrated graphically that the contraction of the papillary
muscles occurs somewhat later than that of the wall of the ventricle.
The slight pause between auricular and ventricular systole may be
referred to the fact that the muscular bridge between the two
chambers is small. We have experimental evidence that the con-
traction wave proceeds more slowly through a narrow bridge of this
sort. In the dog's heart the time interval between the contractions
of the auricle and ventricle is about y1^- second. Since the con-
necting auriculo-ventricular bundle has a length of 10 to 15 mms.
the velocity of the conduction through this bundle must be about
10 to 15 cms. per second.

The Electrical Variation. — The contraction of the heart
muscle, like that of skeletal muscle, is accompanied by an electrical
change. That is, where the muscle substance is in contraction its
electrical potential is different from that of the resting muscle.
The advancing wave of contraction causes a corresponding electrical
change. If two points of the heart are connected with an electrom-
eter an electrical current will be shown, since the electrical change

* Fredericq, "Archives Internationales de Physiologic," 1906, iv., 57.
fSee Tigerstedt, "Die Physiologic des Kreislaufes, " 1893, p. 80, for
literature.

32

498

CIRCULATION OF BLOOD AND LYMPH.

will affect the electrodes at different times. This electrical varia-
tion of the contracting heart muscle may be shown easily by
means of the rheoscopic muscle-nerve preparation (see p. 99). If
the heart is exposed and the nerve of the preparation is laid over its
surface each ventricular systole is accompanied by a kick of the
muscle, since the nerve by connecting separated points acts as a
conducting wire for the current generated, and is stimulated, there-
fore, at each systole. Since the muscle-nerve preparation gives
only a simple contraction for each ventricular systole, we may
assume that this latter contraction is itself simple, — that is, due
to a single stimulus. The electrical variation may be obtained also
by means of the capillary electrometer (p. 94), and since the move-
ment of the mercury in this instrument may be photographed the

Fig. 209. — Electrocardiogram obtained by photographing the movements of a sensitive
galvanometer. The upper figure shows the photographed curve, while the [lower one is a
diagram constructed from the photograph to make clearer the electrical changes in a single
cardiac cycle. To obtain this record the electrodes were connected with the right and left
hands. Waves with the apex upward indicate that the base of the heart (or the right ven-
tricle) is negative to the apex (or left ventricle). Waves with the apex downward have
the opposite significance. Wave P is due to the contraction of the auricle. Waves Q,
R, S, and T occur during the systole of the ventricle. The curve seems to show that the
contraction in the ventricles begins first toward the apex (or in the left ventricle), since
the negativity first appears toward that side (wave Q). (Einthoven).

results can be studied in detail. Owing to the sensitiveness of the
instrument, the beat of the human heart may be registered in
this way (Waller) when the right hand, giving the potential changes
of the base of the heart, is connected with one electrode, and the
left hand (apex of heart) is connected with the other. The electro-
cardiograms thus obtained photographically show that, in the
ventricle at least, the electrical variation exhibits several phases,
and the character of these phases, that is, whether the base or the
apex first shows a negative potential, has been used in discussions

THE HEART BEAT. 499

upon the direction of the wave of contraction. Since the character
of the electrocardiogram depends so much on the delicacy of the
instruments used, arguments based on this evidence have not so
far proved very satisfactory, particularly as the later records
are quite complex and difficult to interpret (see Fig. 209 and legend).
Change in Form of the Ventricle During Systole. — The
systole of the ventricle diminishes, of course, the cavity within and
forces out the blood. Whether the cavity is completely obliterated
under ordinary conditions — that is, whether the ventricles empty
themselves at each beat — is not certain. Under what we may
designate as unusual conditions — such, for instance, as an unusually
high pressure in the aorta — it seems certain that the ventricle can not
empty itself completely or at least can not continue to do so, and the
result in such cases is a backing up of blood and a rise of pressure in
the left auricle and pulmonary vein. Much attention has been paid
to the external change of form of the ventricle during systole.
Does it diminish in size i.n all diameters or only in certain diam-
eters? The question is one that cannot be answered definitely for
all normal conditions, owing to the fact that the form of the heart
during diastole varies with the posture of the body. During
diastole the heart muscle is quite soft and relaxed, and consequently
its shape is influenced by gravity. The exact change of form
that it undergoes in passing from diastole* to systole will vary with
its shape, whatever that may happen to be, in diastole. During
systole the musculature, on the contrary, is hard and resisting and
the form of the heart in this phase is probably constant. The
change from the variable diastolic to the constant systolic form will
naturally be different in different positions. With an excised frog's
heart one can show that the ventricle is elongated in passing from
diastole to systole or one can show the reverse. If the heart is laid
upon its side it flattens in diastole so as to increase in length,
and systole causes a shortening. If the heart is held or placed
with its apex pointing upward it flattens during diastole so as
to shorten the diameter from base to apex and during systole
this diameter is lengthened. In ourselves the exact change of
shape is probably different in the erect from what it is in the
recumbent posture. Speaking generally, the accounts agree in
stating that the long diameter of the heart is decreased, base and
apex are brought closer together, and the diameter from right to
left is also decreased, while the anteroposterior or ventrodorsal
diameter is increased. That is, the outline of the base of the heart
during diastole is an ellipse with its short diameter in the ventro-
dorsal direction. During systole this outline approaches that of a
circle.* A more interesting change is described for the apex of the
* See Haycraft and Edes, "Journal of Physiology," 12, 426.

500 CIRCULATION OF BLOOD AND LYMPH.

ventricle. Owing to the whorl made by the superficial fibers at
this point as they turn to pass into the interior (see Fig. 208, 7),
the systole causes a rotation of the apex, which is thereby
forced more firmly against the chest wall. This rotation and
erection of the apex during systole may be seen upon the exposed
heart of the lower mammals and has been described also for man
in cases in which the heart is covered only by the skin, owing to
malformation in the chest wall (ectopia cordis) or to surgical
operations.

The Apex Beat.— -The apex of the heart rests against the chest
wall at the fourth or fifth intercostal space, and here the systole
may be seen and felt in consequence of a slight protrusion of the
wall. Much discussion has ensued as to why this protrusion
occurs during systole, since the apex is drawn toward the base
and the volume of the heart is diminished by the output of
blood. The fact seems to be explained satisfactorily by two con-
siderations: The heart during diastole rests against the chest wall
at its apex and a portion of its anterior surface, but causes no pro-
trusion of the wall because the tenseness of this latter is sufficient
to flatten or deform the softer heart muscle. During systole the
hardened heart muscle, on the contrary, overcomes the now rela-
tively less resistant integument. The rotation of the apex tends
also to maintain the contact; so that, although the heart is short-
ened in its long diameter, the extent of the movement is not
sufficient to draw it away from the chest wall. In the second place,
the discharge of the heart contents into the curved aorta by tending
to straighten this tube causes a movement of the whole heart
downward which counteracts the effect of the shortening in the
long diameter. The apex beat is proof that the apex remains
against the chest wall during systole and in mammals corroborative
experiments have been made by running needles through the chest
wall into the base and the apex of the heart. Such needles act as
levers with a fulcrum in the skin, and from the movement of the
projecting portion it has been shown that, while the basal portion
of the heart moves downward during systole, the apex remains
more or less stationary except for the lateral movements due to
the rotation.

The Cardiogram. — The apex beat may be recorded easily by
means of appropriate tambours. Several instruments have been
especially devised for this purpose and are designated as cardio-
graphs. The cardiograph described by Marey is shown in Fig. 209.
It consists essentially of a tambour inclosed in a metal box. The
rubber membrane of the tambour carries a button which can be
brought to bear, under a suitable pressure, upon the apex of the
heart. The movements of this button cause pressure changes in

THE HEART BEAT.

501

the air of the tambour which are transmitted through tubing to a
recording tambour and recorded on a kymographion. A simple
and effective cardiograph may be made by pressing a funnel
against the skin over the apex and connecting the stem of the

Fig. 210. — Marey's cardiograph. The button on the tambour is pressed upon the
chest over the apex. The movements are transmitted through the tube to the right to a
recording tambour.

funnel by tubing to a suitable recording tambour. The car-
diograms obtained by such methods have been the subject of
much discussion. The form of the curve varies somewhat with
the instrument used, the way in which it is applied, the position of
the heart apex with reference to the chest wall, and with the con-

Fig. 211. — Two cardiograms from the same individual to show characteristic records: a,
Beginning of systole ; b-c, systolic plateau. — (After Marey.)

ditions of the circulation, and it is often difficult to give it a correct
interpretation. An uncomplicated form of the cardiogram is
represented in Fig. 211, 7, and a curve more difficult to interpret in
Fig. 211, 8. It should be borne in mind that the cardiograph curve

502 CIRCULATION OF BLOOD AND LYMPH.

is partly a pressure curve and partly a volume curve, — that is, the
changes in volume as well as the changes in pressure of the heart
during systole will affect the instrument.

The Intraventricular Pressure During Systole. — The best
analyses of the details of the systole of the ventricle have been made
by a study of the changes in pressure within the ventricle. For
this purpose a tube filled with liquid is introduced into the cavity of
the ventricle. A tube used for such a purpose is designated as a
heart-sound. For the right ventricle it is introduced through an
opening in the jugular vein and pushed down until it lies in the
ventricle. For the left ventricle it is introduced by way of the
carotid or subclavian artery and in this case is forced through the
opening guarded by the semilunar valves. The sound is then
connected to a suitable recording apparatus by rigid tubing filled
with liquid. The changes in pressure in the ventricle are extensive

Fig. 212. — Synchronous record of the intra ventricular pressure (F), and the aortic
pressure (A): S, The time record, — each vibration = ^io s^c- • 0-5, corresponding ordi-
nates in the two curves; 1 marks the opening of the semilunar valves; 3 marks the
closure of these valves and the beginning of diastole. — (Hiirthle.)

and very rapid. To register them accurately the recording instru-
ment must respond with great promptness and at the same time
must be free from inertia movements. A mercury manometer, for
instance, would be entirely useless for such a purpose, since the
heavy mass of mercury could not follow accurately the quick changes
in pressure. The recording manometer devised by Hiirthle (p.
462) seems to have met the requirements more satisfactorily than
any other of the numerous instruments described. Atypical curve
obtained by means of the Hiirthle manometer is given in Fig. 212, V.
(Consult also the classical curve obtained by Chauveau and Marey
from the heart of the horse [Fig. 207].) It will be seen that the
pressure in the heart rises suddenly with the beginning of the ven-
tricular contraction and a certain time elapses before this pressure
is strong enough to open the semilunar valves. The moment that
this occurs (1, on the ventricular curve in Fig. 212) is determined

THE HEART BEAT. 503

by simultaneous measurement of the pressure in the aorta, it
being evident that the pressure will begin to rise in this latter
vessel the moment that the valves open. It is interesting to find
that the yielding of the valves to the rising pressure in the ventricle
is not indicated on the curve itself by any variation, — a fact which
indicates that the valves open smoothly, and are not thrown back
with a sudden shock. A very characteristic feature of the ventric-
ular curve is its flat top, or plateau as it is called. ' In some cases
the plateau slopes more or less upward, in other cases downward,
depending, doubtless, on the respective values of the force of the
heart contraction and the aortic tension, for during the whole
time of the plateau the semilunar valves are open and the ven-
tricle is discharging a column of blood into the aorta. The
different features of the ventricular systole as gathered from these
pressure curves are expressed by Hiirthle* as follows:

I. Systole, phase of contraction of the muscle fibers (0 to 3 in Fig. 212, V).

(a) Period of tension (0 to 1), during which the auricula-ventricular and
semilunar valves are both closed and the heart muscle is squeezing
upon the contained blood. This period ends at the opening of the
semilunar valves.

(6) Period of emptying (1 to 3). During this time the heart is empty-
ing itself into the aorta and the intraventricular pressure remains
above aortic pressure. It ends with the cessation of the contrac-
tion of the muscle and the beginning of the rapid relaxation.
II. Diastole, phase of relaxation and rest of the muscle fibers.

(a) Period of relaxation from 3 until the curve reaches a horizontal.
At the beginning of the relaxation the semilunar valves are closed,
and from comparison with the aortic curve the instant of the occur-
rence of this closure is placed at 4.

(6) Period of filling. This period begins as soon as the auriculo-ventric-
ular valves open and the stream of blood, which had been flowing
into the auricle throughout the ventricular systole, is permitted to
enter the ventricle. During this period of filling the ventricular
pressure rises slightly as the heart becomes turgid with blood. This
increase of pressure is indicated in most cardiograms by a gradual
rise of the curve during this period. It is shown in the curve of
Chauveau and Marey, given in Fig. 207.

The Heart Sounds. — An interesting and important feature of
the heart beat is the occurrence of the heart sounds. Two sounds
are heard, one at the beginning, the other at the end of the ventricu-
lar systole. The first sound has a deeper pitch and is longer than
the second, and their relative pitch and duration are represented
frequently by the syllables lubb-dup. According to Haycraft,t
both tones from a musical standpoint fall in the bass clef, and are
separated by a musical interval of a minor third. The sounds are
readily heard by applying the ear to the thorax over the heart, but
for diagnostic purposes the stethoscope is usually employed, and

* Hurthle, "Archiv f. d. gesammte Physiologic," 49, 84, 1891.
t Journal of Physiology," 11, 486, 1890.

504 CIRCULATION OF BLOOD AND LYMPH.

this method of investigation by hearing is designated as auscultation.
The importance of these heart sounds in diagnosis was first em-
phasized by Laennec (1819), and since his time a great number of
theories have been proposed to explain their causation. Indeed,
the subject is not yet closed, although certain general views regard-
ing their cause and the time of their occurrence are generally
accepted. The second sound is found to follow immediately upon
the closure of the semilunar valves. The usual view, therefore, is
that the sound is due ultimately to the vibrations set up in these
valves by their sudden closure. These vibrations are transmitted
to the column of blood in the aorta (or pulmonary artery) and then
to the intervening tissue of the chest wall. This view is made
probable by a number of experimental results, some of the most
important of which were brought out by Williams in a report (1836)
of a committee appointed by the British Association for the
special purpose of investigating the subject. It has been shown:
(1) That the second sound disappears before the first sound when
the animal is bled to death, and indeed as soon as the heart ceases
to throw out a supply of blood sufficient to maintain aortic tension.
It disappears also when cuts are made in the ventricles so that the
blood may escape otherwise than through the arteries. (2) When
the valves of the pulmonary artery and aorta are hooked back in the
living animal the second sound is replaced by a murmur due to the
rushing back of the blood into the ventricle, and if the valves are
dropped back into place the normal second sound is again heard.
(3) Similar sounds may be produced if the root of the aorta with its
valves in place is excised and attached to a glass tube carrying a
column of water. With such an arrangement, if the valves are held
open for a moment and then closed sharply by the pressure of the
column of water a sound similar to that of the second heart sound
is heard.

The physician uses this view of the cause of the second sound in
auscultation, and it is evident that the nature of the sound or its
replacement by murmurs will give useful testimony regarding the
condition of the semilunar valves. The first heart sound has of-
fered more difficulty. It occurs at or shortly before the closure of the
auriculo-ventricular valves, and it would seem natural, therefore, to
attribute it to the vibration of these valves when suddenly put under
tension by the ventricular systole. Most authors, indeed, believe
that this factor is at least partially responsible for the sound, —
that is, that the sound contains a valvular element. But that this
is not the sole cause is shown by the fact that the bloodless beating
heart still gives a sound at the time of the ventricular systole.
Indeed, if the apex of the rabbit's heart is cut off, it continues
to beat for a few minutes and during this time gives a first heart

THE HEART BEAT. 505

sound. It is usually said, therefore, that the first heart sound is
caused by the combination of at least two factors, — a valvular
element due to the vibration of the auriculo- ventricular valves, and
a muscular element due to the vibration of the contracting muscular
mass. Accepting this view, there is a further difficulty in explain-
ing the origin of the muscular element. According to some, it is
due to the fact that the contraction of the muscle fibers is not
simultaneous throughout the ventricle and the friction of the inter-
lacing fibers sets up vibration in the muscular mass; according to
others, the so-called muscular element is mainly a resonance tone of
the ear membrane of the auscultator, — the shock of the contracting
heart sets the tympanic membrane to vibrating. It seems useless
to attempt a detailed discussion of these conflicting views, since no
convincing statements can be made. Practically, the time at which
the heart sounds occur is of great importance. A number of
observers have recorded the time upon a cardiographic tracing of

Fig. 213. — To show the time relation of the heart sounds to the ventricular beat

iMarey) : V.D., Tracing of the ventricular pressure in the right ventricle of the horse. Be-
ow the two marks show, respectively, the time of the first and second sounds. The first
occurs immediately after the beginning of systole, the second immediately after the begin-
ning of diastole.

the heart beat with results such as are shown in Fig. 213. The
figure shows clearly the general fact that the first sound is heard
very shortly after the beginning of systole and the second one
immediately after the end of systole. The first sound is therefore
systolic, and the second sound diastolic. A more exact and de-
tailed study of the time relations of the heart sounds has been made
by Einthoven and Geluk.* These authors obtained graphic records
of the heart sounds. The sounds received first by a microphone
were transmitted to a capillary electrometer and the movements
of the latter were photographed. As one result of their work they
give the schema shown in Fig. 214. It will be seen from this figure
that the first sound begins about 0.01 sec. before the cardiogram
shows the commencement of systole, and that for the first 0.06 sec.
the sound is heard only over the apex of the heart (a-6). Over the

* Einthoven and Geluk, "Archiv f. d. gesammte Physiologic, " 57, 617,
1894. Einthoven, ibid., 1907, vol. 117.

506 CIRCULATION OF BLOOD AND LYMPH.

base of the heart (second intercostal space) the first sound is heard
(6 to c-d) just at the time when the semilunar valves are opened
(&'), — that is, at the beginning of the period of emptying according
to the classification given on p. 503. The first sound ceases long
before the ventricular contraction itself is over, — a fact which
would seem to indicate that the muscular element in the first sound
is not a muscular sound, such as is given out by a contracting
skeletal muscle. The beginning of the second sound seems to mark
exactly the time of closure of the semilunar valves. The character
and the time relations of the murmurs that accompany or replace
the heart sounds form the interesting practical continuation of this
theme; but the subject is so large that the student must be referred
for this information to the works upon clinical methods.

The Events That Occur during a Single Cardiac Cycle. —
By a complete cardiac cycle is meant the time from any given

Fig. 214. — Schematic representation of the relation of the heart sounds to the ventric-
ular beat: C, The cardiogram; 1, to show the duration of the first heart sound; 2, the
duration of the second heart sound; AS, the time record, each division corresponding to
0.02 sec. In 1, a-a' marks the instant that the first heart sound is heard over the apex,
and b-b' the moment that it is heard at the second intercostal space. — (Einthoven and
Oeluk.)

feature of the heart beat until that feature is again produced. It
may be helpful to summarize the events in such a cycle both as
regards the heart and as regards the blood contained in it. We
may begin with the closure of the semilunar valves. At that
moment the second heart sound is heard and at that moment
the ventricle is quickly relaxing from its previous contraction.
Since the auriculo- ventricular valves are still closed, the ventricles
for a brief interval are shut off on both sides. The blood is flowing
steadily into the auricles and dilating them. As soon as the
ventricular relaxation is complete the pressure of blood in the
auricles opens the auriculo- ventricular valves, and from that moment
until the beginning of the auricular systole the blood from the large
veins is filling both ventricles and auricles. The ventricles become
more tense and the auriculo-ventricular valves are floated into
position ready for closure. The auricular systole sends a sudden
wave of blood into the ventricles, dilating them still further and

THE HEART BEAT. 507

momentarily blocking or retarding the flow from the large veins,
and causing one of the waves seen in the normal venous pulse as
recorded in the jugular veins. The ventricular systole follows
at once upon the auricular systole, the exact relations in this case
depending somewhat upon the pulse rate. As the ventricle enters
into contraction the auriculo- ventricular valves are tightly closed,
the first sound is heard, a/id for a short interval the ventricular
cavity is again shut off on both sides. Soon the rising pressure in
the interior forces open the semilunar valves, and then a column
of blood is discharged into the aorta and pulmonary artery as long
as the contraction lasts. During this interval the flow at the
venous end of the heart continues, the blood being received into
the yielding auricles. Indeed, this capacity for receiving the
venous inflow during the comparatively long-lasting ventricular
systole may be considered as one valuable mechanical function
fulfilled by the auricles. The venous flow is never completely
blocked and at the most suffers only a slight retardation during
the very brief auricular systole. At the end of the ventricular sys-
tole the excess of pressure in the aorta and the pulmonary artery
closes the semilunar valves and completes the cycle.

Time Relations of Systole and Diastole. — The duration of the
separate phases of the heart beat depends naturally on the rate
of beat. Assuming a low pulse rate of 70 per minute, the average
duration of the different phases may be estimated as follows:

Ventricular systole = 0.379 sec.

Ventricular diastole and pause = 0.483 "

Auricular systole =0.1 to 0.17 "

Auricular diastole and pause = 0.762 to 0.692 "

Einthoven and Geluk, in the investigation referred to above,
measured the time intervals of systole and diastole during fifteen
heart periods of a healthy man, and found that the time for the
ventricular systole varied between 0.312 and 0.346 sec., while that
for the diastole varied from 0.385 to 0.518 sec. Experiments by
a number of observers indicate that in the great changes of rate
which the heart may undergo under normal conditions the diastolic
phase is affected relatively much more than the systolic, as we
should expect.

The Normal Capacity of the Ventricles and the Work
Done by the Heart. — Various efforts have been made to measure
the normal capacity of the ventricles, but the determination has
encountered many difficulties. Experiments and observations made
upon the excised heart are of little value, since the distensible
walls of the ventricles yield readily to pressure, and it is difficult
or impossible to imitate exactly the conditions of pressure that
prevail during life. Nor is it certain whether normally the ventricles
empty themselves completely during systole. The older observers

508 CIRCULATION OF BLOOD AND LYMPH.

(Volkmann, Vierordt) attempted to arrive at a determination of the
normal output of the ventricles by calculations based upon the
velocity of the blood in the carotid and the width of the stream
bed. From observations on many animals they arrived at the
generalization that at each systole the amount of blood ejected
from the ventricles is equal to about T^ °f the body weight. For
a man weighing, say, 72 kilograms (158 Ibs.) this ratio would give
an output for each systole of 180 gms. (6 ozs.). More recent
observers, however, have found this estimate too high. Howell
and Donaldson* measured the output directly for the heart of the
dog, making use of a heart isolated from the body and kept beating
by an artificial circulation. The ratio of the output varied with the
rate of beat; for a rate of 180 beats per minute it was equal to
0.00117 (TST) °f the body weight; for a rate of 120 beats per minute
it was equal to 0.0014 (y^j-). This ratio is therefore about one-half
of that proposed by Volkmann. Tigerstedt, from observations
upon rabbits, obtained a lower ratio still (0.00042); but from his
own results and those obtained by other workers he concludes!
that an average valuation for the volume of blood discharged by
each ventricle of the human heart is from 50 to 100 c.c. On this
basis one may make an approximate estimate of the work done
at each beat. Using Tigerstedt's figures, such results as the follow-
ing are obtained: On the left side the heart empties its 100 c.c.
against a pressure of 150 mms. Hg. (0.150 meter) and on the right
side against a pressure of, say, 60 mms. Hg. (0.06 meter). The
work done is calculated from the formula w=pr, in which p repre-
sents the weight of the mass thrown out and r the resistance or
mean aortic pressure. This latter factor must be multiplied by
13.6, the density of mercury, to reduce to a column of blood.

Lett ventricle, 100 gms. X (0.150 X 13.6) = 204.0 grammeters.
Right " 100 " X (0.06 X 13.6) = 81.6

285.6 grammeters.

To this must be added the energy represented by the velocity
of the mass ejected into the aorta. Placing this velocity at 500
mms. (0.5 meter) for both aorta and pulmonary artery, the energy
represented in mechanical work is estimated from the formula ~
in which p represents the weight of the mass moved, v the velocity
of its movement, and g the accelerating force of gravity. Applying
this formula we have for each ventricle ^^^= 1.28 grammeters,
or fer both ventricles 2.56 grammeters, making a total of over 288

* Howell and Donaldson, " Philosophical Transactions/' Royal Soc., Lon-
don, 1884.

t Tigerstedt, "Lehrbuch der Physiologic des Kreislaufes," p. 152, 1893.

THE HEART BEAT. 509

grammeters of work. That is, the mechanical work done at each
contraction of the heart is equal to that necessary to raise 288 gms.
a meter in height. The calculations made by different authors as
to the amount of blood discharged from each ventricle during
systole may be tabulated as follows:

Thomas Young 45 gms.

Volkmann 188

Vierordt .*. . 180

Fick 50-73

Howell and Donaldson 75-90

Hoorvveg 47

Zuntz 60

Tigerstedt 50-100

Plumier 70

Loewy and v. Schrotter .... 55

for weight of 72 kgms.

« « ti U II

65

60-65 kgms.

The Coronary Circulation during the Heart Beat. — The

condition of the blood-flow in the coronary vessels during the phases
of the heart beat has been the subject of much speculation and
experiment, since it has entered as a factor in the discussion of
several mechanical and nutritive problems that are connected with
the physiology of the heart. According to a view usually attributed
to Thebesius (1708), the flaps of the semilunar valves are thrown
back during systole and shut off the coronary circulation, and
therefore the coronary vessels, unlike those of other organs, are
filled during diastole. In modern times this view has been revived
by Briicke, who made it a part of his theory of the " self-regulation "
of the heart beat. According to this view, the coronaries are shut
off from the aorta during systole by the flaps of the semilunar valves,
so that the contraction of the ventricle is not opposed by the
distended arteries, while, on the other hand, the reinjection of these
vessels from the aorta during diastole aids in the dilatation of the
ventricular cavities. Experimental work has shown decisively that
the part of this theory relating to the closure of the coronary arteries
by the semilunar valves is incorrect.* Records of pressure changes
in the coronary arteries during the heart beat made by Martin and
Sedgwick and by Porter show that they are substantially identical
with those in the carotid or aorta, and records of the velocity of the
blood-flow made by Rebatel show that at the beginning of systole
the flow in the coronaries suffers a sudden systolic acceleration as in
the case of other arteries. During systole, therefore, the mouths of
the coronary arteries are in free communication with the aorta.
But the coronary system — arteries, capillaries, and veins — is in
part imbedded in the musculature of the ventricles, and we should
suppose that the great pressure exerted by the contracting muscu-

*See Porter, "American Journal of Physiology," 1, 145, 1898, for dis-
cussion and literature.

510 CIRCULATION OF BLOOD AND LYMPH.

lature would at the height of systole clamp off this system and stop
the coronary circulation. That this result really happens is indi-
dicated by Rebatel's curves of the velocity of the flow in the coro-
nary arteries. As shown in Fig. 215, the great acceleration (a) in
velocity at the beginning of systole is quickly followed by a drop to
zero (6) or even a negative value, — that is, a flow in the other direc-
tion,, toward the aorta. At the end of the first (relaxation) phase
of diastole there is again a sudden increase in velocity (c), corre-
sponding with the injection of the arteries from the aorta, followed
again by a decrease at the end of the diastole at the time when the
ventricular cavity is filled with venous blood under some pressure.
Porter, moreover, has shown in an interesting series of experiments
that when a piece of the ventricle is kept beating, by supplying it
with blood through its nutrient artery from a reservoir at con-
stant pressure, each systole causes a jet of blood from the sev-

Fig. 215. — Simultaneous record of the blood -pressure (4) and the blood-velocity (B)
in the coronary arteries (Chauveau and Rebatef): a, Marks the beginning of the systole
(there is a rise in pressure and in velocity) ; 6, marks a second rise of pressure (.A) due to
the closure of the coronary capillaries* by the contracting ventricle (at this moment in B
the velocity falls off rapidly) ; c, curve (B) shows an increase in velocity due to the open-
ing of the small coronary vessels at the beginning of diastole.

ered vessels at the margin of the piece. In fact, the rhythmical
squeeze of its own vessels during systole accelerates effectively the
coronary circulation. The volume of blood flowing through the
heart vessels increases with the frequency or the force of the beat,
since each systole empties the coronary system more or less com-
pletely toward the venous side and at each diastole the distended
aorta quickly fills the empty vessel.

The Suction-pump Action of the Heart. — So far in con-
sidering the mechanics of the circulation attention has been directed
only to the force-pump action of the heart. All of the energy of the
circulation, the velocity of the flow and the internal pressure, has
been referred to the force of contraction of the ventricles as the
main cause, and to certain accessory factors, such as the respiratory
movements and the contractions of the skeletal muscles, as subsid-
iary causes. It is possible, however, that the heart may also act as

THE HEART BEAT. 511

a suction-pump, sucking in blood from the venous side in conse-
quence of an active dilatation. According to this view, the heart
works after the manner of a syringe bulb, which when squeezed
forces out liquid from one end and when relaxed sucks it in from
the other in consequence of its elastic dilatation. While this view
has long been entertained, modern interest in it was aroused chiefly
perhaps by the experiments of Goltz and Gaule, which showed that
at some point in the heart beat there is or may be a strong negative
pressure in the interior of the ventricles.* Their method consisted
in connecting a manometer with the interior of the ventricle and
interposing between the two a valve that opened only toward the
heart. The manometer was thus converted into a minimum
manometer, which registered the lowest pressure reached during
the period of observation. By this method they and others have
shown that in an animal (dog) with an opened thorax the pressure
in the interior of the ventricles may be negative to an extent equal
to 20, 30, or even 50 mms. of mercury. Moreover, by the use of
some form of elastic manometer, such as the Hiirthle instrument
(p. 462), it has been shown that this negative pressure occurs at the
end of the period of relaxation, at the time, therefore, at which it
might be supposed to exert a marked influence upon the inflow of
venous blood. It should be added, however, that a negative
pressure can not be shown for every heart beat. It may be absent
altogether or slight in amount, varying, no doubt, with the force of
contraction and the condition of the heart. Physiologists have
attempted to determine the cause of this negative pressure and the
extent of its influence on the blood-flow. With regard to the first
question, so many answers have been proposed that it is difficult
to arrive at a satisfactory opinion. According to some, the heart
tends to dilate at the end of its systole by virtue of its own elasticity,
— that is, the elasticity of its own musculature or of the connective
tissue contained in its substance, for example, beneath the en-
docardium, in the walls of the arteries, etc. This view, however,
finds little or no support from direct experiments made upon the
fresh, living heart. If such a heart in a bloodless condition is
squeezed by hand there is no evidence of an elastic recoil as in the
case of a syringe bulb. Others have explained the negative pressure
as due not to a simple elastic expansion, but to what may be
called a physiological expansion, — that is, an expansion due to
physiological processes, such as anabolic changes. Such a view,
however, is at present more or less speculative and can not be con-
clusively demonstrated. Still others have traced the expansion of

* For a complete discussion of this subject and the literature see the ar-
ticle by Ebstein, " Die Diastole des Herzens," in the " Ergebnisse der Physi-
ologic," vol. iii, part n, 1904.

512 CIRCULATION OF BLOOD AND LYMPH.

the ventricle and the resulting negative pressure to the sudden in-
jection of the coronary system from the aorta at the beginning of
diastole. The heart in contracting exerts a force greater than that
of the blood in the coronary vessels, and probably, therefore, these
vessels are emptied and their cavities obliterated in part. At the
beginning of diastole they are reinjected with blood under a pressure
of perhaps 100 mms. of mercury, and this fact seems to offer a
probable explanation for a partial dilatation of the ventricular cavity
and a production of negative pressure in the brief interval before the
opening of the auriculo- ventricular valves. No view, however, has
met with general acceptance, and the cause or causes that produce the
negative intraventricular pressure are still a subject for investiga-
tion. Regarding the second question proposed above, — namely,
the extent of the influence of this negative pressure on the flow
of venous blood to the ventricles, — much diversity of opinion also
exists. Direct experiments made by Martin and Donaldson*
indicate that this factor has little or no actual influence upon the
venous flow. These authors used an isolated dog's heart kept
beating by an artificial supply of blood. At a given moment the
stream of blood into the vena cava was shut off and the auricle of
the heart was brought into communication with a U tube filled
with blood. It was found that the auricle took blood from this
tube only so long as the pressure in it was positive. Although the
heart continued to beat vigorously, whatever negative pressure was
present in the ventricle was unable to suck any blood into the
auricle from the U tube. Porter f also has shown that at the time
of a strong negative pressure in the ventricle the auricle may. give
little or no evidence of a similar fall in pressure. It would seem
most probable, therefore, that the negative pressure observed under
certain conditions in the ventricles is a fleeting phenomenon, and
disappears with the entrance of the first portion of the blood from
the auricles. While it may be of value in accelerating the opening
of the auriculo- ventricular valves, its influence does not extend to an
actual suction of the blood from the veins toward the heart. Other
authors, however, on theoretical grounds attribute more actual im-
portance to the negative pressure as a factor in moving the blood.
Occlusion of the Coronary Vessels. — The coronary vessels
supply the tissues of the heart with nutrition, including oxygen,
so that if the circulation is interrupted the normal contractions soon
cease. The branches of the large coronaries form what are known
as terminal arteries, — that is, each supplies a separate region of the

* Martin and Donaldson, " Studies from the Biological Laboratory, Johns
Hopkins University," 4, 37, 1887; also Martin's "Physiological Papers,"
Baltimore, 1895. See also, for confirmatory results, von den Velden, " Zeit-
schrift f. exp. Pathol. u. Therapie, 1906, iii., 432.

t "Journal of Physiology," 13, 513, 1892.

THE HEART BEAT. 513

musculature, and although anastomoses may exist they appear
to be too incomplete to allow a collateral circulation to be estab-
lished when one of the main arteries is occluded. The portion of
the heart supplied by it dies, or to use the pathological term, under-
goes necrosis. On account of the pathological interests involved —
the known serious results that may follow occlusion of any of the coro-
nary vessels or even any interference with the normal structure of the
vessels — a number of investigations have been made upon animals
to determine the effect of occluding one or more of the coronary
vessels.* It would seem from Porter's experiments that the results
of such an operation vary according to the size of the area deprived
of its blood. When the arteria septi alone was occluded the heart
was not affected, when the arteria coronaria dextra was occluded
the ventricular contractions were arrested in 18 per cent, of the
cases observed. Occlusion of the ramus descendens of the left
coronary artery caused arrest of the ventricles in 50 per cent, of the
cases, while occlusion of the circumflex branch of the same artery
caused arrest in 80 per cent, of the cases. Ligation of three of the
arteries caused stoppage of the heart in all cases.

Fibrillar Contractions. — The arrest of the ventricles in the
experiments just described followed immediately or within a short
period, and the ventricles went into fibrillar contractions. In this
curious condition the various fibers of the ventricular muscle, in-
stead of contracting together in a co-ordinated fashion, contract
separately and irregularly; so that the surface of the ventricle has
the appearance of a vibrating, twitching mass. Such a condition
in the ventricle is usually fatal, — that is, the musculature is not able
to recover its co-ordinated movement. This condition may come
on with great suddenness as the result of occlusion of the arteries,
of injury to certain parts of the heart, or from strong electrical
stimulation. Fibrillation of the auricles also occurs frequently
under experimental conditions, but the musculature in this part of
the heart seems to be able to return to its normal co-ordinated
contractions with much less difficulty. The cause of the sudden
change from co-ordinated to fibrillar contractions has never been
satisfactorily explained. In this connection it is interesting to
recall also that when any injury is done to either ventricle suf-
ficient to stop the contractions or cause fibrillation both ventricles
stop together. This result is doubtless due to the fact that their
musculature is, after all, one set of fibers common to both chambers.

* For a description of results and the literature see Porter, " Journal of
Physiology," 15, 121, 1893; also "Journal of Experimental Medicine," 1, 1.
1896.

CHAPTER XXIX.

THE CAUSE AND THE SEQUENCE OF THE HEART
BEAT— PROPERTIES OF THE HEART MUSCLE.

General Statement. — The cause of the heart beat has naturally
constituted one of the fundamental objects of physiological inquiry.
The various views that have been proposed in different centuries
reflect more or less accurately the advancement of the science.
With each new discovery of general significance a new point of view
is obtained and the theories of the heart beat, like those of the other
great problems of physiology, shift their standpoint from generation
to generation. The general modern conception of this problem
is referred usually to Haller (1757), who first taught that the
activity of the heart is not dependent on its connections with the
central nervous system. As we shall see, the heart beat is controlled
and influenced constantly by the central nervous system, but never-
theless the important point has been established beyond question
that the heart continues to beat when all these nervous connections
are severed. The central nervous system regulates the activity of
the heart, but has nothing to do with the cause of its rhythmical
contractions. The heart, in other words, is an automatic organ.
When in 1848 Remak discovered that nerve cells are contained in
the frog's heart it was natural that the causation of the beat should
be attributed to this tissue. Subsequent histological work has
demonstrated the existence of numerous nerve cells in the substance
of the heart tissue of all vertebrates, and the view that the au-
tomaticity of the heart is due in reality to the properties of the
contained nerve cells was the prevalent view throughout the
middle and latter part of the nineteenth century. In the latter part
of the century an opposite view arose, — namely, that the muscular
tissue of the heart itself possesses the property of automatic
rhythmical contractility. Both these points of view persist to day.
The theory that refers the automaticity of the heart beat to the
contained nerve cells is designated as the neurogenic theory of the
heart beat; the one that refers this property to the muscle tissue
itself is known as the myogenic theory. Beyond this question lies
the still deeper problem of the explanation of the automaticity
itself, the cause or causes of the rhythmical excitation, whether
occurring primarily in the muscle cells or in the nerve cells.

514

PROPERTIES OF THE HEART MUSCLE. 515

The dividing line between the ancient and the modern views of the heart
beat is found in the work of William Harvey (1628). Before his time physi-
cians thought along the lines laid down by the ancient masters, Hippocrates,
Aristotle, and Galen, in that they believed that the diastole of the heart is
the active part of the beat. They believed that the heart dilated at the mo-
ment of the apex beat, the dilatation being due to the implanted heat, the
vital spirits, a special pulsatile force, etc. The arteries dilated at the same
time for a similar reason. For a period of over two thousand years men's
minds were so chained to this belief that they apparently could take no other
view. Harvey, however, had, the boldness and originality to look at the
matter differently. He saw and proved that the active movement of the heart
is a contraction during systole, which drives blood out of the ventricles into the
arteries, and consequently that the pulse of the arteries is not due to their
active dilatation, but to a distension by the blood forced into them. Harvey
may be considered also as the founder of the myogenic theory of the heart
beat. For although he did not speculate concerning the cause of the beat,
he taught that the systole is an active contraction of the heart's own muscu-
lature not dependent upon any external influence. In the same century the
first neurogenic hypothesis was formulated. Willis conceived that the cere-
bellum controls the activity of the involuntary organs-, including the heart.
The animal spirits engendered in the cerebellum were conveyed to the heart
by the vagus nerve and caused its beat. Borelli formulated a somewhat
different view. According to him the nerve juice, succus spirituosus, elabo-
rated in the central nervous system was transmitted to the heart through the
cardiac nerves and, distilling slowly into the musculature, set up an ebullition
which caused an active expansion of the fibers. This expansion constituted
the systole and drove the blood out of the heart. Both of these views were
disproved or rendered improbable largely by the work of Haller, who in 1757
published the second myogenic theory in a form which, somewhat modified,
prevails to-day. Haller believed that the contraction of the heart is due to the
inherent irritability of its musculature, and that the venous blood as it enters
the heart stimulates it to contraction. Haller's views were generally accepted
for some years, but some physiologists continued to believe that the heart beat
is controlled directly by the central nervous system. This theory found its
most definite expression in the work of Legallois, 1812, who advanced what
may be called the second neurogenic hypothesis. From experiments made
upon animals he concluded that the principle or force that causes the heart
beat is formed in the spinal cord, in all of its parts, and reaches the heart
through the branches of The sympathetic nerve supplying this organ. Legallois's
conclusions wrere soon shown to be erroneous, but the general view advocated
by him was entertained by some as late as the middle of the 19th century,
in fact until experimental physiology had demonstrated the true functions
of the vagus and accelerator nerves writh reference to the heart. Toward the
middle of the 19th century a third form of neurogenic hypothesis arose, which
in the beginning seems to have been due to the work or the system of Bichat.
According to this author the ganglionic or sympathetic system supplies the
tissues of the organic life, meaning thereby the visceral organs which are not
under the direct influence of the will. In 1844 Remak discovered that the
heart possesses intrinsic nerve ganglia, and this fact seems to have induced most
physiologists to believe that these ganglia constitute a motor center for the
heart, initiating and co-ordinating its beat. For a period of forty years this
form of the neurogenic hypothesis enjoyed almost universal acceptance. In
1881-83 Gaskell published experiments upon the heart of the frog and tortoise
in which he gave strong reasons for believing that the beat is myogenic in
origin, and that the intrinsic ganglia are simply a part of the inhibitory ap-
paratus of the heart. Since that time many physiologists have adopted the
myogenic view, and the current arguments tending to support this rather than
the neurogenic hypothesis are presented in the text. The most significant
addition to our knowledge of the cause of the heart beat made during the
last quarter of a century is the discovery that the inorganic salts of the blood
and lymph play a special and essential role. The facts bearing upon this
interesting discovery are sufficiently described in the text.

516 CIRCULATION OF BLOOD AND LYMPH.

The Neurogenic Theory of the Heart Beat. — The literature
upon this topic is very large.* The neurogenic theory has suffered
some changes in its details since first proposed by Volkmann,
particularly in the specific functions assigned to the different ganglia
that exist in the heart. In general, however, the theory assumes
that the excitation to each beat arises within the nerve cells, and
since the cardiac cycle begins with a contraction at what may be
called the venous end of the heart, — that is, at the junction of the
veins with the auricles, — it is assumed that the excitation or inner
stimulus arises in the nerve cells situated in this region. These cells
constitute, therefore, what may be called the automatic motor
center of the heart. The stimuli generated within it are transmitted
through its axons first to the musculature of the venous end of
the heart. The subsequent orderly march of this contraction, to
auricles and then to ventricles, is also upon this theory usually
attributed to the intrinsic nerve cells and fibers. Through a definite
mechanism the impulses generated in the motor center are trans-
mitted to subordinate nerve centers through which the auricles are
excited, and then to other nerve cells lying in or near the auric ulo-
ventricular groove through which the ventricles are excited. In
this form the theory assumes for the heart an intrinsic central
nervous system, as it were, with a principal motor center in which
the property of automaticity is chiefly developed and subordinate
centers whose activity usually depends upon the principal center,
but which may show automatic properties of a lower order if the
connections between them and the main center are interrupted.
This intrinsic nervous system is responsible not only for the spon-
taneous origination and normal sequence of the beat, but also fpr
its co-ordination. The many muscular fibers of the ventricle
contract normally in a definite manner and sequence, so that their
effect is summated. Under abnormal conditions the fibers may
contract irregularly, giving the so-called fibrillar contractions of the
heart, which are inco-ordinated. It may be said that this con-
ception of the connections of the intrinsic nervous system rests
mainly upon deductions from physiological experiments. The
histological details regarding the connections of the nerve cells in the
heart are not yet sufficiently known, but it can not be said at present
that they give any positive support to such a view. In regard to
the neurogenic theory the following general statements may be made :

1. Most of the very numerous facts known regarding the heart

* For recent general presentations from different standpoints see Gaskell,
article on " The Contraction of Cardiac Muscle," in Schafer's " Text-book of
Physiology," vol. ii, 1900; Langendorff, "Herzmuskel und intrakardiale In-
nervation" in "Ergebnisse der Physiologic," vol. i, part n, 1902; and Cyon,
" L'innervation du cceur " Richet's " Dictionnaire du Physiologic." vol. iv,
1900.

PROPERTIES OF THE HEART MUSCLE. 517

beat and its variations under experimental conditions may be
explained in terms of the theory, or at least do not contradict it.
The same statement, however, may be made regarding the myogenic
theory. Both theories may be applied successfully from a logical
standpoint to the explanation of known facts.

2. No single fact is known which can be cited as positive proof
that the nerves participate in the production of the normal beat
of the vertebrate heart. The experiment by Kronecker and Schmey
is sometimes given this significance. These observers have shown
that, when a needle is thrust into a certain spot in the dog's
ventricle, the regularly contracting heart falls suddenly into fibrillar
contractions so far as the ventricles are concerned. The ex-
periment is certainly a striking and interesting one. The needle
may be thrust many times into certain portions of the muscu-
lar mass without affecting the powerful co-ordinated contractions,
but in the region specified by Kronecker a single puncture, if
it reaches the right spot, causes the ventricle to fall into ir-
regular fibrillar twitches from which it does not recover. The
spot as described by Kronecker is along the line of the septum at the
lower border of its upper third. The experiment frequently fails;
and it would seem that there must be a definite and quite circum-
scribed structure whose lesion produces the effect described. We
have no evidence as yet what this structure is, and are therefore in
no condition to make positive inferences with regard to the bearing
of the experiment upon the origin of the heart beat. Carlson *
has described experiments upon the heart of the horseshoe crab
(Limulus) which seem to show conclusively that in this animal
the rhythmical contractions are dependent upon the intrinsic nerve
cells. These latter are placed superficially, forming a cord that
runs the length of the tubular heart. When this cord is removed
the heart ceases to beat. There are reasons, however, which at
present make it doubtful whether we can apply the results of this
experiment to the vertebrate heart. The crustacean heart differs
from the vertebrate heart in its fundamental properties; unlike the
latter, it has no refractory period (see p. 523), can be tetanized, and
gives submaximal contractions.f It is a tissue, therefore, that
resembles in its properties ordinary skeletal muscle in the verte-
brate, and, like this muscle, it seems to be lacking in automaticity.
Carlson's experiments give, however, another instance of automatic
rhythmicity in nerve tissue, and to that extent support the neuro-
genic theory.

The Myogenic Theory of the Heart Beat. — The myogenic

* Carlson, "American Journal of Physiology," 12, 67, and 471, 1905.
t Hunt, Bookman, and Tierney, " Centralblatt f. Physiologie," 11, 275,
1897.

518 CIRCULATION OF BLOOD AND LYMPH.

theory has been developed chiefly by Gaskell and by Engelmann.
It assumes that the heart muscle itself possesses the property of
automatic rhythmicity and that this property is most highly de-
veloped at the venous end. This portion of the heart, therefore,
contracts first and the wave of contraction spreads directly to the
musculature of the auricle and thence to that of the ventricle. The
quickly beating venous end sets the pace, as it were, for the entire
heart. The nerve cells and nerve fibers that are present in the heart
are upon this theory supposed to be connected with the extrinsic
nerves through which the rate and force of the heart beat are regu-
lated, but they are not concerned in the production of the beat.
Many experimental facts have been accumulated which give
probability to this view, and it has been adopted by many, perhaps
most, of the recent workers in this field. Some of the facts that
favor this theory are as follows:

1. The anatomical arrangement of the musculature of the
heart is not opposed to such a theory. It was formerly stated quite
positively that there is no muscular connection between the auricles
and ventricles in the mammalian heart, but a number of observers
have now demonstrated the existence of a muscular bridge, the
auriculo- ventricular bundle, between the two chambers (see p. 496).

2. The fact that a contraction started at one part of the heart
may travel to other portions through the intervening musculature
may be said to be demonstrated. Thus, Engelmann has shown
that if the ventricle in the frog's heart is cut in a zigzag fashion,
so that strips are obtained which are connected only by narrow
bridges, a stimulation applied at one end starts a wave of con-
traction which propagates itself over all of the pieces. This and
similar experiments scarcely permit of explanation on the supposi-
tion that conduction from piece to piece is effected by a definite
nervous mechanism. So too it has been shown that under certain
conditions the normal auriculo-ventricular rhythm can be changed
at will to a ventriculo-auricular rhythm. If, for instance, a ligature
be tied around the frog's heart between the sinus venosus and the
auricle (first ligature of Stannius) the auricle and ventricle cease
to beat. In this quiescent condition a slight mechanical stimulus
to the ventricle causes it to beat and its contraction is immediately
followed by that of the auricle. A similar reversed rhythm may be
obtained from the mammalian heart under suitable conditions.
Such an experiment makes it most probable that the contraction
is propagated from one chamber to the other directly through
the muscular connections. It is not possible at present to conceive
that a definite mechanism of neurons should work thus in either
direction.

3. There is much probable proof that the heart muscle tissue
possesses the property of automatic rhythmical contractions. Ex-

PROPERTIES OF THE HEART MUSCLE. 519

periments, initiated by Gaskell and since extended by numerous
observers, show that in the cold-blooded animals strips of heart
muscle taken from various parts of the heart will under proper
conditions develop rhythmical contractions. It is very improbable
that each of these strips, no matter how made, contains its own
resident nerve cells or nerve tissue which act as a motor center.
These results seem to demonstrate an inherent property of rhythm-
icity in cardiac muscle, whether or not this rhythmicity is directly
responsible for the normal beat.

4. It has been shown that in the embryo chick the heart pul-
sates normally before the nerve cells have grown into it, and it
is stated that in the hearts of a number of invertebrates no nerve
cells can be found. Much weight can not be given, however, to
negative evidence of this kind, since, in the first place, better
technical methods may demonstrate the existence of such cells,
and even if absent from the heart itself it is conceivable that they
may be present in the surrounding tissue and send their fibers
to the heart. It is evident from this brief and imperfect presenta-
tion that it is not possible to claim that either the neurogenic or
the myogenic theory is demonstrated, but most physiologists per-
haps at present believe that the latter view is more in accord
with the facts.*

Automaticity of the Heart. — As was said above, the ques-
tion of the cause or causes of the automatic rhythmical con-
tractions must be sought for whether the phenomenon turns out to
be a property of the muscular tissue or of the nervous tissue of the
heart. When we say that a given tissue is automatic we mean
that the stimuli which excite it to activity arise within the tissue
itself, and are not brought to it through extrinsic nerves. In the
heart, therefore, we assume that a stimulus is continually being
produced, and we speak of it as the inner stimuli's. Experiment and
speculation have been directed toward unraveling the nature of
this inner stimulus. Most of the physiologists who have expressed
an opinion upon the subject have sought an explanation in the
composition of the blood or lymph bathing the heart tissue, or in the
products of metabolism of the tissue itself. Regarding this latter
view there is nothing of the nature of direct experimental evidence
in its favor. No product of the metabolism of the heart tissue
capable of exerting this stimulating effect has been isolated. In
regard to the former view, that the inner stimulus is connected
with a definite composition of the blood or lymph, there has been
considerable experimental work wrhich is of fundamental signifi-
cance. While the older 'physiologists paid attention mainly to the

* For a compromise view, partly myogenic and partly neurogenic, see
Fredericq, "Archives internationales de Physiologic, " 1906, iv., 57.

520 CIRCULATION OF BLOOD AND LYMPH.

organic substances in the blood, it has been shown in recent years
that the inorganic salts are the elements whose influence upon
the heart beat is most striking. These salts are in solution in the
liquid of the tissue' and are therefore probably more or less com-
pletely ionized. Attention has been directed mainly to the influence
of the metallic ions, the cations, of which three are especially
important,— namely, the sodium, the calcium, and the potassium.

The Action of the Calcium, Potassium, and Sodium Ions in
the Blood and Lymph. — It has long been known that the heart
of a frog or terrapin may be kept beating normally for hours after
removal from the body, provided it is supplied with an artificial
circulation of blood or lymph, so arranged that this liquid enters
the heart through the veins from a reservoir of some sort and is
pumped out through the arteries leading from the ventricle. It
was first shown by Merunowicz, working under Ludwig's direction,
that an aqueous extract of the ash of the blood possesses a similar
action.

Ringer afterwards proved that the frog's heart can be kept
beating for long periods upon a mixture of sodium chlorid, potassium
chlorid, and calcium phosphate or chlorid, and he laid especial
stress upon the importance of the calcium. This work was after-
wards confirmed and extended by Howell, Loeb, and others, who
attempted to analyze the part played by the several ions.* If
a frog's or terrapin's heart is fed with a solution of physiological
saline (Nad, 0.7 per cent.) it beats well for a while, but the
beats soon weaken and gradually fade out. If in this condition
the heart is fed with a proper mixture of sodium, potassium,
and calcium chlorids it beats vigorously and well for very many
hours. A solution containing these three salts in proper propor-
tions is known usually as Ringer's mixture. The exact com-
position has been varied by different workers, but for the heart
of the frog or terrapin the following composition is most effective :

NaCl . = 0.7 percent.

KC1 = 0.03

CaCl = 0.025 "

The addition of a trace of alkali, HNaCO3, 0.003 per cent.,
often increases the effectiveness of the solution, but it can not be
considered an essential constituent in the same sense as sodium,
potassium, and calcium. It has been shown, moreover, that even
the mammalian heart can be kept beating for long periods when
fed with a Ringer solution if provision is made for a larger supply

* For literature and discussion see Howell, "American Journal of Phys-
iology," 2, 47, 1898, and 6, 181, 1901, and "Journal of the American Medical
Association," 1906.

PROPERTIES OF THE HEART MUSCLE. 521

of oxygen than can be obtained by simple exposure to the air.
For the irrigation of the isolated mammalian heart different
forms of Ringer's solution have been employed, but the mixture
most frequently used is that recommended by Locke, consisting
of NaCl, 0.9 per cent.; CaCl2, 0.024 per cent.; KC1, 0.042 per
cent.; NaHCO3, 0.01 to 0.03 per cent.; and dextrose, 0.1 per cent.
The solution is fed to the heart under an atmosphere of oxygen,
and with this solution Locke and others have kept the mammalian
heart beating for many hours. The dextrose, while not essential
to the action of the irrigating liquid, is said to increase its efficiency.
The general fact that comes out of these experiments is that the
heart can beat for very long periods upon what has been called
an inorganic diet. Moreover, the salts that are used cannot be
chosen at random; it is necessary to have salts of the three metals
named, and substitution is possible only to a very limited extent.
Thus, strontium salts may replace those of calcium more or less
perfectly.

It is evident that these salts play some very important part
in the production of the rhythmical beat of the heart; and analysis
has shown that the sodium, calcium, and potassium has each
its special role. We may say that the presence of these salts
in normal proportions is an absolute necessity for heart activity.
A striking experiment which shows the importance of the calcium
is to irrigate a terrapin's heart with blood from which the
calcium has been removed by precipitation with sodium oxalate.
In spite of the fact that all other constituents of the blood are
present the heart ceases to beat, and normal contractions can be
started again promptly by adding calcium chlorid in right amounts
to the oxalated blood. Regarding the specific part taken by each
of the cations in the production of the alternate contractions and
relaxations, much diversity of opinion exists, owing to our ignorance
of the chemical changes going on in the heart during systole and
diastole and to the difficulty of controlling experimental conditions.
Thus, while it is an easy matter to control accurately the com-
position of the liquids supplied to the heart, a variable and uncon-
trollable factor is introduced by the fact that within the tissue
elements themselves there is a store of combined calcium, potassium,
and sodium which may serve to supply these elements to a greater
or less extent to the tissue liquids.

The controversial details upon this question can not be presented
in an elementary book, but the following brief statements may
be made regarding one view of the specific effects of the separate
cations: (1) The sodium salts in the blood and lymph take the
chief part in the maintenance of normal osmotic pressure. The

522 CIRCULATION OF BLOOD AND LYMPH.

sodium chlorid exists in blood-plasma to the extent of 0.5 to 0.6
per cent., and the normal osmotic pressure of the blood is mainly
dependent upon it. A solution of sodium chlorid of 0.7 to 0.9 per
cent, forms what is known as physiological saline, and although
not adequate to maintain the normal composition and properties
of the tissues it fulfills this purpose more perfectly than the solution
of any other single substance. The sodium ions have in addition
a specific influence upon the state of the heart tissue. Contractility
and irritability disappear when they are absent ; when present alone,
in physiological concentration, in the medium bathing the heart mus-
cles they produce relaxation of the muscle tissue. (2) The calcium
ions are present in relatively very small quantities in the blood, but
they also are absolutely necessary to contractility and irritability.
When present in quantities above normal or when in a propor-
tional excess over the sodium or potassium ions they cause a con-
dition of tonic contraction that has been designated as calcium
rigor. (3) The potassium ions are present also in very small quan-
tities, and, unlike the calcium and sodium ions, their presence in
the circulating liquid does not seem to be absolutely necessary to
rhythmical activity. Under proper conditions a terrapin's heart
beats well for a time upon a solution containing only sodium and
calcium salts. The potassium seems to promote relaxation of the
muscle and in physiological doses it exercises through this effect
a regulating influence upon the rate of beat. When the proportion
of potassium ions is increased the heart rate is proportionally
slowed, and finally the contractions cease altogether, the heart
coming to rest in a state of extreme relaxation, known sometimes
as potassium inhibition. (4) It appears from these statements
that there is a well-marked antagonism between the effects of the
calcium, on the one hand, and the potassium and sodium, on the
other. The calcium promotes a state of contraction, the sodium
and the potassium a state of relaxation. It is conceivable, there-
fore, that the alternate states of contraction and relaxation which
characterize the rhythmical action of heart muscle are connected
in some way with an interaction of an alternating kind between
these ions and the living contractile substance of the heart. It is
impossible to say positively whether or not the inorganic salts
are directly connected with the cause of the beat, — that is, with
the origination of the inner stimulus. According to one point of
view, they are necessary only to the irritability and contractility
of the heart tissue. The inner stimulus is produced otherwise
by some unknown reaction, but it is not able to cause a contraction
of the heart muscle in the absence of the proper inorganic salts.
According to another view, the reaction of these ions with the

PROPERTIES OF THE HEART MUSCLE. 523

living substance constitutes or leads to the development of the
inner stimulus.

Physiological Properties of Cardiac Muscle. — Cardiac muscle
exhibits certain properties which distinguish it sharply from skeletal
muscular tissue and which have a direct bearing upon the rhyth-
micity of the contractions and the sequence shown by the different
chambers. The most characteristic of these properties are the
following :

1. The contractions of heart muscle are always maximal. In
skeletal muscle and in plain muscle the extent of contraction is
related to the strength of the stimulus, and we recognize the exis-
tence of a series of submaximal contractions of varying heights.
This is not true of heart muscle. As was first shown by Bow-
ditch, a piece of ventricular muscle when stimulated responds, if
it responds at all, with a maximal contraction. The apex of a
frog's heart does not beat spontaneously, but contracts upon
electrical stimulation. If such an apex is connected with a lever
to register its contractions, and the electrical stimulus applied to
it is gradually increased, the first contraction to appear is maxi-
mal, and it is not further increased by augmenting the stimulus.
This property is sometimes described by saying (Ranvier) that
the contraction of the heart muscle is all or none. This fact
must not, however, be interpreted to mean that the force of
contraction of heart muscle is invariable under all conditions.
Such is not the case. The heart muscle under favorable nutritive
conditions may give a much larger and more forcible contraction
than is possible under conditions of poor nutrition; but the point
is, that, whatever may be the condition of the muscle at any
given moment, its contraction in response to artificial stimulation
is maximal for that condition, — that is, does not vary with the
strength of the stimulus. As was said above, this property is not
exhibited by the crustacean (lobster) heart, but has been shown
to be true for the mammalian heart muscle.*

2. The refractory period of the beat. It was shown by Marey f that
the heart muscle is irritable to artificial (electrical) stimuli only
during the period of diastole. During the period of systole an elec-
trical stimulus has no effect; during the period of diastole such a
stimulus calls forth an extra contraction and the latent period
preceding the extra contraction is shorter the later the stimulus is
applied in the diastolic phase. This relationship is well shown by
Marey's curves reproduced in Fig. 216. The period of inexcitability
is designated as the refractory period of the heart beat. Marey

* For experiments on mammalian heart and literature, see Woodworth,
"American Journal of Physiology," 8, 213, 1903.
f Marey, " Travaux du laboratoire," 1876, p. 73.

524

CIRCULATION OF BLOOD AND LYMPH.

defined this refractory period as falling within the first part of the
systole, and stated that its duration varies with the actual strength

~

f -\ r\

r\ r

Fig. 216. — To show the effect of a short electrical stimulus applied at different times
in the heart beat. — (Marey.) The record is taken from the frog's heart. In 1, 2, and 3 the
stimulus (e) falls into the heart during systole (refractory period) and has no effect. In
4, 5, 6, 7, and 8 the stimulus falls into the heart toward the end of systole or during diastole,
and is followed by an extra systole and corresponding compensatory pause. It will be
noted that the latent period (shaded area) between the stimulus and the extra systole is
shorter the longer the diastole has preceded before the stimulus is applied.

PROPERTIES OF THE HEART MUSCLE. 525

of the stimulus. Later experiments by other investigators make it
probable that the refractory period lasts during practically the entire
systole.* According to this point of view, therefore, the heart muscle
during its period of actual contraction is entirely unirritable, and in
this respect it offers a striking difference to skeletal and plain muscle.
The existence of this refractory period explains why the heart
muscle cannot be thrown into complete tetanic contractions by
rapidly repeated stimuli. Since each contraction is accompanied
by a condition of loss of irritability, it is obvious that those stimuli
that fall into the heart during this period must prove ineffective.
The refractory period and the gradual increase in irritability during
the diastole may throw some light also on the rhythmical character
of the beat. The occurrence of the refractory period and the
subsequent gradual return of irritability are connected no doubt
with the metabolic changes taking place in the heart muscle. It
is in the character of this metabolism that we must seek for the
final explanation of these two phenomena and the cause of the
rhythmicity of the contractions. As was stated above, it has been
shown that the crustacean (lobster) heart muscle does not obey the
all-or-none law, shows no refractory period, and is capable of
giving tetanic contractions when rapidly stimulated. In all these
respects it differs from the typical heart muscle of the vertebrate,
but the difference is perhaps sufficiently explained by the discovery
(p. 517) that the crustacean heart, in one form at least, is not an
automatically rhythmical tissue. Its rhythmical contractions, like
those of the diaphragmatic muscle in the higher vertebrates, depend
upon rhythmical impulses received from nerve centers.

The Compensatory Pause. — It has been observed that when an extra
systole is produced by stimulating a ventricle it is followed by a pause longer
than usual; the pause, in fact, is of such a length as to compensate exactly
for the extra beat ; so that the total rate of beat remains the same. The pro-
longed pause under these conditions is therefore frequently designated as the
compensatory pause. It has been shown, f however, that the exact compen-
sation in this case is not referable to a property of heart muscle, but is due to
the dependence of the ventricular upon the auricular beat. When the auricle
or ventricle is isolated and stimulated the phenomenon of exact compensation
is not observed. In an entire heart, on the contrary, the beat originates at
the venous end of the auricle and is propagated to the ventricle. If the latter
chamber is stimulated so as to give an extra beat out of sequence it will remain
in diastole until the next auricular beat stimulates it, and will thus pick up
the regular sequence of the heart beat.

'The Normal Sequence of the Heart Beat. — The normal
rhythm of the heart beat is first a contraction of the auricles, then
one of the ventricles, or probably first the mouths of the great veins,
then auricle and ventricle. This sequence from venous to arterial

* See paper by Wood worth, loc. cit. Also Schultz, "American Journal of
Physiology," 1906, xvi., 483.

fCushny and Matthews, "Journal of Physiology," 21, 227, 1897.

526 CIRCULATION OF BLOOD AND LYMPH.

end is beautifully shown in the frog's heart, in which the contraction
begins in the sinus venosus, spreads to the auricles, thence to the
ventricle, and finally to the bulbus arteriosus. Under normal
conditions this sequence is never reversed, and an explanation of
the natural order forms obviously an important part of any complete
theory of the heart beat. Those who hold to the neurogenic theory
naturally explain the sequence of the beat by reference to the
intrinsic nervous apparatus. If the motor ganglia lie toward the
venous end of the heart one can imagine that their discharges may
affect the different chambers in sequence, the pause between
auricular and ventricular contraction being due, let us say, to the
fact that the motor impulses to the ventricle have to act through
subordinate nerve cells in the auriculo-ventricular region, and the
time necessary for this action brings the ventricular contraction
a certain interval later than that of the auricle. There is no
immediate proof or disproof of such a view. The numerous exper-
iments made upon the rapidity of conduction of the wave of
contraction over the heart are not conclusive either for or against
the view. The fact, however, that in the quiescent but still irritable
heart the rhythm may be reversed by artificially stimulating the
ventricle first seems to the author to speak strongly against the
dependence of the sequence upon any definite arrangement of
neuron complexes. On the myogenic theory the sequence of the
heart beat is accounted for readily by relatively simple assumptions.
Gaskell and Engelmann have each laid emphasis upon the facts in
this connection, and the application of the myogenic theory to the
explanation of the normal sequence of contractions forms one of its
most attractive features. Gaskell assumes * that the rhythmical
power of the muscle at the venous end is greater than that at the
ventricular end, — that is, if pieces from the two ends are examined
separately it will be found that the spontaneous rhythm of the
tissue from the venous end is more rapid. This portion of the
heart, therefore, beating more rapidly, sets the rhythm for the
whole organ, since a contraction started at the venous end will
propagate itself from chamber to chamber. The pause between the
contractions of the successive chambers — between auricle and
ventricle, for instance — is due, in the heart of the tortoise, to the
fact that the muscular tissue at the junction of auricle and ventricle
has a relatively low rate of conduction. At this point, indeed,
the muscular fibers form a ring around the orifice, preserving,
therefore, the arrangement found in the embryo at the time that
the heart has the form of a tube. Gaskell has given reasons for
believing that the conduction of the wave of contraction is slower

* Gaskell, "Journal of Physiology," 4, 61, 1883; also vol. ii, p. 180, of
Schafer's " Text-book of Physiology," 1900.

PROPERTIES OF THE HEART MUSCLE. 527

through this ring. In the mammalian heart the direct conduction
of the wave of contraction from auricle to ventricle through interven-
ing muscular tissue is made quite possible, since so many indepen-
dent observers have established the existence of a connecting
bundle (p. 496). If with Gaskell we assume that the conduction
through this bundle is slower than it is over the surface of the auricle
or ventricle, then the pause between auricular and ventricular
systole is sufficiently explained. That each chamber of the heart has
a rhythm of its own and that the rhythm of the venous end is the
more rapid and constitutes the rhythm of the intact heart has been
shown in various ways upon the hearts of different animals. Thus,
Tigerstedt has devised an instrument, the atriotome,* by means of
which the connections between auricle and ventricle may be
crushed without hemorrhage. Under such conditions the ventricle
continues to beat, but with a much slower rhythm and with a
rhythm entirely independent of that of the auricles. The same re-
sult has been obtained recently in a very striking way by Erlanger.
This observer arranged a clamp by means of which he could com-
press the small bundle of fibers connecting auricle and ventricle.
When the compression is made the ventricle, after an interval,
exhibits a slower rhythm and one entirely independent of that of
the auricles. When the compression is removed the ventricle falls
in again with the auricular rhythm. By variations in the pressure
upon the bundle intermediate conditions may be obtained in which
the "block" between auricle and ventricle is only partial, and in
which, therefore, the ventricular systole follows regularly every
second or third auricular contraction. When the "block" is com-
plete the ventricular rhythm ceases to have any definite relation-
ship to that of the auricle, it beats entirely independently and its
rate is slower than that of the auricle. It is interesting to remember
that cases of complete or partial heart block occur in man. In
the condition known as the Stokes-Adams syndrome the striking
feature in addition to attacks of syncope is a permanently slowed
pulse, the heart beat falling to 30 or 20 beats per minute or lower.
Erlanger has shown that in such cases there may be complete or
partial heart block. In the former condition the rhythm of the
ventricle is entirely independent of that of the auricle and of course
much slower. The ventricles may be beating at 27 per minute and
the auricles at 90. In partial block the ratio between the ventric-
ular and auricular rate is definite, every second or third auricular
beat being followed by a ventricular systole (see Fig. 217). The
lesion producing this condition has not been determined in many
cases, but it is probable that the trouble will be found in the auriculo-
*See " Lehrbuch der Physiologic des Kreislaufes," 1893.

528 CIRCULATION OF BLOOD AND LYMPH.

ventricular bundle, which constitutes the physiological link con-
necting the auricles and ventricles.*

In the hearts of the cold-blooded animals the same general
results are readily obtained when the tissue between the different
chambers is compressed or destroyed. In the frog's heart, for
instance, if one ties a ligature (first ligature of Stannius) between
the sinus venosus and the auricle, the auricle and ventricle cease
beating while the sinus continues pulsating with its normal rhythm.
Later the auricle and ventricle may commence beating again, but
if this happens their rhythm is slower than that of the sinus and
independent of it. So in the terrapin's heart, in which the sequence
of beat is so beautifully exhibited, if one ties a ligature between
auricle and ventricle, or cuts off the ventricle entirely, the sinus
venosus and auricle continue beating at their normal rhythm, while

1 2

Fig. 217. — Cardiogram from a case of Stokes-Adams disease, showing two auricular beats
(1, 2) to each ventricular beat. — (Erlanger.) The time-record marks fifths of a second.

the ventricle remains usually entirely quiescent so long as normal
blood flows through it. It would seem from these facts that in the
mammalian heart the ventricle when disconnected from the auricle
is capable of maintaining a fairly rapid rhythm of its own. At the
other extreme, the terrapin's ventricle when similarly treated shows
no spontaneous beats at all. These and many other facts that
might be quoted support well the general view proposed by Gaskell,
that the venous end of the heart possesses the greater rhythmical
power and starts the heart beat, and that the wave of contraction
is propagated from chamber to chamber through the intervening
muscular substance.

There remains a deeper question as to what occasions this greater rhyth-
micity at the venous end, — a question that is, of course, bound up with the
problem of the ultimate cause or conditions of automatic rhythmicity. In
connection with this latter problem the absolute necessity of the presence of
certain inorganic salts in certain proportions has been emphasized. In this
same general line the author has called attention to the fact that in the ter-
rapin the amount of potassium salts present in the blood explains in itself
why the sinus sets the heart rate. In blood, or in Ringer's solution con-
taining potassium salts in the same amounts as blood, the ventricular muscle
is not automatically contractile; the sinus end of the heart, on the contrary,
beats well in such media, while an increase in the potassium contents will

* See Erlanger, "Journal of Experimental Medicine," 1905, vii., 1906,
viii., and "American Journal of Physiology," 1906, xv. and xvi.

PROPERTIES OF THE HEART MUSCLE. 529

bring it to rest also. In this animal, therefore, the amount of potassium in
the blood is so adapted that it holds the ventricular end entirely quiescent.
In the mammalian heart it may be assumed that the amount of potassium is
sufficient to keep the spontaneous rhythm of the ventricle slower than that
of the auricles or veins, and therefore subordinates the rhythm of the whole
heart to that of the venous end. In the terrapin's heart, at least, the re-
moval or reduction of the potassium or the increase of the calcium may lead
to an independent ventricular rhythm — the beat of the heart becomes arhyth-
mical.

The Tonicity of the Heart Muscle. — In describing the phys-
iology of skeletal and plain muscle attention was called to their
property of tonicity, — that property by means of which they remain
in a more or less permanent although variable condition of con-
traction. So far as the skeletal muscles are concerned, this con-
dition is dependent upon their connections with the nervous system.
Cut the motor nerve, or destroy the motor center, and the muscle
loses its tone, — becomes completely relaxed. Tonicity or tonic
activity is therefore characteristic of the motor nerve centers, and
is due, no doubt, to a more or less continuous inflow of sensory
impulses into those centers. The tonus of the nerve centers is a
reflex tonus. In the plain muscle the condition of tonus is also
marked. The blood-vessels, the bladder, the various viscera are
rarely, if ever, entirely relaxed for any length of time. This tonus
is also dependent, in many cases, upon a constant innervation
through the motor nerves, but after these latter have been destroyed
the plain muscle still shows this property of tonicity. So in the
heart muscle the power to maintain a certain degree of contraction,
a certain state of muscle tension quite independently of the sharp
systolic contractions, is very characteristic. At the end of a normal
diastole, for example, the ventricle is not entirely relaxed, it retains
a certain amount of tonicity as compared with its condition when
inhibited through the vagus nerve or when dead. The degree of
this tonicity determines, of course, the size of the ventricular
cavity and the extent of the charge it will take from the auricles.
Like the property of rhythmicity, that of tonicity is most developed
at the venous end of the heart. At least this is the case with the
heart of the cold-blooded animals upon which this property has
been studied most carefully. The ventricle of the terrapin, or
strips excised from the ventricle and suspended so that their move-
ments can be recorded, often vary greatly in length with differences
in condition. These variations are due to changes in tone. Not
infrequently these changes take on a rhythmical character; so
that if the ventricle is beating one sees upon the record regular
tone waves, an alternate slow shortening and slow relaxation quite
independent of the rhythmical beats. The tissue of the auricle and

34

530 CIRCULATION OF BLOOD AND LYMPH.

especially of the sinus venosus exhibits this property to a much
more marked extent (see Fig. 218). The tone, — that is, the length
of the piece, — if in strips, or the capacity of the chamber, if used
entire, is continually changing and oftentimes in a rhythmical
way. Fano* has made a special study of this property and has
suggested that the tone changes or contractions may be due to
the activity of a substance in the heart different from that which
mediates the ordinary contractions. Botazzif suggests that, while
the usual sharp systolic contraction is due to the cross-striated
(anisotropous) substance, the slower tone changes may be due

Fig. 218. — To show tone waves in heart muscle. The record shows contractions of a
strip ofthe sinus venosus (terrapin's heart) suspended in a bath of blood-serum. In addi-
tion to the sharp contractions marked by the lines there are longer, wave-like shortenings
and relaxations, irregular in character, which are due to variations in tone.

to the undifferentiated sarcoplasm. However this may be, the
property of tonicity is an important one in the physiology of the
heart and of the other visceral organs. Through it a certain tension
of the musculature is maintained, and the size of the cavities is
controlled. The property may be of special regulative value in
the large veins where they open into the auricles, but at present
we have little positive knowledge of the conditions that control
the tonicity, of the extent of its regulating action normally, or
of the extent of its derangement under pathological conditions.

*Fano, "Beitrage zur Physiologie." C. Ludwig, zu s. 70 Geburtstage
gewid. Leipzig, 1887.

t "Journal of Physiology," 21, 1, 1897.

CHAPTER XXX.

THE CARDIAC NERVES AND THEIR PHYSIOLOGICAL

ACTION.

The heart receives two sets of efferent nerve fibers from the
central nervous system. One set reaches the heart through the
vagus nerves, and, since their activity slows or stops the heart
beat, they are spoken of as the inhibitory nerve fibers. The other
set passes to the heart by way of the sympathetic chain, and since
their activity accelerates or augments the heart beat they are
designated usually as the accelerator nerve fibers. In addition the
heart is provided with a set of afferent nerve fibers. Regarding
the functional activity of these latter fibers, our experimental
knowledge is limited to the fact that when excited they cause a
fall of blood-pressure by reflex action upon the vasomotor center.
For this reason they are described as depressor nerve fibers. These
latter fibers may run as a separate nerve or may be included in the
trunk of the vagus.

The Course of the Cardiac Fibers. — The vagus nerve gives
off several branches that supply the heart. The superior cardiac
branches arise from the vagus in the neck somewhere between
the origins of the superior and the inferior laryngeal nerves. The
inferior cardiac branches arise from the thoracic portion of the
vagus near the origin of the inferior laryngeal and indeed some
of these branches may spring directly from the inferior laryngeal.
The inhibitory fibers probably arise in these inferior branches
chiefly. Both superior and inferior cardiac branches pass toward
the heart and unite with the cardiac branches from the sympathetic
chain to form the cardiac plexus. This plexus lies on the arch
and ascending portion of the aorta, and from it the heart receives
directly both its inhibitory and accelerator fibers. The inhibitory
fibers of the heart form a part of the outflow of autonomic fibers
(p. 234) through the vagus nerve. The preganglionic fibers probably
end around ganglion cells in the heart, which in turn send their
axons as postganglionic fibers to the heart muscle.

The Action of the Inhibitory Fibers. — If the vagus nerve
in the neck of an animal is cut and its peripheral end is stimulated
the heart is slowed or stopped altogether according to the strength
of the stimulus. This effect is illustrated in Figs. 219 and 220.

531

532

CIRCULATION OF BLOOD AND LYMPH.

This inhibitory influence upon the heart beat was first described
in 1845 by the two brothers, Edward Weber and E. H. Weber.
It was a physiological discovery of the first importance, not only
as regards the physiology of the heart, but from the standpoint
of general physiology, since it gave the first clear instance of the
possibility of inhibitory action through nerve fibers.

If the heart is examined during its complete inhibition it will

be seen that it stops in diastole,
and indeed the diastole is more
complete than normal, — the heart
dilates to a very large extent, and
becomes swollen with blood. This
latter fact is taken usually as proof
that the action of the inhibitory
fibers not only prevents the usual
systole, but also removes the to-
nicity of the musculature. Some
observers believe that the unusual
dilatation is due simply to the effect
of the increased venous pressure
(Roy and Adami). Examination of
the heart shows also that the inhi-
bition affects the whole heart, — both
auricles and ventricles are slowed or
stopped, as the case may be. That
the vagus nerve in man also con-
tains inhibitory fibers to the heart
is made highly probable by every-
thing known concerning the condi-
tions under which the heart is
slowed or stopped temporarily, and
has, moreover, been demonstrated

Fig. 219.— To show the inhibition
of the terrapin's heart due to stimula-
tion of the vagus nerve. The upper
tracing (/) records the contractions of
the left auricle ; the lower (//) the con-

tracing (/) recorcis the contractions of directly in several instances upon

tractions of the ventricle. The vagus Hvillg men'* TheS6 inhibitory fi-

was stimulated three times, each
chamber coming to a complete stop.
On removing the stimulus it will be
noted that the auricular contractions
increase gradually to their normal,
while the ventricular contractions
start off at full strength.

bers have been shown to exist in all
classes of vertebrates and in a num-
ber of the invertebrates, — a fact
which in itself would indicate the
great importance of their influence
upon the effective activity of the heart. In the mammals gener-
ally employed in laboratory experiments the inhibitory fibers
occur in both vagi; in some of the lower vertebrates, however,

*See especially Thanhoffer, " Centralblatt f. d. med. Wiss.," 1875, who
gives an account of an experiment in which the vagi were compressed in the
neck, with a resulting stoppage of the heart and loss of consciousness.

THE CARDIAC NERVES. 533

especially in the terrapin, the inhibitory fibers are found exclusively
or mainly in the right vagus.

Analysis of the Action of the Inhibitory Fibers. — The prom-
inent effect of the action of the inhibitory fibers is the slowing

Fig. 220. — To show the inhibition of the heart from stimulation of the vagus in the
dog. Record B is the blood-pressure tracing. The vagus was stimulated twice. The
marks x, x, indicate the beginning and end of the stimulus. The first stimulation was
weak ; it will be noted that the heart escaped and began beating before the stimulus was
withdrawn. The second stimulus was stronger ; the inhibition lasted some time after re-
moval of the stimulus. The upper curve (K) is a plethysmographic (oncometer) tracing
of the volume of the kidney. It will be noted that when the heart stops and blood-pressure
falls the kidney, like the other organs, diminishes in volume. (Dawson.)

of the rate of the heart beat. Numerous observers have called
attention to the fact that the vagus fibers may also cause a weaken-
ing in the force of the beat as well as a slowing in the rate, or,
indeed, the two effects may be obtained separately. This fact has
been shown especially for the auricles.* In the heart of the terrapin
one may, by using weak stimuli, obtain only a weakening of the
*See Bayliss and Starling, "Journal of Physiology," 13, 410, 1892.

534

CIRCULATION OF BLOOD AND LYMPH.

auricular beats without any interference with the rate (Fig. 221),
while by increasing the stimulus the slowing in rate becomes evident
combined with a diminution in force or extent. Although the
force of the beat may be influenced without altering the rate, the
reverse does not hold. Usually, for the auricle, at least, any stimulus
that slows the beat also weakens the individual beat. Whether
the vagus fibers exercise a similar double influence directly upon
the ventricle is not so clear. Some observers find that when the
ventricle is inhibited the beats, although slower, are stronger, while
others obtain an opposite result. It seems probable, as stated
by Johansson and Tigerstedt, that the result obtained depends

largely on the strength of stimulus
used. These observers found* that
with relatively weak stimuli the
contractions of the ventricle, though
slower, are stronger, while with
stronger stimuli the contractions are
diminished in strength as well as
rate. The question is complicated
by the difficulty of separating the
direct effect of the vagus on the
ventricle from the indirect effect
brought about by the changes in the
auricular beat. The inhibitory in-
fluence makes itself felt also upon
the conductivity of the heart. This
fact has been noted by several ob-
servers. A striking example is seen
in the case of partial heart block.
When as the result of some injury
or pressure in the auric ulo- ventricu-
lar region or from some other less

evident cause there is a partial block, so that the ventricle con-
tracts once to two or three beats of the auricle, vagus stimulation
/nay be followed at once, as an after-effect, by a return to the
normal beat, a re-establishment of a one-to-one rhythm. Under
other circumstances the contrary effect of vagus stimulation
has been described. From the results cited it seems evident that
the vagus nerve may affect the rate and the force of the con-
tractions, and also the conductivity or the propagation of the
wave of contraction. These separate influences have been referred
by some authors to the existence of different kinds of nerve fibers,
each exerting its own influence, but it seems preferable to assume,
* See Tigerstedt, " Lehrbuch der Physiologic des Kreislaufes," 1893, p. 247.

Fig. 221.— To show the effect of
vagus stimulation on the force only of
the auricular beat in the terrapin's
heart: A, Record of the auricular
beats; V, record of the ventricular
beats. The vagus was stimulated be-
tween x and x. It will be noted that
the ventricular beats are not affected,
and that the auricular beats diminish
in extent without any change in rate.

THE CARDIAC NERVES. 535

on the contrary, that only one kind of fiber is present, and that
its influence on the metabolic changes in the heart muscle expresses
itself differently upon the several different properties of the tissue
according to the extent of its action.

Engelmann has made the most complete attempt to analyze the influence
exerted by the cardiac nerves (inhibitory and accelerator). He designates
these influences under four different heads with the further supposition that
they are mediated by different fibers : (1) The chronotropic influence, affecting
the rate of contraction, positive 'chronotropic actions causing an acceleration
and negative chronotropic actions a slowing of the rate. (2) The bathmo-
tropic influence, affecting the irritability of the muscular tissue; this also may
be positive or negative. (3) The dromotropic influence, positive or negative,
affecting the conductivity of the tissue. (4) The inotropic influence, posi-
tive or negative, affecting the force or energy of the contractions.*

Does the Vagus Affect Both Auricle and Ventricle? — The

inhibitory action of the vagus is most marked upon the venous
end of the heart, and the question has arisen as to whether it affects
the ventricle directly or not. Gaskell gave evidence to indicate
that in the terrapin the auricle only is inhibited, the ventricle stop-
ping because it fails to receive its normal impulse from the
auricle. When this heart is inhibited the contractions of the
auricle after cessation of inhibition gradually increase in amplitude
until the normal size is reached; in the ventricle, on the contrary,
the first contraction after inhibition is of normal size or greater
than normal (see Fig. 219). When a block is produced in the
mammalian heart between auricle and ventricle — by clamping the
connecting muscular bundle, for instance — stimulation of the
vagus stops the auricle only (Erlanger), and this result would seem
to indicate that the vagus affects only the auricle, unless it is as-
sumed that the clamp has interrupted the inhibitory paths to the
ventricle. On the other hand, in favor of the view that the vagus
fibers reach the ventricle and influence its beats directly, we have the
fact, emphasized by Tigerstedt, namely, that when the connection
between auricle and ventricle is severed suddenly the ventricle
frequently continues to beat at its own rhythm without any obvious
pause. It would seem from this fact that when the whole heart
is inhibited by stimulation of the vagus the ventricle does not
stop simply because the auricle fails to send on its usual contraction
wave, since, if that were so, cutting off the auricle or clamping the
connection between it and the ventricle should also bring on a
ventricular pause, as happens in the case of the terrapin's heart.
It seems, however, to be the general belief of those who have experi-
mented with the subject that the action of the vagus is exerted
mainly upon the auricles.

* Engelmann, "Archiv f. Physiologic," 1900, p. 313, and 1902, suppl.
volume, p. 1.

536 CIRCULATION OF BLOOD AND LYMPH.

Escape from Inhibition. — Strong stimulation of the vagus
may stop the entire heart, but the length of time during which the
heart may be maintained in this condition varies in different species
and indeed to some extent in different individuals.* In some ani-
mals— cats, for example — the strongest stimulation of the nerve
serves frequently only to slow the heart instead of causing complete
standstill. In dogs the heart is stopped by relatively weak stimu-
lation, although if the stimulation is maintained the heart, as a
rule, escapes from the inhibition. In some dogs the heart may
be held inhibited long enough to cause the death of the animal
unless artificial respiration is maintained, but usually the heart
beat soon breaks through the complete inhibition. The " inner
stimulus" in such cases increases in strength sufficiently to overcome
the opposing inhibitory influence, and this circumstance may be
regarded as an argument against those views that trace the origin of
the "inner stimulus" to some of the products formed during the ca-
tabolism of contraction. Moderate stimulation of the vagus, suffi-
cient simply to slow the rate of beat, can be maintained without dimi-
nution in effect for very long periods; indeed, as is explained in the
next section, the heart beat is kept partially inhibited more or less
continuously through life by a constant activity of the vagus. In
the cold-blooded animals, especially the terrapin, the heart may
be kept completely inhibited for hours by stimulation of the vagus.
Mills reports that he has kept the heart of the terrapin in this
condition for more than four hours. f Most observers state that
complete inhibition can be maintained for a longer time when the
stimulus is applied alternately to the two vagi, but it is possible
that this result is due to the fact that continuous stimulation applied
to a nerve usually results in some local loss of irritability.

Reflex Inhibition of the Heart Beat — Cardio-inhibitory
Center. — The inhibitory fibers may be stimulated reflexly by action
upon various sensory nerves or surfaces. One of the first experi-
mental proofs of this fact was furnished by Goltz's often-quoted
"Klopfversuch."J In this experiment, made upon frogs, the ob-
server obtained standstill of the heart by light, rapid taps on the
abdomen, and the effect upon the heart failed to appear when the
vagi were cut. In the mammals every laboratory worker has had
numerous opportunities to observe that stimulation of the central
stumps of sensory nerves may cause a reflex slowing of the heart
beat. The effect is usually very marked when the central stump
of one vagus is stimulated, the other vagus being intact. The
vagus carries afferent fibers from the thoracic and abdominal

*See Hough, "Journal of Physiology," 18, 161, 1895.

t " Journal of Physiology, " 6, 246.

JGoltz, " Virchow's Archiv f. pathol. Anatomie, etc.," 26, 11, 1863.

THE CARDIAC NERVES. 537

viscera, and most observers state that the heart may be reflexly
inhibited most readily by stimulation of the sensory surfaces of
the abdominal viscera, by a blow upon the viscera, for example,
or by sudden distension of the stomach. In man similar results
are noticed very frequently. Acute dyspepsia, inflammation of
the peritoneum, painful stimulation of sensory surfaces, — the
testes, for instance, or the rpiddle ear, — may cause a marked slowing
of the heart, — a condition designated as bradycardia. What
takes place in all such cases is that the afferent impulses carried
into the central nervous system reflexly stimulate the nerve cells
in the medulla which give origin to the inhibitory fibers •* These
cells form a part of the great motor nucleus (N. ambiguus) from
which arise the motor fibers of the vagus and the glossopharyngeus.
The particular group of cells from which the inhibitory fibers to the
heart originate has not been delimited anatomically. Efforts have
been made to locate them by vivisection experiments, but thia
method has shown no more perhaps than that they are found in the
region of origin of the vagus nerve. Physiologically, however, this
group of cells forms a center which is of the greatest importance in
controlling the activity of the heart. It is designated, therefore, as
the cardio-inhibitari/ center. We may define the cardio-inhibitory
center as a bilateral group of cells lying in the medulla at the level of
the nucleus of the vagus and giving rise to the inhibitory fibers
of the heart. The two sides are probably connected by commis-
sural cells or else each nucleus sends fibers to the vagus of each
side. Through this center all reflexes that affect the heart by way of
the inhibitory fibers must take place. These reflexes may be occa-
sioned by incoming sensory impulses through the spinal or cranial
nerves, or by impulses coming down from the higher portions of
the brain. The center may also be stimulated directly, either by
pressure upon the medulla, which may give rise to slow heart beats
or, as they are sometimes called, vagal beats, or by changes in the
composition of the blood. With regard to the reflex stimulation of
this center it is important to bear in mind the general physiological
rule that afferent impulses may either excite or inhibit the activity
of nerve centers. In the former case the heart rate would be
slowed, in the latter case it would be quickened if the center were
previously in a state of activity.

The Tonic Activity of the Cardio-inhibitory Center.— The
cells of the cardio-inhibitory center are in constant activity to a
greater or less extent. As a consequence, the heart beat is kept con-
tinually at a slower rate than it would normally assume if the
inhibitory apparatus did not exist. This tonic activity of the vagus
is beautifully exhibited by simple section of the two vagi, or by inter-

538

CIRCULATION OF BLOOD AND LYMPH.

rupting, in some other way — cooling, for example — the connection
between the center and the heart. When the two vagi are cut the
heart rate increases greatly and the blood-pressure rises on account
of the greater output of blood in a unit of time (Fig. 222). Section
of one vagus gives usually a partial effect, — that is, the heart rate
is increased somewhat, — but it is still further increased by section
of the second vagus. The exact result obtained when the nerves are

Fig. 222. — To show the effect of section of the two vagi in the dog upon the rate of
heart beat and the blood-pressure : 1 marks the section of the vagus on the right side ;
2, section of the second vagus. The numerals on the vertical mark the blood-pressures ;
the numerals on the blood-pressure record give the rate of heart beats. (Dawson.)

severed separately varies undoubtedly with the conditions, — for
instance, with the intensity of the tonic activity of the center.
Throughout life, speaking in general terms, the cardio-inhibitory
center keeps the "brakes" on the heart rate, and the extent of its
action varies under different conditions. When its tonic action is
increased the rate becomes slower; when it is decreased the rate
becomes faster. In all probability, this tonic action of the center,
like that of the motor centers generally, is in reality a reflex tonus.

THE CARDIAC NERVES. 539

That is, it is not due to automatic processes generated within the
nerve cells by their own metabolism or by changes in their liquid
environment, but to stimulations received through sensory nerves.
The continuous though varying inflow of impulses into the central
nervous system through different nerve paths keeps the center in
that state of permanent gentle activity which we designate as
"tone." It is possible, of bourse, that certain afferent paths may
be in specially close functional relationship to the center. One may
suppose, from the anatomical relations and from physiological
experiments, that the afferent paths from the abdominal viscera
play such a role.

The Action of Drugs on the Inhibitory Apparatus. — The
existence of the inhibitory fibers to the heart furnishes a means
of explaining the cardiac action of a number of drugs, — atropin,
muscarin or pilocarpin, nicotin, curare, digitalis, etc., — for the
details of which reference must be made to works on pharmacology.*
The action of the first three named illustrates especially well the
application that has been made of physiology in modern pharma-
cology. Atropin administered to those animals, such as the dog
or man, in which the inhibitory fibers of the vagus are in constant
activity, causes a quickening of the heart rate. Indeed, the heart
beats as rapidly as if both vagi were cut. After the use of atropin,
moreover, stimulation of the vagus nerve fails to produce inhibition.
The action of atropin is satisfactorily explained by assuming that
it paralyzes the endings of the (postganglionic) inhibitory fibers
in the heart muscle, just as curare paralyzes the terminations of
the motor fibers in skeletal muscle. Atropin exercises a similar
effect upon the nerve terminations in the intrinsic muscles of the
eyeball and in many of the glands. On the contrary, when mus-
carin or pilocarpin is administered it causes a slowing and finally
a cessation of the heart beat. Since this effect may be removed
by the subsequent use of atropin it is assumed that the two former
drugs excite or stimulate the endings of the inhibitory fibers in
the heart and thus bring the organ to rest in diastole, as happens
after electrical stimulation of the vagus nerve. Some authors,
however, believe that the pilocarpin or muscarin may have a deeper
effect in that it acts directly on the heart muscle itself, and that
the antagonistic atropin affects the muscular tissue also as well
as the endings of the fibers. A final statement can not be made
upon this point, but the current belief is that the atropin paralyzes
while the muscarin or pilocarpin stimulates the endings of the
inhibitory fibers in the substance of the heart.

The Nature of Inhibition. — Since the discovery of the inhibi-
tory nerves of the heart furnished the first conclusive proof of the

* Consult Cushny, " Text-book of Pharmacology and Therapeutics."
Philadelphia, 1903.

540 CIRCULATION OF BLOOD AND LYMPH.

existence in the body of definite nerve fibers with apparently the
sole function of inhibition, it seems appropriate in this connection
to refer to the views regarding the nature of this process. Several
general views of the nature of inhibition have been proposed, but
the one that is most definite and has met with most favor is that
suggested by Gaskell.* This author has shown that the after-effects
of stimulation of the inhibitory fibers are beneficial rather than in-
jurious to the heart; that is, under certain circumstances an improve-
ment may be noticed in the rate or force of the beat or in the con-
ductivity. He has also shown, by an interesting experiment, that
during the state of inhibition the heart tissue is made increasingly
electropositive in comparison with a dead portion of the tissue.
To show this fact the tip of the auricle was killed by heat and this spot
(a) and a point at the base of the auricle (b) were connected with a
galvanometer. Under such conditions a strong demarcation cur-
rent was obtained flowing through the galvanometer from 6 to a,
If the auricle contracted a negative variation resulted, since during
activity b became less positive as regards a. If, on the contrary,
the auricle was inhibited by stimulation of the inhibitory fibers
a positive variation was obtained; b became more positive
toward a. On the basis of such results Gaskell concludes that
inhibition in the heart is due to a set of metabolic changes of an
opposite character to those occurring during contraction. In the
latter condition the metabolism is catabolic, and consists in the
breaking down of complex substances into simpler ones with the
liberation of energy as heat and work. During inhibition, on the
contrary, the processes are anabolic or synthetic and result in the
formation of increased contractile material whereby the condition
of the heart is improved. He would regard the inhibitory fibers,
therefore, as the anabolic nerve of the heart and their constant
action throughout life as an aid to the nutrition of the heart. The
same general view may be extended to all cases of inhibition, and
Gaskell believes that all muscular tissues are supplied with anabolic
(inhibitory) and catabolic (motor) fibers, t

The heart muscle possesses a motor (accelerator) as well as an
inhibitory nerve. They exercise opposite effects upon the heart
muscle, and this result finds a satisfactory provisional explanation
in GaskelFs hypothesis, just stated. But the further question arises
as to why they should have opposite effects. Is it due to a differ-
ence in the character of the nerve impulses they carry or is it due to

* Gaskell, "Philosophical Transactions of the Royal Society," London;
Croonian Lecture, part in, 1882; also " Beitrage zur Physiologic/' dedicated
to C. Ludwig, 1887 ; and " Journal of Physiology," 7, 46.

t For a general discussion of this idea and of the importance of inhibitory
actions see Meltzer, "Inhibition," "New York Medical Journal," May 13,
20, 27, 1899.

THE CARDIAC NERVES.

541

some difference in their place or manner of ending in the muscular
tissue? Views differ upon this point and many physiologists have
suggested that the impulses vary in quality; that the inhibitory
nerve impulse differs in some unknown way from a motor impulse,
and therefore causes an opposite reaction in the muscle. This latter
view seems, however, to be entirely disproved by the results of
experiments. Langley has shown upon blood-vessels (p. 76) that
an inhibitory nerve made
to grow down a motor path
causes when stimulated
only motor effects and vice
versa. And in the case in
point Erlanger * has proved
that, when an ordinary spinal
nerve (fifth cervical) is su-
tured to the peripheral end
of the cut vagus, it will,
after time for regeneration
has been allowed, cause when
stimulated the usual stop-
page of the heart. So far as
our facts go, therefore, we
must assume that motor
and inhibitory fibers have
opposite effects upon the
muscular fibers in which
they end because they ter-
minate differently in these
fibers, f

The Course of the Ac-
celerator Fiber s. — T h e
heart receives efferent or
motor nerve fibers from the
sympathetic system in ad-
dition to those reaching it
by way of the vagus nerve.
Attention was first called to
these sympathetic fibers by
Legallois (1812), but our re-
cent knowledge dates from
the experiments made by von Bezold (1862), which were afterward

* Erlanger, "American Journal of Physiology," 13, 372, 1905.

t For a special theory of heart inhibition and acceleration see Howell,

1 T«,, „„! ~C "DU,.-™^!^.™-., » 1 Or»A i'ir OQft nnr\ " Trvnmol r\f "PV-.iroirkli-.mr "

Fig. 223. — Schematic representation of the
course of the accelerator fibers to the dog's heart
— right side. — (Modified from Pawlow.) The sym-
pathetic nerve is represented in solid black. The
course of the accelerator fibers is indicated by ar-
rows. /, Cervical sympathetic combined in neck
with, 10, the vagus; //, ///, IV, rami communi-
cantes from the second, third, and fourth thoracic
spinal nerves, carrying most of the accelerator fi-
bers to the sympathetic chain ; 7, annulus of Vieus-
sens; 8, inferior cervical ganglion; 2, 3, 4, 5,
branches from vagus and vago-sym pathetic trunk
going to cardiac plexus (some of these — 3, 5, —
carry accelerator fibers; 9, the inferior laryngeal
nerve.

" American Journal of Physiology,
1906, xxxv., 131.

1906, xv., 280, and "Journal of Physiology/

542

CIRCULATION OF BLOOD AND LYMPH.

completed by the Cyon brothers — M. and E. Cyon * — 1866. These
fibers when stimulated cause an increased rate of beat and are there-
fore designated as the accelerator nerve of the heart. Their course
has been worked out physiologically in a number of animals. Among
the mammalia and indeed among different animals of the same species
there is some variation, but a general conception of their origin and
course may be obtained from Figs. 223 and 224, which represent in a
schematic way the anatomical path taken by these fibers. They
emerge from the spinal cord in the anterior roots of the second, third,
and fourth thoracic spinal nerves. According to some authors, they

may be found also in the fifth
thoracic and the first thoracic or
even the lower cervical spinal
nerves. They pass then by way
of the white rami to the stellate
or first thoracic ganglion (6), and
thence by way of the annulus of
Vieussens (7) to the inferior cer-
vical ganglion. A number of
branches leave the sympathetic
system and the vagus in this
region to pass to the cardiac
plexus and thence to the heart.
The accelerator fibers are found
in some of these branches, mixed
in some cases with inhibitory
fibers from the vagus. In the cat
Boehm has described a special
branch (nervus accelerans) which
runs from the stellate ganglion
directly to the cardiac plexus
(Fig. 224). The preganglionic
portion of some of the accelerator
fibers ends around the ganglion
cells in the first thoracic ganglion, while others apparently make
their first termination in the inferior cervical ganglion. The accele-
rator fibers may be stimulated in the spinal roots in which they
emerge (II, III, IV), in the annulus or in some of the branches that
arise from the annulus or from the inferior cervical ganglion (5, 3,
2). It will be borne in mind that no accelerator fibers are found
in the cervical sympathetic above the inferior cervical ganglion.

At various times investigators have asserted that accelerator fibers are
contained also in the vagus nerve. Thus, it has been shown that, after the

* For the history and literature of the accelerator nerves see Cyon, article
"Cceur,"p. 103, in Richet's " Dictionnaire de Physiologic, " 1900; or Tiger-
stedt, "Lehrbuch der Physiologic des Kreislaufes, " 260, 1893.

Fig. 224.— Sketch to show the accel-
erator (and augmentor) branches from the
stellate ganglion (in the cat, left side) : 1,
The ventral branch of the annulus ; 2,
small branch not constantly present ; 3,
Boehm's accelerator nerve (N. cardiacus e
ganglio stella to).

THE CARDIAC NERVES. 543

paralysis of the inhibitory fibers in the heart by atropin, stimulation of the
vagus causes an acceleration of the heart. Little attention has been paid to
the physiology of these fibers, since it seems evident that the great outflow of
accelerators is made via the sympathetic system.

The Action of the Accelerator Fibers. — In experimental
work the accelerators are usually stimulated in one or more of the
branches represented schematically as 5, 3, 6, in Fig. 223, or 3, in
Fig. 224. The effect is an increase in the rate of beat of the heart,
which may be very evident, amounting to as much as 70 per cent,
or more of the original rate, or may be very slight. When accelera-
tion is obtained the latent period is considerable and the heart
does not return at once to its normal rate upon cessation of the
stimulus (see Fig. 225). In some cases the effect upon the heart
is an acceleration pure and simple, — that is, the rate of beat is
increased without any evidence of an increase in the force of the
beats. The larger number of beats is offset by the smaller amplitude
of each beat; so that the blood-pressure in the arteries is unchanged.
In other cases the effect upon the heart may be an increase not only
in rate but also in the force or energy of the beats, or the rate may
remain unaffected and only the force of the heart beats be increased.
For these reasons most authors favor the view that the accelerator
nerves, so called, contain in reality two sets of fibers, one, the
accelerators proper, whose function is simply to accelerate the rate,
and one, the augmentors, that cause a more forcible beat. The
augmenting action is obtained especially from the nerves of the
left side.

Tonicity of the Accelerators and Reflex Acceleration. —
The results of the most careful work show, without doubt, that the
accelerators to the heart are normally in a state of tonic activity.*
When these nerves are cut upon both sides the heart rate is decreased.
We must believe, therefore, that under normal conditions the heart
muscle is under the constant influence of two antagonistic influ-
ences, one through the inhibitory fibers tending to slow the rate,
one through the accelerator fibers tending to quicken the rate. The
actual rate at any moment is the resultant of these two influences.
While such an arrangement seems at first sight to be unnecessary
from a mechanical standpoint, it is doubtless true that it possesses
some distinct advantage. Possibly it makes the heart more
promptly responsive to reflex regulation. Balanced mechanisms
of this kind are found in other parts of the body where smooth and
prompt reactions to stimulation seem to be especially necessary, —
for example, the constrictor and dilator fibers of the iris, the ex-
tensor and flexor muscles of the joints, etc. Physiologists have

* For a discussion of this and other points in the physiology of the ac-
celerators see Hunt, " American Journal of Physiology," 2, 395, 1899, and
"Journal of Experimental Medicine," 2, 151, 1897.

544 CIRCULATION OF BLOOD AND LYMPH.

studied experimentally the effect upon the heart of stimulating
simultaneously the inhibitory and the accelerator nerves. The work
done upon this subject by Hunt seems to make it very certain that
in all such cases the result, so far as the rate is concerned, is the
algebraic sum of the effects of the separate stimulations of the nerve.
The inhibitory and the accelerator fibers must be considered,
therefore, as true antagonists, acting in opposite ways upon the
same part of the heart. The existence of the accelerator nerves
makes possible, of course, their reflex stimulation. Experimentally
it is found that stimulation of various sensory nerves — those of the
limbs or trunk, for instance — may cause reflexly either an increase
or decrease in the heart rate, and as a matter of experience we know
that our heart rate may be increased by various changes, particu-
larly by emotional states. The natural explanation of such ac-
celerations is that they are due to reflex stimulation of the nerve
cells in the central nervous system which give rise to the accelerator
fibers. But another point of view is possible. An increase in heart
rate may be brought about either by a reflex stimulation of the
accelerator fibers or by a reflex inhibition of the cardio-inhibitory
center. Hunt especially has presented many experimental facts

Fig. 225. — To show the acceleration and augmentation produced by a strong stimulus.
Isolated cat's heart, stimulation on left side. The upper curve gives the ventricular
contractions, the lower one the auricular contractions. The lowermost line gives the
time in seconds and the line above indicates the duration of the stimulation of the accel-
erator nerve.

which indicate that an increase in heart rate from reflex action may
be produced by an inhibition of the tonic activity of the cardio-
inhibitory center. He finds, for instance, that when the two vagi
are cut stimulation of various sensory nerves fails to give any
increase in the already rapid heart rate, while, on the contrary,
when the two accelerator paths are cut a reflex increase in heart
rate may be obtained readily. Hering,* on the other hand, gives
experimental evidence to show that the acceleration of the heart
following upon muscular exercise does not occur when the accel-
erator nerves are cut, a fact which seems to show that these nerves
may be reflexly stimulated. We may conclude, therefore, that
the accelerator and the inhibitory fibers are working constantly
* Bering, " Centralblatt f. Physiol.," 1894, viii., 75.

THE CARDIAC NERVES. 545

on the heart, and that its rate is the resultant or algebraic sum of
their effects, and that sudden changes in this rate, such as result
from sensory or psychical disturbances of any kind, may be referred
to a reflex effect upon either the cardio-inhibitory or the accelerator
center. While physiology has demonstrated the general properties
of the regulating nerves of the heart, the inhibitory, on the one
hand, and the accelerator and augmentor on the other, it is necessary
for much more work to be' done in order to explain satisfactorily
how these nerves participate in the various normal and pathological
changes of rate and force of beat.

The Accelerator Center. — The accelerator fibers arise primarily in
the central nervous system. Since stimulation of the upper cervical region
of the cord causes acceleration, it seems evident that the path must begin
somewhere in the brain. It has been assumed that, like the inhibitory fibers,
the path starts in the medulla, and that, therefore, the cells in that organ
which give rise to the accelerator fibers constitute the accelerator center
through which reflex effects, if any, take place. As a matter of fact, the
location of these cells of origin has not been made out satisfactorily. The
matter offers unusual difficulty on the experimental side, owing to the existence
of the cardio-inhibitory center in the medulla and the absence of any entirely
satisfactory method of distinguishing certainly between reflex acceleration
through this center and through the accelerator center.

35

CHAPTER XXXI.

THE RATE OF THE HEART BEAT AND ITS VARIA-
TIONS UNDER NORMAL CONDITIONS.

The rate of heart beat changes quickly in response to variations
in either the internal or external conditions. Therein lies, in fact,
the great value of the regulatory (inhibitory and accelerator) nerves.
Through their agency, in large part, the pump of the circulation is
reflexly adjusted to suit the changing needs of the organism and
adapted more or less successfully to alterations in the external
environment. The variations in the rate of beat may be considered
under three general heads: (I) Fixed adjustments to the different
mechanical conditions of the circulation. (II) Variations caused
by reflex effects upon the inhibitory or accelerator nerves. (Ill)
Variations caused by changes in the physical or chemical conditions
of the blood.

The Fixed Adjustments of Rate. — When we speak of the
normal pulse rate we mean the rate in an adult when in a condition
of mental and bodily repose. Examination shows that under these
circumstances there are great individual variations. The average
normal rate for man may be estimated at 70 beats per minute;
for woman, 78 to 80 beats; but the normal rate for some individuals
may be much lower (50) or much higher (90). Among the condi-
tions for which the heart rate shows a certain constant fixed adapta-
tion the following may be mentioned :

Variations with Sex. — The average pulse rate in women is, as
a rule, higher than that in men, and this difference seems to hold
for all periods of life.

Variations with Size. — Tall individuals have a slower pulse
rate than short persons of the same age. Several observers have
thought that they could detect a constant relationship between
size and pulse rate. Thus, Volkmann believed that the pulse
rate varies inversely as the five-ninth power of the height. In
the same direction it is found that small animals, as a rule, have
a higher pulse rate than larger ones. Thus, elephant, 25-28;
horse and ox, 36-50; sheep, 60-80; dog, 100-120; rabbit, 150;
small rodents, 175 or more. It would seem, from these facts, that
the fast rate in the small animals, with their shorter circulatory
path and smaller volume of blood, is necessary to the mechanical

546

THE RATE OF THE HEART BEAT. 547

fulfillment of the functions of the blood, and has been preserved
by natural selection.

Variations with Age. — In line with the last condition it is found
in man that the pulse rate is highest in infancy, sinks quite rapidly
at first and then more slowly up to adult life, and rises again
slightly in very old age at the time that the body undergoes a
perceptible shrinkage. The most extensive data upon this point
are found in the works of the older observers.* According to Guy,
a condensed summary of the average results obtained at different
periods of life, both sexes included, may be given as follows :

At birth 140

Infancy 120

Childhood 100

Youth 90

Adult age 75

Old age 70

Extreme age 75-80

The Variations in Pulse Rate Effected through the In-
hibitory and Accelerator Nerves. — Most of the sudden adaptive
changes of the heart rate come under this head. In the laboratory
we find that stimulation of all sensory nerve trunks may affect
the heart rate, in some cases increasing it, in others the reverse.
In life we find that the pulse rate is very responsive to our changing
sensations and especially to mental conditions that indicate
deep interest or emotional excitement. In a previous paragraph
(p. 543) the physiological cause of this effect has been discussed
briefly. It may arise either from a reflex excitation of the accelera-
tor nerves or a reflex inhibition of the tonic activity of the inhibitory
nerves. The facts at present seem to favor this latter explanation.
In addition to these reflexes associated with conscious states the
heart is susceptible to reflex influences of a totally unconscious
character connected with the states of activity of the visceral organs.
For example, after meals the heart beat increases usually in rate
and especially in force of beat, thereby counteracting the effect on
blood pressure of the large vascular dilatation in the intestinal area.

Variations in Heart Rate with the Condition of Blood-pressure. —
It has long been known that when the blood-pressure in the arteries
falls the pulse rate increases and when it rises the pulse rate de-
creases. Thus, the low blood-pressure that is characteristic of
the condition of surgical shock is associated with a very rapid
rate of heart beat. There is a certain inverse relationship between
pressure and rate which has the characteristics of a purposeful
adaptation. The quicker pulse rate following upon the low pressure
tends to increase the output of blood and raise the pressure. There

*See Volkmann, "Die Hamodynamik," p. 427, 1850; also Guy, article
" Pulse" in Todd's "Cyclopaedia of Anatomy and Physiology," 1847-49.

548 CIRCULATION OF BLOOD AND LYMPH.

was formerly much discussion as to whether this relationship is
brought about by reflexes through the extrinsic nerves of the
heart or whether it is due to some direct, perhaps mechanical,
effect upon the heart. The experiments of Newell Martin upon
the isolated heart seem to have settled the matter satisfactorily.*
By a method devised by him he kept dogs' hearts beating for
many hours when isolated from all connections with the body
except the lungs. Under these conditions it was found that even
extreme variations in blood-pressure did not affect the heart rate.
Consequently, the variation that does take place under normal
conditions must be due to a reflex stimulation of the cardiac nerves.
The origin of the sensory stimulus in this reflex is not clearly known;
possibly the afferent nerves of the heart itself are stimulated or
afferent fibers distributed to the walls of the aorta.

Variations with Muscular Exercise. — It is a matter of everyday
experience that the heart rate increases with muscular exercise.
A simple change in posture, in fact, suffices to affect the heart
rate. The rate is higher when standing (80) than when sitting
(70) and higher in this latter condition than when lying down
(66). Unusual exertion, as in running, causes a very marked and
long-lasting increase in the pulse rate. The purposeful charac-
ter of this adaptation is very evident. Increase in muscular activity
calls for a more rapid circulation to supply the oxygen and other
elements of nutrition, but the physiological mechanism by which
this adaptation is obtained is not explained satisfactorily. Johans-
son,! who has studied the matter carefully, concludes that the
effect is due mainly to two causes: First, to the effect of the chem-
ical products of metabolism in the active muscle, which are given
off to the circulation and are then carried to the nerve centers
where they affect the cardiac nerves, or possibly to an effect of
these metabolic products on the heart directly. He considers this
factor as of relatively subordinate importance. Second, the chief
factor is found in an associated activity of the accelerator nerves.
That is, the discharge of impulses along the voluntary motor paths
(pyramidal) sets into activity at the same time and proportionally
the center of the accelerator nerve fibers. Hering, } on the con-
trary, gives experimental evidence for the view that the
increase in heart rate after exercise is due to a reflex stim-
ulation of the accelerator nerves of the heart. After pro-
longed or excessive muscular exertion the heart rate remains
accelerated for a considerable period after cessation of the work, — a
fact which would indicate some long-lasting influence, such as is im-

* Martin, "Studies from the Biological Laboratory, Johns Hopkins Uni-
versity," 2, 213, 1882; also "Collected Physiological Papers," p. 25, 1895.
f Johannson, "Skandinavisches Archiv f. Physiologic," 5, 20, 1895.
j "Centralblatt f. Physiologic," 8, 75, 1894.

THE RATE OF THE HEART BEAT.

549

plied in the first factor given above, — the effect of the products of
muscular metabolism.

Variations with the Gaseous Conditions of the Blood. — In con-
ditions of asphyxia the altered gaseous contents of the blood
increase in CO2 and decrease in 02, act upon the medullary centers
of the cardiac nerves, causing, first,
an increase and then a decrease in
heart rate.

The Variations in Pulse Rate
Due to Changes in the Composi-
tion or Properties of the Blood.—
The condition under this head that
has the most marked influence upon
the heart rate is the temperature of
the blood. Speaking generally, the
rate of beat increases regularly with
the temperature of the blood or
other circulating liquid up to a cer-
tain optimum temperature. On the
heart of the cold-blooded animal this
relationship is easily demonstrated
by supplying the heart with an arti-
ficial circulation of Ringer's solu-
tion, which can be heated or cooled
at pleasure. The rate and force of
the beat increase to a maximum,
which is reached at about 30° C.
(see Fig. 226). Beyond this opti-
mum temperature the beats decrease
in force and also in rate, becoming
irregular or fibrillar before the heart
finally comes to rest. Newell Mar-
tin* has shown the same relation-
ship in a very conclusive way upon
the isolated heart of the dog.
Within physiological limits the rate
of beat rises and falls substantially parallel to the variations in
temperature as is shown by the chart reproduced in Fig. 227. The
accelerated heart rate in fevers is therefore due probably to the
direct influence of the high temperature upon the heart itself. The
same observer determined experimentally the upper and lower
lethal limits of temperature for the mammalian heart. The experi-
ments were made upon cats' hearts kept alive by an artificial circu-

* Martin, " Croonian Lecture, Philosophical Transactions, Royal Society,"
London, 174, 663, 1883; also "Collected Physiological Papers," p. 40, 1895.

Fig. 226. — To show the effect of
temperature on the rate and force of
the heart beat. Contractions of the
terrapin's ventricle at different tem-
peratures. Kymograph moving at
the same speed. At 30° the rate is
still increasing, but the extent of con-
traction has passed its optimum.

550

CIRCULATION OF BLOOD AND LYMPH.

lation through the coronary arteries.* It was found that the high-
est temperature at which the heart will beat is about 44° to 45° C.,
although a slightly higher temperature may be withstood under
special conditions. At the other extreme the mammalian heart
ceases to beat when the temperature falls as low as 17° to 18° C.

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:ed curve express the temperatures of the blood flowinf
ine express the corresponding rate of heart beat. I
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The rate of the heart beat may be influenced also by many sub-
stances added to the blood. The influence of atropin and muscarin
has already been alluded to, but changes also in the normal con-
stituents of the blood may have similar effects. Thus, an increase in
the sodium carbonate of the blood affects the heart beat, particu-
larly, however, in regard to the amplitude or force of the contraction

* Martin and Applegarth, " Studies from the Biological Laboratory,
Johns Hopkins University," 4, 275, 1890; also " Collected Physiological
Papers," p. 97, 1895.

CHAPTER XXXII.

THE VASOMOTOR NERVES AND THEIR PHYSIO-
LOGICAL ACTIVITY.

During the first half of the nineteenth century the physical or
mechanical conditions of the circulation were carefully studied and
great emphasis was laid upon such properties as the elasticity of
the coats of the vessels. The physical adaptability thereby con-
ferred upon the vascular tubes was thought to be sufficient for the
purposes of the circulation. We now know that many of the blood-
vessels are supplied with motor and inhibitory nerve fibers through
whose activity the size of the vascular bed and the distribution of
blood to the various organs are regulated. We know, also, that
without this nervous control the vascular system fails entirely to
meet what seems to be the most important condition of a normal
circulation, — namely, the maintenance of a high arterial pressure.
Although a number of physiologists had assumed the existence of
nerve fibers capable of acting upon the muscular coats of the blood-
vessels, the experimental proof of the existence of such nerves,
and the beginning of the modern development of the theory of
vasomotor regulation were a part of the brilliant contributions to
physiology made by Claude Bernard.* In 1851 Bernard discovered
that when the sympathetic nerve is cut in the neck of a rabbit the
blood-vessels in the ear on the same side become very much dilated.
He and other observers afterward showed that if the peripheral
(head) end of the served nerve is stimulated electrically the ear
becomes blanched, owing to a constriction of the blood-vessels.
Thus the existence of vasoconstrictor nerve fibers to the blood-vessels
was demonstrated. A vast amount of experimental work has been
done since to ascertain the exact distribution of these fibers to the
various organs and the reflex conditions under which they function
normally. Few subjects in physiology are of more practical im-
portance to the physician than that of vasomotor regulation; it
plays such a large and constant part in the normal activity of the
various organs. Bernard was doubly fortunate in being the first
to demonstrate the existence of a second class of nerve fibers, which,
when stimulated, cause a dilatation of the blood-vessels and which

* See "Life of Claude Bernard," by Sir Michael Foster, 1899, in the series,
'"Masters of Medicine."

551

552 CIRCULATION OF BLOOD AND LYMPH.

are therefore designated as vasodilator nerve fibers. This discovery
was made in connection with the chorda tympani nerve, a branch
of the facial, which sends secretory fibers to the submaxillary gland.
When this nerve is cut and the peripheral end is stimulated a secre-
tion of saliva results and at the same time, as Bernard showed, the
blood-vessels of the gland dilate; the flow of blood is greatly in-
creased in the efferent vein and may even show a pulse.

In the nervous regulation of the blood-vessels we have to con-
sider, therefore, the existence and physiological activities of two
antagonistic sets of nerve fibers: First, the vasoconstrictor fibers,
whose action causes a contraction of the muscular coats of the ar-
teries and therefore a diminution in the size of the vessels. Second,
the vasodilator nerve fibers, whose action causes an increase in size
of the blood-vessels, due probably to a relaxation (inhibition) of the
muscular coats of the arteries. Before attempting to describe the
present state of our knowledge upon these points it will be help-
ful to refer to some of the methods by means of which the existence
of vasomotor fibers has been demonstrated.

Methods Used to Determine Vasomotor Action. — The
simplest and most direct proof is obtained from mere inspection,
when this is possible. If stimulation of the nerve to an organ
causes it to blanch, the presence of vasoconstrictor fibers is dem-
onstrated unless the organ is muscular and the blanching may be
regarded as a mechanical result. On the other hand, if stimulation
of the nerve to an organ causes it to become congested or flushed
with blood the presence of vasodilator fibers may be accepted. It
is obvious, however, that this method is applicable in only a few
instances and that in no case does it lend itself to quantitative
study. 2. Vasomotor effects may be determined by measur-
ing the outflow of blood from the veins. If stimulation of the
nerve to an organ causes a decrease in the flow of blood from the
veins of that organ, this fact implies the existence of vasoconstrictor
fibers, while an opposite result indicates vasodilator fibers. 3.
By variations in arterial and venous pressures. When vaso-
constrictor fibers are stimulated there is a rise of pressure in the
artery supplying the organ and a fall of pressure in the veins
emerging from the organ. This result is what we should expect if
the constriction takes place in the region of the arterioles. The
diminution in size of these vessels by increasing peripheral resistance
augments the internal pressure on the arterial side of the resistance,
and causes a fall of side pressure on the venous side (see p. 475).
If the area involved is large enough the increased resistance will
make a perceptible difference in pressure, not only in the organ
supplied, but also in the aorta; there will be a rise of general (dias-
tolic) blood-pressure. On the other hand, a vasodilator action in

THE VASOMOTOR NERVES. 553

any organ is accompanied by the reverse changes. Peripheral
resistance being diminished there will be a fall of pressure on the
arterial side and a rise of pressure on the venous side. When,
therefore, the stimulation of any nerve brings about a rise of
arterial pressure that can not be referred to a change in the heart
beat the inference made is that the result is due to a vasocon-
striction. When the method is applied to a definite organ — the
brain, for instance — it becomes conclusive only when simultaneous
observations are made upon the pressure in the artery and the vein
of the organ, and proof is obtained that the pressures at these points
vary in opposite directions. 4. By observations upon the volume
of the organ. It is obvious that, other conditions remaining un-
changed, a vasoconstriction in an organ will be accompanied by
a diminution in volume, and a vasodilatation by an increase in
volume. This method of studying the blood-supply of an organ is
designated as plethysmography, and any instrument designed to
record the changes in volume of an organ is a plethysmograph*
Plethysmographs have been designed for special organs, and in such
cases they have sometimes been given special names. Thus, the
plethysmograph used upon the kidney and spleen has been desig-
nated as an oncometer. The precise form and structure of a
plethysmograph varies, of course, with the organ studied, but
the principle used is the same in all cases. The organ is inclosed
in a box with rigid walls that have an opening at some one
point only, and this opening is placed in connection with a recorder
of some kind by tubing with rigid walls. The connections between
recorder and plethysmograph and the space in the interior of the
latter not occupied by the organ may be filled with air, or as is
more usually the case with water. The idea of a plethysmograph
may be illustrated by the skull. This structure forms a natural
plethysmograph for the brain. If a hole is bored through the skull
at any point and a connection is then made with a recorder of some
kind, such as a tambour, the volume changes of the brain may be
recorded successfully.

The plethysmograph generally employed in laboratories, particularly for in-
vestigations on man, is some modification of the form devised by Mosso (see
Fig. 228). The hand and more or less of the arm is placed in a glass cylinder
which is swung freely from a support. The opening around the arm is shut
off by a cuff of rubber dam that must be chosen of such a size as to
fit the arm snugly without compression of the superficial veins. The
forward end of the plethysmograph is connected by tubing with a re-
corder. Through appropriate openings the cylinder and connecting tubes
are filled with warm water and then all openings are closed except the
one leading to the recorder. Any increase in volume of the arm will drive
water from the plethysmograph to the recorder, and any decrease, on

* For a description of the development of this method, see Frangois-Franck-
Marey's "Travaux du Laboratoire, " 1876, p. 1.

554

CIRCULATION OF BLOOD AND LYMPH.

the contrary, will suck water from the recorder into the plethysmograph.
In the author's laboratory a modification that has been found most conve-
nient is represented in Fig. 229. To avoid escape of water at the upper end
of the tube and at the same time to prevent compression of the veins of the
arm a very thin rubber glove with long gauntlet is used. The gauntlet
is strengthened by cuffs of dam tubing, as shown in the illustration, and all
are reflected over the end of the plethysmograph. The outer cuff (3) may
be omitted. The hand is inserted into the cylinder and is held in place by
flexing the fingers through the rings. The plethysmograph being suspended
freely from the ceiling, any movement of the arm will move the instrument as
a whole without disturbing the position of the arm in the instrument. By
means of rings of hard rubber (D,E), one fitting around the rim of the plethys-
mograph and the other adapted more or less closely to the size of the forearm,
the reflected portion of the gauntlet and cuff is held in place and prevented
from giving way readily to any rise of pressure in the plethysmograph. The

Fig. 228. — A schematic diagram of Mosso's plethysmograph for the arms: a, the glass
cylinder for the arm, with rubber sleeve and two tubulatures for filling with warm water;
8, the spiral spring swinging the test tube, t. The spring is so calibrated that the level of
the liquid in the test tube above the arm remains unchanged as the tube is filled and
emptied. The movements of the tube are recorded on a drum by the writing point, p.

interior of the latter is connected, as shown in Fig. 228, to a test tube swung
by a spiral spring (Bowditch's recorder). The spring is so adjusted by trial that
it sinks and rises exactly in proportion to the inflow or outflow of water. By
this means the level of the water in the tube is kept constant, and since the posi-
tion of this level determines the pressure upon the outside of the arm in the
plethysmograph this pressure is also kept constant independently of the
changes in volume of the arm. The level should be set in the beginning
so as to make a slight positive pressure on the arm sufficient to flatten
the thin glove to the skin and thus drive out the air between the two.
When the apparatus is conveniently arranged, with slings to support the
elbow, observations may be made upon the changes in volume of the arm
during long periods. The results so obtained are referred to under several
headings. With the form of recorder described the plethysmograph gives
usually only the slow changes in volume of the arm, due to a greater or less
amount of blood. By using a more sensitive recorder and making the con-

THE VASOMOTOR NERVES. 555

nections entirely rigid the smaller, quicker changes in volume caused by the
heart beat are also recorded. A volume pulse is obtained resembling in its
general form the pressure pulse given by the sphygmograph. When used
for this purpose the instrument is described as a hydrosphygmograph.

Records taken of the volume of the hand, foot, brain, or any
other organ show that in addition to the changes caused by the
heart beat and by the respiratory movements, there are other more
irregular variations that are continually occurring the cause of which
is to be found in the variations in the amount of blood in the organ.
Day and night these changes in volume take place, and they are
referable to the activity of the vasomotor system. Vasoconstriction
or vasodilatation in the organ itself cause what may be called

Fig. 229. — Detailed drawing of the glass plethysmograph with the arrangement of rub-
ber glove to prevent leaking without compressing the veins. 2, The glove with its gauntlet
reflected over the end of the glass cylinder; 1 and 3, supporting pieces ot stout rubber tub-
ing ; D and E, sections of outer and inner rings of hard rubber to fasten the reflected rubber
tubing and reduce the opening for the arm.

an active change in volume. But vasoconstriction or vasodilata-
tion in other organs may cause a perceptible change, of a passive
kind, in the volume of the organ under observation. For, since
the amount of blood remains the same, a change in any one organ
must affect more or less the volume — that is, the blood contents —
of all other organs.

General Distribution and Course of the Vasoconstrictor
Nerve Fibers. — These fibers belong to the autonomic system, and
consist, therefore, of a preganglionic fiber arising in the central
nervous system and a postganglionic fiber arising from the cell of
some sympathetic ganglion. The general arrangement of the auto-
nomic system (p. 234) should be reviewed in this connection. It
has been shown by experiments of the kind described under the last
heading that vasoconstrictor fibers are present in numerous nerve

556

CIRCULATION OF BLOOD AND LYMPH.

trunks, but especially in those distributed to the skin and to the
abdominal and pelvic organs. If, for instance, the sciatic or the
splanchnic nerve be cut, to avoid reflex effects, and the peripheral
end be stimulated, there will be a strong constriction of the vessels,
which may be detected by ocular inspection, blanching; by the
increase in arterial pressure ; or by the diminution in volume of the
organs. The vasoconstrictor fibers supplying these two great
regions arise immediately (postganglionic fibers) from one or other
of the ganglia constituting the sympathetic chain, or from the large
pre vertebral ganglia (celiac ganglion, for instance) directly con-
nected with it. Ultimately, of course, they arise in the central
nervous system (preganglionic fiber), and it has been shown that,
for the regions under consideration, they all, with a few compara-
tively unimportant exceptions, leave the spinal cord in the great

Fig. 230. — -Schema to show the path of the preganglionic and postganglionic portions
of a vasoconstrictor nerve fiber: a, Anterior root, showing the course of the preganglionic
fiber as a dotted line ; d, v, dorsal and ventral branches of the spinal nerve ; r, the ramus
communicans ; g, the sympathetic ganglion. The postganglionic fibers in each ramus come
from the sympathetic ganglion with which it is connected. The preganglionic fibers enter-
ing at any ganglion may pass up or down to end in the cells of some other ganglion.

outflow that takes place in the thoracic region from the second
thoracic to the second lumbar nerves (p. 236). In this outflow
they are mixed with other autonomic fibers, such as the sweat
fibers, pilomotor fibers, accelerator fibers to heart, pupilodilator
fibers, visceromotor fibers, etc. Emerging in the anterior roots, they
pass to the sympathetic chain by way of the corresponding ramus
communicans. Having reached the chain, they end in one or other
of the ganglia, not necessarily in the ganglion with which the ramus
connects anatomically. The preganglionic fibers for the blood-
vessels of the submaxillary gland, for instance, enter the first
thoracic ganglion of the sympathetic chain, but do not actually
terminate until they reach the superior cervical ganglion high in the
neck. The postganglionic fibers arise in the ganglion in which the

THE VASOMOTOR NERVES.

557

preganglionic fibers terminate. Those destined to supply the skin
of the trunk and extremities pass from the ganglion to the cor-
responding spinal nerve by way of the ramus communicans (gray
ramus) and after reaching the spinal nerve they are distributed with
it to its corresponding region (Fig. 230). In the general region

Fig. 231. — Vasomotor effect of stimulation of the splanchnic nerve — peripheral end —
in the dog (Dawson) : 1. The line of zero pressure ; 2, the line of the stimulating pen ; on
and off mark the beginning and end of the stimulation; 3, the time record in seconds; 4,
the blood-pressure record (stimulation causes a marked rise of blood -pressure due to stimu-
lation of vasoconstrict9r fibers) ; 5, plethysmographic tracing of the volume of the kidney
(oncometer) ; stimulation of the splanchnic causes a diminution in volume of the kidney
owing to the constriction of its arterioles.

under consideration (lower cervical to upper lumbar) each ramus
communicans between a spinal nerve and a sympathetic ganglion
consists, therefore, of two parts, one (white ramus) of preganglionic
fibers passing from the spinal nerve to the ganglion, the other
(gray ramus) of postganglionic fibers coming from the ganglion to

558 CIRCULATION OF BLOOD AND LYMPH.

the spinal nerve for distribution to the peripheral tissues. It should
be borne in mind that the fibers in the white ramus do not
return to the spinal nerve by the gray portion of the same ramus,
but passing upward or downward in the sympathetic chain
return to some other spinal nerve as postganglionic fibers. In this
way, therefore, it happens that the various intercostal nerves and
the nerves of the brachial and sciatic plexus contain vasoconstrictor
fibers as postganglionic or sympathetic fibers. On the other hand,
the vasoconstrictor fibers destined for the great vascular region of
the intestines and other abdominal viscera, after reaching the sym-
pathetic chain by way of the white rami as preganglionic fibers, do
not return to the spinal nerves by the gray rami. They leave the
sympathetic chain, still as preganglionic fibers, in the branches of the
splanchnic nerves and through them pass to the celiac ganglion,
where they mainly end, and their path is continued by the post-
ganglionic or sympathetic fibers arising from this ganglion.. More
specific information concerning the origin of the vasomotor fibers
to the different organs is given in condensed form farther on. It is
quite important in the beginning, however, to obtain a clear general
conception of the paths taken by the constrictor fibers from their
origin in the spinal cord to their termination, on the one hand,
in the vessels of the skin, or, on the other, in the vessels of the
abdominal and pelvic viscera.

The Tonic Activity of the Vasoconstrictor Fibers. — A very
important fact regarding the vasoconstrictor nerve fibers is that
they are constantly in action to a greater or less extent. This
fact is demonstrated by the simple experiment of cutting them.
If the sympathetic nerve in the neck is cut in the rabbit the blood-
vessels of the ear become dilated. If the splanchnic nerves on
the two sides are cut the intestinal region becomes congested,
and the effect in this case is so great that the general arterial pressure
falls to a very low point. From these and numerous similar ex-
periments we may conclude that normally the arteries — that is,
the arterioles — are kept in a condition of tone by impulses received
through the vasoconstrictor fibers. Cut these nerves and the arte-
ries lose their tone and dilate, with the result that, the peripheral
resistance being diminished, the lateral pressure falls on the arterial
side and rises on the venous side. The relatively enormous effect
upon aortic pressure caused by paralysis of the tone of the arteries
in the splanchnic area shows that under normal conditions the
peripheral resistance in this great area plays a predominating part
in the maintenance of normal arterial pressure, and by the same
reasoning variations in tone in the arteries of this region must
play a very large part in the regulation of arterial pressure.

The Vasoconstrictor Center. — As stated in the last two para-

THE VASOMOTOR NERVES.

559

-•*

graphs, the vasoconstrictor fibers emerge from the cord over a
definite region, and they exhibit constant tonic activity. It has
been shown, moreover, that if the cord be cut anywhere in the
cervical region all of the constrictor fibers lose their tone; a great
vascular dilatation results in both the splanchnic and skin areas.
We may infer from this fact that the vasoconstrictor paths originate
from nerve cells in the brain and that their tonic activity is to
be traced to these cells. Such a group of cells exists in the medulla
oblongata, and forms the vaso-
constrictor center. The axons
given off from these cells de-
scend in the cervical cord and
terminate at various levels in
the anterior horn of gray mat-
ter in the region from the upper
thoracic to the upper lumbar
spinal nerves. A spinal neuron
continues the path as the pre-
ganglionic vasoconstrictor fiber
which terminates, as already
described, in some sympathetic
ganglion, whence the path is
further continued by the post-
ganglionic fiber. This arrange-
ment of the constrictor paths is
indicated schematically in Fig.
232. The exact location of the
group of cells that plays the im-
portant role of a vasoconstrictor
center has not been determined
histologically. The region has,
however, been delimited roughly
by physiological experiments. If
the brain is cut through at the
level of the midbrain there is no
marked loss of vascular tone in
the body at large. If, however,
similar sections are made farther
and farther back a point is

reached at which vascular paralysis begins to be apparent and a
point farther down at which this paralysis is as complete as it
would be if the cervical cord were cut. Between these two points
the vasoconstrictor center must lie. The careful experiments of
this kind made by Dittmar* are now somewhat old. According
* " Berichte d. Sachs. Akademie, Math.-phys. Klasse, " 1873, p. 449.

Fig. 232.— Schema to show the path
of the vasoconstrictor fibers from the vaso-
constrictor center to the blood-vessels and
the mechanism for the reflex stimulation
of these fibers : r. c., The vasoconstrictor
center; 1, the central neuron of the vaso-
constrictor path ; 2, the spinal neuron
vpreganglionic fiber); 3, the sympathetic
neuron (postganglionic fiber); a, the arte-
riole ; 4, the sensory fibers of the posterior
root making connections by collaterals
with the vasoconstrictor center ; 5, an in-
tercentral fiber (efferent) acting upon the
vasoconstrictor center.

560 CIRCULATION OF BLOOD AND LYMPH.

to his description, the center is bilateral, — that is, consists of a
group of cells on each side, — and lies about the middle of the fourth
ventricle in the tegmental region, in the neighborhood of the nucleus
of the facial and of the superior olivary. In the rabbit it has a
length of 3 mms., a breadth of 1 to 1.5 mms., and lies about 2
to 2.5 mms. lateral to the mid-line. Assuming the existence of
this group of cells, we must attribute to them functions of the first
importance. Like other motor cells, they are capable of being
stimulated reflexly and by this means the regulation of the blood-
flow is largely controlled. Moreover, they are in constant activity,
— due doubtless also to a constant reflex stimulus from the inflow
of afferent impulses. The complete loss of this tonic influence
would result in a complete vascular paralysis, the small arteries
would be dilated, peripheral resistance would be greatly diminished,
and the arterial pressure in the aorta would fall from a level of
100-150 mms. Hg to about 20 or 30 mms. Hg, — a pressure insuffi-
cient to maintain the life of the organism. There seems to be no
question now that in those conditions known as surgical shock the
loss of control by the vasomotor center, and the consequent vascular
paralysis and fall of blood-pressure, are the chief conditions of a
serious character. We must conceive, also, that in this vasocon-
strictor center the different cells are connected by definite paths
with the vasoconstrictor fibers to the different regions of the body;
that some of the cells, for instance, control the activity of the
fibers distributed to the intestinal area, and others govern the
vessels of the skin. Under physiological conditions the different
parts of the center may, of course, be acted upon separately.

Vasoconstrictor Reflexes — Pressor and Depressor Nerve
Fibers. — It is obvious that such a mechanism as that described
above is susceptible of reflex stimulation through sensory nerves,
and according to our general knowledge we should suppose that
a tonic center of this kind may have its tonicity increased (excita-
tion) or decreased (inhibition). Numerous experiments in phys-
iology warrant the view that both kinds of effects take place
normally. Those afferent nerve fibers which when stimulated
cause reflexly an excitation of the vasoconstrictor center, and
therefore a peripheral vasoconstriction and rise of arterial pressure,
are frequently designated as pressor fibers, or their effect upon the
circulation is designated as a pressor effect. Those afferent fibers,
on the contrary, which when stimulated cause a diminution in
the tone of the vasoconstrictor center and therefore a periph-
eral vasodilatation and fall of arterial pressure, are designated as
depressor nerve fibers, or their effect upon the circulation is a de-
pressor effect. Pressor effects may be obtained by stimulation of
almost any of the large nerves containing afferent fibers, but espe-

THE VASOMOTOR NERVES. 561

cially perhaps of the cutaneous nerves. And there is abundance
of evidence to show that similar results can be obtained in man.
The pressor effect manifests itself by a rise in general arterial pres-
sure, if a sufficiently large region is involved, and by a diminution
in size of the organ involved. On the other hand, depressor effects
may also be obtained from stimulation of many of the large nerve
trunks. If one stimulates" the central end of the sciatic nerve,
for example, one obtains a pressor effect on the circulation in most
cases, but under certain conditions a marked depressor effect fol-
lows the stimulation.* The simplest explanation of such a result
is that the nerve trunks contain afferent fibers of both kinds.
When we apply our electrodes to a nerve we stimulate every fiber
in it and the actual result will depend upon which group of fibers
exerts the stronger action, and this may vary with the condition

Fig. 233. — Plethysmographic curve of forearm. The volume of the arm was recorded
by means of a counter-weighted tambour and the record shows the pulse waves. A problem
in mental arithmetic — the product of 24 by 43 — caused a marked constriction of the arm.

of the nerve, the condition of the center, the anesthetic used, etc.
Under normal conditions no such gross stimulation occurs. The
pressor fibers are stimulated under some circumstances, the de-
pressor fibers under others. For instance, when the skin is exposed
M cold it is blanched not by a direct, but by a reflex, effect. The
low temperature stimulates the sensory (cold) fibers in the skin,
and the nerve impulses thus aroused reflexly stimulate the vaso-
constrictor center, or a part of it, and cause blanching of the skin.
Exposure to high temperatures, on the contrary, flushes the skin,
and in this case we may suppose that the sensory impulses carried
by the heat nerves inhibit the tone of the vasoconstrictor center
and cause dilatation or flushing of the skin. So far as man is
concerned, experiments made with the plethysmograph show very

*See Hunt, ''Journal of Physiology," 18,381, 1895.
36

562

CIRCULATION OF BLOOD AND LYMPH.

clearly that the vasoconstrictor center is easily affected in a pressor
or depressor manner by psychical states or activities. Mental
work, especially mental interest, however aroused, is followed by
a constriction of the blood-vessels of the skin, — a pressor effect (see
Fig. 233) ; and we may find an explanation of the value of the reflex
in the supposition that the rise of arterial pressure thus produced

4. — Effect of stimulating the central end of the depressor nerve of the heart in
a rabbit. The time record marks seconds. Or and off mark the beginning and end of
the stimulation. The blood-pressure rises slowly after the removal of the stimulus and
eventually reaches the norn.al level. This complete recovery is not shown in the port:on
of the record reproduced. (Dawson.)

forces more blood through the brain (p. 579). On the other hand,
feelings of embarrassment or shame may be associated with a de-
pressor effect, a dilatation in the vessels of the skin manifested, for
example, in the act of blushing. In both cases we must assume
intracentral nerve paths between the cortex and the center in the
medulla, the impulses along one path exciting the center, while
those along the other inhibit its tone, or, as explained below, excite

THE VASOMOTOR NERVES. 563

a vasodilator center. Among the many depressor effects that
have been observed on stimulation of afferent nerve fibers
one has aroused especial interest, — namely, that caused by
certain afferent fibers from the heart. These fibers in some ani-
mals— the dog, for instance — run in the vagus nerve, but in
other animals, the rabbit, they form a separate nerve, the so-called
depressor nerve of the heart, — discovered by Ludwig and Cyon
(1866). In the rabbit this nerve forms a branch of the vagus,
arising high in the neck by two roots, one from the trunk of the
vagus and one from the superior laryngeal branch. It runs toward
the heart in the sheath with the vagus and the cervical sympa-
thetic. The nerve is entirely afferent. If it is cut and the peripheral
end is stimulated no result follows. If, however, the central end
is stimulated a fall of blood-pressure occurs and also perhaps a
slowing of the heart beat (see Fig. 234). The latter effect is due
to a reflex stimulation of the cardio-inhibitory center and may
be eliminated by previous section of the vagus. The fall of
blood-pressure is explained by supposing that the nerve, when
stimulated, inhibits, to a greater or less extent, the tonic activ-
ity of the vasoconstrictor center.* Physiological experiments
indicate that the nerve plays an important regulatory role.f When,
for instance, blood-pressure rises above normal limits it may be
supposed that the endings of this nerve in the heart are stimulated
by the mechanical effect, and the blood-pressure is thereby lowered
by an inhibition of the tone of the constrictor center. It is possible,
according to recent work, that the depressor fibers end in the walls
of the aorta outside the heart. J In this position the effect of
supranormal aortic pressures may readily effect a stimulation of
their endings and cause a fall of pressure.

A most suggestive example of the regulating action of the depressor nerve
is given by Sewall. When the carotids in a rabbit are clamped a variable
and not very large rise of arterial pressure is observed. If, however, the
depressor nerves are first cut, clamping the carotids causes an extraordinary
rise of arterial pressure. When the carotids are closed we may suppose that
the resulting anemia of the medulla stimulates the vasoconstrictor center
and thus tends to raise arterial pressure, but this effect is neutralized because
as the pressure rises the depressor fibers of the heart are stimulated. It
seems evident that during life the depressor fibers must exert a very important
regulating effect upon the circulation.

A similar nerve has been described anatomically in man, while
in animals like the dog, in which it is not present as a separate
anatomical structure, it probably exists within the trunk of the
vagus. If this latter nerve is cut in the dog and the central end
is stimulated a depressor effect is usually obtained.

* See Porter and Beyer, " American Journal of Physiology, " 4, 283, 1900 ;
also Bayliss, "Journal of Physiology," 14, 303, 1893.

t Sewall and Steiner, "Journal of Physiology, " G, 162, 1885.

t Koster and Tschermak, " Archiv f . die gesammte Physiologic, " 93, 24,
1902.

564 CIRCULATION OF BLOOD AND LYMPH.

Vasoconstrictor Centers in the Spinal Cord. — From the description of the
vasoconstrictor mechanism given above the probable inference may be made
that throughout the thoracic region the cells of origin of the preganglionic
fibers may, under special conditions, act as subordinate vasoconstrictor centers
capable of giving reflexes and of exhibiting some tonic activity. Numerous
experiments tend to support this inference When the spinal cord is cut in
the lower thoracic region there is a paralysis of vascular tone in the posterior
extremities. If, however, the animal is kept alive the vessels gradually re-
cover their tone, although not connected with the medullary center. The re-
sumption of tone in this case may be attributed to the nerve cells in the lower
thoracic and upper lumbar region, since vascular paralysis is again produced
when this portion of the cord is destroyed. Finally, Goltz has shown that
when the entire cord is destroyed, except the cervical region (p. 145), vascular
tone may be restored finally in the blood-vessels affected. In this case the re-
sumption of tonicity must be referred either to the properties of the muscular
coats of the arteries themselves reacting to the stimulus of the internal pres-
sure, or to the activity of the sympathetic nerve cells that give rise to the
postganglionic fibers. Under normal conditions it seems quite clear that the
great vasoconstrictor center in the medulla is the important seat of [tonic and
of reflex activity. If the connections of this center with the blood-vessels are
destroyed suddenly — for example, by cutting the cervical cord — blood-pressure
falls at once to such a low level, 20 to 30 mms. Hg., that death usually results
unless artificial means are employed to sustain the animal.

Rhythmical Activity of the Vasoconstrictor Center. —

Throughout life the vasoconstrictor center is in tone the intensity

Fig. 235. — Rhythmical vasomotor waves of blood-pressure in a dog (Traube-Hering
waves). The upper tracing (1) is the blood-pressure record as taken with the mercury
manometer; the lower tracing (2) is taken with a Hiirthle manometer. Seven distinct
respiratory waves of blood-pressure may be recognized on each large wave. (Dawson.)

of which varies with the intensity and character of the reflex im-
pulses playing upon it. Under certain unusual conditions the
center may exhibit rhythmical variations in tonicity which make
themselves visible as rhythmical rises and falls in the general
arterial pressure (Fig. 235), the waves being much longer than
those due to the respiratory movements. These waves of blood-
pressure are observed often in experiments upon animals, but
their ultimate cause is not understood. They are usually desig-

THE VASOMOTOR NERVES. 565

nated as Traube-Hering waves, although this term, strictly speak-
ing, belongs to waves, synchronous with the respiratory move-
ments, that were observed by Traube upon animals in which
the diaphragm was paralyzed and the thorax was opened.
These latter waves are also due to a rhythmical action of the
vasomoter center. During sleep certain much longer, wave-like
variations in the blood-pressure also occur that are again due
doubtless to a rhythmical change of tone in the vasoconstrictor
center.

General Course and Distribution of the Vasodilator Fibers.
— By definition a vasodilator fiber is an efferent fiber which when
stimulated causes a dilatation of the arteries in the region supplied.
In searching for the existence of such fibers in the various nerve
trunks physiologists have used all the methods referred to above, —
namely, the flushing of the organ as seen by the eye, the increased
blood-flow, the increase in volume, or the fall in blood-pressure on
the arterial side associated with a rise on the venous side. By
these methods vasodilator fibers have been demonstrated in the
following regions :

1. In the facial nerve. The dilator fibers are found in the chorda tym-

pani branch and are distributed to the salivary glands (submaxil-
lary and sublingual) and to the anterior two-thirds of the tongue.

2. In the glossopharyngeal nerve. Supplies dilator fibers to the posterior

third of tongue, tonsils, pharynx, parotid gland (nerve of Jacobson).

3. In the sympathetic chain. In the cervical portion of the sympathetic

dilator fibers are carried which are distributed to the mucous mem-
brane of the mouth (lips, gums, and palate), nostrils, and the skin
of the cheeks. These fibers pass up the neck to the superior cervi-
cal ganglion and thence by communicating branches reach the Gas-
serian ganglion and are distributed to the bucco-facial region hi the
branches of the fifth cranial nerve.* From the thoracic portion of
the sympathetic vasodilator fibers pass to the abdominal viscera by
way of the splanchnic nerves and to the limbs by way of the
branches of the brachial and lumbar plexuses, but the data regarding
the dilator fibers for these regions are not as yet entirely satisfactory.
Goltz and others have shown that dilator fibers are found in the
nerves of the limbs, but the origin of these fibers from the sympa-
thetic chain has not been demonstrated.

4. In the nervi erigentes. Eckhard first gave conclusive proof that the

erection of the penis is essentially a vasodilator phenomenon. The
fibers arise from the first, second, and third sacral spinal nerves, pass
to the hypogastric plexus as the nervi erigentes, and thence are dis-
tributed to the erectile tissues of the penis.

The General Properties of the Vasodilator Nerve Fibers. —

Unlike the vasoconstrictors, the vasodilators are not in tonic
activity; at least, no experimental proof has been given that they
are. In the case of the erectile tissue of the penis and the dilators
of the glands it would seem that the fibers are in activity otily

* See " Recherches experimentales sur le systeme nerveux vasomoteur, "
Dastre and Morat, 1884.

566 CIRCULATION OF BLOOD AND LYMPH.

during the functional use of the organ, at which time they are
excited reflexly. There has been much discussion in physiology as
to the nature of the action of the dilator fibers. The muscular
coat of the small arteries runs transversely to the length of the
vessel, and it is easy to see that when stimulated to greater con-
traction through the constrictor fibers it must cause a narrowing
of the artery. It is not so evident how the nerve impulses carried
by the dilator fibers bring about a widening of the artery. At
one time peripheral sympathetic ganglia in the neighborhood of
the arteries were used to aid in the explanation, but, since histo-
logical evidence of the existence of such ganglia is lacking, the
view that seems to meet with most favor at present is as follows:
The dilator fibers end presumably in the muscle of the walls of
the arteries, and when stimulated their impulses inhibit the tonic
contraction of this musculature and thus indirectly bring about a
relaxation. Dilatation caused by a vasodilator nerve fiber always
presupposes therefore a previous condition of tonic contraction in
the walls of the artery, this tonic condition being produced either
by the action of vasoconstrictor fibers or possibly by the intrinsic
properties of the muscle itself. In the nerves of the limbs, as
stated above, both vasoconstrictor and vasodilator effects may be
detected by stimulation. It has been shown that the separate
fibers may be differentiated by certain differences in properties.
Thus, if the peripheral end of the cut sciatic nerve is stimulated
by rapidly repeated induction shocks a vasoconstrictor effect is
obtained as shown plethysmographically by a diminution in volume
of the limb. If, however, the same nerve is stimulated by slowly
repeated induction shocks the dilator effect will predominate,*
indicating a greater degree of irritability on the part of these latter
fibers. After section of the sciatic nerve the vasodilators degen-
erate more slowly than the vasoconstrictors, and they retain
their irritability when heated or cooled for a longer time than
the constrictors. t

Vasodilator Center and Vasodilator Reflexes. — Since the
vasodilator fibers form a system similar to that of the vasocon-
strictors, it might be supposed that, like the latter, their activity
is controlled from a general center, forming a vasodilator center in
the brain similar to the vasoconstrictor center. What evidence
we have, however, is against this view. In the dog with his spinal
cord severed in the lower thoracic region the penis may show normal
erection when the glans is stimulated, — a fact that indicates a
reflex center for these dilator fibers in the lumbar cord. For the
other clear cases of vasodilator fibers we have no reason at present

* Bowditch and Warren, "Journal of Physiology," 7, 439, 1886.

t Howell, Budgett, and Leonard. "Journal of Physiology," 16, 298, 1894.

THE VASOMOTOR NERVES. 567

to believe that they are ail normally connected with a single group
of nerve cells located in a definite part of the nervous system. The
dilator fibers in the facial, glossopharyngeal, and cervical sympa-
thetic (distributed through the trigeminal) all arise probably in the
medulla, but not, so far as is known, from a common nucleus.
Intimately connected with the question of the existence of a general
vasodilator center is the ppssibility of definite reflex stimulation
of the vasodilator fibers. As stated above, reflex dilatation of the
blood-vessels may be produced by stimulating various nerve trunks
containing afferent fibers. The depressor nerve fibers of the heart
give only this effect, and the sensory fibers from certain other
regions, notably the middle ear and the testis, cause mainly, if not
exclusively, a fall of arterial pressure due presumably to vascular
dilatation. The sensory nerves of the trunk and limbs, when
stimulated by the gross methods of the laboratory, give either
reflex vasoconstriction or reflex vasodilatation, and, as was stated
above, there is reason to believe that these trunks contain two kinds
of afferent fibers, — the pressor and the depressor. The action of the
former predominates usually, but in deep anesthesia, and particu-
larly in those conditions of exposure and exhaustion that precede
the appearance of "shock," the depressor effect is most marked or,
indeed, may^ be the only one obtained. To explain such depressor
effects we have two possible theories. They may be due to reflex
excitation of the centers giving origin to the vasodilator fibers or to
reflex inhibition of the tonic activity of the vasoconstrictor centers.
The latter explanation is the one usually given, especially for the
typical and perhaps special effect of the depressor nerve of the heart.
This explanation seems justified by the general consideration that
in the two great vascular areas through whose variations in capacity
the blood-flow is chiefly regulated, — namely, the abdominal viscera
and the skin, — the vasoconstrictor fibers are chiefly in evidence
and are, moreover, in constant tonic activity. On the other hand,
the fact that vasodilator fibers exist is presumptive evidence that
they are stimulated reflexly, since it is by this means only that they
can normally affect the blood-vessels. Some of the many depressor
effects occurring in the body must be due, therefore, to reflex
stimulation of the dilators and others to reflex inhibition of the
constrictors. It would be convenient to retain the name depressor
for the sensory fibers causing the latter effect, and to designate
those of the former class by a different name, such as reflex vaso-
dilator fibers.* Only experimental work can determine positively
to which effect any given reflex dilatation is due, but provisionally
at least it would seem justifiable to assume that dilatation by reflex
stimulation of the vasodilator fibers occurs in those parts of the
body in which vasodilator fibers are known to exist. Thus, the
*See Hunt, "Journal of Physiology/' 18, 381, 1895.

568

CIRCULATION OF BLOOD AND LYMPH.

erection of the penis from stimulation of the glans may be explained
in this way, also the congestion of the salivary glands during activity,
the blushing of the face from emotions, and possibly the dilatation
in the skeletal muscles during contraction. Gaskell and others
have given reasons for believing that the vessels in the muscles are
supplied with vasodilator nerve fibers, and Kleen * has shown that
mechanical stimulation of the muscles — kneading, massage, etc.—
causes a fall of arterial pressure.

Vasodilatation Due to Antidromic Impulses. — The existence of definite effer-
ent vasodilator fibers in the nerve trunks to the limbs has been made doubt-
ful by the work of Bayliss. This author has discovered certain facts which at
present tend to make the (question of vasodilatation more obscure, but which,
when fully understood, will doubtless give us a much deeper insight into the
subject. Briefly stated, he has shownf that stimulation of the posterior roots
of the nerves supplying the lumbo-sacral and the brachial plexus causes vas-
cular dilatation in the corresponding limbs. He has shown that the fibers
involved are sensory fibers from the limbs and that therefore when stimulated
they must conduct the impulses in a direction opposite to the normal, — anti-
dromic. It is most difficult to understand how such impulses, conveyed to the
terminations of the sensory fibers, can affect the muscular tissue of the blood-
vessels. It is most difficult to understand also how such anatomically afferent
fibers can be stimulated reflexly in the central nervous system. Bayliss gives
reasons for believing that the limbs receive no vasodilator fibers via the sym-
pathetic system, and that either the blood-vessels in this region are lacking
altogether in such fibers or else the sensory fibers function in the way described.

General Schema. — The main facts regarding the vasomotor
apparatus may be summarized briefly in tabular form as follows:

Efferent vasomotor
nerve fibers.

Afferent fibers giving
vasomotor reflexes.

I.

II.

I.

Vasoconstrictor fibers — distributed mainly to
the skin and the abdominal viscera (splanch-
nic area), all connected with a general center
in the medulla oblongata, and in constant
tonic activity.

Vasodilator fibers — distributed especially to
the erectile tissue, glands, bucco-f acial region,
and muscles; not connected with a general
center and not in tonic activity.

Pressor fibers. Cause vascular constriction and
rise of arterial pressure from reflex stimula-
tion of the vasoconstrictor center — e. g.,
sensory nerves of skin.

II. Depressor fibers. Cause vascular dilatation and
fall of arterial pressure from reflex inhibition
of the tonic activity of the vasoconstrictor
center, — e. g., depressor nerve of heart.
III. Depressor (or reflex vasodilator) fibers. Cause
vascular dilatation and fall of arterial pres-
sure from stimulation of the vasodilator
center, — e. g., erectile tissue, congestion of
glands in functional activity.

It may be supposed that under normal conditions the activity
of this mechanism is adjusted so as to control the blood-flow through

* Kleen, " Skandinavisches Archiv f . Physiologic," 247, 1887.

t Bayliss, "Journal of Physiology," 26, 173, 1900, and 28, 276, 1902.

THE VASOMOTOR NERVES. 569

the different organs in proportion to their needs. When the blood-
vessels of a given organ are constricted the flow through that organ
is diminished, while that through the rest of the body is increased
to a greater or less extent corresponding to the size of the area in-
volved in the constriction. When the blood-vessels of a given
organ are dilated the blood-flow through that organ is increased and
that through the rest of the body diminished more or less. The
adaptability of the vascular system is wonderfully complete, and
is worked out mainly through the reflex activity of the nervous
system exerted partly through the vasomotor fibers and partly
through the regulatory nerves of the heart.

Regulation of the Blood-supply by Chemical and Mechan-
ical Stimuli. — From time to time attention has been called to
the fact that the calibre of the blood-vessels may be influenced
otherwise than through the agency of vasoconstrictor and vaso-
dilator nerve fibers. Gaskell, for example, has shown that acids
in slight concentration cause a vascular dilatation. Bayliss * has
recently generalized the facts of this kind, and has suggested that
in addition to the nervous regulation described in the preceding
pages there may be formed chemical substances of a definite char-
acter which exert a similar useful regulating action. As examples
of this influence, we have the lactic acid produced in muscles during
activity and probably also the carbon dioxid produced in this as
in other tissues. These substances may act to produce a local
dilatation during functional activity and thus provide the organ
with more blood at the time that it is needed. On the other hand,
the internal secretion of the adrenal glands (adrenalin) and possi-
bly also of the infundibular portion of the pituitary gland have
the reverse effect, causing a vasoconstriction and thus tending to
maintain normal vascular tone. In a similar way it is probable that
the distension of the arteries by internal pressure acts as a mechani-
cal stimulus which leads to increased tone and thus aids in main-
taining a normal arterial tension.

* Bayliss in "Ergebnisse der Physiologic," 1906, v., 319

CHAPTER XXXIII.

THE VASOMOTOR SUPPLY OF THE DIFFERENT
ORGANS.

There are three important organs of the body — namely, the
heart, the lungs, and the brain — in which the existence of a vaso-
motor supply is still a matter of uncertainty. A very great deal
of investigation has been attempted with reference to these organs,
but the technical difficulties in each case are so great that no entirely
satisfactory conclusion has been reached. A brief review of some
of the experimental work on record will suffice to make evident the
present condition of our knowledge.

Vasomotors of the Heart. — The coronary vessels lie in or on
the musculature of the heart. Any variation in the force of con-
traction or tonicity of the heart muscle itself will therefore affect
possibly the caliber of the arterioles and the rate of blood-flow in the
coronary system. At each contraction of the ventricles the coro-
nary circulation is probably interrupted by a compression of the
smaller arteries and veins, and the size of these vessels during dias-
tole will naturally vary with the extent of relaxation of the cardiac
muscle. Since stimulation of either of the efferent nerves supplying
the heart, vagus and sympathetic, affects the condition of the mus-
culature, it is evident at once how difficult it is to distinguish a.
simultaneous effect upon the coronary arteries, if any such exists.
Newell Martin* found that stimulation of the vagus causes dilata-
tion of the small arteries on the surface of the heart as seen through
a hand lens. Moreover, when the heart is exposed and artificial
respiration is stopped the arteries may be seen to dilate before
the asphyxia causes any general rise of arterial pressure. Martin
interpreted these observations to mean that the coronary arteries
receive vasodilator fibers through the vagus. Porterf measured
the outflow through the coronary veins in an isolated cat's heart
kept alive by feeding it with blood through the coronary arteries.
He found that this outflow is diminished when the vagus nerve
is stimulated, and hence concluded that the vagus carries vasocon-
strictor fibers to the heart. MaasJ reports similar results also

* Martin, " Transactions Medical and Chirurgical Faculty of Maryland,"
1891.

t Porter, " Boston Medical and Surgical Journal, " January 9, 1896.
j Maas, " Archiv f. die gesammte Physiologic," 74, 281, 1899.

570

VASOMOTOR SUPPLY OF THE ORGANS. 571

obtained from cats' hearts kept alive by an artificial circulation
through the coronary arteries. Stimulation of the vagus slowed
the stream (vasoconstrictor fibers), while stimulation of the sympa-
thetic path quickened the flow (vasodilator fibers). Neither Maas
nor Porter gives conclusive proof that the heart musculature
was not affected by the stimulation. Schaefer,* on the con-
trary, gets entirely opposite results. When an artificial circulation
was maintained through the coronary system and the amount
of outflow was determined he found that this quantity was not
definitely influenced by stimulation of either the sympathetic or
the vagus branches. Moreover, injection of adrenalin into the
coronary circulation had no influence upon the outflow, and since
this substance causes an extreme constriction in the vessels of organs
provided with vasoconstrictor fibers the author concludes that the
coronary arteries have no vasomotor nerve fibers. It is evident
from a consideration of these results that the existence of vaso-
motor fibers to the heart vessels is still a matter open to investi-
gation.

Vasomotors of the Pulmonary Arteries. — The pulmonary
circulation is complete in itself and, as was stated on p. 481, it
differs from the systemic circulation chiefly in that the peripheral
resistance in the capillary area is much smaller. Consequently
the arterial pressure in the' pulmonary artery is small, while the
velocity of the blood-flow is greatef than in the systemic circuit, —
that is, a larger portion of the energy of the contraction of the
right ventricle is used in moving the blood. From the mechanical
conditions present it is obvious that the pressure in the pulmonary
artery might be increased by a vasoconstriction of the smaller
lung arteries, or, on the other hand, by an increase in the blood*
flow to the right ventricle through the venae cavae, or, last, by
back pressure from the left auricle when the left ventricle is not
emptying itself as well as usual on account of high aortic pressure.
While it is comparatively easy, therefore, to measure the pressure
in the pulmonary artery, it is difficult, in the interpretation of the
changes that occur, to exclude the possibility of the effects being
due indirectly to the systemic circulation. Bradford and Dean,f
by comparing carefully the simultaneous records of the pressures
in the aorta and a branch of the pulmonary artery, came to the
conclusion that the latter may be affected independently by stimu-
lation of the third, fourth, and fifth thoracic spinal nerves, and
hence concluded that these nerves contain vasoconstrictor fibers
to the pulmonary vessels, the course of the fibers being, in general,
that taken by the accelerator fibers to the heart, — namely, to the

*" Archives des sciences biologiques," 11, suppl. volume, 251, 1905.
t Bradford and Dean, " Journal of Physiology/ ' 16, 34, 1894.

572 CIRCULATION OF BLOOD AND LYMPH.

first thoracic sympathetic ganglion by the rami communicantes
and thence to the pulmonary plexus. They give evidence to show
that these fibers are stimulated during asphyxia. The authors
state, however, that the effects obtained upon the pressure in the
pulmonary artery are relatively and absolutely small as compared
with the vasomotor effects in the aortic system. Similar results
have been obtained by other observers ( Franc, ois-Franck). Using
another and more direct method, Brodie and Dixon* have come
to an opposite conclusion. These authors maintained an artificial
circulation through the lungs and measured the rate of outflow
when the nerves supplying the lungs were stimulated. Under these
conditions stimulation of the vagus or the sympathetic caused no
definite change in the rate of flow, — a result which would indicate
that neither nerve conveys vasomotor fibers to the lung vessels.
This conclusion was strengthened by the fact that in similar per-
fusions made upon other organs (intestines) vasomotor effects were
easily demonstrated. Moreover, adrenalin, pilocarpin, and mus-
carin cause marked vasoconstriction when irrigated through the
intestine, but have no such effect upon the vessels in the lungs.
These authors conclude that the lung vessels have no vasomotor
nerves at all, and their experimental evidence might be accepted
as satisfactory except for the fact that a similar method in the
hands of another observer has given* opposite results. Plumierf
finds that the outflow through a perfused lung is diminished in
some cases by stimulation of the sympathetic branches to the lungs,
and also by the use of adrenalin. Under such conditions it is
necessary to defer a decision until more experiments are reported.
Regarding the vasomotors of the lungs, one can only say, as in
the case of the heart, that their existence has not been demonstrated.

The Circulation in the Brain and Its Regulation. — The
question of the existence of vasomotor nerves to the brain brings
up necessarily the larger question of the special characteristics of
the cranial circulation. The brain is contained in a rigid box so
that its free expansion or contraction with variations in the amount
of blood can not take place as in other organs and we have to con-
sider in how far this fact modifies its circulation.

The Arterial Supply of the Brain. — The brain is supplied through
the two internal carotids and the two vertebrals, which together
form the circle of Willis. It will be remembered also that the
vertebral arteries give off the posterior and the anterior spinal
arteries, which supply the spinal cord, and that the last-named
artery makes anastomoses along the cord with the intercostal arteries

* Brodie and Dixon, "Journal of Physiology," 30, 476, 1904.
f Plumier, " Journal de physiologie et de pathologic generate, " 6, 665,
1904; see also "Archives internationales de physiologie," 1, 189, 1904.

VASOMOTOR SUPPLY OF THE ORGANS.

57S

and other branches from the descending aorta. From the ana-
tomical arrangement alone it is evident that the circulation in the
brain is very well protected from the possibility of being inter-
rupted by the accidental closure of one or more of its arteries. In
some animals, the dog, one can ligate both internal carotids and
both vertebrals without causing unconsciousness or the death of the
animal. In an animal under these conditions a collateral circula-
tion must be brought into play through the anastomoses of the
spinal arteries. In man, on the contrary, it is stated that ligation
of both carotids is dangerous or fatal.

The Venous Supply. — The venous system of the brain is peculiar,
especially in the matter of the venous sinuses. These large spaces
are contained between folds of the dura mater or, on the base of
the skull, between the dura mater and the bone. The channel
hollowed out in the bone is covered with a roof of tough, inex-
tensible dura mater, and indeed in some animals the basal sinuses

— 7"""^ • -^~^T~~-

Cerebrum..

Fig. 236 — Diagram to represent the relations of the meningeal membranes of the cere-
brum, the position of the subarachnoidal space and of the venous sinuses.

may in part be entirely incased in bone. The larger cerebral veins
open into these sinuses; the openings have no valves, buf, on the
contrary, are kept patent and protected from closure by the struc-
ture of the dura mater around the orifice. The smaller veins are
very thin walled and free from valves. The venous blood emerges
from the skull in man mainly through the opening of the lateral
sinuses into the internal jugular vein, although there is also a
communication in the orbit between the cavernous sinus and the
ophthalmic veins through which the cranial blood may pass into
the system of facial veins, another communication with the venous
plexuses of the cord, and a number of small emissary veins. In
some of the lower animals — the dog, for instance — the main outflow
is into the external jugular through what is known as the superior
cerebral vein. A point of physiological interest is that the venous
sinuses and their points of emergence from the skull are by their
structure well protected from closure by compression.

574

CIRCULATION OF BLOOD AND LYMPH.

The Meningeal Spaces. — The general arrangement of the menin-
geal membranes, and particularly of the meningeal spaces, is im-
portant in connection with the mechanics of the brain circulation.
In the skull the dura mater adheres to tke bone, the pia mater
invests closely the surface of the brain, while between lies the
arachnoid (Fig. 236). The capillary space between the arachnoid
and the dura, the so-called subdural space, may be neglected.
Between the arachnoid and the pia mater, however, lies the sub-
arachnoidal space more or
less intersected by septa of
connective tissue, but in free
communication throughout
the brain and cord. This
subarachnoidal space is filled
with a liquid, the cerebro-
spinal liquid, which forms a
pad inclosing the brain and
cord on all sides. The liquid
surrounding the cord is in
free communication with
that in the brain, as is indi-
cated in the accompanying
schematic figure (Fig. 237).
Within the brain itself there
are certain points at the an-
gles and hollows of the differ-
ent parts of the brain at which
the subarachnoidal space
is much enlarged, forming
the so-called cisternae, which
are in communication one
with another by means of the
less conspicuous canals (see
Fig. 238) . The whole system
is also in direct communica-
tion with the ventricles of
the brain on the one hand,
through the foramen of

Magendie, the foramina of Luschka, and perhaps at other places,
and on the other hand, along the cranial and spinal nerves it is
continued outward in the tissue spaces of the sheaths of these nerves.
The Pacchionian bodies constitute also a peculiar feature of the sub-
arachnoidal space. These bodies occur in numbers that vary with
the individual and with age, and are found along the sinuses,
especially the superior longitudinal sinus. Each body is a minute,

Fig. 237. — Diagram to show the connec-
tion of the subarachnoidal space in the brain
and the cord.

VASOMOTOR SUPPLY OF THE ORGANS.

575

pear-shaped protrusion of the arachnoidal membrane into the inte-
rior of a sinus, as represented schematically in Fig. 239. Through
these bodies the cerebrospinal
liquid is brought into . close
contact with the venous
blood, the two being sepa-
rated only by a thin layer
of dura and the very thin
arachnoid. The number of
the Pacchionian bodies is
hardly sufficient to lead us
to suppose that they have a
special physiological impor-
tance. The cerebrospinal liq-
uid found in the subarach-
noidal space and the ventri-
cles of the brain is a very
thin, watery liquid having a
specific gravity of only 1.007
to 1.008. It contains only
traces of proteins and other
organic substances, which may vary under pathological condi-
tions. It is thinner and more watery than the lymph, resembling
rather the aqueous humor of the eye. The amount of this fluid

Fig. 238. — Diagram to show the location
of the cisterase and canals of the
noidal space. — (Poirier and Charpy.)

subarach-

Fig. 239. — Schema to show the relations of the Pacchionian bodies to the sinuses:
d, d, Folds of the dura mater, inclosing a sinus between them ; v.b., the blood in the
sinus; a, the arachnoidal membrane; p, the pia mater; Pa., the Pacchionian body as
a projection of the arachnoid into the blood sinus.

present normally is difficult to determine. Various figures have
been given, but it is usually stated to amount to 60 to 80 c.c. If

576 CIRCULATION OF BLOOD AND LYMPH.

these figures are correct it evidently does not form a thick envelope
to the nervous system. Under abnormal conditions (hydroceph-
alus, etc.) the quantity may be greatly increased. It is physio-
logically interesting to find that this liquid may be formed very
promptly from the blood and, when in excess, be absorbed quickly
by the blood. In fractures of the base of the skull, for instance,
the liquid has been observed to drain off steadily at the rate of 200
c.c. or more per day. On the other hand, when one injects physio-
logical saline into the subarachnoidal space under some pressure it
is absorbed with surprising rapidity. After death, also, the liquid
present in the subarachnoidal space is soon absorbed.

Intracranial Pressure. — By intracranial pressure is meant the
pressure in the space between the skull and the brain, — therefore
the pressure in the subarachnoidal liquid and presumably also the
pressure in the ventricles of the brain, since the two spaces are in
communication. This pressure may be measured by boring a hole
through the skull, dividing the dura, and connecting the under-
lying space with a manometer. Observers who have measured this
pressure state that it is always the same as the venous pressure
within the sinuses. This we can understand when we remember
the close relations between the subarachnoidal liquid and the large
veins and sinuses. We may consider that the large veins are sur-
rounded by the cerebrospinal liquid, and consequently an equilib-
rium of pressure must be established between them ; any rise in the
intracranial pressure raises venous pressure by compression of the
veins. This statement holds true at least so far as the intracranial
pressure is due to the circulation. Variations of pressure from
pathological causes — tumors, clots, abscesses, etc. — may exercise
apparently a local effect. The intracranial pressure is caused
and controlled normally by the pressure within the arteries and
capillaries. This pressure, by enlarging these vessels, tends to
expand the brain against the skull, and exercises a pressure, there-
fore, upon the intervening cerebrospinal liquid. This pressure,
however, can not exceed- that in the veins, since, as said, an ex-
cess will be equalized by a corresponding compression of the veins.
The venous pressure in the end determines, therefore, the actual
amount of intracranial pressure. Conditions which alter the
pressure in the cerebral veins affect the intracranial pressure
correspondingly. Thus, compression of the veins of the neck raises
the pressure in the cerebral veins and also intracranial pressure,
and a higher general arterial pressure also results finally in a higher
pressure in the cerebral veins and therefore in the subarachnoidal
space.

Reduced to its simplest form, the conditions may be represented by a
schema such as is given in Fig. 240. A system with an artery, capillary area,

VASOMOTOR SUPPLY OF THE 6RGANS.

577

and a vein is represented as inclosed in a rigid box and surrounded by an
incompressible liquid. According to the conditions prevailing in the body,
the pressure in the interior of A and its branches is much higher than in V.
If, now, the pressure in A is increased the greater pressure brought to bear
on the walls will tend to expand them; a greater pressure will thereby be
communicated to the outside liquid, which, in turn, will compress the veins
correspondingly. The expansion on the arterial side is made possible by a
corresponding diminution on the
venous side where the internal
pressure is least.

The recorded measure-
ments of the intracranial
pressure show that it may
vary from 50 to 60 mms. of
mercury, obtained during the
great rise of pressure following
strychnin poisoning, to zero or
less, as obtained by Hill * from
a man while in the erect pos-
ture. In this position the
negative influence of gravity
is at its maximum.

The Effect of Variations
in Arterial Pressure upon
the Blood-flow through the
Brain. — Quite a number of
observers f have proved ex-
perimentally that a rise of
general arterial pressure is fol-
lowed, not only by an increase
in the intracranial tension, but
also by an increased blood-flow
through the brain. There has
been much discussion as to

whether a rise of arterial pressure in the basilar arteries can cause
any actual increase in the amount of blood in the brain or whether
it expresses itself solely or mainly as an increased amount of flow.
In the other organs of the body, except perhaps the bones, a general
rise of pressure, not accompanied by a constriction of the organ's
own arteries, causes a dilatation or congestion of the organ together
with an increased blood-flow. Physiologically the congestion —
that is, the increased capacity of the vessels — is of no value; the
important thing is the increase in the quantity of blood flowing

* Bayliss and Hill, " Journal of Physiology," 18, 356, 1895.

t See Gartner and Wagner, " Wiener med. Wochenschrift," 1887; de
Boeck and Verhorgen, " Journal de Medecine, etc.," Brussels; Roy and Sher-
rington, "Journal of Physiology," 11, 85, 1890; Reiner and Schnitzler,
"Archiv f. exp. Pathol. u. Pharmakol. , " 38, 249, 1897.
37

Fig. 240. — Schema to represent the
transmission of arterial pressure through
the brain substance to the veins: A, The
artery, V, the vein, represented as entering
into and emerging from a box with rigid
walls and filled with incompressible liquid;
c, c, the intervening area of small arte-
ries, etc. An expansion of the walls of
the arterial system by the pulse wave or by
a rise of arterial pressure increases the pres-
sure on the surrounding liquid and this is
transmitted through the liquid to the walls
of the veins and compresses them, since at
this point of the circuit the intravascular
pressure is low.

578 CIRCULATION OF BLOOD AND LYMPH.

through. In the brain, owing to the peculiarities of its position,
it has been suggested that perhaps no actual increase in size is
possible. It is evident, however, that the existence of the liquid
in the subarachnoidal space makes possible some actual expan-
sion of the organ. For as the pressure upon this liquid increases it
may be driven into the dural sac of the cord (Fig. 237) and along the
sheaths of the cranial and spinal nerves. To what extent this is
actually possible in man we do not know, nor do we know how much
cerebrospinal liquid is contained in the skull and brain of man. In
the dog Hill* finds experimentally that the brain can expand only
by an amount equal to 2 or 3 c.c. without causing a rise of intra-
cranial tension ; so that probably these figures represent the amount
of expansion possible in this animal by simple squeezing out of the
cerebrospinal liquid. If the rise of arterial pressure is such as to
expand the brain beyond this point, then it may not only force
out cerebrospinal liquid, if any remains, but, as explained in the
last paragraph, it will compress the veins and raise intracranial

Fig. 241. — Simultaneous record of pulse in the circle of Willis (c) and in the torcu-
lar Herophili (f). The tracing from the circle of Willis was obtained by means of a
Hurthle manometer connected with the head end of the internal carotid. It will be noted
that the pulses are simultaneous, indicating that the venous pulse is due to the transmis-
sion of the arterial pulse through the brain substance.

pressure. To the extent that the veins are compressed as the ar-
teries expand no actual increase in the size or blood-capacity of the
brain takes place. That an expansion of the brain arteries com-
presses the veins is indicated very clearly by the normal occurrence
of a venous pulse in this organ. The blood flows out of the veins of
the brain in pulses synchronous with the arterial pulses, and this
venous pulse may be recorded easily as shown in Fig. 241. In this
case the sudden expansion of the arteries compresses the cerebral
veins, giving a synchronous rise of pressure in the interior of the
sinuses. Some authors (Geigel, Grashey), on purely theoretical
grounds, have held that this compression of the veins may result in
a diminished blood-flow through the organ, — a sort of self-strangu-
lation of its own circulation. Actual experiment shows that
this is not the case. Any ordinary rise of general arterial pressure
is accompanied by a greater blood-flow through the brain, and
* Hill, "The Physiology and Pathology of the Cerebral Circulation."
London, 1896.

VASOMOTOR SUPPLY OF THE ORGANS. 579

the author* has shown that sudden variations of arterial pressure
far beyond possible normal limits cause no blocking of the venous
outflow. Whether the brain increases in volume as a result of
a rise of arterial pressure is, on the physiological side, unimportant;
the main point is that the amount of blood flowing through it is
increased under such circumstances as would cause a like result
in other organs. That the compression of the veins does not
produce any sensible obstruction to the blood-flow may be under-
stood easily. In the first place, this compression does not take
place at the narrow exit from the skull, — since at that point the
sinuses are protected from the action of intracranial pressure.
The compression takes place doubtless upon the cerebral veins
emptying into the sinuses, and at this point the venous bed,
taken as a whole, is so large that the expansion due to an
ordinary rise of arterial pressure is distributed and has but little
effect on the volume of the flow. Secondly, very great increases in
arterial pressure, up to the point of rupture of the walls, have less
and less effect in actually expanding the arteries; a point is reached
eventually at which these tubes become practically rigid, so that
farther expansion is impossible. This, of course, is true for every
organ.

The Regulation of the Brain Circulation. — It is still a matter
of uncertainty whether the arteries of the brain possess vasomotor
nerves. Most of the authors who have studied the matter experi-
mentally have concluded that there are none.f These authors were
unable to show that stimulation of any of the nerve paths that
might innervate the brain vessels causes local effects upon the brain
circulation. Whenever such stimulations caused a change in pres-
sure or amount of flow in the brain the result was referable to an alter-
ation of general arterial pressure produced by a vasomotor change
elsewhere in the body. When as a result of such stimulation the
pressure rises in the circle of Willis, one may infer that if this is due
to a local constriction in the cerebral arterioles there should be a
fall of pressure in the venous sinuses and a diminished flow of blood;
if, on the contrary, it is due to a constriction elsewhere in the body
that has increased general arterial pressure, but has not constricted
the brain circuit, then there should be a rise in venous pressure and
intracranial pressure, together with a greater flow of blood through
the brain. Most observers obtain this latter result. Some inves-
tigators,— Hurthle, Franc. ois-Franck, Cavazanni,J on the other

* Howell, " American Journal of Physiology," 1, 57, 1898.
t See Roy and Sherrington, Bayliss and Hill, Hill, Gaertner and Wagner,
loc. cit., and Hill and MacLeod, "Journal of Physiology," 26, 394, 1901.

580 CIRCULATION OF BLOOD AND LYMPH.

hand, have obtained results, especially from stimulation of the
cervical sympathetic, which indicated local vasoconstriction or vaso-
dilatation in the brain. It would seem, however, that these latter
observers have not excluded the possibility that the variations
in pressure obtained by them were due to reflex effects upon the
blood-vessels of the body, especially as Frangois-Franck has
shown that the sympathetic in the neck contains afferent fibers
which give such reflexes.* In experiments made upon an
isolated brain (in the skull) perfused with an artificial circulation,
Wiggers f states that addition of adrenalin caused a diminution
in the outflow from the organ, thus showing that the adrenalin had
caused a constriction somewhere in the circuit. If, as some authors
believe, adrenalin acts only on plain muscle that is innervated by
sympathetic nerve fibers this result furnishes indirect evidence
for the existence of such fibers in the case of the brain vessels. As
another argument in favor of the presence of vasomotor fibers it
may also be mentioned that a number of observers — Gulland,
Huber, Hunter J — have demonstrated that the vessels of the brain
are provided with perivascular nerve plexuses. It must be ad-
mitted, however, that this histological fact is not satisfactory
unless it is supplemented by experimental evidence. Judged
from this latter standpoint, we have no convincing proof at present
of the existence of cerebral vasomotors, and, assuming that there
are no such fibers, we may ask by what means is the circulation in the
brain regulated? The simplest view is that proposed by Roy and
Sherrington. According to these authors, the blood-flow through
the brain is controlled indirectly by vasomotor effects upon the
rest of the body. When, for example, a vasoconstriction occurs
in the skin or the splanchnic area the result is a rise of pressure
in the aorta and therefore a rise of pressure in the circle of Willis,
which then forces more blood through the brain. Adopting this
view, we can understand the teleology of certain well-known vaso-
motor reflexes. Stimulation of the skin generally causes a reflex
constriction and rise of pressure, and one can well understand that
this result is valuable if it means a greater flow of blood through
the brain, since under the conditions of nature such stimulation,
especially when painful, demands alertness and increased activity
on the part of the animal. Attention has also been called to the
fact that in plethysmographic observations on man the most
certain and extensive constrictions of the skin vessels are those
caused by increased mental activity. Mosso has shown by observa-
tions upon men with trephine holes in the skull that the constriction
of the limbs is always accompanied by a dilatation of the brain.

Francois-Franck, " Journal de phys. et de path, gen.," 1,
Wiggers, 'American Journal of Physiology/' 1905, xiv.,
See Hunter, "Journal of Physiologic/' 26, 465, 1902.

VASOMOTOR SUPPLY OF THE ORGANS. 581

This fact, therefore, fits exactly the view that is being considered.
The peripheral constriction, by raising general blood-pressure, dilates
the brain more or less, and, what is more important, drives more
blood through it. It is difficult to understand why psychical
activity is always associated in this way with a peripheral con-
striction unless the object of the reflex is to increase the blood-
supply to the brain. Even if vasomotor fibers are subsequently
shown to be present in the brain, the importance of this reflex in
providing a greater flow to the central organ at the time that it is
in activity must still be admitted. A general irrigation, so to speak,
is provided for by this means. Local vasomotors may be used to
divert this flow mainly through one or another cerebral area.

Vasomotor Nerves of the Head Region. — The vasomotor
supply of the various parts of the head, including the mouth cavity,
has been investigated by many observers. It would appear from
the results of most of these investigations that the vasoconstrictor
supply for the skin, including the ears, the eye, the mouth, and
buccal glands, is derived mainly, if not entirely, from the sympa-
thetic nervous system. These fibers arise from the spinal cord in the
upper thoracic nerves, first to the fifth or sixth, emerge by the rami
communicantes to the sympathetic chain, in which they pass upward
and end, for the most part, in the superior cervical ganglion. From
this ganglion they are distributed, by various routes, as postgan-
glionic fibers, in one interesting instance the constrictor fibers
for the head were supposed to take a somewhat different course.
It was shown by Schiff, long ago, that in the rabbit the ear receives
vasomotor fibers from the auricularis magnus nerve, a branch of the
third cervical nerve. Later investigations indicate (Meltzer) that
the ear, in fact, receives most of its vasoconstrictor fibers by this
route. Fletcher, however, has shown that these fibers do not emerge
from the brain in the roots of the third cervical, but rather in the
general outflow from the thoracic region. After reaching the sym-
pathetic chain these particular fibers pass to the third cervical by
the gray rami from the first thoracic ganglion, which communicate
with a number of the cervical nerves. On the other hand, the
vasodilator fibers for the head are supplied in part by way of the
cervical sympathetic, following the same general path as the con-
strictors, and in part by way of the cranial nerves (seventh, ninth)
and the sympathetic ganglia with which they connect. According
to Langley, the outflow of the seventh nerve passes to the spheno-
palatine ganglion, whence as postganglionic fibers they accompany
the branches of the superior maxillary nerve and cause vasodila-
fation in the membrane of the nose, soft palate, tonsils, uvula, roof
of mouth, upper lips, gums, and pharynx. The well-known dilators
of the submaxillary and sublingual glands are contained in the

582 CIRCULATION OF BLOOD AND LYMPH.

chorda tympani branch of the seventh nerve; the preganglionic
fibers terminate probably in the small peripheral ganglia connected
with these glands. The fibers that emerge in the ninth pass in
part directly to the tongue and in part terminate first in the otic
ganglion, whence they are distributed with the branches of the
inferior maxillary to the lower lips, cheeks, gums, and parotid and
orbital glands. Dastre and Morat describe the vasodilators in the
cervical sympathetic as reaching the fifth cranial nerve by com-
municating branches from the superior cervical ganglion and state
that they cause dilatation of the bucco-facial region, — that is,
the lips, the gums, cheeks, palate, nasal mucous membrane, and
the corresponding skin areas.

The Trunk and the Limbs. — The vasoconstrictor fibers for
these regions are distributed, so far as is known, chiefly to the skin.
They are all derived immediately from the sympathetic chain and
ultimately from the outflow in the anterior roots of the thoracic
and lumbar spinal nerves. Those for the upper limbs arise from
the midthoracic region chiefly (fourth to ninth thoracic nerves),
those for the lower limbs arise in the nerves of the lower thoracic
and upper lumbar region (eleventh, twelfth, thirteenth thoracic
[dog] and first and second lumbar). The vasodilator fibers in the
nerves of the limbs have been demonstrated frequently, as already
explained. Whether or not these fibers also pass through the
sympathetic system, following the same general course as the
vaso constrictors, has not been shown conclusively. The most
definite work at present (Bayliss) indicates that the vasodilator
effect is directly caused in some unknown way by fibers found
in the posterior roots of the nerves forming the brachial and the
sciatic plexus. The unsatisfactory explanations offered for this
result have been referred to (p. 568).

The Abdominal Organs.— The stomach and intestines receive
their most important supply of vasoconstrictor fibers by way of the
splanchnic nerves and celiac ganglion. These fibers emerge from
the cord in the lower thoracic spinal nerves, from the fifth down,
and the upper lumbar nerves, and they supply the whole mesenteric
circulation as far as the descending colon. According to some
observers (Frangois-Franck and Hallion), the mesenteric vessels
receive a supply of vasodilator fibers by the same general route, and
it is also stated that similar fibers reach this region through the vagus
nerve. Concerning this latter statement at least further con-
firmation is necessary. The pancreas has been shown to receive
vasoconstrictor fibers by way of the splanchnics, and the kidney,
according to Bradford, receives vasodilator as well as vasocor^
stricter fibers from the same nerve. Most of the vasomotor fibers to
the kidney of the dog emerge from the cord in the roots of the

VASOMOTOR SUPPLY OF THE ORGANS. 583

eleventh, twelfth, and thirteenth thoracic nerves, and those for the
liver (Francois-Franck and Hallion) come from about the same
region. The vasoconstrictors to the spleen are said to leave the
spinal cord chiefly in the anterior roots of the sixth, seventh, and
eighth thoracic nerves.

The Genital Organs. — Both vasoconstrictor and vasodilator
fibers have been discovered for the external genital organs (penis,
scrotum, clitoris, vulva). The vasoconstrictors arise in the dog
from the thirteenth thoracic to the fourth lumbar nerves, pass over
to the sympathetic chain, and thence reach the organs either by
way of the hypogastric nerve and pelvic plexus or by way of the
sacral sympathetic ganglia and their branches to the pudic nerves.
The vasodilator fibers arise from the sacral spinal nerve, being the
best known of the sacral autonomic system. They enter the ner-
vns erigens and thence reach the organs by way of the pelvic
plexus. The especial importance of these fibers in the process of
erection is described in the section on the physiology of the repro-
ductive organs. The internal genital organs — uterus, vagina,
vas deferens, seminal vesicles, etc. — receive no vasomotor fibers
from the sacral autonomic system, — that is, from the nervi erigentes
— but do receive a supply of constrictor fibers from the sympathetic
system. These latter fibers emerge from the cord in the roots of
the upper lumbar nerves and reach the organs by way of the in-
ferior mesenteric ganglion and hypogastric nerve.*

Vasomotor Supply of the Skeletal Muscles. — Gaskellf es-
pecially has given evidence of the existence of vasomotor fibers in
the muscles. He concludes, as the result of his work, that the blood-
vessels of the muscles receive both vasoconstrictor and vasodilator
fibers, but that the latter greatly predominate, — at least, their
physiological effect is much more evident in experimental work.
As proof of the presence of dilator fibers he gives such results as
these: The mylohyoid muscle of the frog is thin enough to be
observed directly under the microscope. When curarized and
stimulated through its motor nerve the small vessels may be seen
to dilate and there is an augmented flow of blood. In a dog section
of the motor nerve to a muscle is followed by a greatly increased
flow of blood, which, however, is only temporary and is referable to
a mechanical stimulation of the dilator fibers. Direct stimulation
of the severed nerve causes an increased flow of blood through the
muscles, but if the muscles are first completely curarized stimulation
causes, on the contrary, a decreased flow. This last result is ex-
plained on the supposition that curare paralyzes the endings of the

* For the bibliography of the vasomotor supply to the various organs see
Langley, "Ergebnisse der Physiologic," vol. ii., part n., p. 820, 1903.
tGaskell, ' Journal of Physiology," 1, 262, 1878-79.

584 CIRCULATION OF BLOOD AND LYMPH.

dilator fibers and thus allows the effects of the constrictors to mani-
fest themselves. Since, however, Bayliss has given evidence to
show (p. 568) that the dilator effect in the limbs is due to the anti-
dromic action of afferent fibers, it is evident that this important
question needs reinvestigation. Various physiologists have shown
that muscular activity is accompanied by an increase in the blood-
flow through the muscle, as we should expect, but it remains uncer-
tain whether this result is brought about solely by an increased
activity of the heart or by the combined effect of vasodilatation and
increase in heart-work. Kaufmann * takes this latter view in con-
sequence of some interesting results obtained upon horses. He
measured the blood-flow through the masseter muscle and the
elevator of the lip in a horse in which the muscles were exercised
normally by the act of eating. The blood-flow was increased as
much as five times over that observed during rest, and that this
increase was due in part at least to a local dilatation seems to be
proved by the fact that the blood-pressure in the artery supplying
the muscle fell, while that in the vein rose. While, therefore, our
experimental knowledge of the vasomotors of the muscles needs
further investigation, we may provisionally accept the view ad-
vocated by Gaskell, — namely, that the vasomotor supply to the
muscles consists essentially of dilator fibers and that these fibers
are brought into action reflexly whenever the muscles contract,
thus providing an increased blood-flow in proportion to the func-
tional activity. It should be added that the local dilatation in
the muscles during activity may be due also to the chemical action
of the (acid) metabolic products on the blood-vessels (p. 569).

The Vasomotor Nerves to the Veins. — It is assumed in physi-
ology that the vasoconstrictors and vasodilators end in the muscula-
ture of the small arteries. The veins also have a muscular coat,
and it is possible that if this musculature were innervated from
the central nervous system we should have another efficient factor
in controlling the blood-flow. Mall has given very clear proof that
the portal vein receives vasoconstrictor fibers from the splanchnic
nerve,f but this supply may be exceptional, as the portal system
itself is unique. The portal vein, indeed, plays the role physiolog-
ically of an artery in regard to the liver. Roy and Sherrington J
give some evidence for the existence of venomotor nerves to the
large veins of the neck, and Thompson, as also Bancroft,§ reports
experiments in which it was found that stimulation of the sciatic
nerve caused a visible constriction of the superficial veins of the

* Kaufmann, " Archives de physiologic normale et pathologique," 1892,
pp. 279 and 495.

VASOMOTOR SUPPLY OF THE ORGANS. 585

hind limbs. The whole subject, however, of venomotor nerves
has been but little investigated, and at present little or no use is
made of this possible system in explaining the facts of the circu-
lation.

THE CIRCULATION OF THE LYMPH.

The direction of flow of the lymph is from the tissues toward the large
lymphatic trunks, the thoracic and the right lymphatic duct. The flow is
maintained in this direction mainly by a difference in pressure at the two ends.
At the opening of the large trunks into the veins the pressure is very low;
in the vein, in fact, it may be zero or even negative. The opening between the
lymph vessel and the vein is protected by a valve which opens toward the
vein, and the lymph, therefore, will flow into the vein as long as the pres-
sure in the latter is lower than that in the lymphatic duct. At the other ex-
tremity of the system, in the tissue spaces to which the lymphatic capillaries
are distributed, the pressure, on the contrary, is high. Its exact amount is
not known, but, since the pressure in the blood capillaries is equal to 40-60
mms. Hg., the pressure in the liquid of the surrounding tissues must also be
considerable. The tissues are, in fact, in a condition of turgidity owing to«
the pressure of the lymph in the tissue-spaces. This difference in pressure
at the two ends of the lymphatic system is the main constant factor in mov-
ing the lymph. It is obvious that in the long run it is dependent upon the
pressure within the blood-vessels and therefore upon the force of the heart
beat. The contractions of the heart supply the energy, not only for the move-
ment of the blood, but also for the much slower movement of the lymph. The-
circulation of the lymph is aided, however, by many accessory factors. In
some animals there are genuine lymph hearts upon the course of the vessels, —
that is, pulsatile expansions of the lymph vessels whose force of beat, con-
trolled by valves, is directly applied to moving the lymph. No such structures
are found in the mammalia, but according to some observers the large re-
ceptacle at the beginning of the thoracic duct, receptaculum chyli may
undergo contractions, and is, besides, under the influence of motor and
inhibitory nerves. Such movements, if they occur, must be equivalent to the
action of a lymph heart in their influence upon the flow of lymph. The
flow of lymph or chyle in the intestinal area is also, without doubt, greatly
assisted by the peristaltic and especially by the rhythmic contractions of the-
musculature of the intestines. The volume of the lymph in this region is
especially large and the lymph capillaries and veins are provided with valves.
Rhythmical contractions of the musculature of the intestine must squeeze
the lymph toward the thoracic duct, acting like a local pump to accelerate
the flow of lymph. A similar influence is exerted by the contractions of the
skeletal muscles. The compression exerted by the shortened fibers squeezes
the lymph vessels and, on account of the valves present, forces the lymph
onward toward the larger ducts. The flow of lymph from the resting muscles
— the arms and legs, for instance— ^is normally small in quantity, but during
muscular exercise and massage it is obviously increased. This increase may
be observed in experimental work by placing a cannula in the thoracic duct.
Active or passive movements of the limbs under these conditions will cause a
noticeable increase in the outflow from the duct. Still another factor which
exercises an influence upon the flow of lymph is found in the respiratory move-
ments of the thorax. At each inspiration the pressure within the thorax is
diminished (increase of negative pressure), and this factor influences the lymph
flow in several ways : By increasing the flow of blood through the large veins
at the edge of the thorax, jugulars and subclavians, it doubtless aspirates
lymph from the thoracic and right lymphatic ducts into these veins. More-
over, by lowering the pressure upon the intrathoracic portion of the thoracic
duct it also aspirates the lymph from the abdominal portion of this vessel.

When we place a cannula in the thoracic duct and measure the outflow
directly it is found to be exceedingly slow and variable. Older measure-

£86 CIRCULATION OF BLOOD AND LYMPH.

ments (Weiss) indicate that it has a velocity in the duct in the neck of about
4 mms. per second, but this velocity changes naturally with the conditions
influencing the production of lymph in the tissues. Heidenhain estimates that
for a dog weighing 10 kgms. the total outflow from the thoracic duct in 24
hours is equal to 640 c.c. Munk and Rosenstein, from observations upon a
case with a lymph fistula, estimated that in man the flow may be equal to
50 to 100 or 120 c.c. per hour.

SECTION VI.
PHYSIOLOGY OF RESPIRATION.

Historical. — The term respiration as usually employed in
physiology refers to the process of gaseous exchange between an
organism and its environment. This exchange consists essentially
in the absorption of oxygen by the living matter and the elimination
of carbon dioxid. It is one of the generalizations of physiology that
all living matter, with the exception perhaps of the anaerobic
organisms, requires oxygen for its vital processes, — that is, its
characteristic metabolism. On the other hand, one of the universal
end-products of this metabolism is carbon dioxid. Hence, respira-
tion in some form is one great characteristic of living things. In
the simplest animals and plants, the unicellular organisms, the
exchange between the air (or water) and the organism takes place
directly, but in the more complex animals some form of respiratory
apparatus is developed whose function consists either in bringing
the air or oxygen-laden water to the constituent cells, as in the air
tubes of the insects, or in bringing the circulating blood into contact
with the air or water, as in the case of animals provided with lungs
or gills. In man and the air-breathing vertebrates the latter device
is employed and one may distinguish in such animals between
internal and external respiration. By the latter term is meant the
gaseous exchange, absorption of oxygen and elimination of carbon
dioxid, that takes place in the lungs between the blood in the pul-
monary capillaries and the air in the alveoli. By internal respira-
tion is meant the similar exchange that takes place in the systemic
capillaries between the blood and the tissue elements. All of this
exchange is, so to speak, secondary, since the essential process
consists in the history of the oxygen after it is absorbed into the
tissues, — that is, the part taken by the oxygen in the metabolism of
living matter. This process, however, is a part of the subject of
nutrition. The food absorbed from the digestive organs and the
oxygen taken from the blood have a common history, or at least
their reactions are indissolubly connected after they come within
the field of influence of the living molecules. This side of the func-
tion of the oxygen may be considered, therefore, more appropriately
in the section on nutrition. In the present section attention will be
directed to the beautiful means that have been adapted to the pur-

587

588 PHYSIOLOGY OP RESPIRATION.

pose of supplying the tissues with oxygen and of removing the
carbon dioxid.

The true understanding of the object of the act of respiration we
owe to Lavoisier, the discoverer of oxygen. In his paper published
in 1777, entitled "Experiments on the Respiration of Animals and
on the Changes which the Air Undergoes in Passing through the
Lungs," he laid the foundations of our present knowledge, and
in subsequent work he developed a conception of the nature of
physiological oxidations which has dominated the physiological
theories of nutrition up to the present time. The discovery of the
physiological meaning of respiration and the function of the lungs
constitutes the most interesting part of the history of physiology.
All the great physiologists of past ages contributed their part to
the story, and as we look back we can count distinctly the different
steps made toward the truth as we understand it to-day. The
history of this subject is not only most instructive in demonstrating
the triumphant although slow progress of scientific investigation,
but it illustrates well also the intimate interrelations of physiology
with the sister sciences of chemistry and physics and the great value
of the experimental method. The theory of respiration held in each
century was formulated to explain, as far as possible, the facts that
were known, and as we look back from our vantage point it is most
impressive to realize how well-known phenomena, imperfectly
understood, were apparently explained by theories which we now
know to be incorrect. Without doubt, many of the explanations
accepted to-day will in later times be found to rest upon a similar
incomplete knowledge. Each generation must do the best it can
with the knowledge of its times.

The history of respiration, the successive steps in its progress may
be summarized in a few words. Aristotle thought that the main
function of respiration is to regulate the heat of the body, which was
supposed to be produced in the heart; hence the increased respira-
tions after muscular exercise when the body-heat is increased. At
the same time he believed, with the philosophers of his times, that
the body receives something from the air that is necessary to life, a
subtle something that he designated as the " pneuma." Praxagoras
taught that blood is contained only in the veins, and that the ar-
teries are filled with a gaseous substance, the "pneuma" derived
from the air, an unfortunate error that prevailed in medicine for
several centuries. The two celebrated anatomists and physiologists
of the Alexandrian school, Herophilus and Erasistratus, distin-
guished two kinds of pneuma, the vital spirits, which are made or
extracted from the air in the lungs and whose production consti-
tutes the chief function of respiration, and the animal spirits, elabo-
rated in the brain from the vital spirits and responsible for the

HISTORICAL. 589

functions of motion and sensation. Galen (131 A. D.) demonstrated
that the arteries as well as the veins contain blood, but still believed
that the chief function of the respiratory movements is to furnish
pneuma or vital spirits to the heart. This great physiologist noticed
also that the air is necessary for combustion as it is for life, and
stated his belief that the explanation of one of these acts would
be also an explanation of the other. This thought seems to have
been accepted by all the physiologists of subsequent times, but it
required over sixteen hundred years of investigation before a satis-
factory solution was reached. Galen recognized, moreover, that
not only does the blood take something of essential importance from
the air, — namely, vital spirits, — but it also gives off something to the
air that is injurious to the body, a something which he compared to
the smoke of combustion and designated as the "fuliginous vapor. "
If we substitute oxygen for vital spirits and carbon dioxid for
fuliginous vapor we realize that the essential problem of respiration
was already clearly formulated, but could not make further advance
until chemical knowledge was more fully developed. Such is the
case with some of our physiological problems to-day. Galen also
explained satisfactorily the respiratory movements, the action of the
muscles of inspiration and expiration, thus destroying the older
erroneous theories that the expansion and contraction of the lungs
are due to processes of heating and cooling.

Galen's physiology held undisputed sway until the seventeenth
century. At that time there arose a school of physiologists, the
iatromechanists, who proposed to explain all vital phenomena upon
known mechanical principles, — the laws of physics and chemistry.
For the mystical view of vital spirits they proposed to substitute a
more rational and concrete theory. The blood in the lungs becomes
red simply because it is minutely subdivided and shaken, just as a
tube of blood becomes red when violently agitated. Thus an effort
to be more scientific, to use the exact knowledge of physics, led to
the adoption of views which we now know were far more erroneous
than the ancient and intrinsically correct conception that the blood
receives something from the air in the lungs.

In the seventeenth century, however, began those discoveries
in chemistry and physiology which eventually led to our present
knowledge. Van Helmont (1577-1644) discovered that in the
burning of charcoal, the fermentation of wine, and the action of
vinegar on chalk a special gas is produced which he called gas
sylvestre and which we call carbon dioxid. Robert Boyle (1627-
1691) published a most interesting series of experiments made with
the aid of the recently discovered air-pump which demonstrated the
correctness of the view held by Galen that the air contains some-
thing necessary for life and for combustion. He showed, moreover,

590 PHYSIOLOGY OF RESPIRATION.

that air that had been repeatedly inspired was no longer capable
of maintaining life. Robert Hooke (1635-1703) introduced a
method of artificial respiration by means of a bellows, and demon-
strated by sending a continuous stream of air through the lungs
that the respiratory movements of these organs are in themselves,
as a mechanical process, in no wise an essential feature of respiration.
John Mayow in 1688-1674 discovered that air is not a simple ele-
ment, but contains a definite substance necessary to life and to
combustion. He designated this substance as the nitro-aerian
vapor or nitrous particles, because he believed that the same
substance is present in condensed form, as it were, in common niter,
having found that combustion is possible even in a vacuum in the
presence of niter.

In the eighteenth century, as is shown in the work of the great
physiologist, Haller, the theories of respiration were in many
respects in a most unsatisfactory state. The new facts that had
been discovered made the old views untenable, but were not in
themselves sufficient to explain clearly what actually takes place.
Such periods of uncertainty and dissatisfaction are frequent enough
in the history of science. In 1757 Joseph Black rediscovered carbon
dioxid, calling it fixed air, and showed that it is present in expired
air. A little later Priestly discovered and isolated oxygen and
nitrogen; but, under the influence of an erroneous view of combus-
tion that had been advanced by Stahl, was unable to give his
discoveries a clear and satisfactory application. The final step
in this progress was made by the wonderful work of Lavoisier
between the years 1771 and 1780. He made correct analyses of
air and of carbon dioxid, he explained combustion as an oxidation
with the formation of CO2 and H2O, he showed that in respiration
the same process occurs, and that the blood takes oxygen from
the air and gives back to it in expiration the carbon dioxid and
water formed by combustion within the body. He gave us the
essential facts in the modern theories of respiration and physio-
logical oxidations.

After Lavoisier the chief positive advances that have been made
have been in reference to the condition of the gases in the blood.
By means of the gas-pump Magnus (1837) obtained these gases
quantitatively and thus procured data which, as Liebig showed,
demonstrate that the oxygen is held in the blood, not in simple
solution, but in some form of chemical combination, probably
with the red corpuscles. Finally it was shown by Stokes and
Hoppe-Seyler that the oxygen is held in definite chemical com-
bination with the hemoglobin. The nature of the combination of
the carbon dioxid in the blood is not yet entirely understood, while

EXTERNAL RESPIRATION AND RESPIRATORY MOVEMENTS. 591

the actual nature of physiological oxidations — that is, the part
taken by the oxygen in the chemical reactions of living matter—
is one of the great problems of nutrition which may need many years
for solution.

CHAPTER XXXIV.

THE ORGANS OF EXTERNAL RESPIRATION AND THE
RESPIRATORY MOVEMENTS.

Anatomical Considerations. — Some of the anatomical ar-
rangements in the lungs which have an immediate physiological
interest may be recalled briefly. The structures of the trachea and
bronchi are admirably adapted to their functions as air tubes, in that
the walls possess flexibility combined with rigidity. The lining of
ciliated epithelium throughout the air passages is of importance,
primarily it may be assumed, in removing mucus and foreign
material from these passages. The smaller bronchi possess a dis-
tinct muscular layer, and, as we shall see, this musculature is under
the control of a special set of nerve fibers through whose reflex
activity the capacity and resistance of the bronchial system may be
modified. The smallest bronchioles are expanded into a system of
membranous air cells, and in the walls of these thin sacs the capil-
laries of the pulmonary artery are distributed. The great efficiency
of this apparatus is evident when one recalls that every one of the
infinite number of red corpuscles is exposed separately to the air in
the air cells, so that although the time of transit is brief the entire
amount of hemoglobin is nearly completely saturated with oxygen.
Each lung is enveloped in its own pleural sac. The space between
the parietal and the visceral layer of each sac is the so-called
pleural cavity, but it must be borne in mind that under all normal
conditions this cavity is only potential, — that is, the parietal and
visceral layers are everywhere in contact with each other. Under
pathological or accidental conditions air or exudations may enter
this space and form an actual cavity. Along the mid-line of the
body and around the roots of the lungs we have the mediastinal
spaces lying between the pleural sacs of the two sides, but entirely
filled with the various thoracic viscera, such as the heart, aorta and
its branches, pulmonary artery and veins, venae cavae, azygos vein,
trachea, esophagus, thoracic duct, various nerves, and lymph
glands. All these organs, therefore, lie outside the lungs. A
schematic view of these relations is represented in Fig. 242.

592

PHYSIOLOGY OF RESPIRATION.

The Thorax as a Closed Cavity. — The thorax is a cavity entirely
shut off from the outside and from the abdominal cavity. In this
cavity lie the lungs and the various viscera enumerated above.
The lungs may be considered as two large, membranous sacs, as
represented in Fig. 242, the interior of which communicates freely
with the outside air through the trachea, glottis, etc., while the
outside of the sacs is protected from atmospheric pressure by the
walls of the chest. The atmospheric pressure on the interior
surfaces of the lungs expands these structures under normal con-
ditions until they fill the en-
tire thoracic cavity not occu-
pied by other organs. How-
ever the size of the chest
cavity varies, that of the
lungs must change accord-
ingly; so that at all times the
lungs fully fill up every part of
the cavity not otherwise occu-
pied. If the wall of the thorax
is opened at any point so as to
make communication with the
outside air, or, if the wall of
the lung is pierced so that the
air can communicate with the
pleural cavity from the inside,
then at once the lungs shrink

in gize since the atmospheric

pressure is then equalized on
the outside and the inside of
the sacs. We may consider,
therefore, that the thoracic

cavity is much larger than the lungs, and that the latter are blown
out to fill this cavity by the atmospheric pressure on the inside.

The Normal Position of the Thorax — Inspiration and Expira-
tion.—During life the size of the thorax is continually changing with
the respiratory movements. But the size and position taken at the
end of a normal expiration may be regarded as the normal position
of the thorax; that is, its position when all of the muscles of respira-
tion are at rest, and substantially, therefore, the position of the
thorax in the cadaver. Starting from this position, any enlarge-
ment of the thorax constitutes an active inspiration, the result of
which will be to draw more air into the lungs ; while starting from
the normal position any diminution in the size of the thorax
constitutes an active expiration, which will drive some air out of the
lungs. It is evident, however, that after an active inspiration the

the pleural sacs, and the position of the me-
diastinal space: P, the potential pleural
cavity in each sac; M, the mediastinal
space; R.L. and L.L., the cavity of the
right and the left lung, respectively; T, the
trachea. The outlines of the pleura on each
side are represented in dotted lines.

EXTERNAL RESPIRATION AND RESPIRATORY MOVEMENTS. 593

thorax may return passively to its normal position, giving what is
known as a passive expiration, — that is, an expiration not caused
by muscular effort. So after an active expiration the thorax may
return passively to its normal position, giving a passive inspiration.
Our normal respiratory movements consist of an active inspiration
followed by a passive expiration,

Mechanism of the Inspiration. — The chest cavity may be
enlarged and an inspiration, therefore, be produced by two methods,
— namely, by a contraction of the diaphragm and by an elevation
of the ribs.

Contraction of the Diaphragm. — From the anatomy of the
diaphragm it is evident that its fixed attachment is found in its
muscular connections with the lumbar vertebrae, the ribs, and the
ensiform cartilage. From these attachments the muscular sheet
extends anteriorly along the walls of the thorax and then bends over
to form the arch which ends in the central tendon. This latter
structure is not entirely free, since it is attached to the pericar-
dium of the heart ; but, relatively, it is the movable portion of
the diaphragm. Speaking generally, a contraction of the dia-
phragmatic muscle draws the central tendon downward toward the
abdominal cavity and therefore enlarges the chest in the vertical
diameter, while an increase in the thoracic cavity around the
periphery of the diaphragm is caused also by the flattening of the
muscular arch. Two results follow this movement: The lungs are
expanded exactly in proportion as the cavity enlarges. There is,
of course, at no time any space between the lungs and the dia-
phragm : as the latter moves downward the lungs follow because of
the excess of pressure on their interior. Although ordinarily we
speak of the new air being sucked into the lungs during this move-
ment, it is, of course, strictly speaking, forced in by the pressure of
the outside atmosphere. On the other hand, the descent of the dia-
phragm raises the pressure in the abdominal cavity. This cavity is
entirely full of viscera and for mechanical purposes may be regarded
as being full of liquid. The rise of pressure is transmitted throughout
the abdomen and causes the abdominal wall to protrude. Inspiration
caused by a contraction of the diaphragm is therefore spoken of
either as diaphragmatic respiration or as abdominal respiration, the
latter term having reference to the visible effect on the abdominal
walls. In strong contractions of the diaphragm the heart also is
pulled downward, and if the movement is forced the lower ribs may
be pulled inward to some extent. This last effect would diminish
the size of the thorax and therefore would tend to antagonize the
inspiratory action of the diaphragm, and other muscles are appar-
ently brought into play to prevent this result. As stated below, the

38

594

PHYSIOLOGY OF RESPIRATION.

Fig. 243. — Sixth dorsal vertebra and
rib.— (Reichert.)

quadratus lumborum and the serratus posticus inferior may have

this function of fixating the lower
ribs in violent inspirations. The
diaphragmatic muscle is innervated
on each side by the corresponding
phrenic nerve. This nerve arises
in the neck from the fourth and
fifth cervical spinal nerves, and
passes downward in the chest in
the mediastinal space, lying close
to the heart in part of its course.
Section of this nerve paralyzes, of
course, the diaphragm on the cor-
responding side.

Elevation of the Ribs. — As a
necessary result of the structure of
the bony thorax, every elevation
of the ribs must cause an enlarge-
ment of the thoracic cavity in the
dorsoventral and the lateral diam-
eters. We are justified in saying
that every muscle whose contrac-
tion causes an elevation of the ribs is an inspiratory muscle. This
result is due, in the first place, to the slant
of the ribs. Each rib is attached to the
spinal column at two points: the head to
the body of the vertebra and the tubercle
to the transverse process. The up-and-
down movements of the ribs may be re-
garded as rotations around an axis joining
these two points, — that is, each point in
the rib as it moves up or down describes
a circle around this axis (see Fig. 243).
If our ribs were set upon the vertebral col-
umn so that the plane of the rib formed a
right angle with the column, then every
movement of the rib up or down would
decrease the size of the thorax and there-
fore cause an expiration. As a matter
of fact, however, the ribs slant downward,
so that if elevated the sternal end is car-
ried farther away from the sternum and
the chest is enlarged in the dorsoventral
direction (see Fig. 244). Moreover, as the rib moves upward there

-K

Fig. 244.— Diagram to il-
lustrate the effect of the slant
of the ribs: S, The spinal col-
umn; a, the position of the
rib in normal expiration; (a')
its position (exaggerated) in
inspiration (the distance be-
tween the spinal column and
the sternum (at.), the anterq-
posterior or dorsoventral di-
ameter of the chest is in-
creased). Any movement from
the position a' would cause an
expiration.

EXTERNAL RESPIRATION AND RESPIRATORY MOVEMENTS. 595

is an obvious enlargement of the chest in the lateral diameter.
This result may be referred to two causes: In the first place, the
axis of the rotation of the ribs, — that is, the line joining the head
and the tubercle of the rib is inclined downward so that the plane
of rotation, which is, of course, at right angles to this axis, will be
inclined outward. As the rib is moved upward, therefore, it must
also move outward. Secondly the cartilaginous ends of the ribs are
fixed at the sternum so tha1 1 as they move upward and outward
they will be twisted or everted somewhat in the middle, with a
torsion of the cartilaginous ends.

The Muscles of Inspiration. — In addition to the diaphragm,
all muscles attached to the thorax whose contraction causes an
elevation of the ribs must be classed as inspiratory muscles. In
regard to this latter group the action of some of them is either
evident from their anatomical attachments, or the muscles may be
stimulated directly and the effect of their contraction be noted. In
other cases, however, it is necessary to make use of the method
first suggested by Newell Martin, — namely, the determination
whether the contraction of the muscle in respiration occurs simul-
taneously with that of the diaphragm or alternately with it. In the
former case it is inspiratory, in the latter expiratory. The following
muscles may be classed as inspiratory: Levatore costarum. They
arise from the transverse processes of the seventh cervical and first to
eleventh thoracic vertebrae and are inserted into the next rib or the
second rib below. Intercostales externi muscles. They lie in the inter-
costal spaces extending from the lower edge of one rib to the upper
edge of the rib below; they slant downward and toward the mid-line.
These muscles have been assigned different functions by different
authors, but the experiments made by Hough,* using the method
of Martin described above, show that they are inspiratory. It
was found that in the dog they contract synchronously with the
diaphragm. The same authors find that the intercartilaginous
portions of the internal intercostals are also inspiratory. The
scaleni — anterior, medius, and posterior — arise from the transverse
processes of the cervical vertebrae and are inserted into the first and
second ribs. M. sterno-cleido-mastoideus extends from the mastoid
process to the sternum and sternal extremity of the clavicle. M.
pectoralis minor extends from the coracoid process of the scapula
to the anterior surface of the second to the fifth rib. M. serratus
posticus superior extends from the spinous processes of the lower
cervical and upper dorsal vertebrae to the second to fifth rib.

The Muscles of Expiration. — Expiration — that is, diminution

* Hough, "Studies from the Biological Laboratory, John Hopkins
University," 5, 91, 1893, and Bergendal and Bergman, • " Skandinavisches
Archiv f. Physiologie, " 7, 178, 1896.

596 PHYSIOLOGY OF RESPIRATION.

in size of the thorax — may also be produced in two ways: First,
by forcing the diaphragm farther into the thoracic cavity. This
result is obtained, not by any direct action of the diaphragm, but
by contracting the muscular walls of the abdomen, the external and
internal oblique, the rectus, and the transversus. The contraction
of these muscles, which form what has been called the abdominal
press, raises the pressure in the abdomen and this, acting upon the
under surface of the diaphragm, forces it up into the thorax, pro-
vided the glottis is open. If the glottis is kept closed firmly the
increased abdominal pressure is felt mainly upon the pelvic organs,
and this effect is observed in micturition, defecation, and parturition.
Second, by depressing the ribs. The muscles which may be sup-
posed to exert this action are as follows: M. inter costales interni.
The expiratory action of these muscles, so far as the interosseous
portion is concerned, was first definitely shown by Martin, who
proved that when they contract they act alternately with the dia-
phragm. * M . triangularis sterni or the m. transversus thoracis is found
on the interior of the thorax on the anterior wall. Its fibers pass
from the sternum, running upward and outward, to be inserted into
the third to sixth rib. The expiratory action of this muscle was
demonstrated by Hough according to the method of Martin. M.
iliocostalis lumborum. The anatomical attachments of this muscle
are such as would enable it to depress the ribs; but its functional
activity in expiration has not been demonstrated. The m. serratus
posticus inferior and m. quadratus lumborum are both placed
anatomically, especially the former, so that their contractions
serve to depress the ribs. It has been suggested, however, that-
they may act in forced inspirations so as to antagonize the ten-
dency of the diaphragm to pull the lower ribs inward. Whether
they really act with the diaphragm or alternately with it can only be
determined by actual experiment.

Quiet and Forced Respiratory Movements; Eupnea and
Dyspnea. — Our respiratory movements vary much in amplitude,
and the muscles actually involved differ naturally with the extent
of the movement. In general, we distinguish two different forms of
breathing movements. The ordinary quiet respirations, made
without obvious effort, form a condition of respiration designated
as eupnea. Difficult or labored breathing is known as dyspnea.
It is impossible to draw a sharp line between the two. There are
many degrees of dyspnea, and doubtless in quiet breathing the
amplitude of the movements may vary considerably before they
become distinctly dyspneic. In all conditions of eupnea the chief
point to bear in mind is that the expiration is entirely passive.
* Martin and Hartwell, " Journal of Physiology, " 2, 24, 1879.

EXTERNAL RESPIRATION AND RESPIRATORY MOVEMENTS. 597

The inspiration in man is made by the diaphragm alone or by the
diaphragm together with some action of the levatores costarum and
the external intercostals. At the end of the inspiration the ribs and
diaphragm are brought back to the normal position by purely
physical forces, — the elasticity of the distended abdominal wall,
the elasticity of the expanded lungs, the weight and torsion of
the ribs, etc. As soon as the breathing movements become at all
forced the action of the above-named inspiratory muscles is in-
creased in intensity, and the other inspiratory muscles, all elevators
of the ribs, come into play. Quiet breathing in man at least is
mainly diaphragmatic or abdominal, while dyspneic breathing is
characterized by a greater action of the elevators of the ribs.
When dyspnea reaches a certain stage the expiration also becomes
active or forced. The expiratory act is hastened by a contraction
of the abdominal muscles or of the depressors of the ribs, and
indeed the action of these muscles may compress the chest beyond
its normal position, so that the expiration is followed by a passive
inspiration which brings the chest to its normal position before the
next active inspiration begins.

Costal and Abdominal Types of Respiration. — These two
types of respiration are based upon the character of the inspiratory
movement. An inspiration in which the movement of the abdomen,
due to contraction of the diaphragm, is the chief or only feature
belongs to the abdominal type. An inspiration in which the eleva-
tion of the ribs is a noticeable factor belongs to the costal type.
Hutchinson, who introduced this nomenclature,* laid emphasis
chiefly upon the order of the movements. In the abdominal
type the abdomen bulges outward first, and this is followed by
a movement of the thorax; the movement spreads from the
abdomen to the thorax, and, " like a wave, is lost over the thoracic
region." In costal breathing the upper ribs move first and the
abdomen second. The terms are meant to apply chiefly to human
respiration and have aroused interest in connection with the
fact that in quiet breathing in the erect posture the respiration
of man belongs to the abdominal type and that of woman to the
costal type. It has been a question whether this difference is a
genuine sexual distinction or depends simply upon differences
in dress. Hutchinson inclined to the view that it forms what we
should call a secondary sexual characteristic, and that its physio-
logical value for woman lies in the fact that provision is thus made,
as it were, against the period of pregnancy. He states that in
twenty-four young girls examined between the ages of eleven and
fourteen the costal type was present, although none of them had

*See Hutchinson, article on "Thorax," Todd 's " Cyclopaedia of Anat-
omy and Physiology, " 1849.

598 PHYSIOLOGY OF RESPIRATION.

worn tight dress. Later observers, however (Mays, Kellogg, and
others), state that Indian and Chinese women who have not worn
tight dress exhibit the abdominal type, and the same statement is
made regarding civilized white women who habitually wear loose
clothing. It would appear, therefore, that the assumption of the
costal type by women in general is due to the hindrance offered by
the clothing to the movements of the abdomen. From an exami-
nation of four hundred and seven cases Fitz * concludes that when
the restricting effect of dress is removed there is little or no differ-
ence in the type of respiration in the two sexes. The natural type
is one in which " the movement is fairly equally balanced between
chest and abdomen, the abdominal being somewhat in excess."
When the respiration becomes dyspneic it takes on a distinctly
costal type, and Fitz and others have shown that for an equal in-
crease in girth the thoracic movements cause a greater enlargement
of the lungs.

Accessory Respiratory Movements. — In addition to the mus-
cles whose action directly enlarges or diminishes the capacity of the
thorax certain other muscles connected with the air passages con-
tract rhythmically with the inspirations, and may be designated
properly as accessory muscles of inspiration. The muscles es-
pecially concerned are those controlling the size of the glottis and
the opening of the external nares. At each inspiration the elevators
of the wings of the nose come into play. This movement occurs in
normal breathing in many animals, such as the rabbit and horse,
and in some men, while in dyspneic breathing it is invariably
present. The useful result of the movement is to reduce the resis-
tance to the inflow of air. So in many animals the glottis is dilated
at each inspiration by the contraction of the posterior crico-aryte-
noid muscles, and in man also this movement is evident when
the breathing is at all forced. The useful result in this case also is
a reduction in the resistance offered to the inflow of air.

The Registration of the Rate and Amplitude of the Respira-
tory Movements.: — Many methods are employed to register the
rate or amplitude of the respiratory movements. Upon man the
amplitude may be measured directly by a tape placed at different
levels to ascertain the increase in girth, or it may be recorded by
some form of lever or tambour applied to the chest or abdomen.
A convenient instrument for this purpose is the pneumograph
described by Marey, which is illustrated and described in Fig. 245.
In animal experimentation the various methods that are employed
may be classified under four heads: (1) Methods in which the
change in circumference or diameter of the chest or abdomen is
recorded. (2) Methods in which the change of pressure in the air
* Fitz, "Journal of Experimental Medicine/' 1, 1896.

EXTERNAL RESPIRATION AND RESPIRATORY MOVEMENTS. 599

passages is recorded. In these methods a tube may be inserted into
one of the nostrils for instance, and then connected to a tambour the
lever of which makes its record on a kymographion, or if the animal
is tracheotomized a side tube upon the tracheal cannula may be
connected to a tambour. This method indicates well the rate of
movement and the relative amplitude, but has the defect that it

Fig. 245. — Figure of Marey'.s pneumograph. — (Verdin.) The instrument consists of
a tambour (I), mounted on a flexible metal plate (p). By means of the bands c and c
the metal plate is tied to the chest. Any increase or decrease in the size of the chest will
then affect the tambour by the lever arrangement shown in the figure. These changes in
the tambour are transmitted through the tube r as pressure changes in the contained air
to a second tambour (not shown in the figure) which records them upon a smoked drum.

does not record the pause, if any, at the end of inspiration or ex-
piration. A modification of this method that permits an accurate
record of the amplitude and duration of the movements consists in
connecting the trachea or nostrils with a large bottle of air. The
animal breathes into and out of the bottle, and the corresponding

Fig. 246. — Curve of normal respiratory movements. — (Marey.) Curve A, full line,
represents the movements when the respiration is entirely normal. Downstroke, inspira-
tion; upstroke, expiration. CurveO, dotted line, represents the increased amplitude of the
movements, slight dyspnea, caused by breathing through a narrow tube.

variations in pressure are recorded by a tambour also connected
with the interior of the bottle. (3) Methods in which the change
of pressure in the thoracic cavity is recorded. This end may be
reached by inserting a cannula into the thoracic wall so that its
opening lies in the pleural cavity, or, more simply, a catheter or
sound connected at the other end to a tambour may be passed down

600

PHYSIOLOGY OF RESPIRATION.

the esophagus until its end lies in the intrathoracic portion.
Variations in pressure in the mediastinal space synchronous with
the respiratory movements affect the esophagus and through it
the sound. (4) Methods in which the movements of the dia-
phragm are recorded either by a tambour or lever thrust between
the diaphragm and liver, or by hooks attached directly to muscular
slips of the diaphragm. Registration of the movements in man

during quiet breathing give us such a
record as is seen in Fig. 246. It will
be seen that the inspiration (descend-
ing limb) is followed at once by an
expiration, as we should expect,
since, as soon as the inspiratory
muscles cease to act, the physical
factors mentioned above at once tend
to bring the chest back to its normal
position. The expiration (ascending
limb) is at first rapid and toward the
end very gradual, so that there is al-
most a condition of rest, — an expira-
tory pause.

The Volumes of Air Respired
and the Capacity of the Lungs.—
The volume of air respired varies, of
course, with the extent of the move-
ments and the size of the individual.
This volume may be determined
readily in any given case by means
of a spir&meter, — a form of gasometer
adapted to this purpose. The con-
struction of this apparatus is repre-
sented in Fig. 247. It consists of a
graduated cylinder (A) and a receiver
(5) filled with water. The cylinder
A is counterbalanced by a weight (g)
so as to move up and down in the
water of B with the least possible re-
sistance. The tube C passes through
the wall of B and ends in the interior of A above the level of the
water. The free end of this tube is connected with the mouth
or nose. When one breathes through this tube the expired air
passes into A, which rises from the water to receive it. If A is
graduated the amount of air breathed out may be measured
directly. The following terms are used: Vital capacity. By
vital capacity is meant the quantity of air that can be breathed

Fig. 247.— Wintrich 's modifi-
cation of Hutchinson's spirometer.
—(Reichert.)

EXTERNAL RESPIRATION AND RESPIRATORY MOVEMENTS. 601

out by the deepest possible expiration after making the deepest
possible inspiration. It gives a rough measure of lung capacity,
and is used in gymnasiums and physical examinations for this pur-
pose. The actual amount varies with the individual; an average
figure for the adult man is 3700 c.c. Tidal air. By this term is
meant the amount of air breathed out in a normal quiet expiration.
A similar amount is breathed in, of course, in the previous inspira-
tion, and the term tidal air designates the amount of air that flows
in and out of the lungs with each quiet respiratory movement.
Here, again, there are individual variations. The average figure
for the adult man is 500 c.c. The complemental air. This term
designates the amount of air that can be breathed in over and above
the tidal air by the deepest possible inspiration. It is estimated
at 1600 c.c. The supplemental air. By this term is meant the
amount of air that can be breathed out, after a quiet expiration, by
the most forcible expiration. It is equal also to 1600 c.c. It is
evident that the complemental air plus the supplemental air plus
the tidal air constitute the vital capacity. The residual air. After
the most forcible expiration the lungs are far from being entirely
collapsed. The volume of air that remains behind, after the sup-
plemental air has been driven out, is known as the residual air.
The amount of this air has been estimated directly on the cadaver
(Hermann). The thorax was first pressed into a position of forced
expiration; the trachea was then ligated, the chest opened, the lungs
removed and their volume estimated by the amount of water dis-
placed when they were immersed. The average result from such
estimations was, in round numbers, 1000 c.c. Under conditions of
normal breathing the reserve supply of air in the lungs is equal to
the residual air plus the supplemental air, — that is, 2600 c.c. Mini-
mal air. When the thorax is opened the lungs collapse, driving out
the supplemental and residual air, but not quite completely. Before
the air cells are entirely emptied the small bronchi leading to them
collapse ahd their walls adhere with sufficient force to entrap a little
air in the alveoli. It is on this account that the excised lungs float
in water and are designated as lights by the butcher. The small
amount of air caught in this way is designated as the minimal air.
In the fetus before birth the lungs are entirely solid, but after
birth, if respirations are made, the lungs do not collapse completely
on account of the capture of the minimal air. Whether or not the
lungs will float has constituted, therefore, one of the facts used in
medicolegal cases to determine if a child was stillborn. The lungs
during life may, under certain conditions, again become in parts
entirely solid. If any of the alveoli become completely shut off
from the trachea, by an accident or by pathological conditions, the
air caught in them may be completely absorbed, after a certain
interval, by the circulating blood.

602 PHYSIOLOGY OF RESPIRATION.

The Size of the Bronchial Tree arid the Ventilation of the
Lungs. — Since the reserve supply of air in the lungs may amount to
2600 c.c., while the new air breathed in at each inspiration amounts
to only 500 c.c., it would seem at first that the alveolar air is not
very efficiently renewed by a quiet inspiration. The actual amount
of ventilation effected depends on the capacity of the bronchial
tree, sometimes known as the "dead space" of the lungs, since
the air filling this space is not useful in the respiratory processes.
According to observations founded partly on measurements of
casts of the tree and partly upon physiological determinations
made by breathing air poor in oxygen, it would seem that this
volume may be reckoned at 140 c.c.* At each inspiration, there-
fore, at least 360 c.c. of air penetrate into the alveoli, and if evenly
disseminated through the lungs add about -£$ to the volume of
each alveolus. Once in the alveoli, diffusion must tend to spread
the tidal air rapidly, and that this occurs is shown by an interesting
experiment performed by Grehant. He breathed in 500 c.c. of
hydrogen instead of air and then examined the amounts of hy-
drogen breathed out in successive expirations. Only 170 c.c.
were recovered in the first expiration, 180 c.c. in the second, 41 in
the third, and 40 in the fourth.

Artificial Respiration. — In laboratory experiments artificial
respiration is employed frequently after the use of curare ; when it is
necessary to open the chest; after cessation of respirations from
overdoses of chloroform or ether, etc. The method used in almost
all cases is the reverse of the normal procedure, — that is, the lungs
are expanded by positive pressure (pressure in excess of atmos-
pheric). A bellows or blast worked by hand or machinery is con-
nected with the trachea and the lungs are dilated by rhythmical
strokes. Provision is made for the escape of expired air by the use
of valves or by a side hole in the tracheal cannula. Numerous
forms of respiration pumps have been devised for this purpose.

In cases of suspended respiration in human beings from drown-
ing, electrical shocks, pressure upon the medulla, etc., it is necessary
to use artificial respiration in order to restore normal breathing.
Bellows ordinarily cannot be used in such cases. Some method
must be employed to expand and contract the chest alternately, and
several different ways have been devised. The Marshall Hall
method consists in placing the subject face down and rolling the
body from this to a lateral position, making some pressure upon the
back while in the prone position. The Sylvester method, which is
frequently used, consists in raising the arms above the head and
then bringing them down against the sides of the chest so as to
compress the latter. The Howard method consists in simply com-
* See Loewy, " Archiv f. die gesammte Physiologic," 58, 416.

EXTERNAL RESPIRATION AND RESPIRATORY MOVEMENTS. 603

pressing the lower part of the chest while the subject is in a supine
position. Schaefer, who has recently compared these different
methods, suggests one of his own, which seems to be effective, saves
labor, and is less injurious to the subject.* He describes it as fol-
lows: "It consists in laying the subject in the prone posture,
preferably on the ground, with a thick folded garment underneath
the chest and epigastrium. The operator puts himself athwart or
at the side of the subject, facing his head (see Fig. 248) and places
his hands on each side over the lower part of the back (lowest ribs).
He then slowly throws the weight of his body forward to bear upon

£tg. 248. — Shows the position to be adopted for effecting artificial respiration in cases
of drowning. — (Schaefer.)

his own arms, and thus presses upon the thorax of the subject and
forces air out of the lungs. This being effected, he gradually re-
laxes the pressure by bringing his own body up again to a more
erect position, but without moving the hands." These movements
are repeated quite regularly at a rate of twelve to fifteen times a
minute until normal respiration begins or the possibility of its
restoration is abandoned. A half-hour or more may be required
before normal breathing movements start.

* Schaefer. " Medico-chirurgical Transactions, " London, vol. Ixxxvii.
1904.

CHAPTER XXXV.

THE PRESSURE CONDITIONS IN THE LUNGS AND

THORAX AND THEIR INFLUENCE UPON THE

CIRCULATION.

In considering the pressure changes in respiration the distinction
between the pressure in the thorax outside the lungs and the pres-
sure within the lungs and air passages must be kept clearly in mind.
The pressure in the thoracic cavity outside the lungs may be
designated as the intrathoracic pressure; it is the pressure exerted
upon the heart, great blood-
vessels, thoracic duct, esopha-
gus, etc. The pressure in the
interior of the lungs and air
passages may be designated as
intrapulmonic pressure. The
relations of the two pressures
with reference to the outside
atmosphere is indicated sche-
matically in Fig. 249.

The Intrapulmonic Pres-
sure and its Variations. — The
air passages and the alveoli of
the lungs are in free communi-
cation with the external air;
consequently in every position
of rest, whether at the end of
inspiration or expiration, the
pressure in these cavities is
equal to that of the atmos-
phere outside.* During the act
of inspiration, however, the in-
trapulmonic pressure falls tem-
porarily below that of the atmosphere, — that is, during the inflow of
air. The extent to which the pressure falls depends naturally upon
the rapidity and amplitude of the inspiratory movement and upon
the size of the opening to the exterior. The narrowest portion of
the air passages is the glottis; consequently the variations in pres-
sure below this point are probably greater than in the pharynx or

* Strictly speaking, a correction must be made for the aqueous tension
in the lungs (see p. 628).

604

Fig. 249. — Diagram to illustrate how
the pressure of the air is exerted through
the lung walls upon the heart (H) and other
organs in the mediastinal space. The pres-
sure on these organs (intrathoracic pressure)
is equal to one atmosphere minus the amount
of the opposing pressure exerted by the ex-
panded lungs.

PRESSURE CONDITIONS IN LUNGS AND THORAX. 605

nasal cavities. If the air passages are abnormally constricted at
any point the fall of pressure during inspiration will be correspond-
ingly magnified in the parts below the constriction, as happens, for
instance, in bronchial asthma, edema of the glottis, cold in the
head, etc. Under normal conditions the fall of pressure during a,
quiet inspiration is not large. Bonders determined it in man by
connecting a water manometer with one nostril and found that it
was equal to — 9 or — 10 mms. water. At the end of an inspiration,
if there is a pause, the pressure within the lungs again rises, of course,
to atmospheric. During expiration, on the other hand, the collapse
of the chest wall takes place with sufficient rapidity to compress the
air somewhat during its escape and cause a temporary rise of pres-
sure. In normal expiration Bonders estimated this rise as equal to
7 or 8 mms. water. The intrapulmonic pressure may vary greatly
from these figures in the positive or negative direction according to
the factors mentioned above, especially the intensity of the respira-
tory movement and the size of the opening to the exterior. The
extreme variations are obtained when the opening to the outside is
entirely shut off. When an inspiration or an expiration is made
with the glottis firmly closed the pressure in the lungs, of course,
rises and falls with the rarefaction or compression of the contained
air. A strong inspiration under such conditions may lower the
pressure by 30 to 80 mms. of mercury, while a strong expiration
raises the pressure by an amount equal to 60 to 100 mms. Hg. In
the act of coughing we get a similar result: the strong spasmodic
expirations are made with a closed glottis and consequently cause a
marked rise in the intrapulmonic pressure. Such great variations
in pressure have a marked influence on the heart and the circula-
tion, as is explained below.

Intrathoracic Pressure. — When a reference is made to the
pressure within the thorax, it is the intrathoracic pressure that is
meant, — that is, the pressure in the pleural cavity and mediastinal
spaces. This pressure, under normal conditions, is always negative,
— that is, is always less than one atmosphere. The reason for this
is simply that the lungs are distended to fill the thoracic cavity, and
consequently the organs, like the heart, which lie in this cavity
outside the lungs, are exposed to a pressure of one atmosphere,
minus the force of elastic recoil of the lungs (see Fig. 249). The heart
and other intrathoracic organs are protected from the direct pres-
sure of the air by the thoracic walls; they are pressed upon, how-
ever, through the lungs, but naturally the atmospheric pressure is
reduced by an amount equal to the elastic force of the distended
lungs. Intrathoracic pressure, in fact, may be defined as intra-
pulmonic pressure minus the elastic pull of the lungs, and since
under usual conditions the intrapulmonic pressure is equal to that

606 PHYSIOLOGY OF RESPIRATION.

of the atmosphere, the intrathoracic pressure is less than an
atmosphere by an amount equal to the recoil of the lungs. The
negative pressure in the thorax is, therefore, equal to the elastic
force of the lungs, and is larger the more the lungs are put upon
a stretch, — that is, the deeper the inspiration. The amount of this
negative pressure has been measured upon both animals and men
by two methods : First by Bonder's method of attaching a manom-
eter to the trachea and then opening the thoracic walls so as to
allow the atmosphere to press upon the exterior face of the lungs.
In this way the elastic force of the lungs is determined, and, as
explained above, this is equivalent to the negative pressure. Second,
by thrusting a trocar through the thoracic wall so that its open end
may lie in the pleural or mediastinal cavity, the other end being
appropriately connected with a manometer. The older observers
(Hutchinson) also made experiments upon freshly excised human
lungs, determining their elastic force when distended by known
amounts of air. The figures obtained by these different methods
have shown some variations, but the following quotations give
an idea of the average extent of this negative pressure. Heynsius,*
making use of the figures obtained by Hutchinson, estimates that
in man the negative pressure in the thorax at the end of expiration
is — 4.5 mms. Hg, while at the end of an inspiration it is equal to
— 7.5 mms. Hg, — a variation during respiration, therefore, of 3 mms.
Hg. That is, assuming that the atmospheric pressure is 760 mms.
Hg, the conditions of pressure in the thorax and lungs at the end of
inspiration and expiration are as follows:

AT THE END OF INSPIRATION. AT THE END OP EXPIRATION.
Intrapulmonic pressure . . . 760 mms. Hg. 760 mms. Hg.

Intrathoracic pressure 752.5 " " 755.5 " "

Aron gives results obtained from a healthy man in whom a can-
nula was connected directly with the pleural cavity.f From 36
determinations he obtained the average result that at the end of
quiet inspiration the negative pressure is — 4.64 mms. Hg and at
the end of expiration — 3.02 mms. Hg — results considerably
lower than those estimated by Heynsius. It should be borne
in mind, however, that these values depend upon the condition
of expansion of the chest, — that is, the position of the body and
the depth of inspiration. On dogs Heynsius reports as follows:
At end of inspiration, — 9.4 mms. Hg; end of expiration, — 3.9 mms.
Hg. On rabbits, — 4.5 mms. and — 2.5 mms. Hg.

Variations of Intrathoracic Pressure with Forced and Unusual
Respirations. — After the most forcible expiration, when the air-

* "Archiv f. die gesammte Physiologic," 29, 265, 1882.

t Aron, quoted from Emerson, " Johns Hopkins Hospital Reports," 11,
194, 1903.

PRESSURE CONDITIONS IN LUNGS AND THORAX. 607

passages are open, the intrathoracic pressure is still negative by a
small amount, since the lungs are still expanded beyond what
might be called their normal size, — that is, their size when the pres-
sure inside and outside is the same. If, however, a forced expira-
tion is made with the glottis closed, as in the straining movements
of defecation, parturition, etc., then naturally the intrathoracic
pressure rises with the intrapulmonary pressure. The increased
pressure from the compressed air in the lungs is felt upon the organs
in the mediastinal spaces. The large veins especially are affected,
and the flow in them is partially blocked, as is shown by the swelling
of the veins in the neck outside the thorax. The maintenance of
such conditions for a considerable period may seriously affect the
circulation. The same general effect is obtained also in attacks of
coughing, the violent spasmodic expirations with closed glottis
causing a visible venous congestion in the head from the obstruction
to the venous flow into the heart. Forcible inspirations, on the
other hand, lower the intrathoracic pressure — that is, increase the
negativity — whether the glottis is open or closed. When the glottis
is freely open and a deep inspiration is made the intrathoracic
pressure may fall as much as 30 mms. Hg, — that is, become equal
to 730 mms. The lungs being much more expanded exert a corre-
spondingly greater elastic force. If the glottis is closed during a
deep inspiration then there is little actual expansion of the lungs,
but the intrapulmonary pressure falls from the rarefaction of the air
in the lungs, and the intrathoracic pressure, of course, falls with it.
The Origin of the Negative Pressure in the Thorax. — As is evi-
dent from the above explanation, the fact that the pressure in the
thorax is less than one atmosphere is due in the long run to the
circumstance that the lungs are smaller than the thoracic cavity
which they occupy. In the fetus the lungs are solid, and completely
fill the thoracic cavity, except for the part occupied by the other
organs. It has been a question whether after birth the size of the
thoracic cavity is suddenly and permanently increased by the first
inspiratory movements, and a negative intrathoracic pressure thus
produced at once. The careful experiments of Hermann* seem to
have settled this point. He proved that newly-born children
between the first and the fourth day, show no measurable negative
pressure in the thorax, and at the eighth day the pressure in the
thoracic cavity is less than atmospheric by an amount equal to only
— 0.4 mm. Hg. The negative pressure as we find it in the adult is
evidently developed gradually, and is due to the fact that the
thorax increases in size more rapidly and to a greater extent than
the lungs, so that to fill the cavity the lungs become more and more
expanded. It follows, also, from these facts, that the new-born
* Hermann, " Archiv f. d. gesammte Physiologic," 30, 276, 1883.

608 PHYSIOLOGY OF RESPIRATION

child has practically no reserve supply of air in the lungs; at each
expiration the lungs are entirely emptied (except for the minimal
air). The ventilation of the lung alveoli is correspondingly more
perfect than in older persons.

Pneumo thorax. — When the pleural cavity on either side is opened
by any means air enters and causes a greater or less shrinkage of
the corresponding lung. This condition of air within the pleural
cavity is designated as pneumothorax. It is evident that air may
enter the pleural cavity in one of two general ways : By a puncture
of the parietal pleura such as may be made by gunshot or stab
wounds in the chest, or by a puncture of the visceral pleura, such as
may occur, for example, by the rupture of a tubercle in pulmonary
tuberculosis, the air in this case entering from the alveoli of the
lungs. From the physical conditions involved it is evident
that if the opening into the pleural cavity is kept patent then the
lung will collapse completely and eventually will become entirely
solid, since the small amount of entrapped minimal air will be
absorbed by the blood. The other lung, the heart, etc., will also
be displaced somewhat from their normal position by the unusual
pressure. If, however, the opening is closed, then the air in the
pleural cavity may be absorbed completely by the circulating blood
and the lung again expand as this absorption takes place. In
human beings pneumothorax occurs most frequently in conditions
of disease, particularly pulmonary tuberculosis, and the air in the
thorax is associated also with a liquid effusion, this combination
being designated sometimes as hydropneumothorax.*

The Aspiratory Action of the Thorax. — The negative pres-
sure prevailing in the thoracic cavity must affect the organs in the
mediastinal space. The intrathoracic portion of the esophagus,
for instance, is exposed, at times of swallowing at least, to a full
atmosphere of pressure on its interior, while on its exterior it is under
the diminished intrathoracic pressure. This difference tends to
dilate the tube and may aid in the act of swallowing. The main
effect of the difference in pressure is felt, however, upon the flow
of lymph and blood, especially the latter. The large veins in the
neck and axilla are under the pressure of an atmosphere exerted
through the skin, and the same is true for the inferior cava in the
abdomen. But the superior and inferior cavse and the right auricle
are under a pressure less than one atmosphere. This difference in
pressure must act as a constant favoring condition to the flow of
blood to the heart. The difference is markedly increased at each
inspiration; so that at each such act there is an increase in the
velocity and volume of the flow to the heart, — an effect which is

* See Emerson, "Pneumothorax," Johns Hopkins Hospital Reports,
11, 1, 1903.

PRESSURE CONDITIONS IN LUNGS AND THORAX. 609

usually referred to as the aspiratory action of the thorax. At each
inspiration blood is " sucked " from the extrathoracic into the intra-
thoracic veins. So far as the inferior cava is concerned, this effect
is augmented by the simultaneous increase in abdominal pressure.
For as the diaphragm descends it raises the pressure in the ab-
domen as it lowers the pressure in the thorax. The two fac-
tors co-operate in forcing more blood from the abdominal to
the thoracic portion of the cava. There should be, of course, a
similar effect, but in the opposite direction, upon the flow in the
arteries. Each inspiration should retard the arterial outflow from
the aorta into its extrathoracic branches. As a matter of fact, this
effect probably does not take place. The arteries are thick walled
and are distended by a high internal pressure, so that the small
change of pressure of three or four millimeters of mercury during
inspiration is probably incapable of influencing the caliber of the
arteries, while it has a distinct effect upon the thin- walled veins,
whose internal pressure is very small. The changes in intra-
thoracic pressure during respiration must affect the blood-flow also
in the pulmonary circuit, the flow from the right to the left side of
the heart. This effect is manifested in the so-called respiratory
waves of blood-pressure which may be discussed briefly in this
connection.

Respiratory Waves of Blood-pressure. -^When a record is
taken of the blood-pressure the tracing shows waves, unless the
respiratory movements are very shallow, which are synchronous with
the respiratory movements (see Fig. 250). When the respiration
is dyspneic the waves of pressure are very marked. To ascertain the
exact relations of these variations to the phases of respiration it is
necessary to make simultaneous tracings of blood-pressure and
respiration movements with the recording pens properly superposed.
In the dog it is found that the blood-pressure falls slightly at the
beginning of inspiration, but rises during the rest of the act (Fig.
251). At the beginning of expiration the pressure continues to rise
for a time and then falls during most of this phase. On the whole,
therefore, the effect of inspiration, its final effect, is to cause a rise
of arterial pressure, while the effect of expiration is to cause a fall.
The relationship of the two curves varies in other animals, depend-
ing, among other things, on the rapidity of the respirations;
but, since most of the experimental work has been done upon the
dog, our attention may be confined to the relationship shown by this
animal. Two general explanations may be given for these respira-
tory waves: First, that they are due to an activity of the vaso-
constrictor center synchronous with that of the respiratory center.
Second, that they are due to variations in the amount of blood sent
out from the heart into the aorta, this variation, in turn, being due

610 PHYSIOLOGY OF RESPIRATION.

to the mechanical changes in pressure during respiration and their
effect on the blood-flow, aided also by the fact that the heart beats
more rapidly during inspiration. This second general point of view
has been adopted in physiology, and to verify it numerous experi-
ments have been made upon lungs placed in an artificial thorax in
which the conditions of pressure could be varied at will.* As the out-
come of this work, the following results have been accepted in expla-

Fig. 250. — Respiratory waves of blood-pressure. Typical blood-pressure record as
taken with a mercury manometer: Bp the blood-pressure record, shows the separate
heart beats and the larger respiratory waves, each of which comprises six to seven heart
beats.

nation of the occurrence of the respiratory waves of blood-pressure :
(1) During inspiration there is an increased flow of blood into the
right auricle (aspiratory action of inspiration). (2) During inspira-
tion the capacity of the blood-vessels in the lungs is increased and
also the velocity of the flow ; consequently there is an increased

* For discussion and literature see de Jager, " Archiv f. die gesammte
Physiologie, " 20, 426, 1879, and 27, 152, 1882; also " Journal of Physiology, "
7, 130.

PRESSURE CONDITIONS IN LUNGS AND THORAX.

611

volume of blood flowing through the lungs during inspiration. The
increased capacity of the lung capillaries during the expansion of
the lungs was shown experimentally by Heger-and Spehl. They
opened the anterior mediastinum without wounding the pleura and
proved that if the lungs are tied off at the end of inspiration they con-
tain more blood than when tied off at the end of expiration. The in-
creased velocity of the blood-flow through the lungs during inspira-
tion is explained by the fact that the greater negative pressure affects
the thin- walled pulmonary veins more than the pulmonary artery;
consequently the head of pressure driving the blood through the
lungs, — that is, the difference in pressure between the blood in the
pulmonary artery and veins — is increased. These data explain
satisfactorily the general fact regarding the respiratory waves, — •
namely, that during inspiration there is a rise of aortic pressure due
to a greater output of blood from the heart, and during expiration

Fig. 251. — Diagram to represent the time relation between the respiratory waves of
blood-pressure and the respiratory movements (dog): A represents the blood-pressure
record, showing the heart-beats and the larger respiratory waves. B represents a simul-
taneous record of the respiratory movements. At the beginning of inspiration there is a
fall of blood-pressure, but the final and main effect is a nse. At the beginning of expi-
ration there is a rise of pressure, but the final and main effect is a fall.

the reverse. To account for the subsidiary fact that at the begin-
ning of inspiration the pressure falls and at the beginning of expira-
tion it rises for a time two explanations are offered. De Jager
refers these temporary effects to the changes in capacity of the blood-
bed in the lungs. At the end of inspiration there is a certain ca-
pacity of the bed; when expiration comes on, the lungs shrink, the
capacity of the blood-vessels is thereby diminished, and consequently
some blood is squeezed out of the lungs in the direction of least
resistance, — that is, toward the left auricle. This accounts for the
initial rise of pressure during expiration. At the beginning of inspi-
ration, on the other hand, the sudden increase in capillary capacity
in the lungs retards for a moment the flow of blood to the left auricle,
and thus accounts for the temporary fall of pressure. Tigerstedt,*
on the other hand, finds that shutting off the entire circulation of
one lung may have little or no influence upon the pressure in the

* See Tigerstedt, " Ergebnisse der Physiologic, " Vol. ii, part u, 560, 1903.

612 PHYSIOLOGY OF RESPIRATION.

systemic circulation, and therefore doubts whether small changes in
the capacity of the lung vessels can have any distinct effect on the
inflow into the left auricle. He thinks that the main factor is the
increased flow of blood to the right auricle during inspiration, and
that this increased amount is then passed on to the left auricle and
ventricle, but that this takes some little time, so that the true effect
of inspiration is not felt in the aorta at the very beginning of the
act. This delay may vary in different animals and may account
for the fact that in some animals there is an apparent inversion of
the relations to respiration, the aortic pressure falling throughout
inspiration and rising during expiration.

The increased rate of heart beat during inspiration varies as to
its degree in different individuals. It has been shown by Fredericq
that this change occurs when the chest is widely opened and the
respiratory movements can have no mechanical effect upon the heart.
He suggests, therefore, that the accelerated pulse during inspiration
is due to an associated activity in the nerve centers of the medulla.
When the inspiratory center discharges it affects the neighboring
cardio-inhibitory center in the direction of inhibition, lessening its
tonic activity and thereby increasing the heart rate.

In artificial respiration carried out by means of a bellows —
that is, by expanding the lungs with positive pressure — all the
conditions of pressure in inspiration and expiration are reversed.
During such an inspiration the flow of blood to the right heart, and
through the lungs to the left heart, is decreased. Respiratory
waves of pressure are present under such conditions, but the rela-
tions of rise and fall to the phases of respiration are reversed.

CHAPTER XXXVI.

THE CHEMICAL AND PHYSICAL CHANGES IN THE
AIR AND THE BLOOD CAUSED BY RESPIRATION.

The Inspired and the Expired Air. — The inspired air, atmos-
pheric air, varies in composition in different places. The essential
constituents from a physiological standpoint are the oxygen,
nitrogen, and carbon dioxid. The new elements — argon, krypton,
etc. — have not been shown to have any physiological significance,
and are included with the nitrogen. The accidental constituents
of the air vary with the locality. In average figures, the composi-
tion of this air is, in volume per cent.: nitrogen, 79; oxygen, 20.96;
carbon dioxid, 0.04. The expired air varies in composition with
the depth of the expiration and, of course, with the composition of
the air inspired. Under normal conditions the expired air contains,
in volume per cent. : nitrogen, 79; oxygen, 16.02; carbon dioxid,
4.38. In passing once into the lungs the air, therefore, gains 4.34
volumes of carbon dioxid to each hundred, and loses 4.94 volumes
of oxygen.

N. o. co2.

Inspired 79 20.96 0.04

Expired 79 16.02 4.38

4.94 4.34

This table expresses the main fact of external respiration: the
respired air loses oxygen and gains carbon dioxid and consequently
the blood absorbs oxygen and eliminates carbon dioxid. It will be
noted, also, that the volume of oxygen absorbed is greater than the
volume of carbon dioxid given off. This discrepancy is explained
by the general fact that the oxygen absorbed is used in the long run
to oxidize the carbon and also the hydrogen of the body; conse-
quently, while most of it is eliminated in the expired air as carbon
dioxid, some of it is excreted as water. For the sake of complete-
ness it may be stated that traces of hydrogen and methane are also
found in the expired air. They probably originate in the intestines
from fermentation processes and are carried off in solution in the
blood.

Physical Changes in the Expired Air. — The expired air is
warmed nearly or quite to the body temperature and is nearly
saturated with water vapor. Since, as a rule, the air that we

613

614 PHYSIOLOGY OF RESPIRATION.

inspire is much cooler than the body and is far from being saturated
with water vapor, it is evident that the act of respiration entails
upon the body a loss of heat and of water. Breathing is, in fact,
one of the means by which the body temperature is regulated,
although in man it is a subsidiary means. In other animals — the
dog, for instance — panting is a very important aid in controlling the
body heat. Heat is lost in respiration not simply in warming the
air in the air passages, but also by the evaporation of water in the
alveoli, the conversion of water from the liquid to the gaseous form
being attended by an absorption of heat. Breathing is also one
of the means by which the water contents of the body are regulated.
The water that we ingest or that is formed within the body is kept
within certain limits, and this regulation is effected by the secretions
of urine and sweat mainly, but in part also by the constant loss of
water from the blood as it passes through the lungs.

The Injurious Effect of Breathing Expired Air — Ventila-
tion.— It is generally recognized that in badly ventilated rooms the
air acquires a disagreeable odor, perceptible especially immediately
on entering, and that persons remaining under such conditions for
any length of time suffer from headache, depression, and a general
feeling of uncomfortableness. It has been assumed, although
without sufficient proof, that these effects are due to the vitiation of
the atmosphere by the expired air. When the ventilation is very
imperfect and the room greatly crowded death may result, as, for
instance, in the historical case of the Black Hole of Calcutta. In
extreme cases of this latter kind it is most probable that several
causes combine to produce a fatal result. The conditions are such
as to lead to a very large increase in carbon dioxid and diminution
of oxygen in the respired air, — a result which in itself will cause death;
and in addition the air becomes heated to a high temperature and
saturated with water vapor, both of these latter conditions prevent-
ing loss of heat from the body and producing a fever temperature.
Under the ordinary conditions of life poor ventilation produces its
obviously evil results in rooms temporarily occupied, — schools,
churches, lecture rooms, theaters, etc., — and it is important to know
what is the cause, and how it may be avoided. On the basis of older
work it has been assumed that there is present in the expired air a
volatile organic substance which when breathed again, possibly after
having undergone some further change, exerts a toxic influence. The
evil effects of badly ventilated rooms have been attributed mainly
to this supposed substance. Unfortunately the investigations that
have been made upon this substance are not altogether conclusive.*

* See Haldane and Smith, "Journal of Pathology and Bacteriology, '•
1, 168 and 318, 1893; Merkel, " Archiv f. Hygiene." 15, 1, 1892. Formanek,
"Archiv f. Hygiene," 38, 1, 1900.

CHANGES IN AIR AND BLOOD IN RESPIRATION. 615

It seems to be clear that, when the expired air is condensed by pass-
ing it into a cooled chamber, the water thus obtained, about 100
c.c. for 2500 liters of air, is clear, odorless, and has only a minute
trace of organic matter. If this liquid with or without conden-
sation is injected under the skin or into the blood-vessels no,
evil result follows, according to the testimony of the majority of
observers. But it remains possible, of course, that the substance
if present may be destroyed by this method or may escape precipi-
tation in the condensed water. The experiment that gives the
most positive indication of the existence of an organic (basic) poison
in the expired air is the following, first performed by Brown-
Sequard: A series of — say, five — bottles, each of a capacity of a
liter or more, are connected together in train so that air can be
drawn through them by an aspirator. A live mouse is placed in
each bottle, and between bottles 4 and 5 an absorption tube is ar-
ranged containing sulphuric acid. Under these conditions only the
mouse in bottle 1 gets fresh air, those in the successive bottles get
more and more impure air, while in bottle 5 this air is purified to the
extent of removing the organic matter by passing it through sul-
phuric acid. The result of such an experiment as described by
some observers is that the mouse in bottle 4 dies after a certain num-
ber of hours, the one in bottle 3 later, while those in the first and
last bottles show no injurious effects. The obvious conclusion is that
death in such cases is due to some organic toxic substance, and not
to a mere increase of carbon dioxid, chemical analysis showing that
this latter substance does not accumulate sufficiently under these
conditions to cause a fatal result. Some other observers have failed
to get this effect, but even assuming it to be correct it will be noted
that the experiment gives no proof that the organic substance in
question is excreted in the expired air. Indeed, the seemingly
very careful experiments of Formanek make it probable that in
these experiments the toxic substance is ammonia or an ammonia
compound, which is not given off from the lungs, but from the decom-
position of the urine and feces in the cage. When this latter source
of contamination is removed the expired air is practically free
from ammonia and without injurious effect. The expired air
therefore, according to work of this character, contains no organic
poison which can be regarded as a product of respiration.

Some observers (Hermann, Haldane, and Smith) have made
careful experiments upon men which also seem to throw much
doubt upon the existence of a toxic substance in expired air. In-
dividuals kept in a confined space for a number of hours show no evil
effects except when the accumulation of the carbon dioxid has
reached a concentration of over 4 per cent. At this concentration
rapid breathing is apparent, and if it rises to 10 per cent, great

616 PHYSIOLOGY OF RESPIRATION.

distress is felt and the face becomes congested and blue. These
authors conclude that expired air is injurious in itself only from the
carbon dioxid it contains, and not because of any special poison.
We must admit, therefore, that the existence of an organic poison
in the expired air has not been conclusively demonstrated — in fact,
has been made exceedingly improbable. The definitely known evil
results of breathing the air of crowded, poorly ventilated rooms must
be referred to other possible causes, such as the increase in temper-
ature and moisture. These two conditions cause depression and
malaise even when good ventilation is provided. It is possible, also,
that the material given off from the skin in the perspiration, seba-
ceous secretions, etc., may account sufficiently for the odor and pos-
sibly also for some of the general evil effects. If the ventilation is so
poor that the carbon dioxid accumulates to the extent of 3 to 4 per
cent., then this factor begins to exercise a direct effect upon the res-
piratory movements and the general condition, — an effect which
increases as the percentage of carbon dioxid rises.

Ventilation. — It is obvious from the foregoing statements that
our knowledge is not yet sufficiently complete to enable us to say
positively at what point air in a room becomes injurious to breathe,
whether from products of expiration, or exhalation, or changes in
temperature and moisture. The statement is frequently made in
the books that, when the air contains as much as 1 per cent, of
carbon dioxid (Smith) that has been produced by breathing, evil
results, as judged by one's feelings, are sure to occur, but the ex-
periments of Haldane and Smith seem to disprove this statement
entirely. The practical rule 'in ventilation is to keep the air in
chambers as nearly as possible of the composition of the atmosphere
outside. Since carbon dioxid is the constituent of the air that is
most easily determined the relative purity of room air is judged
conveniently by quantitative estimations of this constituent. Or-
dinary atmospheric air contains, on the average, 0.04 per cent,
of carbon dioxid — that is, 4 parts to 10,000. The hygienists main-
tain that the ventilation should be sufficiently ample to keep the
carbon dioxid down to 6 parts per 10,000, thus leaving 2 parts
per 10,000, 0.02 vol. per cent., as the permissible limit of vitia-
tion by breathing. To determine on this basis the amount of
air necessary for each person the following formula is used:
d == ly in which d represents in liters the delivery of fresh air per
hour; e, the amount of CO2 expired per hour in liters; and r the
ratio of permissible vitiation of the air by CO2. Assuming this
latter factor, in accordance with the above statement, to be equal
to 0.02 per cent., and e to be equal to 20 liters per hour (500 X
0.04 X 17 X 60), the value of d is equal to 100,000 liters of air
per hour for each person. The rapidity of renewal of air will
depend naturally upon the cubic space allotted to each individ-

CHANGES IX AIR AND BLOOD IX RESPIRATIOX. 617

ual. The smaller this space, the more ample must be the ventila-
tion. The following figures * give an idea of the values adopted for
different conditions :

AMOUNT OF VENTILATION CUBIC SPACE PER
PER HOUR PER PERSON PERSON IN CUBIC

IN CUBIC METERS. METERS.

Hospitals i 60-100 30-50

Prisons 50 25

Factories 60-100 30-50

Barracks 30-50 15-25

Theaters 40-50 20-25

Halls and assembly rooms 30-60 15-30

Schools 15-20 7.5-10

.Classrooms for adults 25-30 12-15

The amount of cubic space allowed is based, it will be noted, upon
the supposition that the air is completely renewed by ventilation
during the course of an hour.

The Gases of the Blood. — The gases that are contained in the
blood are oxygen, carbon dioxid, and nitrogen. These gases may
be extracted completely and in a condition for quantitative analysis
by means of some form of gas-pump. The principle of most of the
gas-pumps used in the physiological laboratories is the same. The
apparatus is arranged so that the blood to be examined is brought
into a vacuum while kept at the temperature of the body. Under
these conditions all of the oxygen and nitrogen and part of the car-
bon dioxid are given off and may be collected by suitable means.
A portion of the carbon dioxid present in the blood is in such
stable combination that to remove it it may be necessary to add
some dilute acid, such as phosphoric acid. This portion of the
carbon dioxid is designated in this connection as the fixed carbon
dioxid.

The principle of the gas pump may be explained most easily by describing
the simple form devised by Grehant. The essential parts of this pump are
represented in Fig. 252. The mercury pump consists of two bulbs, one mov-
able (M), the other fixed (F). M may be raised and lowered by the windlass
(P). Above F, there is a three-way stopcock (m) by means of which the
chamber F may be put into communication with the outside air by way of C,
or with the bulb B, which is to contain the blood, or may be shut off com-
pletely. If M is raised so as to fill F entirely, and the stopcock m is shut off,
then on lowering M the mercury will flow into it, leaving a perfect vacuum
in F, since the distance between F and M is greater than the barometric
height. If the stopcock m is turned so as to throw F into communication
with B, the chamber of this latter is brought under the influence of the vac-
uum and any gases that it may contain will be distributed between B and
F. If stopcock m is again turned off and M is raised the gases in F will be
condensed at its upper end, and by turning the stopcock m properly these
gases may be forced to the outside by way of C or may be collected, if de-
sired, in a burette filled with mercury and inverted over the opening from
F contained in the bottom of C. In performing an experiment the flask
B, which is to contain the blood, is connected with F, as shown in the figure,

* Taken from Bergey, " The Principles of Hygiene, " 1904.

618

PHYSIOLOGY OF RESPIRATION.

all joints being protected from leakage by a seal of water outside, as shown
at h, which represents a piece of wide rubber tubing filled with water so as
to protect a joint between two pieces of glass tubing. B is next exhausted
completely by raising and lowering M a number of times in the way described
above until on throwing B into communication with a vacuum in F no further
gas is given off. The last particles of air may be driven out from B by boil-
ing a little water in it. After a complete vacuum has been established in B

Fig. 252.— Gas pump for extracting the gases of blood (Grehant): M and F,
The mercury receivers; P, the windlass for raising and lowering M ; m, a three-way
stopcock protected by a seal of mercury or water; C, a cup with mercury over which
the receiving eudiometer is placed to collect the gases; B, the bulb in which, after a
vacuum is made, the blood is introduced by the graduated syringe, S. By means of the
stopcock m the vacuum in F, caused by the fall of the mercury, can be placed in communi-
cation with B. After the gases have diffused over into F, M is raised, and when the stop-
cock m is properly turned these gases are driven out through C into the receiving tube.
The operation is repeated until no more gas is given off from B.

a measured amount of blood is introduced from a graduated syringe, S, as
represented in the figure. This blood must be taken directly from the vessels
of the animal and be introduced into B at once. B is kept immersed in water
at the temperature of the body, and the bulb M is now raised and lowered a
number of times so that the gases given off from the blood are drawn over
into F and then by proper manipulation of the stopcock are driven into

CHANGES IN AIR AND BLOOD IN RESPIRATION. 619

a burette fastened over the opening of the tube in C. To drive off all of the
carbon dioxid a little dilute phosphoric acid must be added to the blood in
B by means of the syringe, S. The gases thus collected into the burette are
first measured and are then analyzed for the three important constituents
by some of the accepted gasometric methods. The principle involved is to
absorb first from the mixture all of the CO2 by introducing a solution of sodium
or potassium hydrate. The reading of the volume left after this absorption
is completed compared with the first reading gives the volume of CO2. Next,
a freshly made alkaline solution of pyrogallic acid is introduced into the tube.
This solution absorbs all of the oxygen, whose volume is thus easily determined.
The gas that is left unabsorbed after the action of these two solutions is nitro-
gen. The volumes of gases are reduced, as is the custom, to unit pressure
and temperature, — that is, to zero degree centigrade and 760 mms. barometric
pressure. A correction must also be made for the tension or pressure exerted
by the aqueous vapor in the gases. These corrections are made by means
of the folio whig formula:

V(B-T)
760 X (1 + 0.003665 1)

in which V1 represents the corrected volume, V the volume actually observed,
B the barometric height at the tune and place of the observation, T
the aqueous tension at the temperature of the reading, and t the temperature
in degrees centigrade.

By means of such methods the gases in the blood have been de-
termined. The quantities vary somewhat, of course, with the con-
ditions of the animal and with the species of animal. In a quick
analysis of dogs' arterial blood made by Pfliiger the following
figures were obtained reckoned in volumes per cent.: O, 22.6; CO2,
34.3; N, 1.8. In this case each 100 c.c. of arterial blood contained
22.6 c.c. of O and 34.3 c.c. of CO2 measured at O° C. and 760 mms.
Hg. An analysis of human blood (Setschenow) gave closely similar
figures; O, 21.6 per cent.; CO2, 40.3 per cent.; and N, 1.6 per cent.
When the arterial and the venous bloods are compared it is found
that the venous blood has more carbon dioxid and less oxygen.
Average figures showing the difference in composition are as follows:

O. C02. N.

Arterial blood 20 38 1.7

Venous blood 12 45 1.7

Difference .~~8 ~~7 ~~5"

The actual amounts of oxygen and carbon dioxid in the venous
blood vary with the nutritive activity of the tissues, and differ
therefore in the various organs according to the state of activity of
each organ in relation to the volume of its blood supply. This
point is well illustrated by some analyses made by Hill and Na-
barro* of the gases in the venous blood from the brain and the
muscles, respectively. Their average results when both tissues
were at rest were as follows:

OXYGEN. CARBON DIOXID.

Venous blood from limbs (femoral) .... 6.34 per cent. 45.75 per cent
brain (torcular) . . . 13.49 " " 41.65 " "

* Hill and Nabarro, "Journal of Physiology," 18, 218, 1895.

620 PHYSIOLOGY OF RESPIRATION.

It will be seen that under similar conditions there is much less
oxygen used and carbon dioxid formed in the brain than in the
limbs (muscles). In the former organ the physiological oxidations
must either be small compared with those of the muscles, or the
brain tissues receive a relatively ample supply of blood, so that the
tissue metabolism has less effect upon the blood composition. The
venous blood as it comes to the lungs is a mixture of bloods from
different organs, and its composition in gases will be constant only
when the conditions of the body are kept uniform. Much work
has been done in physiology to determine the condition in which
these various gases are held in the blood. The results obtained
show that they are held partly in solution and partly in chemical
combination. To understand the part played by each factor and
the conditions that control the exchange of gases in the lungs and
tissues it is necessary to recall some facts regarding the physical
and chemical properties of gases.

The Pressure of Gases and the Terms Expressing these
Pressures. — The air around us exists under a pressure of one
atmosphere and this pressure is expressed usually in terms of the
height of a column of mercury that it will support, — namely, a
column of 760 mms. Hg, which is known as the normal barometric
pressure at sea-level. Air is a mixture of gases, and according to the
mechanical theory of gas-pressure each constituent exerts a pressure
corresponding to the proportion of that gas present. In atmospheric
air, therefore, the oxygen, being present to the extent of 20 per
cent., exerts a pressure of ^ of an atmosphere or £ X 760 = 152
mms. Hg. When we speak of one atmosphere of gas pressure, '
therefore, we mean a pressure equivalent to 760 mms. Hg, and in
any given mixture the pressure exerted by any constituent may
be expressed in percentages or fractions of an atmosphere, or in the
equivalent height of the mercury column which it will support.

Absorption of Gases in Liquids. — When a gas is brought into
contact with a liquid with which it does not react chemically a
certain number of the moving gaseous molecules penetrate the
liquid and become dissolved. Some of these dissolved molecules
escape from the water from time to time, again becoming
gaseous. It is evident, however, that if a liquid, water, is brought
into contact with a gas under definite pressure, — that is, containing
a definite number of molecules to a unit volume, — an equilibrium
will be established. As many molecules will penetrate the liquid
in a given time as escape from it, and the liquid will hold a definite
number of the gas molecules in solution; it will be saturated for
that pressure of gas. If the pressure of the gas is increased, how-
ever, an equilibrium will be established at a higher level and more
molecules of gas will be dissolved in the liquid. Experiments have
shown, in accordance with this mechanical conception, that the

CHANGES IX AIR AND BLOOD IN RESPIRATION. 621

amount of a given gas dissolved by a given liquid varies, the temper-
ature remaining the same, directly with the pressure, — that is, it in-
creases and decreases proportionally with the rise and fall of the
gas pressure. This is the law of Henry. On the other hand,
the amount of gas dissolved by a liquid varies inversely with the
temperature. It follows, also, from the same mechanical views
that in a mixture of gases ,each gas is dissolved in proportion
to the pressure that it exerts, and not in proportion to the pressure
of the mixture. Air consists, in round numbers, of 4 parts of N and
1 part of O. Consequently, when a volume of water is exposed to
the air the oxygen is dissolved according to its " partial pressure,"
— that is, under a pressure of -J- of an atmosphere (152 mms. Hg).
The water will contain only £ as much oxygen as it would if exposed
to a full atmosphere of oxygen — that is, to pure oxygen. And, on
the other hand, if water has been saturated with oxygen at one
atmosphere (760 mms.) of pressure and is then exposed to air,
four-fifths of the dissolved oxygen will be given off, since the pressure
of the surrounding oxygen has been diminished that much. Ab-
sorption coefficient. By this term is meant the number that ex-
presses the proportion of gas dissolved in a unit volume of the liquid
under one atmosphere of pressure. The absorption coefficient will
vary, of course, with the temperature. The gases that interest us
in this connection are oxygen, nitrogen, and carbon dioxid. The
absorption coefficients of these gases for the blood at the tempera-
ture of the body are as follows: O, 0.0262; N, 0.0130; CO2, 0.5283.*
That is, 1 c.c. of blood at body temperature dissolves 0.0262 of
1 c.c. of oxygen if exposed to an atmosphere of pure oxygen, and
so on. The solubility of the CO2 is therefore twenty times as great
as that of oxygen. Accepting these figures, we may calculate how
much of these three gases can be held in the arterial blood in physical
solution, provided we know the pressure of the gases in the alveoli
of the lungs. The composition of the alveolar air will be discussed
farther on, but we may assume at present that it contains 80 per
cent, of nitrogen, 15 per cent, of oxygen, and 5 per cent, of carbon
dioxid. In 100 c.c. of blood, therefore, the following amounts of
these gases should be held in solution:

Nitrogen 100 X 0.013 X 0.80 = 1.04 c.c.

Oxygen 100 X 0.0262 X 0.15 = 0.393 "

Carbon dioxid 100 X 0.5283 X 0.05 = 2.64 "

As will be seen from the analyses given above of the actual amounts
of these gases obtained from the blood, the nitrogen alone is present
in quantities corresponding to what would be expected if it is
held in simple physical solution.

* As given by Bohr, the absorption coefficients of these three gases at
40° C. are as follows: Oxygen. 0.0231; nitrogen, 0.0118; carbon dioxid, 0.530.

622 PHYSIOLOGY OF RESPIRATION.

The Tension or Pressure of Gases in Solution or Combi-
nation.— When a gas is held in solution the equilibrium is de-
stroyed if the pressure of this gas in the surrounding medium or
atmosphere is changed. If this pressure is increased the liquid
takes up more of the gas, and an equilibrium is established at a
higher level. If the pressure is decreased the liquid gives off
some of the gas. That pressure of the gas in the surrounding
atmosphere at which equilibrium is established measures the tension
of the gas in the liquid at that time. Thus, when a bowl of water is
exposed to the air the tension of the oxygen in solution is 152 mms.
Hg; that of the nitrogen is 608 mms. Hg. If the same water is
exposed to pure oxygen the tension of the oxygen in solution is
equal to 760 mms. Hg, while that of the nitrogen sinks to zero
if the gas that is given off from the water is removed. With
compounds such as oxyhemoglobin the tension under which the
oxygen is held is measured by the pressure of the gas in the sur-
rounding atmosphere at which the compound neither takes up nor
gives off oxygen. If, therefore, it is necessary to determine the
tension of any gas held in solution or in dissociable combination it is
sufficient to determine the percentage of that gas in the surrounding
atmosphere and thus ascertain the partial pressure that it exerts.
If the atmosphere contains 5 per cent, of a given gas the partial
pressure exerted by it is equal to 38 mms. Hg (760 X 0.05), and
this figure expresses the tension under which the gas is held in
solution or combination in a liquid exposed to such an atmosphere.
As regards the tension of the gases in arterial and venous blood,
this procedure is, of course, not possible, since the blood is sur-
rounded, not by an atmosphere whose composition can be analyzed,
but by the liquids of the body, the lymph and cell juices. To
determine the tension of the gases in the blood it is necessary to
remove the blood from the vessels and bring it into contact with an
atmosphere containing a known quantity of O, CO2, or N, according
to the gas to be measured. By trial an atmosphere can be obtained
in which this gas is contained in amounts such that there is no
marked increase or decrease in quantity after standing in diffusion
relations with the blood. The percentage of the gas in the atmos-
phere chosen will measure the tension of that gas in the blood. An
instrument which has been much used for such determinations is
represented diagrammatically in Fig, 253. It is known as an aero-
tonometer (Pfliiger). It consists of a tube (A) which can be con-
nected through b directly with the blood-vessels. This tube A is
surrounded by a jacket (C) containing warm water, so that the blood
may be kept at the body temperature during the experiment. A
is first completely filled with mercury from the bulb M to drive out
the air. An atmosphere of known composition is then sucked into
A by dropping the bulb. Blood is allowed to flow into A through

CHANGES IN AIR AND BLOOD IN RESPIRATION.

623

the stopcock b and to trickle down the sides of the tube. Diffusion
relations are set up between the blood and the known atmosphere,
and after equilibrium has been established the gas is driven out
through a into a convenient receiver and analyzed. If two aero-
tonometers are used, one containing the gas at somewhat higher
pressure than that expected, and the other at a somewhat lower
pressure, an average result is ob-
tained which expresses with suffi-
cient accuracy the pressure of the
given gas in the blood.

It is important not to confuse
the tension at which a gas is held
in a liquid with the volume of the
gas. Thus, blood exposed to the
air contains its oxygen under a
tension of 152 mms. Hg, but the
amount of oxygen is equal to 20
volumes per cent. Water exposed
to the air contains its oxygen un-
der the same tension, but the
amount of gas in solution is less
than 1 volume per cent. Tensions
of gases in liquids are expressed
either in percentages of an atmos-
phere or in millimeters of mercury.
Thus, the tension of oxygen in ar-
terial blood is found to be equal
to about 10 per cent, of an atmos-
phere or 76 mms. Hg. (760 X 0.10).

The Condition and Signifi-
cance of the Nitrogen. — We may
accept the view that the nitrogen
of the blood is held in physical
solution. The amount present
corresponds with this view, and,
moreover, it is found that the
quantity varies directly with the
pressure in accordance with the
law given above. If an animal

is permitted to breathe an atmosphere of oxygen and hydrogen
the nitrogen disappears from the blood, and when ordinary air is
breathed the nitrogen contents of the arterial and venous bloods
exhibit no constant difference in quantity. It seems certain, there-
fore, that the nitrogen plays no direct role in the physiological pro-
It is absorbed by the blood in proportion to its partial

Fig. 253. — Diagram to show the
principle of the aerotonometer: A, The
tube containing a known mixture of

for maintaining a constant body tem-
perature. When stopcock 6 is open
the blood trickles down the sides of A
and enters into diffusion relations with
the contained gases. After equilibrium
is reached the stopcock b is closed and
a is opened. By means of the mer-
cury bulb the gases can then be forced
out of A into a suitable receiver for
analysis.

624

PHYSIOLOGY OF RESPIRATION.

pressure in the alveoli of the lungs and circulates in the blood in
small amounts without exerting any immediate influence upon the
tissues.

Condition of Oxygen in the Blood. — That the oxygen is not
held in the blood merely in solution is indicated, in the first place,
by the large quantity present and, in the second place, by the fact
that this quantity does not vary directly with the pressure in the
surrounding medium. It is definitely known that by far the largest
portion of the oxygen is held in chemical combination with the
hemoglobin of the red corpuscles, while a much smaller portion,
varying with the pressure, is held in solution in the plasma. The
compound oxyhemoglobin possesses the important property that
when the pressure of oxygen in the surrounding medium falls suffi-
ciently it begins to dissociate and free oxygen is given off. The proc-

if

<r

1

I

x

i

NC

CS

i

^

i

i

I

i

3

i

•*•

I

<*:

!

i
s

1
s

i

1

*-

S!

I

1

^

,••*

^

a.S

"^

^

~-

.

^

.

OT<

\

y

V

77

s

(ft

\

\

rot

N,

^v

4ofi

H/t

ft

///• /e/.

7%

z% /f.

Fig. 254. — Curve, dotted line, to show the dissociation of oxyhemoglobin in blood
under different pressures of oxygen. (After Loewy.) The ordinates give the percentages
of saturation of the hemoglobin with oxygen, assuming complete saturation (100 per cent.)
v/hen blood is exposed to atmospheric air. The corresponding pressures of oxygen are
represented along the abscissa, at the top in mms. of mercury, at the bottom in percentages
of an atmosphere.

ess of dissociation is facilitated also by increase of temperature,
provided, of course, that it does not rise to the point of coagulating
the hemoglobin. The amount of dissociation that takes place under
different pressures of oxygen in the surrounding medium has been
studied both for solutions of pure hemoglobin * and for defibrinated
blood. f It would seem from recent work that the compound
between oxygen and hemoglobin is more easily dissociated when the
hemoglobin is in its natural condition in the corpuscles than when it
has been crystallized out and obtained in pure solutions. The
results that have been obtained from experiments upon defibrinated
blood probably represent, therefore, more nearly the conditions

* Hiifner, "Archiv f. Physiologie, " suppl. volume, 1901, p.
tLoewy, "Archiv f. Physiologie," 1904, p. 245.

213.

CHANGES IN AIR AND BLOOD IN RESPIRATION. 625

of dissociation in the body. The results obtained by Loewy are
indicated in the curve of dissociation shown in Fig. 254, obtained
from experiments on human blood. At a pressure of oxygen of
152 mms. — that is, when exposed to ordinary air — the hemoglobin
is nearly or completely saturated with oxygen. If the oxygen
pressure is increased, — if, for instance, the blood is exposed to pure
oxygen (pressure, 760 mms.), — no more oxygen is combined
chemically by the hemoglobin. Additional oxygen will be taken
up by the blood, but only in so far as it can pass into solution in the
blood-plasma. Oxygen thus dissolved in the blood-plasma obeys
the physical law of solution, and will be at once given off when the
oxygen pressure of the surrounding medium is lowered. If the
pressure of oxygen falls below that of the air (152 rums.) the chemi-
cally combined oxyhemoglobin begins to dissociate slowly at first,
but as the pressure falls below 70 mms. the dissociation becomes
much more rapid, and the oxygen thus liberated from chemical
combination is from a quantitative standpoint much more impor-
tant than that freed from solution in the plasma. This, in fact,
is the process that takes place as the blood circulates through the
tissues. The arterial blood enters the capillaries with its hemo-
globin nearly saturated with oxygen, — about 19 c.c. to each 100 c.c.
of blood. After it leaves the capillaries the venous blood contains
only about 12 volumes of oxygen to each 100 c.c. of blood. In the
passage of the capillaries, which takes only about one second, the
blood loses, therefore, about 35 per cent, or more of its oxygen.
The physical theory of respiration furnishes data to show that this
loss is due to a dissociation of the oxyhemoglobin, owing to the fact
that in passing through the capillaries the blood is brought into
exchange with a surrounding medium — lymph, cell liquid — in
which the oxygen pressure is very low.

Condition of the Carbon Dioxid in the Blood. — Carbon
dioxid is evidently contained in the blood in chemical combination
as well as in solution. The amount present, 40 to 45 volumes per
cent., is entirely too great to be accounted for by solution alone.
Moreover, the content of the blood in CO2 does not vary proportion-
ally to the pressure of CO2 in the surrounding medium in accordance
with the law of Henry. Examination of the blood by means of
the gas pump shows that CO2 is contained in both the corpuscles
and the plasma or serum. The results of various analyses would indi-
cate that about one-third of the total amount is held in the corpuscles
and about two-thirds in the liquid of the blood, and, since the cor-
puscles make up about one-third of the bulk of the blood, this fact
would indicate that the CO2 is distributed uniformly throughout the
mass of the blood. The condition of the CO2 in the blood may be
considered under three heads: (1) The part in solution; (2) the part in

40

626 PHYSIOLOGY OF RESPIRATION.

chemical combination in the plasma; (3) the part in chemical com-
bination in the corpuscles. Regarding the part in solution, we may
estimate approximately its~value from our knowledge of the absorp-
tion coefficient of this gas at the temperature of the body. As stated
on p. 621, the calculation would account for 2.6 c.c. of the gas in
each 100 c.c. of blood — that is, about 5 or 6 per cent, of the total
amount present in venous blood. The part of the carbon dioxid
which is chemically combined in the plasma is held partly in an
easily dissociated chemical combination, partly in a more fixed form.
That is to say, if serum or plasma is exposed to a vacuum only a
portion of the CO2 is given off; to obtain the remainder, the so-called
fixed CO2, it is necessary to add some acid. On the contrary, when
the whole blood (plasma and corpuscles) is exposed to a vacuum, at
the temperature of the body, all of the CO2 may be given off. In
this latter case the hemoglobin evidently acts like a weak acid in
breaking up the firm combination of the so-called fixed carbon
dioxid. The portion of the carbon dioxid which exists in the form
of an easily dissociated compound, breaks up and gives off CO., when
the pressure of this gas in the surrounding medium is low. The
nature of this compound is not entirely clear. Some of the CO2 in
the blood is undoubtedly combined with sodium to form sodium
carbonate or bicarbonate. An aqueous solution of sodium bicar-
bonate when exposed to a vacuum gives off some of its CO2 and is
converted to the carbonate, while, on the other hand, a solution of
the carbonate exposed to an atmosphere containing CO., takes up
some of this gas, forming sodium bicarbonate. The reaction in
the two cases may be expressed by a reversible equation, as follows: •

Na2CO3 + CO2 -f H2O ^±. 2HNaCO3

Sodium carbonate. Sodium bicarbonate.

It has been suggested that the respiratory exchange of carbon
dioxid in the body takes place essentially according to this equation.
Experiments upon aqueous solutions of sodium bicarbonate show,
however, that dissociation with liberation of CO2 does not take
place until the tension of the CO2 in the surrounding medium falls
very low, lower than actually exists in the body. Some other
hypothesis must be sought, therefore, to explain the giving off
of the CO2 in the lungs. A supplementary hypothesis of this char-
acter has been suggested. The proteins of the blood have the
property of combining with the bases (Na, K, etc.), and normally,
therefore, the bases present must be divided between the protein
and the acids of the blood. The sodium, for instance, will exist
partly in combination with the protein and partly as sodium car-
bonate or phosphate, taking account only of the combination
with the weak acids. When the tension of the carbon dioxid is
increased, as happens, for instance, in the active tissues, the

CHANGES IN AIR AND BLOOD IN RESPIRATION. 627

equilibrium is disturbed and some of the alkali is taken from the
proteins and combines with the excess of CO2 to form sodium bicar-
bonate. When the blood is brought under conditions of low car-
bon dioxid pressure, as in circulating through the lungs, the sodium
bicarbonate dissociates in part, giving off some CO2. This process
takes place in the blood more readily than in a simple aqueous
solution, because of the affinity of the protein for the base.
According to this view, therefore, the CO2 is carried in the blood
as sodium bicarbonate, and the presence of the protein and its
power of combining with the sodium are used to explain the ease
with which the bicarbonate gives off CO2. It should be added
that this hypothesis does not meet with universal acceptance. Bohr,*
for example, contends that it is necessary to assume that the CO2
forms a dissociable compound with the proteins of the blood, simi-
lar to that which he has shown to be true for hemoglobin.

The Physical Theory of Respiration. — The physical theory
of respiration assumes that the gaseous exchange in the lungs and
in the tissues takes place in accordance with the physical laws of
diffusion of gases. If a permeable membrane separates two vol-
umes of any gas, or two solutions of any gas at different pressures,
the molecules of the gas will pass through the membrane in both
directions until the pressure is equal on both sides. As the excess
of movement is from the point of higher pressure to the point of
lower pressure, attention is paid only to this side of the process,
and we say that the gas diffuses from a point of high tension to
one of lower tension. After equilibrium is established and the
pressure is the same on both sides we must imagine that the
diffusion is equal in both directions, and the condition is the same
as though there were no further diffusion. In order for this
theory to hold for the exchange in the body it must be shown that
the physical conditions are such as it demands. Numerous experi-
ments have been made, therefore, to determine the actual pressure
of the oxygen and carbon dioxid in the venous blood as com-
pared with the pressures of the same gases in the alveolar air, and
the pressures in the arterial blood as compared with those in the
tissues. Although the actual figures obtained have varied some-
what with the method used, the species or condition of the animal,
yet, on the whole, the results tend to support the physical theory.

The Gaseous Exchange in the Lungs. — It is impossible to
determine the exact composition of the alveolar air. The expired
air can, of course, be collected and analyzed, but obviously this is a
mixture of the air in the bronchi and the alveoli, and consequently
has more oxygen and less carbon dioxid than the air in the alveoli.
The probable composition of the alveolar air has been calculated by

* Bohr, in Nagel's "Handbuch d. Physiol. des Menschen," 1905, vol. i.,
part i, p. 111.

628 PHYSIOLOGY OF RESPIRATION.

Zuntz and Loewy for normal quiet breathing in the following way:
The capacity of the bronchial tree is 140 c.c.; and this air may be
considered as similar in composition to atmospheric air, that is, the
inspired air. A normal expiration contains 500 c.c.; hence the
alveolar air constitutes only 360 c.c. or -|-f of the entire amount. If
the expired air contains 4.38 per cent, of CO2, then the alveolar
air must contain 4.38 -*-£•£ or 6 per cent, of carbon dioxid.

Or, to put the mode of calculation in a more general form, the amount
of oxygen in the expired air is equal to the amount of oxygen in the true
alveolar portion of the expired air plus the amount of oxygen in the "dead
space," namely, the trachea and bronchi. Let A equal the volume of expired
air, e the percentage of oxygen in the expired air, a the volume of air in the
dead space, and i the percentage of oxygen in this air or what is the same
thing in the inspired air. According to the above statement we have the fol-
lowing equation, Ae = ai -f (A — a) x, in which x represents the unknown

percentage of oxygen in the alveolar air. We have, therefore, x = "^5?^*-
In ordinary breathing these values are as follows: A — 500 c.c., a = 140 c.c.,
e = 16.02 per cent., and i = 20.96 per cent. Substituting these values, x will be
found equal to 14.1 per cent. Reckoned in millimeters of mercury this would
be equal to (760 X 0.141) 107.2 mm. In order, however, to ascertain the
true pressure exerted by the oxygen allowance must be made for the tension
of the aqueous vapor. At the temperature of the body this is estimated at
50 mm., hence the corrected atmospheric pressure in the alveoli will be 760 — 50
or 710 mm., and this multiplied by 0.141 gives 100 mm. as the pressure of
the oxygen in the alveolar air.

Actual observations made by these authors upon human beings
in whom the expired air was analyzed indicate that the composition
of the alveolar air may vary between the following limits: Oxygen
between 11 and 17 per cent, of an atmosphere; carbon dioxid be-
tween 3.7 and 5.5 per cent, of an atmosphere.

Loewy and von Schrotter have determined also the average ten-
sion of these gases in the blood of man. Their method * consisted
in blocking off one lung or one lobe of a lung by a metal catheter
inserted through the trachea. After the lapse of half an hour or
so the gases in this occluded portion had reached an equilibrium
by interchange with the venous blood which represented the tension
actually existing in the circulating venous blood. A portion of this
air was then withdrawn by means of a suitable device and was
analyzed. Their average result was that in the venous blood the
oxygen exists under a tension of 5.3 per cent, of an atmosphere
(710 X .053 = 37.6 mms. Hg), and the Co, under a tension of 6
per cent. (42.6 mms. Hg). The physical relations of pressure
between the alveolar air and the gases in the venous blood may be
represented as follows :

OXYGEN. CARBON DIOXID.

Alveolar air 100 mms. 35 mms.

Membrane — "-£.

t I

Venous blood ... 37.6 mms. 42.6 mms.

* Loewy and von Schrotter, " Zeitschrift fur experimentelle Pathologie
und Therapie," 1, 197, 1905.

CHANGES IN AIR AND BLOOD IN RESPIRATION. 629

Diffusion must take place, therefore, in the direction indicated
by the arrows. As the oxygen passes through into the blood it is
combined with the hemoglobin and it is estimated that the arterial
blood as it flows away from the lungs is nearly saturated with
oxygen, lacking perhaps only 1 volume per cent, of being completely
saturated (Pfliiger). That is, if the normal arterial blood contains
19 c.c. of oxygen for each 100 c.c. of blood, it is probable that one
more cubic centimeter might be combined by the hemoglobin if
exposed fully to the air or oxygen. The difference in tension
between the carbon dioxid on the two sides of the membrane is not
so great as in the case of the oxygen, but owing to the more rapid
diffusion of this gas it is probable that this difference suffices to
explain the exchange. In this matter one must bear in mind also
the very large expanse of surface offered by the lungs and the very
complete subdivision of the mass of blood in the capillaries. Thus,
following a calculation made by Zuntz, the surface of the human
lungs may be estimated at 90 sq.ms. or 900,000 sq.cms. If we
assume that 300 c.c. of carbon dioxid (500 X 0.04 X 15) are given
off from the blood in a minute this would indicate a diffusion
through each square centimeter of only 0.0003 c.c. (Timnnr)-

Exchange of Gases in the Tissues. — The arterial blood passes
to the tissues nearly saturated with oxygen so far as the hemoglobin
is concerned, and this oxygen is held under a tension equivalent
probably to at least 75 to 80 mms. Hg. The carbon dioxid is less in
quantity than on entering the lungs and exists under a smaller
pressure, which may be assumed to be the same as that of the carbon
dioxid in the alveoli of the lungs, — namely, 3.7 to 5.5 per cent, of an
atmosphere. In the systemic capillaries the blood comes into
diffusion relations with the tissues, and direct examination of the
latter shows that the oxygen in them exists under a very small
pressure, practically zero pressure, while the CO2 is present under
a tension (Strassburg) of 7 to 9 per cent. The high tension of the
CO2 is explained by the fact that it is being formed in the tissues
constantly as a result of their metabolism, while the low tension of
the oxygen is due to the fact that on entering the tissue this sub-
stance is combined in some way in a chemical compound too firm
to dissociate. The physical conditions are, therefore, such as would
cause a stream of CO2 from tissue to blood and a stream of oxygen
in the reverse direction.

OXYGEN. CAHBON DIOXID.
Arterial blood .................. 75 mms. 35 mms.

Wall of capillary ................ I _ "t*

Tissues ........................ 0 mm. 50 to 70 mms.

630 PHYSIOLOGY OF RESPIRATION.

It is to be remembered that in this exchange the blood and
the lymph act as intermediaries. The CO2 diffuses from lymph
to plasma and from tissues to lymph. The oxygen diffuses from
lymph to tissues, from plasma to lymph, and from oxyhemo-
globin to plasma. Bohr* has found experimentally that in blood,
when the oxygen tension is low, an increase in the C02 pressure tends
to dissociate the oxyhemoglobin. Since these conditions prevail in
the capillaries of the body it may be that the mere presence of the
C02 in increased amounts facilitates the liberation of the oxygen.

Suggested Secretory Activity in the Respiratory Exchange.— The
view that the exchange of gases in the lungs and tissues is entirely explained
by the diffusion of the gases from points of high tension to points of low ten-
sion, and that the membranes interposed are entirely passive in the process
has not passed unchallenged. Certain observers (Bohr, Haldane and Smith) f
claim that the tension of the oxygen in the arterial blood may be higher than
the pressure of oxygen in the alveolar air. Bohr, moreover, in a series of
experiments made upon dogs J determined by calculation the tension of oxygen
within the surface layer of the lungs. This tension was found to vary from
35 to 105 mms. The tension of the arterial blood, determined at the same
time, varied from 101 to 144 mms., being in every case distinctly higher than
the tension of the oxygen in the surface layer of the lungs. If- these facts
were fully demonstrated they would show that the physical theory outlined
above is insufficient, and would indicate that the membranes concerned take
an active part in the passage of the gases, exerting possibly a secretory activity.
That the cells of these membranes might secrete the gases is not at all impos-
sible, but at present it seems to be unnecessary to make such a supposition.
The results obtained by the observers mentioned in this paragraph have not
been corroborated by the numerous other observers who have worked in the
same field, and it seems possible that they may be due to experimental errors.
A well-known set of experiments that strengthen this conclusion has been
reported by Wolff berg and by Nussbaum§ and has since been repeated upon
man. In these experiments one bronchus in a dog was completely blocked
by a specially designed lung catheter, so arranged as to occlude the bronchus
and yet allow the observer to draw off a specimen of the air at any time. In
such an occluded lung the captured air is in diffusion relations with the venous
blood of the pulmonary artery, and if these relations are maintained for a
sufficient time an equilibrium should be established on the physical theory,
the tension of the gases in the occluded lungs becoming the same as in the
venous blood. Such was found to be the case. "When at the end of the
experiment air was drawn off and analyzed it was found to contain 3.6 per
cent, of CO 2, while the tension of the CO2 in specimens of the venous blood
taken from the right heart was practically identical. If there is an active
secretion of CO2 from the lungs one should have expected to obtain a higher
tension in the carbon dioxid of the alveolar air than in the venous blood.

* " Skandinavisches Archiv f . Physiologic," 16, 402, 1904.
t See Haldane and Smith,, "Journal of Physiology," 20, 497, 1896.
£ Bohr, in Nagel's "Handbuch der Physiologic des Menschen, 1905, vol. i,
part i, p. 146.

§ "Archiv f. die gesammte Physiologic, " 4, 465, 1871, and 7, 296, 1873.

CHAPTER XXXVII.
INNERVATION OF THE RESPIRATORY MOVEMENTS.

The nervous supply to the respiratory muscles is received from
a number of nerves, the nervous machinery being widely dis-
tributed in the brain and cord. The most important of the motor
nerves of respiration is the phrenic, which supplies the diaphragm
and originates from the fourth and fifth cervical spinal nerves.
The spinal accessory and branches of the cervical and brachial
plexus innervate the muscles of the neck and shoulder which are
concerned in inspiration; the intercostals innervate the muscles of
the thorax and abdomen, while branches of the lumbar plexus send
fibers to the muscles of the groin. Moreover, the facial sends
motor branches to the muscles of the nose and the vagus supplies
the muscles of the larynx. All of these muscles belong to the
skeletal group and are under voluntary control. Under normal
conditions, however, this entire respiratory apparatus works
rhythmically without voluntary control, in alternate inspirations
and expirations, all the inspiratory muscles contracting together,
and all the expiratory muscles together in their turn when the
expirations are active. The co-ordinated activity of such an ex-
tensive mechanism is explained by the existence of a respiratory
center in the medulla oblongata.

The Respiratory Center. — The discovery of the location of the
respiratory center was due mainly to the experiments of two French
physiologists, Legallois and Flourens. The latter placed the
center in the medulla at the level of the calamus scriptorius, and
described it as a very small area or spot, which he designated at first
as the vital knot (nceud vital) under the mistaken impression that
it formed, as it were, a central or focal point of the motor system.
It has since been shown that this center, like the vasomotor
center, is bilateral. If the medulla is cut through in the mid-
line the respirations may proceed in a normal manner. The center
consists of two parts, each connected primarily with the muscula-
ture of its own side. Each half occupies an area that lies some
distance lateral to the mid-line and beneath the floor of the medulla
at the general level of the calamus. According to Gierke,* the area
extends in rabbits from a point 3 or 4 mms. in front of, to a point

* Gierke, " Archiv f. die gesammte Physiologic," 7, 583, 1873; and "Cen-
tralblatt f. d. med. Wissenschaften, " No. 34, 1885.

631

632 PHYSIOLOGY OF RESPIRATION.

2 or 3 mms. posterior to the calamus. No especial group of cells
can be found in this region sufficiently separated anatomically to
make it probable that they constitute the center in question. The
region has been delimited by vivisection experiments only, and,
according to Gierke, corresponds in location to the position of the
solitary bundle (tractus solitarius). According to Mislawsky,*
it lies near the mid-line in the formatio reticularis, while Gad| gives
it a relatively large area in the lateral portion of the formatio
reticularis, the continuation into the medulla of the lateral horn of
the gray matter of the cord. Destruction of these areas or section
of the cord anywhere between this region and the origin of the
phrenic nerve cuts off the respiratory movements, except those of
the nose and larynx, and causes death. The rapid death from
injuries to the cord or medulla in this region — from hanging, for
instance — is explained by the effect upon the respiratory center
or its connections.

There is no doubt that the respiratory center in man occupies the same
general position as in the other mammals. There is on record a easel in
which sections were made of the medulla in a new-born infant. On delivery
it was necessary to puncture the cranium and remove the brain. The child
still lived and the medulla was cut across with scissors. A section at the
posterior end of the calamus stopped the respirations immediately, while
one somewhat anterior had failed to have this effect.

The general idea of the connections of this center with the respir-
atory muscles may be described as follows: The respiratory fibers
arising in the center pass down the cord, probably in the antero-
lateral columns, and end in the gray matter of the cord at the
different levels at which the motor nuclei of the respiratory nerves
are situated. Whether the connection between the respiratory
center and the spinal motor nuclei is made by one or by a series of
neurons is not known, but we may assert that the nerve path from
the respiratory center to the respiratory muscles must be composed
of at least two neurons. According to this conception, the impulses
of inspiration and expiration for the entire respiratory mechanism
originate in the medullary center and are thence distributed in a
co-ordinated way to the lower motor centers in the cord, or, in the
case of the nose and larynx, to the motor centers of the vagus and
facial.

Spinal Respiratory Centers. — At different times various authors
(Brown-Be" quard, Langendorff, et al.} have insisted that there exist one or
more spinal respiratory centers, and that the medullary center has not the
commanding importance indicated in the above description. The fact that,
when the medulla or cervical cord below the medulla is cut, the animal at
once ceases to breathe is explained by these authors on the assumption that

* Mislawsky, " Centralblatt f. die med. Wissenschaften " No. 27, 1885.

t Gad, " Archiv f. Physiologic," 1893, p. 75.

jSee Kehrer, "Monatshefte f. prakt. Dermatol.," 28, 450, 1892.

INNERVATION OF THE RESPIRATORY MOVEMENTS. 633

the operation causes a prolonged inhibition of the underlying spinal centers.
They state that young animals, especially if made hyperirritable by the in-
jection of strychnin, may continue to breathe after section of the cord below
the medulla. This point of view, however, has not prevailed in physiology.
Other operations on the cord or brain are not attended by such profound
inhibition, and indeed Porter and Miihlberg have shown* that, if half of the
cord alone is cut, the movements of the diaphragm on that side are permanently
paralyzed. It is entirely conceivable that under exceptional conditions
the lower neurons, the direct motor centers of the respiratory muscles, might
be made to act rhythmically, since during life they have been rhythmically
stimulated from the medullary center; but the evidence at present is alto-
gether against any distinct physiological independence on the part of these
neurons.

The Automatic Activity of the Respiratory Center. — The
constant activity of the respiratory center throughout life suggests
the question as to its automaticity. Is it automatic like the heart?
That is, are the stimuli discharged from it produced within its own
cells as a result of its own metabolism under the normal conditions
of circulation? Or, on the other hand, is it, like most of the motor
nuclei of the central nervous system, only a reflex center, its motor
discharges being dependent upon impulses received from other
neurons by way of the sensory paths? Obviously the only way to
answer such a question directly is to isolate the center from all
afferent paths and leave it connected with the respiratory muscles
only by motor nerves. If under such conditions the respiratory
rhythm continues the center may be regarded as essentially auto-
matic, however susceptible it may be to reflex influences. A close
approximation at least has been made to such an experiment.
Rosenthal finds that rhythmical respiratory movements continue
after the following operations : first, section of the brain at the cor-
pora quadrigemina to cut off influences from the cerebrum, thala-
mus, and midbrain; second, section of the vagi, to shut off afferent
impulses from the viscera, especially from the lungs; third, section
of the cord at the seventh cervical vertebra to exclude sensory
influences through all the underlying posterior roots; and, fourth,
section of the posterior roots of the cervical spinal nerves. The
medulla with its respiratory center was thus isolated from all
afferent impulses except such as might enter through the fifthr
seventh, eighth, and ninth cranial nerves. Since under these con-
ditions the center continued to act rhythmically we may draw
the probable conclusion that it is essentially automatic, and that
it probably possesses an intrinsic rhythmical activity resembling
that of the heart.

Reflex Stimulation of the Center. — According to the results

of numerous observers, stimulation of any of the sensory nerves

of the body may affect the rate or the amplitude of the respiratory

movements. This experimental result is confirmed by our own.

* " American Journal of Physiology, " 4, 334, 1900.

634

PHYSIOLOGY OF RESPIRATION.

experience, since everyone must have noticed that the respiratory
movements are readily affected by strong stimulation of the cutane-
ous nerves — a dash of cold water,
for example — as well as through
the nerves of sight and hearing.
In addition, emotional states are
apt to be accompanied by notice-
able changes in the respirations,
and corresponding to this fact
experiment shows that stimula-
tion of certain portions of the cor-
tex and midbrain gives distinct
effects upon the respiratory cen-
ter. We must assume, therefore,
that this center is in connection
with the sensory fibers of per-
haps all of the cranial and spinal
nerves, and is influenced also by
intracentral paths passing from
cerebrum to medulla, paths which
are efferent as regards the cere-
brum, but afferent as regards the tion

morliilla Ac cfnforl ohrkx^ fViA by stimulation of the sciatic nerve. Ex-

tneduiia. AS stated above, tne periment upon a rabbit.

effect of these sensory nerves

upon the activity of the respiratory center is varied ; the rate may

Fig. 256. — To show the inhibition of the respiratory movements in a rabbit due to
stimulation of the central end of the vagus. The respiratory movements in this case,
before and after stimulation, were forced, owing to the fact that both vagi were cut.

be changed together with an increased or decreased amplitude, the
inspirations and expirations may each be increased, or one phase

INXERVATION OF THE RESPIRATORY MOVEMENTS. 635

may be affected more markedly than the other. In general, how-
ever, experimental stimulation of a sensory nerve trunk which con-
tains cutaneous fibers gives one of two effects : either a stimulating
action, manifested by quicker, stronger inspirations and active ex-
pirations, or an inhibitory effect, in which the respirations cease
altogether or become slower ,and more feeble (Figs. 255 and 256).
If in this, as in other similar cases, we assume that the two oppo-
site effects are produced by different nerve fibers we may speak of
sensory fibers which have a stimulating or augmenting effect, and
of those that have an inhibiting influence on the center, or following
the terminology used in the case of the vasomotor center, we may
speak of respiratory pressor and respiratory depressor fibers. It is
quite probable that these fibers have other functions, — that is, they
are not distributed exclusively to the respiratory center. A cuta-
neous fiber, which through its central chain of neurons eventually
ends in the cortex cerebri and gives us a sensation of pain, may
by collateral connections affect also the medullary center and pro-
duce effects upon the heart, blood-vessels, and respirations.

The Special Relations of the Afferent Fibers of the Vagus
to the Center. — Although the sensory nerves in general exert a
reflex effect upon the respiratory center, experimental work has
shown that the sensory fibers distributed along the respiratory
passages from the anterior nares to the alveoli have a specially
important relation to this center. This fact is most clearly shown
in the case of the sensory fibers of the vagus, which are distributed
to the lungs themselves. If the two vagi are cut in the neck the
respiratory movements are at once altered in character; they
show a much slower rhythm and greater amplitude (Fig. 257).
The inspirations especially are deeper and longer, with something
of a pause at the end. When only one vagus is cut an intermediate
effect may be obtained, the respiratory movements may be slowed
somewhat and slightly deepened; but the striking effect is observed
only- after section of both nerves. This result is not a temporary
one d\ie to the stimulation of cutting, but is permanent, and there-
fore leads to the conclusion that some influence has been cut off
which normally keeps the respiratory movements at a more rapid
rate. Experiment has shown that this influence consists in the
tonic action of sensory fibers contained in the vagus and distributed
to the lungs. It is the constant effect of these fibers on the respira-
tory center which maintains the normal rhythm; when they are
severed the center drops into a slower, unregulated rhythm. Ex-
periment has shown, also, that when the central stump of the
divided vagus is stimulated artificially the respiratory center is
affected, as indicated by the respiratory movements, in a variety
of ways which depend upon the strength of the stimulus and the

636

PHYSIOLOGY OF RESPIRATION.

condition of the center. The two results which are most constantly
obtained and which may therefore be especially emphasized are as
follows: first, with weak stimuli the inspiratory movements are in-
hibited partially or completely, giving either smaller movements or,
in a condition of narcosis, complete cessation of respirations, with

Fig. 257. — To show the effect of section of the vagi on the respiratory movements
(rabbit). The right vagus was cut at x and caused a slight augmentation and slowing
of the movements. The left vagus was cut at xx and caused first a short inhibition (due
to mechanical stimulation) which was then followed by the typical slow and deep respi-
rations seen under these conditions. — (Dawson.)

the thorax in the stage of passive expiration (Fig. 256), or, second,
the rate of the inspiratory movements may be increased and this
may end finally in an inspiratory standstill, — that is, the respiratory
movements cease with the chest in an inspiratory position (Fig. 258),

Fig. 258. — To illustrate the inspiratory effect from stimulation of the central end of
the vagus. The downstroke represents inspiration; the upstroke, expiration. During-
the period of stimulation the respirations are increased in frequency and the chest remains
in a condition of inspiration. — (Lewandowsky .)

the inspiratory muscles being in a condition of tetanic contraction.
When both the inspiratory and expiratory muscles are considered,
the variety of effects that may be obtained from stimulation of the
afferent fibers of the vagus is perplexing, especially with strong

IXNERVATION OF THE RESPIRATORY MOVEMENTS. 637

stimuli, and has led to much difference of opinion among investi-
gators.* The two main effects described above are usually inter-
preted to mean that the vagus contains two kinds of sensory fibers
which are distributed to the lungs and act normally on the respira-
tory center. These are: (I) The inspiratory fibers, whose effect
is to increase the rate of inspiratory discharge from the respiratory
center; therefore to quicken the rate. (II) The expiratory (or
inspiratory inhibiting) fibers, whose effect is to inhibit the inspira-
tory discharges, partially or completely. Some authors find it
simpler to assume only one kind of sensory fiber and to explain the
different results by a difference in the nature of the stimulus or
in the condition of the center; but it seems advisable at present,
in accordance with the doctrine of specific nerve energies, to hold
to the view of two varieties.

Influence of the Inspiratory and the Inhibitory Fibers of
the Vagus on the Normal Respirations. — It is assumed that
these two sets of fibers are in constant activity and keep the re-
spiratory rate more rapid than it would be otherwise. Hence the
slowing and deepening of the respirations when the vagi are cut.
The way in which these sensory fibers are stimulated normally was
referred by Hering and Breuer to the alternate expansion and
collapse of the lungs. Each inspiration stimulates the inhibitory
fibers in consequence of the expansion of the. lungs, and thus cuts
short the inspiration, prematurely, as it were. So at each expira-
tion the collapse of the lungs stimulates the inspiratory fibers and
brings on an inspiration sooner than would otherwise occur. In
this way the respiratory rate is kept automatically at an accel-
erated rhythm. A stimulation of the sensory fibers as a result of
expansion of the lungs is easy to comprehend and, indeed, it has
been demonstrated by showing that with each expansion an action
current may be obtained in the vagus by means of the galvanometer
or capillary electrometer. But that the normal collapse of the
lungs also acts as a mechanical stimulus to a different set of nerve
endings is not such a probable hypothesis, and most physiologists
believe that it is not necessary to adopt it, — at least for normal
respirations. Head and also Schenck have shown that with a
certain extreme extent of collapse evidence may be obtained of a
stimulation of the inspiratory fibers. We may assume, with Gad,
that the normal rate of respirations is maintained by the action
of the inhibitory fibers alone. Each inspiration is cut short by
the mechanical stimulation of these fibers, but on the collapse of

*For discussion and literature see Meltzer, "Archiv f. Physiologic,"
1892, p. 340; also "New York Medical Journal, " January 18, 1890. Le-
wandowsky, " Archiv f. Physiologic," 1896, pp. 195 and 483.

638 PHYSIOLOGY OF RESPIRATION.

the lungs the new inspiration is due to a normal discharge from the
inspiratory center.

Loewy* has shown by an ingenious experiment that the expansion of
the lungs is the factor that actually stimulates the sensory fibers and quickens
the respiratory rate, as follows : An animal was made to breathe pure oxygen
for a while to displace the nitrogen in the alveoli. The chest on one side —
say, the right side — was then opened with the result that the lung collapsed,
and, owing to the rapid absorption of the oxygen, soon became practically
solid. The respirations (rabbit) showed their normal rate — 66. The vagus
nerve on the left side was then cut and immediately the respirations took
on the character usually shown when both vagi are severed, — respirations
= 34. Next the collapsed right lung was expanded by artificial respiration,
with the result that the respiratory rate at once returned to normal.

Respiratory Reflexes from the Larynx, Pharynx, and Nose.

— The mucous membrane of the larynx receives its sensory fibers
from the superior laryngeal nerve. When this nerve is stimulated
artificially the respirations are always inhibited ; the chest comes to
rest in the position of passive expiration. The same effect may be
obtained from the sensory fibers of the glossopharyngeal supplying
the pharynx, and indeed a temporary inhibition of respirations
occurs through this nerve during every act of swallowing. The
sensory fibers of the nasal mucous membrane (trigeminal) cause a
similar reflex inhibition when stimulated by injurious or so called
irrespirable gases, such as HC1, Cl, NH3, SO2, etc. We may regard
this inhibitory influence exerted by the sensory fibers distributed
along the air passages as a protective reflex which guards the lungs
automatically from injurious gases. This protective action is
made more evident by the fact that, together with the cessation of
respirations, the glottis is reflexly closed by contraction of the ad-
ductor muscles and, if the stimulation is strong, even the bronchial
musculature may be contracted, so that in every way the passage
to the alveoli is made more difficult. The reflex is, of course, more
or less temporary, but it possesses the great advantage of being
automatic, and may enable the animal or individual to escape
unharmed from a dangerous locality before the increasing irritabil-
ity of the respiratory center breaks through the inhibition. In
special cases the inhibition may last for an unusually long time.
Thus, Fredericq states that in aquatic birds water allowed to flow
over the beak so as to penetrate slightly into the nostrils brings
about an inhibition of respirations for many minutes. There
would seem in this case to be a special adaptation of the reflex to
the needs of diving. We know also that irritating gases or foreign
bodies of any sort that enter the larynx may lead to a coughing
reflex, — that is, to a series of expiratory blasts which have a pur-
poseful end in the expulsion of the stimulating object. In this case

* "Archiv f. die gesammte Physiologic, " 42, 273.

INNERVATIOX OF THE RESPIRATORY MOVEMENTS. 639

there is not simply an inhibition of the inspiratory movements,
but a reflex excitation of a peculiar type of expiratory movements.

The Voluntary Control of the Respiratory Movements.—
We can control the respiratory movements within wide limits, make
forced or feeble inspirations or expirations, accelerate the rhythm,
or completely inhibit the respirations in any phase. If, however,
the "breath is held," — that is, if the respiratory movements are
inhibited and the glottis is closed, the increasing irritability of
the respiratory center eventually breaks through the voluntary
inhibition. How far this voluntary control is based upon direct
connections between the cerebrum and the respiratory center and
how far it depends upon voluntary paths to the separate spinal
nuclei of the muscles involved cannot be discussed profitably.

The Nature of the Respiratory Center. — The respiratory
center located in the medulla oblongata might with more propriety
be designated as the inspiratory center. Our normal respirations
throughout life consist of an active inspiration and a passive
expiration. It is the co-ordinated activity of the inspiratory
muscles that is characteristic of the respiratory movements. The
expiratory muscles come into action only occasionally and under
special conditions. It is, in reality, incorrect to speak of the normal
respirations as consisting of alternate inspiratory and expiratory
movements; as a matter of fact, they consist of rhythmical in-
spiratory movements alone. So also when we describe the respira-
tory center as essentially automatic we refer only to the action on
the inspiratory muscles, since a series of active inspiratory move-
ments is the essential feature of respiration. Under certain con-
ditions, however, we do have rhythmical expiratory movements,
active expirations. Such movements may occur independently
of the respirations proper, as in coughing and laughing, or in the
straining movements of defecation, micturition, and parturition;
or they may occur as an integral part of the respirations, as in the
forced movements of dyspnea. Under the conditions of partial
suffocation, for instance, as the blood becomes more and more
venous the respirations increase in force and active expirations
appear. It becomes a question, therefore, as to the existence of
what might be called an expiratory center, a group of nerve cells
controlling the co-ordinated activity of the expiratory muscles.
The mere fact that in dyspnea we have a rhythmical and co-ordi-
nated activity of these muscles seems to imply the existence of such
a center, but there is no definite experimental knowledge as to its
location. Assuming that there is such a center, it may be believed
that it exists in the medulla, since after section below the medulla
there is no evidence of the occurrence of rhythmical expiratory
movements even in extreme conditions of venosity of the blood.

640 PHYSIOLOGY OF RESPIRATION.

The expiratory center may or may not be located in the same
region as the inspiratory center, but the following general char-
acteristics may be assigned to it: In the first place, it is not auto-
matic; at least not under normal conditions. In the second place,
its activity must be dependent in some way upon that of the in-
spiratory center. Even our most violent respiratory movements
show an orderly sequence of inspiration and expiration, — and we
may believe that the action of the expiratory center is conditioned
by the previous discharge of the inspiratory center, just as in the
heart the beat of the ventricle depends upon the previous systole
of the auricle. That an active expiration is not caused reflexly by
the mechanical expansion of the lungs seems to be demonstrated
by the fact that the most forcible voluntary inspiration is followed
by a passive, not an active expiration. Until our knowledge is
extended by further experimental work we may consider the ex-
piratory center as a group of cells connected by definite paths with
the expiratory muscles and capable of being stimulated in one of at
least four general ways: (1) In special reflexes, such as coughing.
(2) By voluntary control from the cerebrum, as in straining. (3)
By stimulation through afferent fibers from the skin, especially the
pain fibers. (4) By the action of an increased venosity of the blood.
Under the latter two conditions it is possible that the irritability
of the center is so increased that it becomes responsive to the in-
fluence of the inspiratory center. The relations of the inspiratory
and expiratory centers under the various conditions of artificial
stimulation are very complex, and although it is possible to rep-
resent these relations more or less completely by schemata of some
sort it does not seem advisable at present to seriously consider
such hypotheses.

The Accessory Respiratory Centers of the Midbrain. — Several observers
have called attention to the existence of a possible accessory respiratory center
in the midbrain at the level of the posterior colliculus. Martin and Booker
found that stimulations in this region caused a marked increase in the rate
of inspiratory movements and finally a standstill in inspiration, — that is,
a complete tetanic contraction of the inspiratory muscles lasting during the
stimulation.* Lewandowskyf has shown that section of the brain stem
at or below the inferior colliculi causes an alteration in the respiratory rhythm
similar to that following section of both vagi. After cutting through the
inferior colliculi further sections more posteriorly do not add to the effect.
He considers that there is an automatic inhibitory center in the midbrain
which influences continually the automatic activity of the medullary center.

The Nature of the Automatic Stimulus to the Respiratory
Center. — We have accepted the view that the respiratory (inspira-
tory) center is essentially automatic, although very sensitive to

* Martin and Booker, "Journal of Physiology," 1, 370, 1878.
f'Archiv f. Physiologic," 1896, 489.

INNERVATION OF THE RESPIRATORY MOVEMENTS. 641

reflex stimulation. The further question arises as to the nature of
the automatic stimulus. Inasmuch as the activity of the center
controls the gaseous exchanges of the blood, it was natural perhaps
for physiologists to look to the gases of the blood for the origin of
the internal stimulus. Experiments show beyond question that
the condition of the gases in the blood has a direct and marked
influence upon the activity of the center. If for any reason the
blood supplying the center becomes more venous, the respirations
are increased in force or rate or both, and indeed the activity of the
center is in a general way increased in proportion to the venosity
of the blood. On the other hand, if the blood supplying the center
is more arterialized than normal, by active ventilation of the lungs,
for instance, the center acts more feebly or may fail to act altogether,
giving the condition known as apnea. These facts may be accepted
as completely demonstrated, but they do not go far enough. When
we speak of the arterial blood being more venous than normal we
mean that it contains less oxygen and more carbon dioxid than
normal arterial blood. Which of these conditions serves to stimulate
the center, and which may be regarded as the constant stimulus
throughout life ? The three possible views have been defended :
(1) That the normal stimulus is a lack of sufficient oxygen (Rosen-
thai). When sufficient O is supplied the center ceases to act,
becomes apneic. (2) That the normal stimulus is the presence of
an excess of CO2 (Traube). When this excretion is quickly re-
moved the center ceases to act, — becomes apneic. (3) It is possible
that the two factors may co-operate. The blood that flows through
the center may stimulate the cells by virtue of the fact that it does
not remove the CO., fast enough and does not supply sufficient
oxygen. Much evidence has been collected to show that the
action of the respiratory center is increased when the tension of the
C02 in the blood is raised without altering that of the oxygen and
that a similar result is obtained if the tension of oxygen is greatly
diminished without any change in that of the carbon dioxid, so
that it must be admitted that a change in either factor, if suffi-
ciently great, acts as a stimulus. Experiments, however, have
indicated that the accumulation of the CO2 is the more efficient
stimulus of the two.* Zuntz reports the following interesting
experiments, in which the extent of the respiratory movements was
measured by the amount of air breathed in a minute. In one series
the amount of oxygen in the air breathed was reduced. This change
did not affect the quantity of carbon dioxid in the blood. The
following results were obtained:

*See Zuntz, "Archiv f. Physiologic," 1897, 379. See also Friedlander
and Herter, "Zeit. f. physiol. Chemie," 2, 99, and 3, 19.
41

642 PHYSIOLOGY OF RESPIRATION.

Normal air volume breathed per minute = 7,325 to 9,000 c.c.

Air with 10 to 11.5 per

cent, oxygen " " " " — 8,166 to 9,428 "

Air with 8 to 10 per

cent, oxygea " = 9,093 to 12,810 "

A reduction of one-half of the oxygen in the air breathed had little
effect upon the respirations. From our present standpoint, how-
ever, the important thing i« not the amount of oxygen in the air,
but the amount in the blood. Paul Bert's experiments* upon
living animals indicate that when the oxygen of the air is reduced
by a half the amount of oxygen in the blood is diminished by about
one-third. Assuming this to be correct, it is evident that a very
considerable reduction may be made in the oxygen of the blood
without noticeably affecting the respirations. A similar conclusion
may be drawn from Haldane's experiments f with carbon monoxid.
He found upon breathing mixtures of this gas that no distinct effects
were observable until the blood was about one-third saturated with
the gas — that is, had lost one-third of its oxygen. Zuntz's ex-
periments, in which the C02 in the air breathed was increased, while
the oxygen remained normal, gave quite different results, as follows :

Normal air volume breathed per minute, 7,433 c.c.

Air of 20.2 per cent. O, 0.95 per

cent. CO2 " " " " 9.060 "

Air of 18.06 per cent. O, 2.97 per

cent. CO2 " ." " " 11,326 "

Air of 18.42 per cent. O, 11.5 per

cent. CO2 " " 32,464 "

These and similar results show that small differences in the
amount of the carbon dioxid in the blood have a distinct effect
upon the activity of the respiratory center. Under normal con-
ditions the respiratory center receives blood containing 19 to 20
volumes per cent, of oxygen, while the venous blood flowing away
from the center still holds 10 to 12 per cent. Considering the
small effect of lowering this oxygen supply by one-third, it is
difficult to believe that normally the amount of oxygen is so
deficient for the normal metabolism as to set up a constant
stimulus. The trend of recent work favors rather the view that
the normal stimulus to the respiratory center is the carbon dioxid.
When this substance is present above a certain amount or tension
it acts as a stimulus and gives rise to the moderate movements of
normal inspiration. If the tension of the carbon dioxid is increased
its stimulating action becomes stronger and leads to the production
of a condition of hyperpnea and dyspnea. On the other hand,
if for any reason, such as active ventilation of the lungs, the tension

*Bert, "La pression barometrique," 1878, 691.
fHaldane, "Journal of Physiology," 18, 442, 1895.

INNERVATION OF THE RESPIRATORY MOVEMENTS. 643

of the carbon dioxid falls below a certain value, estimated by
Zuntz as lying between 19 and 24 mms., no stimulation occurs,
the center is in a condition of apnea and respiratory movements
cease. Under special circumstances other substances may occur
in the blood which act as chemical stimuli to the center, for example,
the acid products formed during muscular contractions (see p. 648).
The Cause of the First Respiratory Movement. — The mam-
malian fetus under normal conditions makes no respiratory move-
ments while in utero. After birth and the interruption of the pla-
cental circulation the first breath is taken. The cause of this
sudden awakening to activity on the part of the respiratory center
must be closely connected, if not identical with, the cause of the
automatic activity of the center throughout life. Two or perhaps
three views have been held regarding its immediate cause: (1)
That it is due to the increased venosity of the blood brought about
by the interruption of the placental circulation; (2) that it is due to
stimulation of the skin by handling, drying, etc. ; (3) that it is due
to a combination of these causes. Preyer has shown that stimula-
tion of the skin of the fetus while in utero and with the placental
circulation intact sufficies to cause respiratory movements. Cohn-
stein and Zuntz* have shown that interruption of the placental
circulation while the fetus is kept bathed in the amniotic liquid also
brings about respirations. Since both of these events occur normally
at birth, we may believe that each aids in causing the first respira-
tion, and indeed it may be necessary at times deliberately to in-
crease the stimulation of the skin in order to bring on respiratory
movements. If the two causes, stimulation through the nerves and
stimulation through the blood, normally co-operate, it may, how-
ever, be said that the essential cause, according to the theory
adopted in the preceding paragraphs, lies in the greater venosity of
the blood, that is, the increased tension of the carbon dioxid follow-
ing interruption of the placental circulation. During the intra-
uterine period it is evident that the fetal blood is aerated so well
by exchange with the maternal blood that it does not act as a
stimulus to the fetal respiratory center. The fetus is, physiolog-
ically speaking, in a condition of apnea. Since the maternal blood
acts upon the respiratory center of the mother, while the fetal
blood which exchanges gases with it does not act on its own respira-
tory center, it follows that the fetal respiratory center possesses a
lower degree of irritability than that of the mother.

Dyspnea, Hyperpnea, Apnea. — By the term dyspnea in its

widest sense we mean any noticeable increase in the force or rate of

the respiratory movements. As said above, such a condition may

be caused either by stimulation of sensory nerves, particularly

*Cohnstein and Zuntz, "Arch. f. die gesammte Physiol.," 42, 342, 1888.

644 PHYSIOLOGY OF RESPIRATION.

the pain nerves, or by an increased venosity of the blood, — that is,
by an increase in the CO2 or by a marked decrease in the oxygen.
Changes of other kinds in the composition of the blood, some of
which are considered in the next chapter, may also stimulate the
respiratory center and cause dyspnea. The dyspneic movements
naturally show many degrees of intensity corresponding with the
strength of the stimulus, and sometimes the initial stages are desig-
nated as hyperpnea, while the term dyspnea is reserved for the more
labored breathing in which the expirations are active and forced.
When dyspnea is produced by withholding air (suffocation) the
respiratory movements become more and more violent until they
take on a convulsive character. This stage is succeeded by one
of apparent calm, indicative of exhaustion of the centers. Deep,

Fig. 259.— To show the recovery from apnea. The animal (rabbit) had been venti-
lated with a bellows and thrown into a condition of apnea shown at the beginning
of the record. The respirations returned first as feeble movements which gradually in-
creased to the normal. — (Dawson.)

long-drawn inspirations follow at intervals and finally cease. The
animal lies quietly, with feeble heart beat and dilated pupils, in
a condition designated as asphyxia or complete asphyxia.

The term apnea means literally a condition of no breathing, and
since this condition may occur from several causes some confusion in
nomenclature has resulted. In medical literature the term is some-
times employed as a synonym for asphyxia or suffocation. In
physiological literature it is restricted to a very interesting con-
dition which is of great importance with reference to the theories
of respiration. This condition is one of cessation of breathing
movements due to lack of stimulation of the respiratory center.
It is brought about by rapid and prolonged ventilation of the
lungs. If, for instance, in a rabbit or other animal, a tracheal

INNERVATION OF THE RESPIRATORY MOVEMENTS. 645

cannula is inserted and connected with a bellows or respiration
apparatus, the lungs may be inflated artificially at a rapid rate
for any given period of time. If such an experiment is per-
formed it will be found that when the blasts are stopped the
animal makes no breathing movements at all, sometimes for a
considerable interval. When the respirations start again they begin
with feeble movements, which gradually increase to the normal
amplitude (Fig. 259). One may produce a similar condition upon
himself, approximately at least, by a series of rapid, forced inspira-
tions. The question of importance is: Why does the respiratory
center cease to act? Rosenthal explained the phenomenon in terms
of his theory that the normal stimulus to the center results from a
lack of oxygen. With vigorous artificial respiration he imagined
that the blood takes up more oxygen and thus fails to act upon
the center. The apnea is due to overoxygenation of the blood,
and indeed this is the definition he gave to the word.* The
numerous researches made upon this condition seem to show
very clearly that in the method used to produce it two factors
co-operate, and that it is necessary, in reality, to distinguish two
different kinds of apnea, the apnoea vera or chemical apnea, and the
apncea vagi or inhibitory apnea. When the lungs are vigorously
inflated by artificial blasts the alveoli are better ventilated, and
consequently the blood takes up somewhat more of oxygen and gives
off more carbon dioxid. It reaches the center in what may be
called a more arterialized or less venous condition. At the same
time the repeated expansions of the lungs cause repeated stimula-
tions of the inhibitory fibers in the vagus, and this tends to bring the
center to rest by inhibition. Either of these factors alone may
cause a condition of apnea and in the method by which the phenom-
enon is usually produced the two co-operate, as may be inferred
from the following facts: If the vagi are cut it is much more difficult
to produce apnea by artificial respirations. If in an animal with
vagi intact the artificial respirations are made with hydrogen in-
stead of air an apneic pause may be obtained, but this is no longer
possible if the vagi are cut.f These two facts indicate the impor-
tance of the inhibitory factor. That chemical apnea in Rosen-
thaPs sense may exist is shown by the fact that after section of
both vagi apnea may still be produced by artificial respiration,
and indeed several observers! find that after section of both vagi
and of the medulla above the center the animal may still be
made apneic. In such cases it is difficult to see any other cause for
the apnea than a change in the gases of the blood. Rosenthal

* See Rosenthal, in vol. iv, p. 264, of Hermann's " Handbuch der Physi-
ologic. "

t See Head, "Journal of Physiology," 10, 1, and 279, 1889.

J Loewy, "Archiv f. die gesammte Physiologic," 42, 245, 1888; and
Langendorff, "Archiv f. Physiologic," 1888, p. 286.

646 PHYSIOLOGY OF RESPIRATION.

assumed that the apnea is due to an overoxygenation of the blood,
but since the vigorous respirations lower especially the contents of
the blood in CO2 it is probable, as insisted upon by Traube, that this
latter factor is the more important. In the preceding paragraphs
some evidence has been given to show that the normal stimulus to
the center is due to the presence of CO2, and it follows logically that
the more complete removal of this gas by ventilation of the lungs
should be considered as the chief cause of true apnea. • Experi-
mentally this view is well borne out by an old observation of Berns,
according to which a condition of apnea in a rabbit may be cut
short instantly at any moment by a blast of C02 sent into the lungs,
a blast of air having no such effect. This observation is further
supported by recent experiments by Mosso * upon men, in which
he shows that apnea cannot be produced by inflation with carbon
dioxid. This author designates the condition of diminished CO2
in the blood as acapnia. According to this terminology, true apnea
is due to a condition of acapnia.

In the intact animal, therefore, we may say that apnea is
due to two causes: first, the removal of C02 from the blood by
better ventilation, whereby the center is stimulated less strongly
or not at all; and, second, the rhythmical inhibition of the center
through the vagus fibers ending in the lungs. The two causes work
together and, as it were, aid each other, for the less the irritability
of the center, the more easily it is inhibited, and the more it is
inhibited, the less the internal stimulus affects it. It is known
that a cessation of respirations may be brought about in still a
third way, namely, by a condition of more or less complete anemia
produced by shutting off the blood-supply to the center. The
lack of activity in this case is not a true apnea in the physiological
sense of the term, since we may suppose that under these conditions
the tension of the carbon dioxid increases rather than decreases.
It is due to a loss of irritability in the center, as a direct result
of the deprivation of the blood-supply, rather than to a diminution
in the normal stimulus.

Innervation of the Bronchial Musculature. — Numerous
investigators, using different methods, have demonstrated that the
bronchial musculature is supplied through the vagus with motor
and inhibitory fibers, bronchoconstrictor and bronchodilator fibers,
as they are usually called. f Stimulation of the constrictors causes
a narrowing of the bronchi, and therefore increases the resistance to
the inflow and outflow of air. Some observers state that these fibers
are normally in a condition of tonic activity (Roy and Brown),
but others find little evidence for this belief. An artificial tonus —

* Mosso, "Archives italiennes de biologie," 40, 1, 1903.
t For a recent paper with references to literature see Dixon and Brodie,
"Journal of Physiology," 29, 97, 1903.

INNERVATION OF THE RESPIRATORY MOVEMENTS. 647

that is, a condition of maintained activity of the constrictor fibers —
may be set up by the action of a number of drugs, such as muscarin,
pilocarpin. and physostigmin, which in this case, as in so many
other instances of autonomic fibers, are supposed to stimulate the
endings of the fibers in the lungs. Their effect is removed by the
action of atropin. These fibers are stimulated also during the ex-
citatory stages of asphyxia. • Reflex stimulation of the constrictors
is obtained most readily (Dixon and Brodie) by irritation of the
nasal mucous membrane, and it seems probable that in bronchial
or spasmodic asthma these fibers are also stimulated reflexly.
The normal conditions under which the constrictors and dilators
are brought into play can scarcely be stated. Irritating vapors or
even CO2 lead to a bronchoconstriction and this reflex, as stated on
p. 638, may be regarded as protective. When a constriction of the
bronchial musculature exists it may be abolished by the paralyzing
action of atropin, or temporarily by injections of extracts of
lobelia or by the anesthetic effect of inhalations of chloroform or
ether. Nicotin also causes a dilatation.

CHAPTER XXXVIII.

THE INFLUENCE OF VARIOUS CONDITIONS UPON
THE RESPIRATIONS,

The Effect of Muscular Work upon the Respiratory Move-
ments.— It is a matter of common experience that muscular ex-
ercise increases the rate and amplitude of the respiratory move-
ments. Roughly speaking, the increase is proportional to the
amount of muscular work, and the relationship is evidently a bene-
ficial adaptation. The greater the amount of work done, the
larger will be the amount of C02 produced and the greater will be
the need of oxygen. The adaptation was formerly explained in
what seemed to be an entirely satisfactory way by assuming that
the increased consumption of O and the greater production of COa
in the muscles resulted in rendering the blood more venous, and
consequently the respiratory center was stimulated more strongly ,
and indeed proportionally to the muscular effort. Geppert and
Zuntz,* however, have shown by gas analyses that whatever may
be the condition of the venous blood during muscular exercise
the arterial blood sent out from the left heart shows no constant,
change in the quantity or tension of the contained gases. They
proved, also, that the effect on the center is not simply a reflex
from the nerves in the muscles, since when the hind limbs were made
to contract by stimulation the respiratory center was affected in
the usual way although all the nerve connections were destroyed.
They conclude, therefore, that the respiratory effect of muscular
work must be due to certain substances produced in the muscle and
given off to the blood. Other experiments (Lehmann) make it
probable that these substances are the acid products, lactic acid and
acid phosphates, known to be formed in muscle during contraction.
Dilute acids injected directly into the veins produce a similar
result. The adaptation is a most interesting one, since the products
that decrease the irritability of the muscle itself seem to cause an
increase in excitability of the group of nerve cells constituting the
respiratory center.

The Effect of Variations in the Composition of the Air
Breathed. — Variations in the amount of nitrogen in the inspired

* Geppert and Zuntz, " Archiv f . die gesammte Physiologic, " 42, 189>
1888.

648

INFLUENCE OF VARIOUS CONDITIONS ON RESPIRATION. 649

air have no distinct physiological effect. The important elements
to consider are the oxygen and the carbon dioxid.

Increased Percentages of Oxygen. — The normal pressure of oxygen
in the air is 20 per cent, or 152 mms. We may increase this pres-
sure either by changing the volume per cent, of the gas or by raising
the barometric pressure by compression. The somewhat natural
supposition that breathing pure oxygen — that is, oxygen at a pres-
sure of 760 mm. — should have a beneficial effect on the oxidations
of the body has found no support in physiological experiments.
Atmospheric air supplies us with an excess of oxygen over the needs
of the body; a still further increase of this excess has no positive
advantage. Paul Bert, in his interesting work on barometric pres-
sures,* has called attention to the fact that at a certain pressure
oxygen is not only not beneficial, but, on the contrary, is markedly
toxic. From experiments made upon a great variety of animals
and plants he concluded that all living things are killed when the
oxygen pressure is sufficiently high, — say, 300 to 400 per cent.
Warm-blooded animals die with convulsions when submitted to
3 atmospheres of pure oxygen or 15 atmospheres of air. At these
high pressures the blood contains about 30 volumes of oxygen to
each 100 c.c. of blood instead of the usual 20 volumes. The ad-
ditional 10 volumes are contained in solution. Fish also are killed
when the oxygen pressure is increased to such a point that the water
contains 10 volumes of dissolved oxygen to each 100 c.c. In more
recent experiments by Smith, f made upon mice, it was found that
oxygen at pressures of 100 per cent, to 130 per cent, proves fatal
in a few days, the animals showing inflammatory changes in the
lungs. Oxygen at 180 per cent, kills mice and birds within twenty-
four hours. Pressures of two atmospheres of air (40 per cent. O)
have no injurious effect. No adequate chemical explanation can
be offered at present for this toxic action of oxygen at high tensions.
The matter is one of practical importance in connection with caisson
and submarine work and the therapeutical use of oxygen.

Decreased Percentages of Oxygen. — Numerous observers (Bert,
Zuntz, et al.) have shown that a fall in oxygen pressure has no
perceptibly injurious result until it reaches about 10 per cent. At
or somewhat below this pressure the hemoglobin is unable to take
up its full amount of oxygen, and the body consequently suffers
from a real deficiency in its oxygen supply, a condition designated
as anoxemia. According to Bert's experimental results, death with
convulsions quickly follows a fall of atmospheric pressure to 250
mms. (oxygen pressure, 50 mms. or 6 to 7 per cent.). Animals
supplied with an atmosphere containing a deficient amount of

* " La pression barometrique, " p. 764, Paris, 1878.
t "Journal of Physiology," 24, 19, 1899.

650 PHYSIOLOGY OF RESPIRATION.

oxygen show dyspneic respirations, which increase in violence and
finally become convulsive. The ordinary symptoms described for
death from asphyxia are due, therefore, to the anoxemia, — that is,
lack of oxygen, — not to the accumulation of CO2.

Increased Percentages of Carbon Dioxid. — It was pointed out
clearly by the researches of Friedlander and Herter* that death
from increased percentages of CO2 is accompanied by symptoms
quite different from those due to lack of oxygen. As the CO2 is
increased a noticeable hyperpnea may be observed (Zuntz) at a
concentration of about 3 per cent. When the concentration of CO2
reaches 8 per cent, to 10 or 15 per cent, there is distinct dyspnea;
but beyond this point further concentration, instead of augmenting
the respirations, decreases them, and the animal dies, at concen-
trations of 40 to 50 per cent., without convulsions, but with the
appearance, rather, of a fatal narcosis.

High and Low Barometric Pressures, Mountain Sickness,
Caisson Disease, etc. — High barometric pressures are used in
submarine work, diving, caisson work, etc. As stated above, it
follows from the work of Bert and Smith that when the pressure
reaches 5 to 6 atmospheres long continuance in it may be followed
by injurious or fatal results due to the toxic action of the oxygen.
If the pressure is increased to 15 atmospheres the toxic influence
of the oxygen brings on death with convulsions. Practically,
however, such pressures are not encountered in submarine work.
A caisson is a wooden or steel chamber arranged so that it may
be sunk under water. The water is driven out by air under pres-
sure. Since the pressure increases 1 atmosphere for each 10
meters (33 feet), it will be seen that very high pressures of air
are not usually required. Caisson workers are at times attacked
by serious or even fatal symptoms, not while in the compressed
air, but during or after the " decompression " that is necessary in
the return to normal conditions. The symptoms consist of pains
in the muscles and joints, paralysis, dyspnea, congestion. Those
who have investigated the subjectf state that the injurious results
are due to a too rapid decompression. When this occurs the gases
in the blood, particularly the nitrogen, are suddenly liberated as
bubbles, which block the capillaries and thus produce anemia in
different organs. If the decompression is effected gradually no evil
results follow.

The effect of low barometric pressures is chiefly of interest in
connection with residence in high altitudes, balloon ascensions,

* Friedlander and Herter, " Zeitschrift f. physiol. Chemie, " 2, 99, 1878,
and 3, 19, 1879.

t See Bert, loc. cit., p. 939; also Hill and MacLeod, "Journal of Physi-
ology," 29, 382, and "Journal of Hygiene," 3, 407.

INFLUENCE OF VARIOUS CONDITIONS ON RESPIRATION. 651

etc. At certain altitudes, from 3000 to 4000 meters, disagreeable
symptoms are experienced by ma-ny persons, especially after
muscular effort, which are designated usually under the term
mountain sickness. The individual so affected suffers from head-
ache, nausea, vertigo, great weakness, etc. Much investigation,
especially of recent years, has been devoted to this subject.* Paul
Bert concluded, from his numerous experiments, that a fall in baro-
metric pressure acts upon the organism only in so far as there is a
diminution of the partial pressure of the oxygen in the air respired.
This view has been generally accepted in physiology, and mountain
sickness and similar disturbances in balloon ascents have been
explained, therefore, as due mainly to the lack of oxygen, — that is,
to the condition of anoxemia. Mosso, on the contrary, has insisted
upon the part played by the carbon dioxid. He gives experi-
ments to show that there is a diminution in the carbon dioxid
contents of the blood (a condition of acapnia), and it is to this,
rather than to the anoxemia, that he would attribute the physio-
logical results of low barometric pressures. Other authors lay
stress upon the mechanical disturbances of the lung circulation,
while still others assume that certain vaguely understood cosmical
influences — such as the electrical condition of the air, its ioniza-
tion, or radiations of some kind — may affect the metabolisms of
the body and thus produce the symptoms in question. It would
seem that the whole matter is more complex than was at first
supposed. At a height of 4000 meters, at which mountain sick-
ness is apt to occur, the barometric pressure is 460 mms., so that
there is an oxygen pressure of 92 mms., — a pressure high enough,
one would suppose, not to endanger the oxygen supply. Mosso
states, also, from experiments upon monkeys, that lowering the
barometric pressure sufficiently (to about 250 mms.) causes un-
consciousness (sleep) even when the partial pressure of the oxygen
is kept normal. The historical incident of the death of Sivel and
Croce-Spinelli at an altitude of 8600 meters (barometric pressure,
262 mms.; oxygen pressure, 52.4 mms.) seems to indicate also that
something more than mere diminution in oxygen pressure is respon-
sible for the effects of extremely high altitudes.

The incidents connected with the ascent in the balloon Zenith of Sivel,
Croce-Spinelli, and Tissandier, April 15, 1875, are described in detail by the
last named in "La Nature," 1875, p. 337, also in Bert's "La pression baro-
metrique, " p. 1061. Only Tissandier survived. The balloonists were pro-
vided with bags containing oxygen (72 percent.), but they were unable to
make satisfactory use of them since shortly after passing 7500 meters they be-
came so weak that the effort to raise the arm to seize the oxygen tube was

* See ' Zuntz et al. Hohenklima u. Bergwanderungen in ihrer Wirk ng
auf d. Menschen, " Berlin, 1906. Mosso and Marro, ''Archives italiennes de
biologic," 39, 387, also vols. 40 and 41. Cohnheim, article on "Alpim'smus, "
"Ergebnisse der Physiologic," vol. ii., part 1, 1903.

652 PHYSIOLOGY OF RESPIRATION.

impossible. Tissandier's graphic description relates that at 8000 meters
it was impossible for him to speak, and that shortly afterward he became
entirely unconscious. None of the three seems to have shown any signs of
the violent dyspnea that precedes asphyxia caused by lack of oxygen. It
is noteworthy, however, that the heart beats were very rapid, and that they
experienced at first great depression of muscular strength without loss of
consciousness. The onset of complete unconsciousness was sudden, but was
preceded by feelings of sleepiness, which, however, were not associated
with any distress. These latter facts recall the conditions of " shock, " and
would suggest that probably the rapid heart beat was an indication of a great
fall in blood-pressure, which may have been directly responsible for the mus-
cular weakness and final unconsciousness and death.

The Respiratory Quotient and its Variations. — In studying
the gaseous exchanges of respiration one may determine the varia-
tions in the oxygen absorbed under different conditions or in the
carbon dioxid eliminated, or finally in the ratio of one to the other,
^, which is known as the respiratory quotient. In short-lasting
experiments the respiratory quotient is not a very reliable indicator
of the extent or character of the physiological oxidations in the body,
since any alteration in the depth or rapidity of the respiratory
movements may, by changing the ventilation of the alveoli, make
a difference in the output of CO2, — a difference, however, which
would have no significance in regard to the nutritive changes of the
body. In longer experiments and in those during which the respira-
tory movements are not altered the determination of this ratio
throws light upon the character of the oxidations that are taking
place, as will be apparent from the following considerations : Under
ordinary conditions of rest and upon a mixed diet the R. Q. varies
between 0.65 and 0.95 (Loewy) or between 0.75 and 0.89 (Magnus
Levy). If, however, the material oxidized in the body is entirely
carbohydrate the R. Q. should be equal to unity: ^2 = 1. All the
oxygen used in the combustion might be considered as uniting with
the C to form CO2, since enough O is present in the sugar to account
for that used in oxidizing the H to H20. Or, as expressed in a
reaction,

Dextrose.

C6H12O6 + 6O2 = 6C02 + 6H2O. R. Q. = £ = 1.

The number of molecules of C02 formed in the oxidation is equal
to the number of molecules of O2 used. If fats alone are oxidized
in the body the R. Q. should be low (0.7), since these substances
are poor in oxygen compared with the amount of C and H present
in the molecule. The combustion of palmitin may be represented
as follows:

Palmitin, C3H5(C16H31O2)3 = C^H^O..
2(C51H88Oa) + 145O2 = 102CO2 + 98H2O.

R. Q. = ill = o.7.

INFLUENCE OF VARIOUS CONDITIONS ON RESPIRATION. 653

In the same way it may be estimated that the R. Q. for the oxidation
of proteins alone is equal to 0.78.

In accordance with these conclusions it is found practically
that the respiratory quotient may be raised to 1, approximately at
least, by feeding exclusively upon carbohydrate foods, while an
excess of proteid or carbohydrate food lowers it to 0.7. In con-
nection with other data, therefore, the R. Q. may be used to
throw light upon the character of the nutrition. Under certain
special conditions the respiratory quotient may exceed unity or
fall distinctly below 0.7. A rise to a value over unity may occur
temporarily because of increased ventilation of the alveoli. Deeper
and more rapid breathing will drive out some of the CO2 in the air
of the lungs and thus increase greatly the R. Q. As previously
stated, this increase has in itself no nutritional significance, but it is

Fig. 260. — Record showing typical Cheyne-Stokes respiration (from a case of aortic and
mitral insufficiency with arteriosclerosis). The tune record gives seconds.

a factor that must be allowed for in such experiments. A more
suggestive increase of the R. Q. is observed during convalescence.
In this period, as is well known, an individual may increase in
weight rapidly, chiefly from the laying on of fat. This fat is made
in large part probably from the carbohydrate of the food. An
oxygen-rich food, therefore, is converted to an oxygen poor one,
so that some of the oxygen must be split off partly as carbon
dioxid, and there is a larger output of this substance in the expired
air. Under many conditions of life — muscular exercise, for example
— in which the oxidations of the body are greatly increased, the
larger production of CO2 is balanced by a larger absorption of O.
It is interesting to find that usually this balance is so well maintained
that the R. Q. does not vary sensibly.

Modified Respiratory Movements. — Laughing, coughing,
yawning, sneezing, sobbing, and even vomiting may be considered

654 PHYSIOLOGY OF RESPIRATION.

as modified respiratory movements, since the same group of muscles
come into play. These are all movements, with the exception of
yawning, which may be regarded as reflexes that have nothing to
do directly with the processes of respiration. A most interesting
variation of the normal type of respiration is known as the Cheyne-
Stokes respiration. It occurs in certain pathological conditions,
such as arteriosclerosis, uremic states, fatty degeneration of the
heart, and especially under conditions of increased intracranial
pressure. It is characterized by the fact that the respiratory
movements occur in groups (10 to 30) separated by apneic pauses,
which may last for a number (30 to 40) of seconds. After each pause
the respirations begin with a small movement, gradually increase
to a maximum, and then fall off gradually to the point of complete
cessation (see Fig. 260). Great variations, however, are shown in
the character and number of the respirations during the so-called
dyspneic phase. From observations made by means of the
sphygmomanometer Eyster* has shown that in this condition
there are also rhythmic waves of blood-pressure (Traube-Hering
waves), and according to the relation of these pressure waves to
the groups of respirations the Cheyne-Stokes cases fall into two
groups. In one group the dyspneic phase coincides with a fall
of blood-pressure and a slowing of the pulse-rate. In the other
group the reverse relations hold, the blood-pressure and pulse-rate
both rising during the dyspneic phase and falling during the apnea.
This latter group consists of cases in which there is evidence of
increased intracranial tension. Under experimental conditions
the author was able to show on dogs that an artificial increase in
intracranial tension calls forth Cheyne-Stokes respirations, whenever
it happens that rhythmic changes in blood-pressure are produced
of such a character that the blood-pressure rises and falls alternately
above and below the line of intracranial pressure. It is probable,
therefore, that in the clinical cases associated with a rise of intra-
cranial pressure the blood-pressure likewise rises and falls above
and below intracranial tension, and that the alternating periods
of apnea and dyspnea are due to this fact in this class of cases.
When the blood-pressure falls below intracranial pressure there
is a condition of deep anemia of the medulla sufficient to suspend
the activity of the respiratory center. The following rise of blood-
pressure by forcing more blood through the medulla calls forth a
group of respiratory movements. More or less rhythmical varia-
tions in the strength of the breathing movements have been de-
scribed also in normal sleep, hibernation, chloral narcosis, etc.,
but nothing so definite and characteristic as in these very interesting
Cheyne-Stokes cases.

* Eyster, "Journal of Experimental Medicine," 1906.

SECTION VII.
PHYSIOLOGY OF DIGESTION AND SECRETION.

CHAPTER XXXIX.
MOVEMENTS OF THE ALIMENTARY CANAL.

Mastication. — Mastication is an entirely voluntary act. The
articulation of the mandibles with the skull permits a variety of
movements; the jaw may be raised and lowered, may be projected
and retracted, or may be moved from side to side, or various com-
binations of these different directions of movement may be effected.
The muscles concerned in these movements and their innervation
are described as follows: The masseter, temporal, and internal
ptery goids raise the jaw; these muscles are innervated through the
inferior maxillary division of the trigeminal. The jaw is depressed
mainly by the action of the digastric muscle, assisted in some cases
by the mylohyoid and the geniohyoid. The two former receive
motor fibers from the inferior maxillary division of the fifth cranial,
the last from a branch of the hypoglossal. The lateral movements
of the jaws are produced by the external pterygoids, when acting
separately. Simultaneous contraction of these muscles on both
sides causes projection of the lower jaw. In this latter case forcible
retraction of the jaw is produced by the contraction of a part of the
temporal muscle. The external pterygoids also receive their motor
fibers from the fifth cranial nerve, through its inferior maxillary
division. The grinding movements commonly used in masticating
the food between the molar teeth are produced by a combination of
the action of the external pteryogids, the elevators, and perhaps
the depressors. At the same time the movements of the tongue
and of the muscles of the cheeks and lips serve to keep the food
properly placed for the action of the teeth, and to gather it into
position for the act of swallowing.

Deglutition. — The act of swallowing is a complicated reflex
movement which may be initiated voluntarily, but is, for the most
part, completed quite independently of the will. The classical
description of the act given by Magendie divides it into three stages,

655

656 PHYSIOLOGY OF DIGESTION AND SECRETION.

corresponding to the three anatomical regions — mouth, pharynx,
and esophagus — through which the swallowed morsel passes on its
way to the stomach. The first stage consists in the passage of the
bolus of food through the isthmus of the fauces, — that is, the
opening lying between the ridges formed by the palatoglossi muscles,
the so-called anterior pillars of the fauces. This part of the act is
usually ascribed to the movements of the tongue itself. The bolus
of food lying upon its upper surface is forced backward by the ele-
vation of the tongue against the soft palate from the tip toward
the base. This portion of the movement may be regarded as vol-
untary, to the extent at least of manipulating the food into its proper
position on the dorsum of the tongue, although it is open to doubt
whether the entire movement is usually effected by a voluntary
act. Under normal conditions the presence of moist food upon the
tongue seems essential to the complete execution of the act ; and an
attempt to make the movement with very dry material upon the
tongue is either not successful or is performed with difficulty. The
second act comprises the passage of the bolus from the isthmus of
the fauces to the esophagus, — that is, its transit through the pharynx.
The pharynx being a common passage for the air and the food, it is
important that this part of the act should be consummated quickly.
According to the older description, the motor power driving the
bolus downward through the pharynx is derived from the contrac-
tion of the pharyngeal muscles, particularly the constrictors, which
contract from above downward and drive the food into the esopha-
gus. Kronecker and Meltzer,* however, have shown that the con-
traction of the mylohyoid muscle in the floor of the mouth is the
most important factor in this act of shooting the food suddenly
through the pharynx into the esophagus. The contraction of this
muscle marks the beginning of the purely involuntary part of the
act of swallowing. The bolus of food lies upon the dorsum of the
tongue and by the pressure of the front of the tongue against the
hard palate it is shut off from the front part of the mouth cavity.
When the mylohyoids contract sharply the bolus is put under pres-
sure and is shot into and through the pharynx. This effect is aided
by the contraction of the hyoglossi muscles, which by moving the
tongue backward and downward tend to increase the pressure put
upon the food. Simultaneously, a number of other muscles are
brought into action, the general effect of which is to shut off the
nasal and laryngeal openings and thus prevent the entrance of

* Kronecker and Meltzer, " Archiv f . Physiologic, " 1883, suppl. volume,
p. 328; also "Journal of Experimental Medicine, " 2, 453, 1897. For later
, consult Cannon and Moser, "American Journal of Physiology," 1,

435, 1898; Schreiber, "Archiv f. exper. Pathol. u. Pharmakologie, " 46,
414, 1901; and Eykman, "Archiv f. die gesammte Physiologic," 99, 513,
1903.

MOVEMENTS OF THE ALIMENTARY CANAL. 657

food into the corresponding cavities. The whole reflex is there-
fore an excellent example of a finely co-ordinated movement.

The following events are described: The mouth cavity is shut
off by the position of the tongue against the palate and by the con-
traction of the muscles of the anterior pillars of the fauces. The
opening into the nasal cavity is closed by the elevation of the soft
palate (action of the leva tor ¥palati and tensor palati muscles) and
the contraction of the posterior pillars of the fauces (palatopharyn-
geal muscles) and the elevation of the uvula (azygos uvuke muscle).
The soft palate, uvula, and posterior pillars thus form a sloping
surface shutting off the nasal chamber and facilitating the passage of
the food backward through the pharynx. The respiratory opening
into the larynx is closed by the adduction of the vocal cords (lateral
crico-arytenoids and constrictors of the glottis) and by the strong
elevation of the entire larynx and a depression of the epiglottis over
the larynx (action of the thyrohyoids, digastrics, geniohyoids, and
mylohyoids and the muscles in the aryteno-epiglottidean folds).
If the elevation of the larynx be prevented by fixation of the thy-
roid the act of swallowing becomes impossible. There is also at
this time, apparently as a regular part of the swallowing reflex,
a slight inspiratory movement of the diaphragm, the so-called
swallowing respiration. The movements of the epiglottis during
this stage of swallowing have been much discussed. The usual
view is that it is pressed down upon the laryngeal orifice like the lid
of a box and thus effectually protects the respiratory passage. It
has been shown, however, that removal of the epiglottis does not
prevent normal swallowing, and Stuart and McCormick* have
reported the case of a man in whom part of the pharynx had been
permanently removed by surgical operation and in whom the
epiglottis could be seen during the act of swallowing. In this
individual, according to their observations, the epiglottis was not
folded back during swallowing, but remained erect. Kanthack and
Anderson f state that in normal individuals the movement of the
epiglottis backward during swallowing may be felt by simply passing
the finger back into the pharynx until it comes into contact with the
epiglottis. According to most observers, it is not necessary for
the protection of the larynx that the epiglottis shall be actually
folded down over it by the contraction of its own muscles. The
forcible lifting of the larynx, together with the descent of the base
of the tongue, effects the same result by mechanically crowding the
parts together, and the larynx is still further guarded by the ap-
proximation of the false and true vocal cords, thus closing the glottis.
The whole act is very rapid as well as complex, so that not more

* "Journal of Anatomy and Physiology," 1892.
t "Journal of Physiology," 14, 154, 1893.
42

658 PHYSIOLOGY OF DIGESTION AND SECRETION.

than a second elapses between the beginning of the contraction of
the mylohyoids and the entrance of the food into the upper end of
the esophagus.

The passage of the food through the esophagus differs apparently
with its consistency. When the food is liquid or very soft Kronecker
and Meltzer have shown that it is shot through the whole length of
the esophagus by the force of the initial act of swallowing. It
arrives at the lower end of the esophagus in about 0.1 sec., and may
pass immediately into the stomach or may lie some moments in the
esophagus according to the conditions of the sphincter guarding
the cardiac orifice. When, however, the food is solid or semi-
solid, as was shown by Cannon and Moser, it is forced down the
esophagus by a peristaltic movement of the musculature. The
circular muscles are constricted from above downward by an ad-
vancing muscular wave, while the longitudinal muscles contract
probably somewhat in advance of this wave so as to dilate the tube
and facilitate the passage of the bolus. The upper portion of the
esophagus contains cross-striated fibers indicating rapid contraction ;
the lower end consists of plain muscle only, while the intermediate
portion is a mixture of the two varieties. Kronecker and Meltzer
believe that each of these segments contracts as a whole and in
orderly succession, but other observers, on the evidence furnished
by Roentgen-ray photographs, agree that there is no perceptible
pause in the downward movement of the wave of contraction. These
same movements occur in the swallowing of liquid or soft food, but
in such cases the peristaltic wave follows the actual descent of the.
food. According to the observation of Kronecker and Meltzer, it
takes about 6 sec. for the peristaltic wave to reach the stomach,
and the passage of the food through the cardia takes place with
sufficient energy to give rise to a murmur that may be heard by
auscultating over this region. In the case of the more liquid food
that is shot at once to the lower end of the stomach within 0.1 sec.,
it may apparently pass at once into the stomach or it may lie in the
lower end of the esophagus until the wave of contraction reaches
it (6 sec.) and forces it through the opening. At this opening, the
cardia or cardiac orifice, the circular layer of muscles acts as a
sphincter which is normally in a condition of tone, particularly
when the stomach contains food. The advancing wave of con-
traction in the esophagus either forces the food through the resis-
tance offered by this sphincter or probably the sphincter suffers
an inhibition at this moment as a part of the general reflex action.
Kronecker and Meltzer have noted the interesting fact that if a
second swallow is made within an interval of six seconds after the
first, the peristaltic wave occasioned by the latter is inhibited at
whatever portion of its path it may have reached. The food carried

MOVEMENTS OF THE ALIMENTARY CANAL. 659

down by the first swallow waits in this case for the arrival of the suc-
ceeding wave before entering the stomach.

Nervous Control of Deglutition. — The entire act of swallowing,
as has been said, is essentially a reflex act. Even the comparatively
simple wave of contraction that sweeps over the esophagus is due
to a reflex nervous stimulation, and is not a simple conduction of
contraction from one portion- of the tube to another. This fact was
demonstrated by the experiments of Mosso,* who found that after
removal of an entire segment from the esophagus the peristaltic
wave passed in due time to the portion of the esophagus left on the
stomach side, in spite of the anatomical break. The same experi-
ment was performed successfully on rabbits by Kronecker and
Meltzer. Observation of the stomach end of the esophagus in this
animal showed that it went into contraction two seconds after the
beginning of a swallowing act whether the esophagus was intact or
ligated or completely divided by a transverse incision. The afferent
nerves concerned in this reflex are the sensory fibers to the mucous
membrane of the pharynx and esophagus, including branches of the
glossopharyngeal, trigeminal, vagus, and superior laryngeal division
of the vagus. Artificial stimulation of this last nerve in the lower
animals is known to produce swallowing movements. Several
observers have attempted to determine the precise area or areas
in the pharyngeal membrane from which the sensory impulses
liberating the reflex normally start. According to Kahn,f the
most effective areas from whose stimulation the reflex may be
produced vary in location in different animals. In the rabbit the
reflex is originated most easily by stimulation at the entrance to
the pharynx — the soft palate — along the line extending from the
posterior edge of the hard palate to the tonsils (superior maxil-
lary branch of trigeminal); in the dog irritation of the posterior
pharyngeal wall is most effective (glossopharyngeal nerve); in
monkeys the area is approximately as in rabbits, — that is, in the
region of the tonsils. The motor fibers concerned in the reflex
comprise the hypoglossal, the trigeminal, the glossopharyngeal,
the vagus, and the spinal accessory. For an act of such complexity
and such perfect co-ordination it has been assumed that there is a
special nerve center, the swallowing or deglutition center, which has
been located in the medulla at the level of the origin of the vagi.
There is little positive knowledge, however, concerning the existence
of this center as a definite group of intermediary nerve cells, after
the type of the vasoconstrictor or respiratory center, which send
their axons to the motor nuclei of the several efferent nerves con-
cerned. As in the case of other complicated reflex acts, we can only

* Moleschott's " Untersuchungen, " 1876, volume xi.

t Kahn, " Archiv f . Physiologie, " 1903, suppl. volume, 386.

660

PHYSIOLOGY OF DIGESTION AND SECRETION.

say that the deglutition reflex is controlled by a definite nervous
mechanism the final motor cells of which are scattered in the several
motor nuclei of the efferent nerves mentioned above.

The Anatomy of the Stomach. — The stomach in man belongs
to the simple type as distinguished from the compound stomachs
of some of the other mammalia, — the ruminating animals, for
example. Physiological and histological investigations have shown,
however, that the so-called simple stomachs are divided into parts
that have different properties and functions. The names and bound-
aries of these parts can not be stated precisely, since they vary in
different animals, and moreover there is at present an unfortunate
want of agreement among different authors regarding the nomen-
clature of the parts of the stomach.* For the purposes of a physio-
logical description we may use the names indicated in the accom-
panying schematic figure. The main interest lies in the separation

Duode

mutt.

,oms«

Pyloric JDartof <stomocJi

"PosiKojtof
trcuisuersekmd,

Intermediate or
brebylorie regioru,

Fig. 261.— Schematic figure to show the different parts of the stomach.— (After Retzius.)

of the pyloric part of the stomach or antrum pylorif from the main
cavity of the stomach. The line of separation is marked by a
fissure on the small curvature, incisura angularis (7. A.) and on the
large curvature by an abrupt change of direction. The pyloric part
makes an angle, therefore, with the body of the stomach and differs
from the latter in its musculature, the macroscopical and microscopi-
cal characteristics of its mucous membrane, and in its functional
importance. The main body of the stomach falls into two sub-
divisions, whose line of demarcation is, however, indefinite. The
fundus proper is the blind, rounded end of the stomach to the left
of the cardia and projecting toward the spleen. The intermediate
or prepyloric region shows in many animals a characteristic struc-

* See His, " Archiy f . Anatomic, " 1903, p. 345.

t Some recent writers confine this term antrum pylori to that portion
of the pyloric region bordering upon the pyloric orifice.

MOVEMENTS OF THE ALIMENTARY CANAL. 661

ture in its secreting glands. It is in this region that the hydro-
chloric acid of the gastric juice is mainly secreted.

The Musculature of the Stomach. — The musculature of the
stomach is usually divided into three layers, — a longitudinal, an
oblique, and a circular coat. The longitudinal coat is continuous
at the cardia with the longitudinal fibers of the esophagus ; it spreads
out from this point along the length of the stomach, forming a layer
of varying thickness; along the curvatures the layer is stronger
than on the front and posterior surfaces, while at the pyloric end it
increases considerably in thickness, and passes over the pylorus to
be continued directly into the longitudinal coat of the duodenum.
The layer of oblique fibers is quite incomplete; it seems to be
continuous with the circular fibers of the esophagus, and spreads
out from the cardia for a certain distance over the front and posterior
surfaces of the fundus of the stomach, but toward the pyloric end
disappears, seeming to pass into the circular fibers. The circular
coat, which is placed between the two preceding layers, is the thick-
est and most important part of the musculature of the stomach.
At the fundus the circular bands are thin and somewhat loosely
placed, but toward the pyloric end they increase much in thickness,
forming a strong, muscular mass, which, as we shall see, plays the
most important part in the movements of the stomach. At the
pylorus itself a special development of this layer functions as a
sphincter pylori, which with the aid of a circular fold of the mucous
membrane makes it possible to shut off the duodenum completely
from the cavity of the stomach. The line of separation between
the antrum pylori and the body of the stomach is made by a
special thickening of the circular fibers which forms a structure
known as the "transverse band" by the older writers,* and de-
scribed more recently! as the "sphincter antri pylorici."

The Movements of the Stomach. — The solid food remains in
the stomach for several hours, and during this time the musculature
contracts in such a way that the thinner portions as they are formed
by digestion are ejected from time to time through the pylorus into
the intestine. Except at the definite intervals when the pyloric
sphincter relaxes the food is entirely shut off from the rest of the
alimentary canal by the tonic closure of the sphincters at the cardia
and the pylorus. There is a certain orderliness in the movements
of the stomach, and especially in the separation and ejection of the
more liquid from the solid parts, which shows the existence of a
specially adapted mechanism. These movements have been studied
by many investigators, making use of various experimental meth-

* See Beaumont, " Physiology of Digestion, " second edition, 1847, p. 104.
f Hofmeister und Schiitz, " Archiv f. exper. Pathologic und Pharmakol-
ogie," 1886, vol. xx.

662 PHYSIOLOGY OF DIGESTION AND SECRETION.

ods. The first noteworthy contributions to this subject were
those made in this country7 by Beaumont in his famous observations
upon Alexis St. Martin, the Canadian voyageur, who had a per-
manent fistulous opening in his stomach as the result of a gunshot
wound.* In recent years the subject has been studied with great
success by means of the X-rays,f on the excised stomach, J and by
means of tambours or sounds introduced into the stomach to meas-
ure the pressure changes. § These researches all unite in em-
phasizing one fundamental point, — namely, that the fundic end
of the stomach is not actively concerned in these movements, but
serves rather as a reservoir for retaining the bulk of the food, while
the muscular pyloric region is the apparatus which triturates and
macerates the food and forces it out from time to time into the
duodenum. According to the observations made with the X-ray
apparatus, movements begin a few minutes after the entrance of
food into the stomach. Small contractions start in the middle
region of the stomach and run toward the pylorus. These moving
waves of contraction appear at regular intervals. The pyloric
portion becomes lengthened and it may be noticed that in this
region the peristaltic waves become more and more forcible as
digestion progresses. These running waves or rings of contraction
serve to press the stomach contents against the pylorus. According
to Cannon, they occur in the cat at intervals of 10 seconds and each
wave requires about 20 seconds to reach the pylorus. While in
human beings, to judge from the sounds which may be heard upon
ausculation when food mixed with air is given, they occur at intervals
of about 20 seconds. The obvious result of these movements is to
mix the food thoroughly, in the intermediate and pyloric portions
of the stomach, with the acid gastric juice and to reduce it to a thin,
liquid mass, — the chyme. At certain intervals the pyloric sphincter
relaxes and the contraction wave squeezes some of the fluid con-
tents into the .duodenum with considerable force. The mechanism
controlling the relaxation of this sphincter is obscure. It does not
occur with the approach of each contraction wave, but at irregular
intervals. Cannon connects it in part with the consistency of the
food, but mainly with the effect of the hydrochloric acid in the
gastric secretion. Solid objects forced against the pylorus prevent
relaxation and retard the passage of the chyme into the intestine.
When liquid food alone is taken into the stomach numerous ob-
servations, made by means of intestinal fistulas, prove that the

* See Osier, "Journal of the American Medical Association," Nov. 15,
1902, for life of Beaumont and account of his work.

t See Cannon, "American Journal of Physiology," 1, 359, 1898; and
Roux and Balthazard, "Archives de Physiologic," 10, 85, 1898.

J Hofmeister and Schiitz, loc. cit.

§ Moritz, " Zeitschrift f . Biologic, " 32, 359, 1895.

MOVEMENTS OF THE ALIMENTARY CANAL. 663

material may be forced into the duodenum within a few minutes.
Hydrochloric acid in the stomach seems to favor or produce a
relaxation of the pyloric sphincter, while in the duodenum, on the
contrary, it causes a contraction of the sphincter. In this way it
may be imagined that after each ejection of acid chyme the sphinc-
ter is kept closed until the acid material in the duodenum is neutral-
ized, and so, automatically, a mechanism is provided by means of
which the duodenum is charged at intervals and at such times as it
is prepared to receive and neutralize a new quantity of the chyme.
According to this description, the portion of the food toward the
pyloric end of the stomach is the first to be thoroughly mixed with
the gastric juice, and to be broken down partly by digestion and
partly by the mechanical action of the contractions. This portion,
as it is liquefied, is expelled, and its place is taken by new material
forced forward from the fundic end. It would seem that this latter
portion of the stomach is in a condition of tone, and the pressure
thus put upon the contents is sufficient to force them slowly toward
the pyloric end as this becomes emptied. The older view was that the
contents of the stomach are kept in a general rotary movement so as
to become more or less uniformly mixed; but Cannon's observations,
and also those of Grutzner,* indicate that the material at the
fundic end may remain undisturbed for a long time and thus
escape mixture with the acid gastric juice. This fact is of impor-
tance in connection with the salivary
digestion of the starchy foods.
Obviously salivary digestion may
proceed for a long time without
being affected by the acid of the
stomach. Grutzner fed rats with
food of different colors and found
that the successive portions were
arranged in definite strata. The
food first taken lay next to the
walls of the stomach, while the stomS of2^rS°gn
succeeding* portions were arranged show the stratification of food given

i i . i . . at different times. — (Grutzner.) The

regularly in the interior in a COn- food was given in three portions and

j. • £ i • -, . , colored differently : first, black ; sec-

CentriC fashion, as Shown in the ond, white (indicated by vertical

° d ""

figure. Such an arrangement of SSSSSj S&3? °

the food is more readily understood

when one recalls that the stomach has never any empty space
within; its cavity is only as large as its contents, so that the first
portion of food eaten entirely fills it and successive portions find
the wall layer occupied and are therefore received into the interior.
The ingestion of much liquid must interfere somewhat with this
* Grutzner, "Archiv f. die gesammte Physiologic," 106, 463, 1905.

664 PHYSIOLOGY OF DIGESTION AND SECRETION.

stratification. Whether the fact of this stratification has any
hygienic bearing with regard to the most desirable sequence in our
articles of diet is not yet apparent. Cannon* has reported some
interesting experiments upon the relative duration of gastric
digestion for carbohydrates, proteids, and fats when fed separately
and combined. The foods were mixed with subnitrate of bismuth
and their position in the stomach and passage into the intestine
were watched by means of the Roentgen rays. It was found that
carbohydrate food begins to pass out from the stomach soon after
ingestion, and requires only about one-half as much time as the pro-
teins for complete gastric digestion. Fats remain long in the
stomach when taken alone, and when combined with the other
foodstuffs markedly delay their exit through the pylorus. This
distinct difference in the main foodstuffs can hardly be referred to
mere mechanical consistency, since the fats are liquefied by the
heat of the body. Cannon has shown that this regulation is not
effected through the agency of the extrinsic nerves. After section of
the splanchnics and vagi the difference in time between the ejection
of carbohydrate and protein material still exists, so that the con-
trol in this matter must be exerted through some local mechanism
in the stomach itself. If, in a given diet, the carbohydrate is fed
before the protein, the former, having the position of advantage
toward the pyloric end, will be ejected promptly into the intestine,
while the protein is retained for gastric digestion. If the order is
reversed and the protein is fed first, the passage of the carbohydrate
out of the stomach will be retarded. This author has also reported
numerous interesting experiments, of medical and surgical interest,
which indicate that the motor activity of both stomach and intes-
tines may be greatly depressed by certain conditions, especially
by mechanical handling or by conditions of general asthenia.

Regarding the general mechanism of the stomach, it may be
pointed out that it forms an admirably adapted apparatus for
receiving at once, or within a short period, a large amount of food
which it reduces to a liquid or semiliquid condition, partly by
digestion, partly mechanically, and that it charges the intestine
at intervals with small amounts of this chyme in such a condition
as to admit of rapid digestion. It seems obvious that without the
stomach our mode of eating would have to be changed, as it would
not be possible to load the intestine rapidly with a large supply of
food such as is consumed at an ordinary meal.

The Relation of the Nerves to the Movements of the
Stomach. — The stomach receives nerve fibers from two sources, —
the vagi and the splanchnics, — but its orderly movements are merely

* Cannon, "American Journal of Physiology," 12, 387, 1904. For a
general review of Cannon's work, see "American Journal of the Medical
Sciences," April, 1906.

MOVEMENTS OF THE ALIMENTARY CANAL. 665

regulated through these extrinsic fibers; it is essentially an auto-
matic organ. Thus, it has been shown that the excised stomach
(Hofmeister and Schutz), when kept warm, continues to execute
regular movements which, if not identical with those observed under
normal conditions, have at least an orderly sequence. So also it
would appear from the results of several observers * that gastric
digestion may proceed normally both as regards secretion and
movements after section of the extrinsic nerves. We may regard
the stomach, considered as a motor mechanism, as an automatic
organ like the heart. Its stimuli to movement arise within itself,
but these movements are regulated by the action of the extrinsic
nerve fibers so as to adapt them to varying conditions. Whether
the automaticity is a property of the plain muscle tissue itself, or
depends upon the rich supply of intrinsic nerve ganglia (plexuses of
Meissner and Auerbach), is a question that cannot be answered
definitely at present. The extrinsic nerves not only supply the
stomach with efferent fibers, motor and secretory, but also carry
afferent fibers from the stomach to the central nervous system.
Regarding the purely efferent action of the extrinsic nerves, the
results of numerous experiments seem to show quite conclusively
that in general the fibers received along the vagus path are motor,
artificial stimulation of them causing more or less well-marked con-
tractions of part or all of the musculature of the stomach. It has
been shown that the sphincter pylori as well as the rest of the muscu-
lature is supplied by motor fibers from these nerves. The fibers
coming through the splanchnics, on the contrary, are mainly inhib-
itory. When stimulated they cause a dilatation of the contracted
stomach and a relaxation of the sphincter pylori. Some observers
have reported experiments which seem to show that this anatomical
separation of the motor and inhibitory fibers is not complete; that
some inhibitory fibers may be found in the vagi and some motor
fibers in the splanchnics. The anatomical courses of these fibers
are insufficiently known, but there seems to be no question as to the
existence of the two physiological varieties. Through their activity,
without doubt, the movements of the stomach may be influenced,
favorably or unfavorably, by conditions directly or indirectly affect-
ing the central nervous system. Wertheimer f has shown experi-
mentally that stimulation of the central end of the sciatic or the
vagus nerve may cause reflex inhibition of the tonus of the stomach,
and Doyon J has confirmed this result in cases in which the move-
ments and tonicity of the stomach were first increased by the action

* See Heidenhain in Hermann's "Handbuch der Physiologic, " vol. v.,
p. 118. Also Cannon, "American Journal of Physiology," 1906.

t " Archives de physiologic normale et pathologique," 1892. p. 379.
$ Ibid., 1895, p. 374.

666 PHYSIOLOGY OF DIGESTION AND SECRETION.

of pilocarpin and strychnin. Cannon, in his observations upon cats,
found that all movements of the stomach ceased as soon as the
animal showed signs of anxiety, rage, or distress.

Movements of the Intestines. — The muscles of the small and
the large intestine are arranged in two layers, — an outer longitudinal
and an inner circular coat, — while between these coats and in the
submucous coat there are present the nerve-plexuses of Auerbach
and Meissner. The general arrangement of muscles and nerves is
similar, therefore, to that prevailing in the stomach, and in accor-
dance with this we find that the physiological activities exhibited
are of much the same character, only, perhaps, not quite so complex.

Two main forms of intestinal movement have been distinguished,
— the peristaltic and the pendular or rhythmic.

Peristalsis. — The peristaltic movement consists in a constriction
of the walls of the intestine, which, beginning at a certain point,
passes downward away from the stomach, from segment to segment,
while the parts behind the advancing zone of constriction gradually
relax. The evident effect of such a movement is to push onward the
contents of the intestines in the direction of the movement. It is
obvious that the circular layer of muscles is chiefly involved in
peristalsis, since constriction can only be produced by contraction
of this layer. To what extent the longitudinal muscles enter into
the movement is not definitely determined. The term " anti-
peristalsis" is used to describe the same form of movement running
in the opposite direction — that is, toward the stomach. Anti-
peristalsis is said not to occur under normal conditions; it has been
observed in isolated pieces of intestine or in the exposed intestine
of living animals when stimulated artificially or after complete
intestinal obstructio n (Cannon) , and Grutzner * reports a number of
curious experiments which seem to show that substances such as
hairs, animal charcoal, etc., introduced into the rectum may travel
upward to the stomach under certain conditions. The peristaltic
wave normally passes downward, and that this direction of move-
ment is dependent upon some definite arrangement in the intestinal
walls is shown by the experiments of Mali f upon reversal of the
intestines. In these experiments a portion of the small intestine
was resected, turned around, and sutured in place again, so that in
this piece what was the lower end became the upper end. In those
animals that made a good recovery the nutritive condition gradually
became very serious, and when the animals were killed and ex-
amined it was found that there was an accumulation of food at the
stomach end of the reversed piece of intestine, and that this region
showed marked dilatation.

*" Deutsche medicinische Wochenschrift," No. 48, 1894.
t" Johns Hopkins Hospital Reports," 1, 93, 1896.

MOVEMENTS OF THE ALIMENTARY CANAL. 667

The peristaltic movements of the intestines may be observed
upon living animals when the abdomen is opened. If the operation
is made in the air and the intestines are exposed to its influence, or
if the conditions of temperature and circulation are otherwise
disturbed, the movements observed are often violent and irregular.
The peristalsis runs rapidly along the intestines and may pass over
the whole length in about a minute; at the same time the con-
traction of the longitudinal muscles gives the bowels a peculiar
writhing movement. Movements of this kind are evidently
abnormal, and only occur in the body under the strong stimulation
of pathological conditions. Normal peristalsis, the object of which
is to move the food slowly along the alimentary tract, is quite a
different- affair. Observers all agree that the wave of contraction
is gentle and progresses slowly, although at different rates perhaps
in different parts of the intestine. According to Bayliss and Star-
ling,* the peristaltic movement is a complicated reflex through the
intrinsic ganglia. When the intestine is stimulated by a bolus
placed within its cavity, the musculature above the point stimulated
is excited, while that below is inhibited. In accordance with this
law they find that in peristalsis the advancing wave of constriction
is preceded by a wave of relaxation or inhibition. The force of the
contraction as measured by Cash f in the dog's intestine is very small.
A weight of five to eight grams was sufficient to check the onward
movement of the substance in the intestine and to set up violent,
colicky contractions which caused the animal evident uneasiness.

Mechanism of the Peristaltic Movement. — The means by which
the peristaltic movement makes its orderly forward progression
have not been determined beyond question. The simplest explana-
tion would be to assume that an impulse is conveyed directly from
cell to cell in the circular muscular coat, so that a contraction started
at any point would spread by direct conduction of the contraction
change. This theory, however, does not explain satisfactorily the
normal conduction of the wave of contraction always in one direc-
tion, nor the fact that the wave of contraction is preceded by a
wave of inhibition. Moreover, Bayliss and Starling state that,
although the peristaltic movements continue after section of the
extrinsic nerves, — indeed, become more marked under these con-
ditions,— the application of cocain or nicotin prevents their oc-
currence. Since these substances may be supposed to act on the
intrinsic nerves, it is probable that the co-ordination of the move-
ment is effected through the local nerve ganglia, but our knowledge
of the mechanism and physiology of these peripheral nerve-plexuses
is as yet quite incomplete.

*" Journal of Physiology," 24, 99, 1899.

t " Proceedings of the Royal Society," London, 41, 1887.

668 PHYSIOLOGY OF DIGESTION AND SECRETION.

Rhythmical Movements. — In addition to the peristaltic wave a
second kind of movement may be observed in the small intestines.
It consists essentially in a series of local constrictions of the intes-
tinal wall, the constrictions occurring rhythmically at those points
at which masses of food lie.

Cannon * has studied these movements most successfully by
means of the Roentgen rays. He finds that as a result of these
contractions the masses or strings of food lying in the intestine are
suddenly segmented, repeatedly and in a definite manner, into a
number of small pieces, which move to and fro as the pieces combine
and are again separated (see Fig. 263). These segmentations may
proceed at the rate of thirty per minute for a certain time, and the
apparent result is that the material is well mixed with the digestive
secretions and is brought thoroughly into contact with the absorp-
tive walls. During these rhythmical contractions there is no steady
progression of the food; it remains in the same region, although
subjected to repeated divisions. From time to time the separated

^>

Fig. 263. — Diagram to show the effect of the rhythmical constricting movements of
the small intestine upon the contained food. A string of food (1) is divided suddenly into
a series of segments (2) ; each of the latter is again divided and the process is repeated a
number of times (3 and 4). Eventually a peristaltic wave sweeps these segments forward
a certain distance and gathers them again into a long string, as in (1). The process of
segmentation is then repeated as described above. (Cannon.)

pieces are caught by an advancing peristaltic wave, moved
forward a certain distance, and gathered again into a new mass.
In this new location the rhythmical contractions again segment
and churn the mass before a new peristaltic wave moves it on.
According to this description, the rhythmical movements are
local contractions (mainly of the circular muscles) which seem
to be due to the local distension caused by the food. They occur
rhythmically for a certain period and then cease until a new series
is started, and it is obvious that they must play a very important
part in promoting both the digestion and absorption of the food.
Mall t has suggested that these rhythmical contractions of the
circular coats may also act as a pumping mechanism upon the
venous plexuses in the walls and thus aid in driving the blood into

* Cannon, "American Journal of Physiology," 6, 251, 1902.
t Mall, "Johns Hopkins Hospital Reports," 1896, i., 37.

MOVEMENTS OF THE ALIMENTARY CANAL. 669

the portal system. Somewhat similar movements have been
described by Bunch,* from observations on the isolated intestine.
The curious observation is reported f that during the period of
fasting (dog) the whole gastro-intestinal canal, although empty,
shows at intervals rhythmical contractions of its musculature
which may last for twenty to thirty minutes (see p. 724).

The Nervous Control of the Intestinal Movements. — There
is some evidence to show that the rhythmical contractions of the
intestines are muscular in origin (myogenic), while the more co-
ordinated peristaltic movements depend upon the intrinsic nervous
mechanism. The intestine is, however, not dependent for either
movement upon its connections with the central nervous system.
Like the stomach, it is an automatic organ whose activity is simply
regulated through its extrinsic nerves.

The small intestine and the greater part of the large intestine
receive visceromotor nerve fibers from the vagi and the sympathetic
chain. The former, according to most observers, when artifically
stimulated cause movements of the intestine, and are therefore
regarded as the motor fibers. It seems probable, however, that the
vagi carry or may carry in some animals inhibitory fibers as well,
and that the motor effects usually obtained upon stimulation are
due to the fact that in these nerves the motor fibers predominate.
The fibers received from the sympathetic chain, on the other hand,
give mainly an inhibitory effect when stimulated, although some
motor fibers apparently may take this path. Bechterew and
Mislawski { state that the sympathetic fibers for the small intestine
emerge from the spinal cord as medullated fibers in the sixth dorsal
to the first lumbar spinal nerves, (or lower — Bunch) and pass to the
sympathetic chain in the splanchnic nerves and thence to the
semilunar plexus. The paths of these fibers through the central
nervous system are not known, but there are evidently connections
extending to the higher brain centers, since psychical states are
known to influence the movements of the intestine, and according
to some observers stimulation of portions of the cerebral cortex
may produce movements or relaxation of the walls of the small and
large intestines.

Effect of Various Conditions upon the Intestinal Move-
ments.— Experiments have shown that the movements of the in-
testines may be evoked in many ways in addition to direct stimu-
lation of the extrinsic nerves. Chemical stimuli may be applied
directly to the intestinal wall. Mechanical stimulation — pinching,
for example, or the introduction of a bolus into the intestinal
cavity — may start peristaltic movements. Violent movements

* Bunch, "Journal of Physiology," 22, 357, 1897.
fBoldireff, " Archives des sciences biologiques, " 11, 1, 1905.
j"Archiv f. Physiologic, " 1889, suppl. volume.

670 PHYSIOLOGY OF DIGESTION AND SECRETION.

may be produced also by shutting off the blood-supply, and again
temporarily when the supply is re-established. A condition of
dyspnea may also start movements in the intestines or in some
cases inhibit movements which are already in progress, the stimu-
lus in this case seeming to act upon the central nervous system and
to stimulate both the motor and the inhibitory fibers. Oxygen gas
within the bowels tends to suspend the movements of the intes-
tine, while CO2, CH4, and H2S act as stimuli, increasing the move-
ments. Organic acids, such as acetic, propionic, formic, and
caprylic, which may be formed normally within the intestine as
the result of bacterial action, act also as strong stimulants.

Movements of the Large Intestine. — The musculature in the
large intestine has the same general arrangement as in the small,
and the usual view has been that the movements are similar,
although more infrequent, so that the material received from the
small intestine is slowly moved along while becoming more and
more solid from the absorption of water, until in the form of feces
it reaches the sigmoid flexure and rectum. Bayliss and Starling
state that their law of intestinal peristalsis holds in this portion of
the intestine, — that is, local excitation causes a constriction above
and a dilatation below the point stimulated. Cannon,* however,
from his studies of the normal movements in cats, as seen by the
Roentgen rays, comes to the conclusion that the movements in the
large intestine show a marked peculiarity previously overlooked.
He divides the large intestine into two parts; in the second, cor-
responding roughly to the descending colon the food is moved
toward the rectum by peristaltic waves. A number of constrictions
may be seen simultaneously within a length of some inches. In
the ascending and transverse colon and cecum, on the contrary, the
most frequent movement is that of antiperistalsis. The food in this
portion of the canal is more or less liquid and its presence sets up
running waves of constriction, which, beginning somewhere in the
colon, pass toward the ileocecal valve. These waves occur in groups
separated by periods of rest. The presence of the ileocecal valve
prevents the material from being forced back into the small in-
testine. The value of this peculiar reversal of the normal move-
ment of the bowels at this particular point would seem to lie in the
fact that it delays the passage of the material toward the rectum
and by thoroughly mixing it gives increased opportunities for the
completion of the processes of digestion and absorption. As the
colon becomes rilled some of the material penetrates into the
descending part where the normal peristalsis carries it toward the
rectum.

The large intestine — particularly the descending colon and
rectum — receives its nerve supply from two sources: (1) Fibers

* Cannon, loc. cit.

MOVEMENTS OF THE ALIMENTARY CANAL. 671

which leave the spinal cord in the lumbar nerves (second to fifth
in cat), pass to the sympathetic chain, and thence to the inferior
mesenteric ganglia, which probably forms the termination of the
preganglionic fiber. From this point the path is continued by fibers
running in the hypogastric nerves and plexus. Stimulation of these
fibers has given different results in the hands of various observers,
but the most recent work* indicates that they are inhibitory. (2)
Fibers that leave the cord in the sacral nerves (second to fourth)
form part of the nervi erigentes and enter into the pelvic plexus.
When stimulated these fibers cause contractions of the muscular
coats; they may be regarded, therefore, as motor fibers. As in the
case of the small intestine and stomach, we may assume that these
motor and inhibitory fibers serve for the reflex regulation and
adaptation of the movements.

Defecation. — The undigested and indigestible parts of the food,
together with some of the debris and secretions from the alimentary
tract eventually reach the sigmoid flexure and rectum. Here the
nearly solid material stimulates by its pressure the sensory nerves of
the rectum and produces a distinct sensation and desire to defecate.
The fecal material is retained within the rectum by the action of
the two sphincter muscles which close the anal opening. One of
these muscles, the internal sphincter, is a strong band of the circular
layer of involuntary muscle which forms one of the coats of the
rectum. When the rectum contains fecal material this muscle
seems to be thrown into a condition of tonic contraction until
the act of defecation begins, when it is relaxed. The sphincter is
composed of involuntary muscle and is innervated by fibers having
the general course given above for the nerves of the large intestine.
The external sphincter ani is composed of striated muscle tissue and
is under the control of the will to a certain extent. When, however,
the stimulus from the rectum is sufficiently intense, voluntary
control is overcome and this sphincter is also relaxed. The act of
defecation is in part voluntary and in part involuntary. The
involuntary factor is found in the contractions of the strongly
developed musculature of the rectum, especially the circular layer
which serves to force the feces onward, and the relaxation of the
internal sphincter. It would seem that these two acts are mainly
caused by reflex stimulation from the lumbar spinal cord, although
it is probable that the rectum, like the rest of the alimentary tract,
is capable of automatic contractions. The rectal muscles receive a
double nervous supply, containing physiologically both motor and
inhibitory fibers. The former come probably from the nervus
erigens by way of the pelvic plexus; the latter from the lumbar cord

*Langley and Anderson, "Journal of Physiology," 18, 67, 1895. Bay-
liss and Starling, ibid., 26, 107, 1900. Also Wischnewsky, in Hermann's
" Jahresbericht der Physiologie/ ' vol. xii., 1905.

672 PHYSIOLOGY OF DIGESTION AND SECRETION.

through the corresponding sympathetic ganglia, inferior mesenteric
ganglion, and hypogastric nerve. It has been asserted that stimu-
lation of the nervus erigens causes contraction of the longitudinal
muscles and inhibition of the circular muscles, while stimulation of
the hypogastric nerve causes contraction of the circular muscles
and inhibition of the longitudinal layer. This division of activity
has not been confirmed by recent experiments.

The voluntary factor in defecation consists in the inhibition of
the external sphincter and the contraction of the abdominal muscles.
When these latter muscles are contracted and at the same time the
diaphragm is prevented from moving upward by the closure of the
glottis, the increased abdominal pressure is brought to bear upon the
abdominal and pelvic viscera, and aids strongly in pressing the
contents of the descending colon and sigmoid flexure into the rectum.
The pressure in the abdominal cavity is still further increased if
a deep inspiration is first made and then maintained during the
contraction of the abdominal muscles. Although the act of defeca-
tion is normally initiated by voluntary effort, it may also be aroused
by a purely involuntary reflex when the sensory stimulus is suf-
ficiently strong. Goltz* has shown that in dogs in which the spinal
cord had been severed in the lower thoracic region defecation was
performed normally. In later experiments, in which the entire
spinal cord was removed, except in the cervical and upper part of
the thoracic region, it was found that the animal, after it had re-
covered from the operation, had normal movement once or twice a
day, indicating that the rectum and lower bowels acted by virtue of
their intrinsic mechanism. An interesting result of these experi-
ments was the fact that the external sphincter suffered no atrophy,
although its motor nerve was destroyed, and that it eventually
regained its tonic activity.

It would seem that the whole act of defecation is, at bottom, an
involuntary reflex. The physiological center for the movement
probably lies in the lumbar cord, and has sensory and motor con-
nections with the rectum and the muscles of defecation; but this
center is probably provided with connections with the centers of
the cerebrum, through which the act may be controlled by volun-
tary impulses and by various psychical states, the effect of emo-
tions upon defecation being a matter of common knowledge. In
infants the essentially involuntary character of the act is well
known.

Vomiting. — The act of vomiting causes an ejection of the con-
tents of the stomach through the esophagus and mouth to the
exterior. It was long debated whether the force producing this
ejection comes from a strong contraction of the walls of the stomach
*"Archiv f. die gesammte Physiologic," 8, 160, 1874; 63, 362, 1896.

MOVEMENTS OF THE ALIMENTARY CANAL. 673

itself or whether it is due mainly to the action of the walls of the
abdomen. A forcible spasmodic contraction of the abdominal
muscles takes place, as may easily be observed by any one upon
himself, and it is now believed that the contraction of these muscles
is the principal factor in vomiting. Magendie found that if the
stomach was extirpated and a bladder containing water was sub-
stituted in its place and connected with the esophagus, injection
of an emetic caused a typical vomiting movement with ejection of
the contents of the bladder. Gianuzzi showed, on the other hand,
that upon a curarized animal vomiting could not be produced by an
emetic — because, apparently, the muscles of the abdomen were
paralyzed by the curare. There are on record a number of ob-
servations which tend to show that the stomach is not passive
during the act. On the contrary, it may exhibit contractions, more
or less violent in character. According to Openchowski,* the
pylorus is closed and the pyloric end of the stomach firmly con-
tracted so as to drive the contents toward the dilated cardiac por-
tion. Cannon states that in cats the normal peristaltic waves pass
over the pyloric portion in the period preceding the vomiting and
that finally a strong contraction at the "transverse band" com-
pletely shuts off the pyloric portion from the body of the stomach,
which at this time is quite relaxed. The act of vomiting is, in fact,
a complex reflex movement into which many muscles enter. The
following events are described : The vomiting is usually preceded by
a sensation of nausea and a reflex flow of saliva into the mouth.
These phenomena are succeeded or accompanied by retching move^
ments, which consist essentially in deep, spasmodic inspirations with
a closed glottis. The effect of these movements is to compress the
stomach by the descent of the diaphragm, and at the same time to
increase decidedly the negative pressure in the thorax, and therefore
in the thoracic portion of the esophagus. During one of these
retching movements the act of vomiting is effected by a convulsive
contraction of the abdominal wall that exerts a sudden additional
strong pressure upon the stomach. At the same time the cardiac
orifice of the stomach is dilated, possibly by an inhibition of the
sphincter, and according to the above description the fundic end
of the stomach is also dilated, while the pyloric end is in strong
contraction. The stomach contents are therefore forced violently
out of the stomach through the esophagus, the negative pressure in
the latter probably assisting in the act. The passage through the
esophagus is effected mainly by the force of the contraction of the
abdominal muscles; there is no evidence of antiperistaltic move-
ments on the part of the esophagus itself. During the ejection of
the contents of the stomach the glottis is kept closed by the adductor

* " Archiv f . Physiologie, " 1889, p. 552.
43

674 PHYSIOLOGY OF DIGESTION AND SECRETION.

muscles, and usually the nasal chamber is likewise shut off from the
pharynx by the contraction of the posterior pillars of the fauces on
the palate and uvula. In violent vomiting, however, the vomited
material may break through this latter barrier and be ejected
partially through the nose.

Nervous Mechanism of Vomiting. — That vomiting is a reflex act
is abundantly shown by the frequency with which it is produced in
consequence of the stimulation of sensory nerves or as the result
of injuries to various parts of the central nervous system. After
lesions or injuries of the brain vomiting often results. Disagreeable
emotions and disturbances of the sense of equilibrium may produce
the same result. Irritation of the mucous membrane of various
parts of the alimentary canal (as, for example, tickling the back
of the pharynx with the finger); disturbances of the urogenital
apparatus, the liver, and other visceral organs; artificial stimula-
tion of the trunk of the vagus and of other sensory nerves, may all
cause vomiting. Under ordinary conditions, however, irritation of
the sensory nerves of the gastric mucous membrane is the most
common cause of vomiting. This effect may result from the prod-
ucts of fermentation in the stomach in cases of indigestion, or may
be produced intentionally by local emetics, such as mustard, taken
into the stomach. The afferent path in this case is through the
sensory fibers of the vagus. The efferent paths of the reflex are
found in the motor nerves innervating the muscles concerned in the
vomiting, — namely, the vagus, the phrenics, and the spinal nerves
supplying the abdominal muscles. Whether or not there is a defi-
nite vomiting center in which the afferent impulses are received
and through which a co-ordinated series of efferent impulses is
sent out to the various muscles has not been satisfactorily deter-
mined. It has been shown that the portion of the nervous system
through which the reflex is effected lies in the medulla, and it may
be observed that the muscles concerned in the act, outside those
of the stomach, are respiratory muscles. Vomiting, in fact, consists
essentially in a simultaneous spasmodic contraction of expiratory
(abdominal) muscles and inspiratory muscles (diaphragm). It has
therefore been suggested that the reflex involves the stimulation of
the respiratory center or some part of it. Thumas claims to have
located a vomiting center in the medulla in the immediate neighbor-
hood of the calamus scriptorius. Further evidence, however, is
required upon this point. The act of vomiting may be produced
not only as a reflex from various sensory nerves, but may also be
caused by direct action upon the medullary centers. The action
of apomorphin is most easily explained by supposing that it acts
directly on the nerve centers.

CHAPTER XL.

GENERAL CONSIDERATIONS UPON THE COMPOSITION
OF THE FOOD AND THE ACTION OF ENZYMES.

Foods and Foodstuffs. — The term food when used in a popular
sense includes everything that we eat for the purpose of nourishing
the body. From this point of view the food of mankind is of a most
varied character, comprising a great variety of products of the
animal and vegetable kingdoms. Chemical analysis of the animal
and vegetable foods shows, however, that they all contain one or
more of five or six different classes of substances which are usually
designated as the foodstuffs (older names, alimentary or proximate
principles) on the belief that they form the useful constituent of our
foods. The classification of foodstuffs usually given is as follows:

Foodstuffs

Water.

Inorganic salts.
Proteins.

Albuminoids, a group of bodies resembling proteins, but hav-
ing in some respects a different nutritive value.
Carbohydrates.
Fats.

From the scientific point of view, a foodstuff or food may be defined
as a substance absolutely necessary to the normal composition of
the body, as in the case of water and salts, or as a substance which
can be acted upon by the tissues of the body in such a way as to
yield energy (heat, for example) or to furnish material for the pro-
duction of living tissue. Moreover, to be a food in the physiological
sense the substance must not directly or indirectly affect injuriously
the normal nutritive processes of the tissues. The five or six
substances named above are all foods in this sense. The water and
certain salts of sodium, potassium, calcium, magnesium, iron, and
perhaps other elements are absolutely necessary to maintain the
normal composition of the tissue. Complete withdrawal of any
one of these constituents would cause the death of the organism.
Proteins, fats, and carbohydrates, on the other hand, are substances
whose molecules have a more or less complex structure. When
eaten and digested they enter the body liquids and are employed
either in the synthesis of the more complex living matter, or they
undergo various chemical changes, spoken of in general as metab-
olism, which result finally in the breaking up of their complex

675

676

PHYSIOLOGY OF DIGESTION AND SECRETION.

molecules into simpler compounds. The chemical changes of metab-
olism or nutrition are, in the long run, mainly exothermic, — that
is, they are attended by the production of heat. Some of the chem-
ical or internal energy that held the complex molecules together
assumes the form of heat, or perhaps muscular work, after these
molecules are broken down by oxidative changes to simpler, more
stable structures, such as water, carbon dioxid, and urea. Proteins,
fats, and carbohydrates form materials that the tissue cells are
adjusted to act upon after they have undergone certain changes
during digestion. Other complex organic compounds containing
chemical energy are either injurious to the tissues, or they have a
structure such that the tissues cannot act upon them. Such
substances cannot be considered as foods in the scientific sense.
When, therefore, we desire to know the food value of any animal
or vegetable product, we analyze it to determine its composition as
regards water, salts, proteins, fats, and carbohydrates. The
following table compiled by Munk from the analyses given by
Konig * may be taken as an indication of the average composition
of the most commonly used foods:

COMPOSITION OF FOODS.

.IN 100 PARTS.

WATER.

PROTEIN.

FAT.

CARBOHYDRATE.

ASH.

DIGESTIBLE.

CELLULOSE.

Meat

76.7
73.7
36-60
87.7
89.7
13.3
35.6
13.7
42.3
13.1
13.1
10.1
12-15
75.5
87.1
90
73-91
84

20.8
12.6
25-33
3.4
2.0
10.2
7.1
11.5
6.1
7.0
9.9
9.0
23-26
2.0
1.0
2-3
4-8
0.5

1.5
12.1
7-30
3.2
3.1
0.9
0.2
2.1
0.4
0.9
4.6
0.3

l*-2
0.2
0.2
0.5
0.5

0.3

3^-7

4.8
5.0
74.8
55.5
69.7
49.2
77.4
68.4
79.0
49-54
20.6
9.3
4-6
3-12
10

0.3
0.3
1.6
0.5
0.6
2.5
0.3
4-7
0.7
1.4
1-2
1-5
4

1.3
1.1
3-4
0.7
0.2
0.5
1.1
1.4
1.5
1.0
1.5
0.5
2-3
1.0
0.9
1.3
1.2
0.5

Eecs

Cheese
Cows' milk ....

Human milk
Wheat flour
Wheat bread
Rye flour

Rye bread

Rice

Corn

Macaroni

Peas, beans, lentils
Potatoes

Carrots . . .

Cabbages

Mushrooms

Fruit .

An examination of this table shows that the animal foods, par-
ticularly the meats, are characterized by their small percentage in
carbohydrate and by a relatively large amount of protein or of
protein and fat. With regard to the last two foodstuffs, meats differ

*See Konig, " Die menschlichen Nahrungs und Genussmittel"; and
Atwater and Bryant, "The Chemical Composition of American Food Mate-
rials," Bulletin 28, United States Department of Agriculture, 1899.

COMPOSITION OF FOOD AND ACTION OF ENZYMES.

677

very much among themselves. Some idea of the limits of variation
may be obtained from the following table, taken chiefly from
Konig's analyses:

WATER.

PROTEIN.

FAT.

CARBOHYDRATE.

ASH.

Beef, moderately fat ....
Veal fat

73.03
72.31

20.96

18.88

5.41
7.41

046
007

1.14
1.33

Mutton, moderately fat. .
Pork, lean

75.99
72.57

17.11
20.05

5.77
6.81

1.33
1.10

Ham salted

6258

2232

868

642

Pork (bacon), very fat* .
Mackerel*

10.00
71 6

3.00

18 8

80.50
8 2

6.5
1.4

The vegetable foods are distinguished, as a rule, by their large
percentage in carbohydrates and the relatively small amounts of
proteins and fats, as seen, for example, in the composition of rice,
corn, wheat, and potatoes. Nevertheless, it will be noticed that the
proportion of protein in some of the vegetables is not at all insignifi-
cant. They are characterized by their excess in carbohydrates
rather than by a deficiency in proteins. The composition of peas
and other leguminous foods is remarkable for the large percentage
of protein, which exceeds that found in meats. Analyses such as
are given here are indispensable in determining the true nutritive
value of foods. Nevertheless, it must be borne in mind that the
chemical composition of a food is not alone sufficient to determine
its precise value in nutrition. It is obviously true that it is not what
we eat, but what we digest and absorb, that is nutritious to the
body; so that, in addition to determining the proportion of food-
stuffs in any given food, it is necessary to determine to what extent
the several constituents are digested. This factor can be obtained
only by actual experiments. It may be said here, however, that
in general the proteins of animal foods are more completely digested
than are those of vegetables, and with them, therefore, chemical
analysis comes nearer to expressing directly the nutritive value.

Accessory Articles of Diet. — In addition to the foodstuffs
proper our foods contain numerous other substances which in one
way or another are useful in nutrition, although not absolutely
necessary. These substances, differing in nature and importance,
may be classified under the three heads of :

Flavors : the various oils or esters that give odor and taste to foods.
Condiments: pepper, salt, mustard, etc.
Stimulants : alcohol, tea, coffee, cocoa, etc.

The specific influence of these substances in digestion and nutrition
is considered in the section on nutrition.

* Atwater: "The Chemistry of Foods and Nutrition," 1887.

678 PHYSIOLOGY OF DIGESTION AND SECRETION.

The Chemical Changes of the Foodstuffs during Digestion.

— The physiology of digestion consists chiefly in the study of the
chemical changes that the food undergoes during its passage through
the alimentary canal. It happens that these chemical changes are
of a peculiar character. The peculiarity is due to the fact that the
changes of digestion are effected through the agency of a group of
bodies known as enzymes, or unorganized ferments, whose chemical
action is more obscure than that of the ordinary reagents with which
we have to deal. It will save repetition to give here certain general
facts that are known with reference to these bodies, reserving for
later treatment the details of the action of the specific enzymes
found in the different digestive secretions.

ENZYMES AND THEIR ACTION.

Historical. — The term fermentation and the idea that it is
meant to convey has varied greatly during the course of years. The
word at first was applied to certain obvious and apparently spon-
taneous changes in organic materials which are accompanied by the
liberation of bubbles of gas: such, for instance, as the alcoholic
fermentations, in which alcohol is formed from sugar; the acid fer-
mentations, as in the souring of milk; and the putrefactive fer-
mentations, by means of which animal substances are disintegrated,
with the production of offensive odors. These mysterious phenom-
ena excited naturally the interest of investigators, and with the
development of chemical knowledge numerous other processes were
discovered which resemble the typical fermentations in that they
seem to be due to specific agents whose mode of action differs from
the usual chemical reactions, especially in the fact that the causa-
tive agent itself, or the ferment as it is called, is not destroyed or
used up in the reaction. Thus it was discovered that germinating
barley grains contain a something which can be extracted by water
and which can convert starch into sugar (Kirchhoff, 1814). Later
this substance was separated by precipitation with alcohol and was
given the name of diastase (Pay en and Persoz, 1833). Schwann
in 1836 demonstrated the existence of a ferment (pepsin) in gastric
juice capable of acting upon albuminous substances, and a number
of similar bodies were soon discovered: trypsin in the pancreatic
juice, amygdalin, invertin, ptyalin, etc. These substances were all
designated as ferments, and their action was compared to that of
the alcoholic fermentation in yeast, the process of putrefaction, etc.
Naturally very many theories have been proposed regarding the
cause of the processes of fermentation. For the historical develop-
ment and interrelation of these theories references must be made to

COMPOSITION OF FOOD AND ACTION OF ENZYMES. 679

special works.* It is sufficient here to say that the brilliant work
of Pasteur established the fact that the fermentations in the old
sense — alcoholic, acid, and putrefactive — are due to the presence
and activity of living organisms. He showed, moreover, that
many diseases are likewise due to the activity of minute living
organisms, and thus justified the view held by some of the older
physicians that there is a close similarity in the processes of fer-
mentation and disease. The clear demonstration of the importance
of living organisms in some fermentations and the equally clear
proof of the existence of another group of ferment actions in which
living material is not directly concerned led to a classification which
is used even at the present day. This classification divided fer-
ments into two great groups : the living or organized ferments, such
as the yeast cell, bacteria, etc.; and the non-living or unorganized
ferments, such as pepsin, trypsin, etc., which later were generally
designated as enzymes (Kuhne). The separation appeared to be
entirely satisfactory until Buchner (1897) showed that an unor-
ganized ferment, an enzyme (zymase) capable of producing alcohol
from sugar, may be extracted from yeast cells. Later the same
observer (1903) succeeded in extracting enzymes from the lactic-
acid-producing bacteria and the acetic-acid-producing bacteria
which are capable of giving the same reactions as the living bacteria.
These discoveries indicate clearly that there is no essential difference
between the activity of living and non-living ferments. The so-
called organized ferments probably produce their effects not by
virtue of their specific life-metabolism, but by the manufacture
within their substance of specific enzymes. If we can accept this
conclusion, then the general explanation of fermentation is to be
sought in the nature of the enzymatic processes. Within recent
years the study of the enzymes has attracted especial attention.
The general point of view regarding the mode of action of enzymes
that is most frequently met with to-day is that advocated especially
by Ostwald. He assumes, reviving an older view (Berzelius),
that the ferment actions are similar to those of catalysis. By
catalysis chemists designated a species of reaction which is brought
about by the mere contact or presence of certain substances, the
catalyzers. Thus, hydrogen and oxygen at ordinary temperatures
do not combine to form water, but if spongy platinum is present
the two gases unite readily. The platinum does not enter into the
reaction, at least it undergoes no change, and it is said, therefore,

* Consult Green, "The Soluble Ferments and Fermentations," 1899;
Effront, "Enzymes and their Applications" (translation by Prescott), 1902;
Oppenheimer, "Die Fermente und ihre Wirkungen," second edition, 1903;
and Moore, in "'Recent Advances in Physiology and Bio-chemistry, London
and New York," 1906.

680 PHYSIOLOGY OF DIGESTION AND SECRETION.

to act by catalysis. Many similar catalytic reactions are known,
and the chemists have reached the important generalization that
in such reactions the catalyzer, platinum in the above instance,
simply hastens a process which would occur without it, but much
more slowly. A catalyzer is a substance, therefore, that alters
the velocity of a reaction, but does not initiate it. This idea is
illustrated very clearly by the catalysis of hydrogen peroxid. This
substance decomposes spontaneously into water and oxygen accord-
ing to the reaction H2O2 = H2O 4* O, but the decomposition is
greatly hastened by the presence of a catalyzer. Thus, Bredig has
shown that platinum in very fine suspension, so-called colloidal
solution, exerts a marked accelerating influence upon this reaction;
one part of the colloidal platinum to 350 million parts of water may
still exercise a perceptible effect. Now, the blood and aqueous ex-
tracts of various tissues also catalyze the hydrogen peroxid readily,
and this effect has been attributed to the action of an enzyme (cata-
lase). The view has been proposed, therefore, that the enzymes of
the body act like the catalyzers of inorganic origin: they influence
the velocity of certain special reactions. Such a general conception
as this unifies the whole subject of fermentation and holds out the
hope that the more precise investigations that are possible in the case
of the inorganic catalyzers will eventually lead to a better under-
standing of the underlying physical causes of fermentation. It
should be borne in mind, however, that some of the best known of the
ferment actions of the body, such as the peptic or tryptic digestion of
protein, fit into this view only theoretically and by analogy. As a
matter of fact, albumins at ordinary temperatures do not split up
spontaneously into the products formed by the action of pepsin;
if we consider that the pepsin simply accelerates a reaction already
taking place, it must be stated that this reaction at ordinary
temperatures is infinitely slow, — that is, practically does not occur.
At higher temperatures, however, similar decompositions of al-
bumin may be obtained without the presence of an enzyme.

Reversible Reactions. — It has been shown that under proper
conditions many chemical reactions are reversible, — that is, may
take place in opposite directions. For instance, acetic acid and
ethyl-alcohol brought together react with the production of ethyl-
acetate and water:

CH3COOH + C2H6OH = CH3COOC2HS + H2O.

Acetic acid. Alcohol. Ethyl-acetate. Water.

On the other hand, when ethyl-acetate and water are brought
together they react with the formation of some acetic acid and
ethyl-alcohol, so that the reaction indicated in the above equation

COMPOSITION OF FOOD AND ACTION OF ENZYMES. 681

takes place in opposite directions, figuratively speaking, — a fact
which may be indicated by a symbol of this kind:

CH3COOH + C2H5OH ^± CH3COOC2H5 + H2O.

It is evident that in a reversible reaction of this sort the opposite
changes will eventually strike an equilibrium, the solution or mix-
ture will contain some of all four substances, and this equilib-
rium will remain constant as long as the conditions are unchanged.
If the conditions are altered, however, — if, for example, some of the
substances formed are removed or the mixture is altered as to its
concentration, — then the reaction will proceed unequally in the two
directions until a new equilibrium is established. The importance,
in the present connection, of this conception of reversibility of reac-
tions is found in the fact that a number of the catalytic reactions
are also reversible. The catalyzer may not only accelerate a reac-
tion between two substances, but may also accelerate the recom-
position of the products into the original substances. An excellent
instance of this double effect has been obtained by Kastle and
Loevenhart in experiments upon one of the enzymes of the animal
body, lipase. Lipase is the enzyme which in the body acts upon the
neutral fats, converting them into fatty acids and glycerin, — a
process that takes place as a usual if not necessary step in the diges-
tion and absorption of fats. The authors above named* made use
of a simple ester analogous to the fats, ethyl-butyrate, and showed
that lipase causes not only an hydrolysis of this substance into ethyl-
alcohol and butyric acid, but also a synthesis of the two last-named
substances into ethyl-butyrate and water. The reaction effected
by the lipase is therefore reversible and may be expressed as:

C3H7COOC2H& + H2O ^± C3H7COOH + C2H5OH.

Ethyl-butyrate. Water. Butyric acid. Ethyl-alcohol.

Lipase is capable of exerting probably a similar reversible reaction on
the fats in the body. Assuming the existence of such an action in
the body, it is possible to explain not only the digestion of fats, but
also their formation in the tissues and their absorption from the
tissues during starvation. That is, according to the conditions of
concentration, etc., one and the same enzyme may cause a splitting
up of the neutral fat into fatty acids and glycerin or a storing up of
neutral fat by the synthesis of fatty acid and glycerin. In the
subcutaneous tissues, therefore, fat may be stored, to a certain point,
or, if the conditions are altered, the fat that is there may be changed
over to the fatty acids and glycerin and be oxidized in the body as
food.

* Kastle and Loevenhart, "American Chemical Journal," 24, 491, 1900.
See also Loevenhart, "American Physiological Journal," 6, 331, 1902.

682 PHYSIOLOGY OF DIGESTION AND SECRETION.

A similar reversibility has been shown for some of the other
enzymes of the body (maltase by Hill, 1898), but whether or not all
of them will be shown to possess this power under the conditions of
temperature, etc., that prevail in the body can only be determined
by actual experiments.

The Specificity of Enzymes.— A most interesting feature of
the activity of enzymes is that it is specific. The enzymes that
act upon the carbohydrates are not capable of affecting the pro-
teins or fats, and vice versa. So in the fermentation of closely
related bodies such as the double sugars, the enzyme that acts
upon the maltose is not capable of affecting the lactose; each re-
quires seemingly its own specific enzyme. In fact, there is no clear
proof that any single enzyme can produce more than one kind of
ferment action. If in any extract or secretion two or more kinds
of ferment action can be demonstrated, the tendency at present
is to attribute these different activities to the existence of separate
and specific enzymes. The pancreatic juice, for example, splits
proteins, starches, and fats and curdles milk, and there are assumed
to be four different enzymes present, — namely, trypsin, diastase,
lipase, and rennin. So if an extract containing diastase is also
capable of decomposing hydrogen peroxid it is believed that this
latter effect is due to the existence of a special enzyme, catalase.
It seems quite probable that this specificity, of the different enzymes
may be related, as Fischer * has suggested, to the geometrical struc-
ture of the substance acted upon. Each ferment is adapted to act
upon or become attached to a molecule with a certain definite
structure, — fitted to it, in fact, as a key to its lock. In this respect
the action of the so-called hydrolytic enzymes differs markedly from
the dilute acids or alkalies which hydrolyze many different substances
without indication of any specificity. Attention has been called to
the fact that this adaptibility of enzymes to certain specific struc-
tures in the molecules acted upon resembles closely the specific
activity of the toxins, and many useful and suggestive com-
parisons may be drawn between the mode of action of enzymes
and toxins. To how complete an extent the idea of the specificity
of the different body enzymes may be carried is a matter for future
experiments. At present the tendency is to attribute each new kind
of activity to a different enzyme, and as a consequence the number
of different enzymes supposed to exist in the body is increasing
rapidly with the spread of experimental work.

Definition and Classification of Enzymes (Ferments). — On

the basis of the considerations presented in the preceding paragraphs

Oppenheimer suggests the following definition: An enzyme is a

substance, produced by living cells, which acts by catalysis. The

* Fischer, ' ' Zeitschrift f. physiolog. Chemie," 26, 71, 1898.

COMPOSITION OF FOOD AND ACTION OF ENZYMES. 683

enzyme itself remains unchanged in this process, and it acts specifi-
cally,— that is, each enzyme exerts its activity only upon substances
whose molecules have a certain definite structural and stereochemi-
cal arrangement. The enzymes of the body are organic substances
of a colloid structure whose chemical composition is unknown.

With regard to the names and classification of the different
enzymes, much difficulty is experienced. There is no consensus
among workers as to the system to be followed. Duclaux has sug-
gested that an enzyme be designated by the name of the body on
which its action is exerted, and that all of them be given the termina-
tion ase. The enzyme acting on fat on this system would be named
lipase; that on starch, amylase; that on maltose, maltase, etc. The
suggestion has been followed in part only, the older enzymes which
were first discovered being referred to most frequently under their
original names. An entirely satisfactory classification is impossible
at present. Having in mind only the needs of animal physi-
ology, the following classification will be used in the treatment of
the subjects of digestion and nutrition:

1. The proteolytic or protein-splitting enzymes. Examples: pepsin

of gastric juice, trypsin of pancreatic juice. They cause a hydro-
lytic cleavage of the protein molecule.

2. The amylolytic or starch-splitting enzymes. Examples: ptyalin

or salivary diastase, amylopsin or pancreatic diastase. Their
action is closely similar to that of the classical enzyme of this group
— diastase — found in germinating barley grains. They cause a
hydrolytic cleavage of the starch molecule.

3. The lipolytic or fat -splitting enzymes. Example: the lipase found

in the pancreatic secretion, in the liver, connective tissues, blood,
etc. They cause a hydrolytic cleavage of the fat molecule.

4. The sugar-splitting enzymes. These again fall into two subgroups:

(a) The inverting enzymes, which convert the double sugars or di-
saccharids into the monosaccharids. Examples: maltase, which
splits maltose to dextrose; invertase, which splits cane-sugar to
dextrose and levulose; and lactase, which splits milk-sugar (lactose)
to dextrose and galactose. (6) The enzymes which split the mono-
saccharids. There is evidence of the presence in the tissues of an
enzyme capable of splitting the sugar of the blood and tissues
(dextrose) into lactic acid.

5. The coagulating enzymes, which convert soluble to insoluble pro-

teins. Examples: fibrin ferment (thrombin or thrombase), that
causes clotting of the blood, and rennin, that causes clotting of milk.

6. The oxidizing enzymes or oxidases. A group of enzymes which set

up oxidation processes. Some of the details of the activity of
these enzymes are considered in the discussion of physiological
oxidations (p. 866).

The enzymes contained in the first, second, third, and fourth (a)
of these groups are the ones that play the chief roles in the digestive
processes, and it will be noticed that they all act by hydrolysis, —
that is, they cause the molecules of the substance to undergo de-
composition or cleavage by a reaction with water. Thus, in the
conversion of maltose to dextrose by the action of maltase the re-
action may be expressed so :

684 PHYSIOLOGY OF DIGESTION AND SECRETION.

CuHaOu + H20 = C6H1206 + C6H1206.

Maltose. Dextrose. Dextrose.

And the hydrolysis of the neutral fats by lipase may be expressed
so:

C3H6(C18H3502)3 + 3H20 = C,H5(OH)1 + 3(CMH»p,).

Tristeann. Glycerin. Stearic acid.

General Properties of Enzymes. — The specific reactions of the
various enzymes of the body are referred to under separate heads.
The following general characteristics may be noted briefly :

Solubility. — Most of the enzymes are soluble in water or salt
solutions, or in glycerin. By these means they may be extracted
conveniently from the various tissues. In some cases, however, such
simple methods do not suffice ; the enzyme is destroyed in the process
of extraction, and to prove its presence pieces of the tissue or the
juice pressed from the tissue must be employed.

Temperature. — The body enzymes are characterized by the fact
that they are destroyed by high temperatures (60° C. to 80° C.) and
that their effect is retarded in part or entirely by low temperatures.
Most of them show an optimum activity at temperatures approxi-
mating that of the body.

Precipitation. — The enzymes are precipitated from their solutions
in part at least by excess of alcohol. This precipitation is frequently
used in obtaining purified specimens of enzymes. The enzymes,
moreover, show an interesting tendency to be carried down mechani-
cally by flocculent precipitates produced in their solutions. If
protein present in the solution is precipitated, for instance, the
enzymes may be carried down with it in part.

Incompleteness of their Action. — In any given mixture of a sub-
stance and its enzyme the action of the latter is usually not com-
plete,— that is, all of the substance does not disappear. An explana-
tion for this fact has been found in the reversibility of the action of
the enzyme. If the reaction proceeds in both directions, then
evidently under fixed conditions a final equilibrium will be reached
in which no further apparent change takes place, although in reality
the condition is not one of rest, but of balance between opposing
processes proceeding at a definite rate. Within the body itself,
on the contrary, the action of an enzyme may be complete, since the
products are removed by absorption and the possibility of a re-
versed reaction is removed. In some cases — for instance, the
coagulating enzymes — the action is apparently always complete.

Active and Inactive Form. — In many cases it can be shown that
the enzyme exists within the cell producing it in an inactive form
or even when secreted it may still be inactive. This antecedent or
inactive stage is usually designated as zymoqen. The zymogen may
be stored in the cell in the form of granules which are converted into

COMPOSITION OF FOOD AND ACTION OF ENZYMES.

685

active enzyme at the moment of secretion, or it may be secreted in
inactive form and require the co-operation of some other substance
before it is capable of effecting its normal reaction. In such cases the
second substance is said to activate the enzyme. An example is
found in the case of the trypsin of the pancreatic secretion.

PARTIAL LIST OF THE ENZYMES CONCERNED IN THE PROC-
ESSES OF DIGESTION AND NUTRITION.

ENZYME.

( Ptyalin (sali-
vary diastase.

Amylopsin
(pancreatic
diastase).

Liver diastase.

Muscle diastase.

o3 -j Invertase.

Is!

Maltase.

Lactase.
Glycolytic?

Lipase (steap-
sin).

f Pepsin.
Trypsin.

Erepsin.

Group of auto-
lytic enzymes.

WHERE CHIEFLY
FOUND.

Salivary secretion.

Pancreatic secre-
tion.

Liver.

Muscles.

Small intestine.

Small intestine,
salivary and
pancreatic se-
cretion.

Small intestine.

Muscles?

Pancreatic secre-
tion, fat tissues,
blood, etc.

Gastric juice.

Pancreatic juice.

ACTION.

Converts starch to sugar

(maltose).
Converts starch to sugar

(maltose).

Converts glycogen to dex-
trose.

Converts glycogen to dex-
trose.

Converts cane-sugar to
dextrose and levulose.

Converts maltose to dex-
trose.

Converts lactose to dex-
trose and galactose.

Splits and oxidizes dex-
trose.

Splits neutral fats to fatty
acids and glycerin.

Converts proteins to pep-
tones and proteoses.

Splits proteins into sim-
pler crystalline prod-
ucts.

Splits peptones into sim-
pler products.

Splits proteins into nitrog-
enous bases and amino-
bodies.

Converts guanin to xan-
thin by splitting off an
NH2 group as ammonia
(NH3).

Converts adenin to hypo-
xanthin by splitting off
an NH2 group as am-
monia (NH3).

Causes oxidation of organ-
ic substances, as in the
conversion of hypoxan-
thin to xanthin and of
xanthin to uric acid.

Decomposes hydrogen
peroxid.

Chemical Composition of the Enzymes. — It was formerly
believed that the enzymes belong to the group of proteins. They

Guanase.

£, ^ Adenase.

i

Oxidases.

Catalase.

Small intestine.
Tissues generally.

Thymus, adrenals,
pancreas.

Spleen, pancreas,
liver.

Lungs, liver, mus-
cle, etc.

Many tissues.

686 PHYSIOLOGY OF DIGESTION AND SECRETION.

are formed from living matter, and the solutions as usually prepared
give protein reactions. Increased study, however, has made this be-
lief uncertain. The enzymes cling to the proteins when precipitated,
and it seems possible that the protein reactions of their solutions may
be due, therefore, to an incomplete purification. In fact, it is stated
that solutions of some of the enzymes may be prepared (pepsin,
invertase, thrombin) which show ferment activity, but give no
protein reactions. Much of the older work upon the composition of
supposedly purified preparations of enzymes is not accepted to-day,
on the ground that the evidence for the purity of the preparations is
insufficient. In spite, however, of the very great amount of atten-
tion that has been paid to these substances in recent years, there is at
present no agreement as to their chemical structure. Some au-
thorities (Arthus) have gone so far as to suggest that the enzymes
or, more properly, enzyme actions, are not due to definite material
substances, but are to be classified as forms of energy like heat,
electricity, etc. The suggestion is not very helpful, but it indicates
forcibly the present uncertainty regarding the real nature of these
bodies.

CHAPTER XLI.

THE SALIVARY GLANDS AND THEIR DIGESTIVE
ACTION.

The first of the secretions with which the food comes into contact
is the saliva. This is a mixed secretion from the large salivary glands
and the small unnamed mucous and serous glands that open into the
mouth cavity.

The Salivary Glands. — The salivary glands in man are three
in number on each side — the parotid, the submaxillary, and
the sublingual. The parotid gland communicates with the mouth
by a large duct (Stenson's duct) which opens upon the inner
surface of the cheek opposite the second molar tooth of the upper
jaw. The submaxillary gland lies below the lower jaw, and its
duct (Wharton's duct) opens into the mouth cavity at the side of
the frenum of the tongue. The sublingual gland lies in the floor of the
mouth to the side of the frenum and opens into the mouth cavity by
a number (eight to twenty) of small ducts, known as the ducts of
Rivinus. One larger duct that runs parallel with the duct of Whar-
ton and opens separately into the mouth cavity is sometimes present
in man. It is known as the duct of Bartholin and occurs normally in
the dog.

The course of the nerve fibers supplying the large salivary glands
is interesting in view of the physiological results of their stimulation.
The description here given applies especially to their arrangement
in the dog. These glands receive their nerve supply from two general
sources, — namely, the bulbar autonomies (or cerebral fibers) and
the sympathetic autonomies. The parotid gland receives its bulbar
autonomic fibers from the glossopharyngeal or ninth cranial nerve;
they pass into a branch of this nerve known as the tympanic
branch or nerve of Jacobson, thence to the small superficial pe-
trosal nerve, through which they reach the otic ganglion. From this
ganglion they pass (postganglionic fibers) by way of the auricu-
lotemporal branch of the inferior maxillary division of the fifth
cranial nerve to the parotid gland (Fig. 264). The sympathetic
autonomies pass to the superior cervical ganglion by way of the
cervical sympathetic (Fig. 105) and thence as postganglionic fibers
in branches which accompany the arteries distributed to the gland.
The bulbar autonomic supply for the submaxillary and sublingual

687

688

PHYSIOLOGY OF DIGESTION AND SECRETION.

glands arises from the brain in the facial nerve and passes out in the
chorda tympani branch (Fig. 265). This latter nerve, after emerging
from the tympanic cavity through the Glaserian fissure, joins the

Otic
Ganglion.

Sliuill superficial
Petrosai nerve

Glosso-hharynoetU
Mue y *

Ganglion.
Fig. 264. — Schematic representation of the course of the cerebral fibers to the parotid gland.

lingual nerve. After running with this nerve for a short distance,
the secretory (and vasodilator) nerve fibers destined for the sub-
maxillary and sublingual glands branch off and pass to the glands,

Fig. 265. — Schematic representation of the course of the chorda tympani nerve to the

submaxillary gland.

following the course of the ducts. Where the chorda tympani fibers
leave the lingual there is a small ganglion which has received the
name of submaxillary ganglion. The nerve fibers to the glands

THE SALIVARY GLANDS. 689

pass close to this ganglion, but Langley has shown that only those
destined for the sublingual gland really connect with the nerve
cells of the ganglion, and he suggests, therefore, that it should
be called the sublingual instead of the submaxillary ganglion. The
nerve fibers for the submaxillary gland make connections with nerve
cells lying mainly within the hilus of the gland itself. The supply
of sympathetic autonomies has the same general course as those
for the parotid, — namely, through the cervical sympathetic to the
superior cervical ganglion and thence to the glands.

Histological Structure. — The salivary glands belong to the type
of compound tubular glands. That is, the secreting portions are
tubular in shape, although in cross-sections these tubes may pre-
sent various outlines according as the plane of the section passes
through them. The parotid is described usually as a typical serous
or albuminous gland. Its secreting epithelium is composed of cells
which in the fresh condition as well as in preserved specimens contain
numerous fine granules and its secretion contains some albumin.
The submaxillary gland differs in histology in different animals.
In some, as the dog or cat, the secretory tubes are composed chiefly
or exclusively of epithelial cells of the mucous type. In man the
gland is of a mixed type, the secretory tubes containing both mucous
and albuminous cells. The sublingual gland in man also contains
both varieties of cells, although the mucous cells predominate. In
accordance with these histological characteristics it is found that the
secretion from the submaxillary and sublingual glands is thick and
mucilaginous as compared with that from the parotid.

In the mucous glands another variety of cell, the so-called demilunes or
crescent cells, is frequently met with, and the physiological significance of
these cells has been the subject of much discussion. The demilunes are
crescent-shaped, granular cells lying between the mucous cells and the base-
ment membrane, and not hi contact, therefore, with the central lumen of
the tube. According to Heidenhain, these demilunes are for the purpose
of replacing the mucous cells. In consequence of long-continued activity
the mucous cells may disintegrate and disappear, and the demilunes then
develop into new mucous cells. Another view is that the demilunes represent
distinct secretory cells of the albuminous type, while others assert that they
are a specific type of cell with probably specific functions.*

The salivary glands possess definite secretory nerves which when
stimulated cause the formation of a secretion. This fact indicates
that there must be a direct contact of some kind between the gland
cells and the terminations of the secretory fibers. The ending of the
nerve fibers in the submaxillary and sublingual glands has been de-
scribed by a number of observers.! The accounts differ somewhat as
to details of the finer anatomy, but it seems to be clearly established
that the secretory fibers from the chorda tympani end first around the

* See Noll, " Archiv f. Physiologic, " 1902, suppl. volume, 166.
t See Huber, "Journal of Experimental Medicine," 1, 281, 1896.
44

690 PHYSIOLOGY OF DIGESTION AND SECRETION.

intrinsic nerve ganglion cells of the glands (preganglionic fibers), and
from these latter cells axons (postganglionic fibers) are distributed
to the secreting cells, passing to these cells along the ducts. The
nerve fibers terminate in a plexus upon the membrana propria of the
alveoli, and from this plexus fine fibrils pass inward to end on and
between the secreting cells. It would seem from these observations
that the nerve fibrils do not penetrate or fuse with the gland cells,
as was formerly supposed, but form a terminal network in contact
with the cells, following thus the general schema for the connection
between nerve fibers and peripheral tissues.

Composition of the Secretion. — The saliva as it is found in the
mouth is a colorless or opalescent, turbid, and mucilaginous liquid of
weakly alkaline reaction and a specific gravity of about 1.003. It
may contain numerous flat cells derived from the epithelium of the
mouth, and the peculiar spherical cells known as salivary corpuscles,
which seem to be altered leucocytes. The important constituents
of the secretion are mucin, a diastatic enzyme known as ptyalin,
maltase, traces of protein and of potassium sulphocyanid, and
inorganic salts such as potassium and sodium chlorid, potassium
sulphate, sodium carbonate, and calcium carbonate and phosphate.
The carbonates are particularly abundant in the saliva, and the
secretion in addition contains much carbon dioxid in solution.
Thus, Pfliiger found that 65 volumes per cent, of CO2 might be
obtained from the saliva, of which 42.5 per cent, was in the form of
carbonates. The amount of CO2 in solution and combined is an
indication of the active chemical changes in the gland.

Of the organic constituents of the saliva the protein exists iri
small and variable quantities, and its exact nature is not determined.
The mucin gives to the saliva its ropy, mucilaginous character.
This substance belongs to the group of combined proteins, glyco-
proteins (see Appendix), consisting of a protein combined with a
carbohydrate group. The most interesting constituent of the mixed
saliva is the ptyalin or salivary diastase. This body belongs to the
group of enzymes or unorganized ferments, whose general properties
have been described. In some animals (dog) ptyalin seems to be
normally absent from the fresh saliva.

The secretions of the parotid and the submaxillary glands can be
obtained separately by inserting a cannula into the openings of the
ducts in the mouth, or, according to the method of Pawlow, by trans-
ferring the end of the duct so that it opens upon the skin instead of
in the mouth, making thus a salivary fistula. The secretion of the
sublingual can only be obtained in sufficient quantities for analysis
from the lower animals. Examination of the separate secretions
shows that the main difference lies in the fact that the parotid saliva
contains no mucin, while that of the submaxillary and especially of

THE SALIVARY GLANDS. 691

the sublingual gland is rich in mucin. The parotid saliva of man
seems to be particularly rich in ptyalin as compared with that of the
submaxillary, while the secretion of the latter and that of the sub-
lingual gland give a stronger alkaline reaction than the parotid saliva.

The Secretory Nerves. — The existence of secretory nerves to the
salivary glands was discovered by Ludwig in 1851. The discovery is
particularly interesting in that it marks the beginning of our knowl-
edge of this kind of nerve fiber. Ludwig found that stimulation of
the chorda tympani nerve causes a flow of saliva from the submaxil-
lary gland. He established also several important facts with regard
to the pressure and composition of the secretion which will be referred
to presently. It was afterward shown that the salivary glands receive
a double nerve supply, — in part by way of the cervical sympathetic
and in part through cerebral nerves. It was discovered also that
not only are secretory fibers carried to the glands by these paths,
but that vasomotor fibers are contained in the same nerves,
and the arrangement of these latter fibers is such that the cerebral
nerves contain vasodilator fibers that cause a dilatation of the small
arteries in the glands and an accelerated blood-flow, while the sym-
pathetic carries vasoconstrictor fibers whose stimulation causes a
constriction of the small arteries and a diminished blood-flow. The
effect of stimulating these two sets of fibers is found to vary somewhat
in different animals. For purposes of description we may confine
ourselves to the effects observed on dogs, since much of our funda-
mental knowledge upon the subject is derived from Heidenhain's*
experiments upon this animal. If the chorda tympani nerve is
stimulated by weak induction shocks, the gland begins to secrete
promptly, and the secretion, by proper regulation of the stimulation,
may be kept up for hours. The secretion thus obtained is thin and
watery, flows freely, is abundant in amount, and contains not more
than 1 or 2 per cent, of total solids. At the same time there is an
increased flow of blood through the gland. The whole gland takes
on a redder hue, the veins are distended, and if cut the blood that
flows from them is of a redder color than in the resting gland, and
may show a distinct pulse — all of which points to a dilatation of the
small arteries. If now the sympathetic fibers are stimulated, quite
different results are obtained. The secretion is relatively small in
amount, flows slowly, is thick and turbid, and may contain as much
as 6 per cent, of total solids. At the same time the gland becomes
pale, and if the veins be cut the flow from them is slower than in
the resting gland, thus indicating that a vasoconstriction has
occurred.

The increased vascular supply to the gland accompanying the

*"Pfliiger's Archiv fiir die gesammte Physiologie, " 17, 1, 1878; also
in Hermann's "Handbuch der Physiologie," 1883, vol. v, part i.

692 PHYSIOLOGY OF DIGESTION AND SECRETION.

abundant flow of "chorda saliva" and the diminished flow of blood
during the scanty secretion of " sympathetic saliva " suggest naturally
the idea that the whole process of secretion may be, at bottom, a
vasomotor phenomenon, the amount of secretion depending only on
the quantity and pressure of the blood flowing through the gland.
It has been shown conclusively that this idea is erroneous and that
definite secretory fibers exist. The following facts may be quoted
in support of this statement: (1) Ludwig showed that if a mercury
manometer is connected with the duct of the submaxillary gland and
the chorda is then stimulated for a certain time, the pressure in the
duct may become greater than the blood-pressure in the gland.
This fact shows that the secretion is not derived entirely by processes
of filtration from the blood. (2) If the blood-flow be shut off
completely from the gland, stimulation of the chorda still gives a
secretion for a short time. (3) If atropin is injected into the gland,
stimulation of the chorda causes vascular dilatation, but no
secretion. This may be explained by supposing that the atropin
paralyzes the secretory, but not the dilator fibers. (4) Hydro-
chlorate of quinin injected into the gland causes vascular dilatation,
but no secretion. In this case the secretory fibers are still irritable,
since stimulation of the chorda gives the usual secretion.

A still more marked difference between the effect of stimulation
of the cerebral and the sympathetic fibers may be observed in the
case of the parotid gland in the dog. Stimulation of the cerebral
fibers, in any part of their course, gives an abundant, thin, and
watery saliva, poor in solid constituents. Stimulation of the sym-
pathetic fibers alone (provided the cerebral fibers have not been
stimulated shortly before and the tympanic nerve has been cut to
prevent a reflex effect) gives usually no perceptible secretion at all.
But in this last stimulation a marked effect is produced upon the
gland, in spite of the absence of a visible secretion. This is shown by
the fact that subsequent or simultaneous stimulation of the cerebral
fibers causes a secretion very unlike that given by the cerebral fibers
alone, in that it is very rich indeed in organic constituents. The
amount of organic matter in the secretion may be tenfold that of the
saliva obtained by stimulation of the cerebral fibers alone.

Relation of the Composition of the Secretion to the Strength of Stimu-
lation.— If the stimulus to the chorda is gradually increased in
strength, care being taken not to fatigue the gland, the chemical
composition of the secretion is found to change with regard to the
relative amounts of the water, the salts, and the organic material.
The water and the salts increase in amount with the increased
strength of stimulus up to a certain maximal limit, which for the
salts is about 0.77 per cent. It is important to observe that this
effect may be obtained from a perfectly fresh gland as well as from a

THE SALIVARY GLANDS. 693

gland which had previously been secreting actively. With regard
to the organic constituents the precise result obtained depends on
the condition of the gland. If previous to the stimulation the gland
was in a resting condition and unfatigued, then increased strength
of stimulation is followed at first by a rise in the percentage of organic
constituents, and this rise in the beginning is more marked than in
the case of the salts. But With continued stimulation the increase
in organic material soon ceases, and finally the amount begins actually
to diminish, and may fall to a low point in spite of the stronger
stimulation. On the other hand, if the gland at the beginning of the
experiment had been previously worked to a considerable extent,
then an increase in the stimulating current, while it augments the
amount of water and salts, either may have no effect at all upon the
organic constituents or may cause only a temporary increase, quickly
followed by a fall. Similar results may be obtained from stimulation
of the cerebral nerves of the parotid gland. The above facts led
Heidenhain to believe that the conditions determining the secretion
of the organic material are different from those controlling the water
and salts, and he gave a rational explanation of the differences
observed, in his theory of trophic and secretory fibers.

Theory of Trophic and Secretory Nerve Fibers. — This theory
supposes that two physiological varieties of nerve fibers are distrib-
uted to the salivary glands. One of these varieties controls the
secretion of the water and inorganic salts and its fibers may be called
secretory fibers proper, while the other, to which the name trophic
is given, causes the formation of the organic constituents of the secre-
tion, probably by a direct influence on the metabolism of the cells.
Were the trophic fibers to act alone, the organic products would be
formed within the cell, but there would be no visible secretion, and
this is the hypothesis which Heidenhain uses to explain the results of
the experiment described above upon stimulation of the sympathetic
fibers to the parotid of the dog. In this animal, apparently, the
sympathetic branches to the parotid contain exclusively or almost
exclusively trophic fibers, while in the cerebral branches both trophic
and secretory fibers proper are present. The results of stimulation
of the cerebral and sympathetic branches to the submaxillary gland
of the same animal may be explained in terms of this theory by
supposing that in the latter nerve trophic fibers preponderate, and
in the former the secretory fibers proper.

It is obvious that this anatomical separation of the two sets of
fibers along the cerebral and sympathetic paths may be open to
individual variations, and that dogs may be found in which the sym-
pathetic branches to the parotid glands contain secretory fibers
proper, and therefore give some flow of secretion on stimulation.
These variations might also be expected to be more marked when

694 PHYSIOLOGY OF DIGESTION AND SECRETION.

animals of different groups are compared. Thus, Langley * finds
that in cats the sympathetic saliva from the submaxillary gland is
less viscid than the chorda saliva, — just the reverse of what occurs
in the dog. To apply Heidenhain's theory to this case it is necessary
to assume that in the cat the trophic fibers run chiefly in the chorda.

The way in which the trophic fibers act has been briefly indicated.
They may be supposed to set up metabolic changes in the proto-
plasm of the cells, leading to the formation of certain definite prod-
ucts, such as mucin or ptyalin. That such changes do occur is
abundantly shown by microscopical examination of the resting and
the active gland, the details of which will be given presently. In
general, these changes may be supposed to be catabolic in nature;
that is, they consist in a disassociation or breaking down of the
complex living material, with the formation of the simpler and
more stable organic constituents of the secretion. That these
changes involve processes of oxidation is shown by the fact that
during activity the gland takes up more oxygen and gives off more
carbon dioxid. There is evidence to show that these gland cells
during activity form fresh material from the nourishment supplied
by the blood; that is, that anabolic or building-up processes occur
along with the catabolic changes. The latter are the more obvious,
and are the changes which are usually associated with the action
of the trophic nerve fibers. It is possible, also, that the anabolic
or growth changes may be under the control of separate fibers,
for which the name anabolic fibers would be appropriate. Satis-
factory proof of the existence of a separate set of anabolic fibers has
not yet been furnished.

The method of action of the secretory fibers proper is difficult to
understand. At present the theories suggested are entirely specula-
tive. Experiments have shown that the amount of water given
off from the blood during secretion is somewhat greater than the
amount contained in the saliva, f and there is reason to believe that
the difference between the two is accounted for by an increase in
the flow of lymph from the gland during activity. A satisfactory
explanation of the causes leading to and controlling the flow of
water cannot yet be given. In a general way we may believe that
the effect of the nerve impulses is to cause the production of sub-
stances within the cells whereby their osmotic pressure is increased,
and a stream of water is set up from the blood in the capillaries
toward the gland cells. The activity of the cells themselves initiates
and controls the flow of water.

Histological Changes during Activity. — The cells of both the
albuminous and mucous glands undergo distinct histological changes

* "Journal of Physiology," 1, 96, 1878.

tBarcroft, "Journal of Physiology," 1900, xxv., 479.

THE SALIVARY GLANDS.

695

in consequence of prolonged activity, and these changes may be
recognized both in preparations from the fresh gland and in preserved
specimens. In the parotid gland Heidenhain studied the changes in
stained sections after hardening in alcohol. In the resting gland
the cells are compactly filled with granules that stain readily and are
imbedded in a clear ground substance that does not stain. The
nucleus is small and more or less irregular in outline. After stimula-
tion of the tympanic nerve the cells show but little alteration, but
stimulation of the sympathetic produces a marked change. The
cells become smaller, the nuclei more rounded, and the granules
more closely packed. This last appearance seems, however, to be

Fig. 266. — Parotid gland of the rabbit in a fresh state, showing portions of the secret-
ing tubules: A, In a resting condition; B, after secretion caused by pilocarpia; C, after
stronger secretion, pilocarpm and stimulation of sympathetic; D, after long-continued
stimulation of sympathetic. — (After Lcmgley.')

due to the hardening reagents used. A truer picture of what occurs
may be obtained from a study of sections of the fresh gland. Lang-
ley,* who first used this method, describes his results as follows:
When the animal is in a fasting condition the cells have a granular
appearance throughout their substance, the outlines of the different
cells being faintly marked by light lines (Fig. 266, A}. When the
gland is made to secrete by giving the animal food, by injecting
pilocarpin, or by stimulating the sympathetic nerves, the granules
begin to disappear from the outer borders of the cells (Fig. 266, B)fi
so that each cell now shows an outer, clear border and an inner,
granular one. If the stimulation is continued the granules become

* "Journal of Physiology," 2, 260, 1879.

696

PHYSIOLOGY OF DIGESTION AND SECRETION.

fewer in number and are collected near the lumen and the margins
of the cells, the clear zone increases in extent, and the cells become
smaller (Fig. 266, C, D). Evidently the granular material is used
in some way to make the organic material of the secretion. Since the
ptyalin is a conspicuous organic constituent of the secretion, it is
assumed that the granules in the resting gland contain the ptyalin,
or rather the preliminary material from which the ptyalin is con-
structed during the act of secretion. On this latter assumption the
granules are frequently spoken of as zymogen granules. During the
act of secretion two distinct processes seem to be going on in the cell,
leaving out of consideration, for the moment, the secretion of the
water and the salts. In the first place, the zymogen granules undergo
a change such that they are forced or dissolved out of the cell, and,
second, a constructive metabolism or anabolism is set up, leading to

the formation of new pro-
toplasmic material from
the substances contained
in the blood and lymph.
The new material thus
formed is the clear, non-
granular substance,
which appears first
toward the basal sides of
the cells. We may sup-
pose that the clear sub-
stance during the resting
periods undergoes meta-
bolic changes, whether of
a catabolic or anabolic
character can not be

safely asserted, leading to the formation of new granules, and the
cells are again ready to form a secretion of normal composition.
It should be borne in mind that in these experiments the glands
were stimulated beyond normal limits. Under ordinary conditions
the cells are probably never depleted of their granular material to
the extent represented in the figures.

In the cells of the mucous glands changes equally marked may
be observed after prolonged activity. In stained sections of the
resting gland the cells are large and clear (Fig. 267), with flattened
nuclei placed well toward the base of the cell. When the gland is
made to secrete the nuclei become more spherical and lie more
toward the middle of the cell, and the cells themselves become
distinctly smaller. After prolonged secretion the changes become
more marked (Fig. 268) and, according to Heidenhain, some of the
mucous cells may break down completely. According to most of

Fig. 267. — Mucous gland: submaxillary of dog; rest-
ing stage.

THE SALIVARY GLANDS.

697

pig. 268.— Mucous gland: submaxillary of

eight hours'

the later observers, however, the mucous cells do not actually dis-

integrate, but form again new material during the period of rest, as in

the case of the goblet cells of the intestine. In the mucous as in the

albuminous cells observations upon pieces of the fresh gland seem

to give more reliable results than those upon preserved specimens.

Langley* has shown that in the fresh mucous cells of the submax-

illary gland numerous large 'granules may be discovered, about 125

to 250 to a cell. These

granules are comparable to

those found in the goblet

cells, and may be inter-

preted as consisting of mu-

cin or some preparatory

material from which mucin

is formed. The granules

are sensitive to reagents;

addition of water causes

them to swell up and dis-

appear. It may be as-

sumed that this happens

during secretion, the gran-

ules becoming converted to a mucin mass which is extruded from

the cell.

Action of Atropin, Pilocarpin, and Nicotin upon the Secre-
tory Nerves. — The action of drugs upon the salivary glands and
their secretions belongs properly to pharmacology, but the effects
of the three drugs mentioned are so decided that they have a
peculiar physiological interest. Atropin in small doses injected
either into the blood or into the gland duct prevents the action of
the cerebral autonomic fibers (tympanic nerve or chorda tympani)
upon the glands. This effect may be explained by assuming that
the atropin paralyzes the endings of the cerebral fibers in the glands.
That it does not act directly upon the gland cells themselves seems
to be assured by the interesting fact that, with doses sufficient to
throw out entirely the secreting action of the cerebral fibers, the
sympathetic fibers are still effective when stimulated. Pilocarpin
has directly the opposite effect to atropin. In minimal doses it
sets up a continuous secretion of saliva, which may be explained upon
the supposition that it stimulates the endings of the secretory fibers
in the gland. Within certain limits these drugs antagonize each
other, — that is, the effect of pilocarpin may be removed by the sub-
sequent application of atropin, and vice versa. Nicotin, according
to the experiments of Langley, f prevents the action of the secretory

*" Journal of Physiology," 10, 433, 1889.

f "Proceedings of the Royal Society," London, 46, 423, 1889.

698 PHYSIOLOGY OF DIGESTION AND SECRETION.

nerves, not by affecting the gland cells or the endings of the nerve
fibers around them, but by paralyzing the connections between the
nerve fibers and the ganglion cells through which the fibers pass on
their way to the gland, — that is, the connection between the pre-
ganglionic and postganglionic fibers. If, for example, the superior
cervical ganglion is painted with a solution of nicotin, stimulation
of the cervical sympathetic below the gland gives no secretion; stim-
ulation, however, of the fibers in the ganglion or between the ganglion
and gland gives the usual effect. By the use of this drug Langley is
led to believe that the cells of the so-called submaxillary ganglion
are really intercalated in the course of the fibers to the sublingual
gland, while the nerve cells with which the submaxillary fibers make
connection are found chiefly in the hilus of the gland itself.

Paralytic Secretion. — A remarkable phenomenon in connection
with the salivary glands is the so-called paralytic secretion. It has
been known for a long time that if the chorda tympani is cut the
submaxillary gland after a certain time, one to three days, begins to
secrete slowly, and the secretion continues uninterruptedly for a long
period — as long, perhaps, as several weeks — and eventually the gland
itself undergoes atrophy. Langley states that section of the chorda
on one side is followed by a continuous secretion from the glands
on both sides; the secretion from the gland of the opposite side he
designates as the antiparalytic or antilytic secretion. After section
of the chorda the nerve fibers peripheral to the section degenerate,
the process being completed within a few days. These fibers, how-
ever, do not run directly to the gland cell; they terminate in end
arborizations around sympathetic nerve cells placed somewhere along
their course, — in the sublingual ganglion, for instance, or within the
gland substance itself. It is the axons from these second nerve units
that end around the secreting cells. Langley has accumulated some
facts to show that within the period of continuance of the paralytic
secretion (five to six weeks) the fibers of the sympathetic cells are
still irritable to stimulation. He is inclined to believe, therefore, that
the continuous secretion is due to a continuous excitation, from some
cause, of the local nervous mechanism in the gland. On the histo-
logical side it is stated * that after section of the chorda the resulting
degenerative changes affect only the cytoplasm, while after the
section of the sympathetic the nuclei of the cells are affected, and
indeed to some extent on the sound as well as on the injured side.

Normal Mechanism of Salivary Secretion. — Under normal
conditions the flow of saliva from the salivary glands is the result
of a reflex stimulation of the secretory nerves. The sensory fibers
concerned in this reflex must be chiefly fibers of the glossopharyngeal
and lingual nerves supplying the mouth and tongue. Sapid bodies
*Gerhardt, " Archiv f. die gesammte Physiologie, " 97, 317, 1903.

THE SALIVARY GLANDS. 699

and various other chemical or mechanical stimuli applied to the
tongue or mucous membrane of the mouth produce a flow of saliva.
The normal flow during mastication must be effected by a reflex of
this kind, the sensory impulse being carried to a center and thence
transmitted through the efferent nerves to the glands. It is found
that section of the chorda prevents the reflex, in spite of the fact that
the sympathetic fibers are still intact. No satisfactory explanation
of the normal functions of the secretory fibers in the sympathetic
has yet been given. Various authors have suggested that possibly
the three large salivary glands respond normally to different stimuli.
This view has been supported by Pawlow, who reports that in
the dog at least the parotid and the submaxillary may react quite
differently. When fistulas were made of the ducts of these glands it
was found that the submaxillary responded readily to a great num-
ber of stimuli, such as the sight of food, chewing of meats, acids, etc.
The parotid, on the contrary, seemed to react only when dry food,
dry powdered meat/or bread was placed in the mouth. Dryness in
this case appeared to be the efficient stimulus.

Pawlow lays great stress upon the adaptability of the secretion of saliva
to the character of the material chewed. Dry, solid food stimulates a large
flow of saliva, such as is necessary in order to chew it properly and to form it
into a bolus for swallowing. Foods containing much water, on the contrary,
excite but little flow of saliva. If one places a handful of clean stones in
the mouth of a dog he will move them around with his tongue for a while
and then drop them from his mouth ; but little or no saliva is secreted.
If the same material is given in the form of fine sand a rich flow of saliva
is produced, and the necessity for the reflex is evident in this case, since
otherwise the material could not be conveniently removed from the mouth.
Such adaptations must be regarded from the physiological point of view
as special reflexes depending upon some difference in the nervous mechanism
set into play.*

Since the flow of saliva is normally a definite reflex, we should
expect a distinct salivary secretion center. This center has been
located by physiological means in the medulla oblongata; its exact
position is not clearly defined, but possibly it is represented by the
nuclei of origin of the secretory fibers which leave the medulla by
way of the facial and glossopharyngeal nerves. Owing to the wide
connections of nerve cells in the central nervous system, we should
expect this center to be affected by stimuli from various sources.
As a matter of fact, it is known that the center and through it the
glands may be called into activity by stimulation of the sensory
fibers of the sciatic, splanchnic, and particularly the vagus nerves.
So, too, various psychical acts, such as the thought of savory food and
the feeling of nausea preceding vomiting, may be accompanied by a
flow of saliva, the effect in this case being due probably to stimula-

*See Pawlow, "The Work of the Digestive Glands," translation by
Thompson, London, 1902; also " Ergebnisse der Physiologic," vol iii., part i,
1904, and "Archives internationales\de physiologie," 1, 119, 1904.

700 PHYSIOLOGY OF DIGESTION AND SECRETION.

tion of the secretion center by nervous impulses descending from the
higher nerve centers. Lastly, the medullary center may be inhibited
as well as stimulated. The well-known effect of fear, embarrassment,
or anxiety in producing a parched throat may be explained in this
way as due to the inhibitory action of nerve impulses arising in the
cerebral centers.

Electrical Changes in the Gland during Activity. — It has been
shown ,that the salivary as well as other glands suffer certain changes
in electrical potential during activity which are comparable in a gen-
eral way to the "action currents" observed in muscles and nerves.*

The Digestive Action of Saliva — Ptyalin. — The digestive action
proper of the saliva is limited to the starchy food. In human
beings and most mammals the saliva contains an active enzyme
belonging to the group of diastases and designated usually as ptyalin
or salivary diastase. It may be prepared in purified form from saliva
by precipitation with alcohol, but its chemical nature, like that of the
other enzymes, is still an unsolved problem. Saliva or preparations
of ptyalin act readily upon boiled starch, converting it into sugar
and dextrin. This action may be demonstrated very readily by
holding a little starch paste or starchy food, such as boiled potatoes,
in the mouth for a few moments. If the solution is then examined the
presence of sugar is readily shown by its reducing action on solutions
of copper sulphate (Fehling's solution). There is no doubt that the
action of ptyalin upon the starch is hydrolytic. Under the influence
of the enzyme the starch molecules take up water and undergo
cleavage into simpler molecules. The steps in the process and the
final products have been investigated by a very large number of
workers, but much yet remains in doubt. The following points
seem to be determined: The end-result of the reaction is the
formation of maltose, a disaccharid, having the general formula
€12H22OU, and some form of dextrin, a non-crystallizable poly-
saccharid. When the digestion is effected in a vessel some dextrose
(C6H12O6) may be found among the products, but this is explained on
the assumption that there is present in the saliva some maltase, an
•enzyme capable of splitting maltose into dextrose. So far as the
ptyalin itself is concerned, its specific action is to convert starch to
maltose and dextrin. It seems very certain, however, that a number
of intermediate products are formed consisting of a variety of dex-
trins, so that the hydrolysis probably takes place in successive
stages. There is little agreement as to the exact nature of the in-
termediate dextrins. The following facts, however, may be easily
demonstrated in a salivary digestion carried on in a vessel and ex-
amined from time to time. The starch at first gives its deep-blue

*See Biedermann, " Electro-physiology," translation by Welby, London,
1896.

THE SALIVARY GLANDS. 701

reaction with iodin; later, instead of a blue, a red reaction is obtained
with iodin, and this has been attributed to a special form of dextrin,
erythrodextrin, so named on account of its red reaction. Still later
this reaction fails and chemical examination shows the presence of
maltose and a form of dextrin which gives no color reaction with
iodin and is therefore named achroodextrin. While the number
of intermediate products may be large, the main result of the action
of the ptyalin is expressed by the following simple schema :

The products formed in this reaction are probably not absorbed as
such. The absorption takes place mainly no doubt after the food
reaches the small intestine, and we have evidence, as will be stated,
that before absorption the maltose and the dextrin are acted upon by
the inverting enzymes (maltase) and converted into the simple
sugar, dextrose. The ptyalin digestion seems therefore to be pre-
paratory, and the combined action of ptyalin and maltase is necessary
to get the starch into a condition ready for nutrition. By way of
comparison it is interesting to remember that when starch is boiled
with dilute acids it is hydrolyzed at once to dextrose. ' A question of
practical importance is as to how far salivary digestion affects the
starchy foods under usual circumstances. The chewing process in
the mouth thoroughly mixes the food and saliva, or should do so,
but the bolus is swallowed much too quickly to enable the enzyme to-
complete its action. In the stomach the gastric juice is sufficiently
acid to destroy the ptyalin, and it was therefore supposed formerly
that salivary digestion is promptly arrested on the entrance of the
food into the stomach, and is therefore normally of but little value
as a digestive process. Our recent increase in knowledge regarding
the conditions in the stomach (p. 663) shows, on the contrary, that
some of the food in an ordinary meal may remain in the fundie
end of the stomach for an hour or more untouched by the acid
secretion. There is every reason to believe, therefore, that salivary
digestion may be carried on in the stomach to an important extent.
Conditions Influencing the Action of Ptyalin. — Temperature.
— As in the case of the other enzymes, ptyalin is very susceptible to-
changes of temperature. At 0° C. its activity is said to be suspended
entirely. The intensity of its action increases with increase of
temperature from this point, and reaches its maximum at about
40° C. If the temperature is raised much beyond this point, the
action decreases, and at from 65° to 70° C. the enzyme is destroyed.
In these latter points ptyalin differs from diastase, the enzyme of
malt. Diastase shows a maximum action at 50° C. and is destroyed
at 80° C.

702 PHYSIOLOGY OF DIGESTION AND SECRETION.

Effect of Reaction. — The normal reaction of saliva is slightly
alkaline. Chittenden has shown, however, that ptyalin acts as well,
or even better, in a perfectly neutral medium. A strong alkaline
reaction retards or prevents its action. The most marked influence
is exerted by acids. Free hydrochloric acid to the extent of only
0.003 per cent. (Chittenden) is sufficient to practically stop the amy-
lolytic action of the enzyme, and a slight further increase in acidity
not only stops the action, but also destroys the enzyme.

Condition of the Starch. — It is a well-known fact that the conver-
sion of starch to sugar by enzymes takes place much more rapidly
with cooked starch — for example, starch paste. In the latter ma-
terial sugar begins to appear in a few minutes, provided a good
enzyme solution is used. With starch in a raw condition, on the
contrary, it may be many minutes, or even several hours, before
sugar can be detected. The longer time required for raw starch is
partly explained by the fact that the starch grains are surrounded
by a layer of cellulose or cellulose-like material that resists the action
of ptyalin. When boiled, this layer breaks and the starch in the
interior becomes exposed. In addition, the starch itself is changed
during the boiling ; it takes up water, and in this hydrated condition
is acted upon* more rapidly by the ptyalin. The practical value of
cooking vegetable foods is evident from these statements.

Functions of the Saliva. — In addition to the digestive action of
the saliva on starchy foods it fulfills other important functions. By
moistening the food it enables us to reduce the material to a consis-
tency suitable for swallowing and for manipulation by the tongue and
other muscles. Moreover, the presence of mucin serves doubtless
as a kind of lubricator that insures a smooth passage along the
esophageal canal. Finally by dissolving dry and solid food it pro-
vides a necessary step in the process of stimulating the taste nerves,
and, as is described below, the activity of the taste sensations may
play an important part in the secretion of the gastric juice.

CHAPTER XLII.

DIGESTION AND ABSORPTION IN THE STOMACH.

The muscular mechanisms by means of which the stomach is
charged with food and in turn discharged, small portions at a time,
into the duodenum have been described. The present chapter deals
only with the chemical and mechanical changes in the food during
its stay in the stomach and the extent to which the products of
digestion are absorbed.

The Gastric Glands. — The tubular glands that permeate the
mucous membrane of the stomach throughout its entire extent differ
in their histological structure, and therefore doubtless in their secre-
tion, in different parts of the stomach. Two, sometimes three, kinds
of glands are distinguished, — the pyloric, fundic (and cardiac).
Those in the pyloric part of the stomach (antrum pylori) are char-
acterized chiefly by the fact that in the secreting part of the tubule
only one type of gland cell is found, the chief or peptic cell, while in
the remainder of the stomach, but particularly in the middle or
prepyloric region the glands (fundic glands) are distinguished by the
presence of two types of cells, — the chief cells and the so-called cover
or border cells (Fig. 269). The third type, the cardiac glands, is found
around the cardia, but its area of distribution varies in different
animals, and its histological characteristics are not very definite.*
There seems to be a general agreement that the chief cells furnish
the digestive enzymes of the stomach — pepsin and rennin — and the
cover cells the hydrochloric acid. From a physiological standpoint
it is important to remember that the cover cells are massed, as it
were, in the glands of the middle or prepyloric region of the stomach,
that they are scanty in the fundus, and absent in the pyloric region.
This fact is indicated to the eye by the deeper red or brownish color
of the mucous membrane in the prepyloric portion. Grutznerf
called especial attention to this relation, and in connection with the
differences in movements of these two parts of the stomach he
suggests that normally the bulk of the food toward the fundus
becomes impregnated first with pepsin; then, as it is slowly moved
into the prepyloric region, the acid constituent is added. The
pyloric glands are said (Heidenhain) to secrete an alkaline liquid
containing pepsin, and, according to Edkins and Starling they
form a substance which is capable of acting as a chemical excitant

* See Haane, "Archiv f. Anatomic," 1905, 1.
t Grutzner, "Archiv f. die gesammte Physiologic," 106, 463, 1905.

703

704

PHYSIOLOGY OF DIGESTION AND SECRETION.

to the glands secreting the gastric juice (gastric secretin or gastric
hormone) .*

Histological Changes in the Gastric Glands during Secretion.
— The cells of the gastric glands, especially the so-called chief cells,
show distinct changes as the result of prolonged activity. Upon
preserved specimens, taken from dogs fed at intervals of twenty-four
hours, Heidenhain found that in the fasting condition the chief cells
were large and clear, that during the first six hours of digestion the
chief cells as well as the border cells increased in size, but that in a
second period, extending from the sixth to the fifteenth hour, the
chief cells became gradually smaller, while the border cells remained

Fig. 269. — Glands of the fundus (dog) : A and A1, during hunger, resting conditipn?;
B, during the first stage of digestion; C and D, the second stage of digestion, showing
the diminution in the size of the "chief" or central cells. — (After Heidenhain.)

large or even increased in size. After the fifteenth hour the chief
cells increased in size, gradually passing back to the fasting condition
(see Fig. 269).

Langley * has succeeded in following the changes in a more satis-
factory way by observations made directly upon the living gland.

* See Starling, " Physiology of Secretion," Chicago, 1906, and Edkins,
"Journal of Physiology," 1906, xxxiv., 133.
t "Journal of Physiology," 3, 269, 1880.

DIGESTION AND ABSORPTION IN THE STOMACH. 705

He finds that the chief cells in the fasting stage are charged with
granules, and that during digestion the granules are dissolved, dis-
appearing first from the base of the cell, which then becomes filled
with a non-granular material. Observations similar to those made
upon other glands demonstrate that these granules represent in all
probability a preliminary material from which the gastric enzymes
are made during the act of secretion. The granules, therefore, are
sometimes described as zymogen granules.

Means of Obtaining the Gastric Secretion and its Normal
Composition. — The secretion of the gastric membrane is formed in
the minute glands scattered over its surface. As there is no com-
mon duct, the difficulty of obtaining the secretion for analysis or
experiment is considerable. This difficulty has been overcome at
different times by the invention of special methods.

The older methods used for obtaining normal gastric juice were
very unsatisfactory. An animal was made to swallow a clean
sponge to w7hich a string was attached so that the sponge could
afterward be removed and its contents be squeezed out; or it was
made to eat some indigestible material, to start the secretion of
juice by mechanical stimulation : the animal was then killed at the
proper time and the contents of its stomach were collected.

The experiments of the older observers on gastric digestion, especially
those of the Abbe Spallanzani (1729-1799), furnish most interesting reading.
Spallanzani, not content with making experiments on numerous animals
(frogs, birds, mammals, etc.) had the courage to carry out a great many
upon himself. He swallowed foods of various kinds and in various conditions
sewed in linen bags or inclosed in perforated wooden tubes which in turn
were covered with linen. The bags and tubes were subsequently passed
in the stools and were examined as to the amount and nature of their contents.
He seems to have experienced no injury from his experiments, although
normally his powers of digestion were quite feeble. As proof that the trit-
urating power of the stomach is not very great he calls attention to the fact
that some of the wooden tubes were made very thin, so that the slightest
pressure would crush them, and yet they were voided uninjured. So also
he found that cherries and grapes when swallowed whole, even if entirely
ripe, were usually passed unbroken.

A better method of obtaining normal juice was suggested by the
famous observations of Beaumont* upon Alexis St. Martin. St.
Martin, by the premature discharge of his gun, was wounded in the
abdomen and stomach. On healing, a fistulous opening remained in
the abdominal wall, leading into the stomach, so that the contents
of the latter could be inspected. Beaumont made numerous inter-
esting and most valuable observations upon his patient. Since that
time it has become customary to make fistulous openings into the
stomachs of dogs whenever it is necessary to have the normal juice

* Beaumont, "The Physiology of Digestion," 1833; second edition, 1847.
For a biographical account of Beaumont, see Osier, " Journal of the American
Medical Association," November 15, 1902.
45

706

PHYSIOLOGY OF DIGESTION AND SECRETION.

for examination. Formerly a silver cannula was placed in the
fistula, and at any time the plug closing the cannula might be re-
moved and gastric juice be obtained. In some cases the esophagus
has been occluded or excised so as to prevent the mixture of saliva
with the gastric juice. Gastric juice may be obtained from human
beings also in cases of vomiting or by means of the stomach tube,
but in such cases it is necessarily more or less diluted or mixed with
food and cannot be used for exact analyses, although specimens
of gastric juice obtained by these methods are employed in the
diagnosis and treatment of gastric troubles.

From the standpoint of experimental investigation a very im-
portant addition to our methods was made by Heidenhain. This
observer showed that a portion of the stomach — the fundic end, for
instance, or the pyloric end — might be cut away from the rest of the

organ and be given an
artificial opening to the
exterior. By this means
the secretion of an isolated
fundic or pyloric sac may
be obtained and examined
as to its quantity and prop-
erties. The method was
subsequently improved by
Pawlow, whose important
contributions are referred
to below. Fig. 270 gives
an idea of the operation as
made by Pawlow to isolate
a fundic sac with its blood
and nerve supply unin-
jured.

The normal gastric se-
cretion is a thin, colorless
or nearly colorless liquid
with a strong acid reaction and a characteristic odor. Its spe-
cific gravity varies, but it is never great, the average being about
1.002 to 1.003. Upon analysis the gastric juice is found to contain
a trace of protein, probably a peptone, some mucin, and inorganic
salts, but the essential constituents are an acid (HC1) and two
enzymes, pepsin and rennin. Satisfactory complete analyses of the
human juice have not been reported, most of the recent observers
confining their attention mainly to the degree of acidity and digestive
power. Gastric juice does not give a coagulum upon boiling, but the
digestive enzymes are thereby destroyed. One of the interesting
facts about this secretion is the way in which it withstands putrefac-
tion. It may be kept for a long time, for months even, without

Fig. 270. — To show Pawlow's operation for
making an isolated fundic sac from the stomach:
v, Cavity of the stomach ; «, the fundic sac, shut off
from the stomach and opening at the abdominal
wall, a, a; b indicates the line of sutures. — (Paw-
low.)

DIGESTION AND ABSORPTION IN THE STOMACH. 707

becoming putrid and with very little change, if any, in its digestive
action or in its total acidity. This fact shows that the juice possesses
antiseptic properties, and it is usually supposed that the presence of
the free acid accounts for this quality.

The Acid of Gastric Juice. — The nature of the free acid in gastric
juice was formerly the subject of dispute, some claiming that the
acidity is due to HC1, since this acid can be distilled off from the gas-
tric juice, others contending that an organic acid, lactic acid, is
present in the secretion. All recent experiments tend to prove that
the acidity is due to HC1. This fact was first demonstrated satis-
factorily by the analyses of Schmidt, who showed that if, in a given
specimen of gastric juice, the chlorids were all precipitated by silver
nitrate and the total amount of chlorin was determined, more was
found than could be held in combination by the bases present in the
secretion. Evidently, some of the chlorin must have been present
in combination with hydrogen as hydrochloric acid. Confirmatory
evidence of one kind or another has since been obtained. Thus it has
been shown that a number of color tests for free mineral acids react
with the gastric juice: methyl- violet solutions are turned blue,
congo-red solutions and test paper are changed from red to blue,
00 tropeolin from a yellowish to a pink red, and so on. A number of
additional tests of the same general character will be found described
in the laboratory handbooks.* It must be added, however, that
lactic acid undoubtedly occurs, or may occur, in the stomach during
digestion. Its presence is usually explained as being due to the fer-
mentation of the carbohydrates, and it is therefore more constantly
present in the stomachs of the herbivora. The amount of free
hydrochloric acid varies according to the duration of digestion;
that is, the secretion does not possess its full acidity in the beginning
owing to the fact (Heidenhain) that in the first periods of digestion,
while the secretion is still scanty in amount, a portion of its acid
is neutralized by the swallowed saliva, the alkaline mucus, and the
alkaline secretion of the pyloric end of the stomach; the secreted
juice has, however, a constant acidity. The acidity of the human
gastric juice is usually estimated at 0.3 per cent., but during diges-
tion it may reach (Hornborg) 0.4 to 0.5 per cent., and these figures ex-
press probably its strength as secreted. The acidity of the dog's gas-
tric juice, according to Pawlow, lies between 0.46 and 0.56 per cent.

The Origin of the HC1. — The gastric juice is the only secretion
of the body that contains a free acid. The fact that the acid is a
mineral acid and is present in considerable strength makes the cir-
cumstance more remarkable. Attempts have been made to ascer-
tain the histological elements concerned in its secretion and the
nature of the chemical reaction or reactions by which it is produced.
With regard to the first point it is generally believed that the border
* Simon, "A Manual of Clinical Diagnosis," 1904.

708 PHYSIOLOGY OF DIGESTION AND SECRETION.

cells of the gastric tubules constitute the acid-secreting cells. This
belief is founded upon the general fact that in the regions in which
these cells are chiefly present — that is, the middle region of the
stomach — the secretion is distinctly acid, and where they are absent
or scanty in number the secretion is alkaline or less acid. In the
pyloric region, for instance, these cells are lacking entirely and the
secretion is alkaline. So also in the fundus the secretion does not
seem to be acid, and this fact corresponds with a marked diminution
or absence of the border cells. With regard to the origin of the acid
it is evident that it is formed in the secreting cells, since none exists in
the blood or lymph. It seems also perfectly evident that the HC1
must be formed from the chlorids of the blood. The chief chlorid
is NaCl and by some means this compound is broken up: the chlorin
is combined with hydrogen, and is then secreted upon the free surface
of the stomach as HC1. In support of this general statement it has
been shown that if the chlorids in the blood are reduced by removing
them from the food for a sufficient tune the secretion of gastric juice
no longer contains acid. On the other hand, addition of NaBr or
KI to the food may cause the formation of some HBr and HI,
together with HC1 in the gastric juice. Maly has suggested that
acid phosphates may be produced in the first instance, and then by
reacting with the sodium chlorid may give hydrochloric acid, accord-
ing to the formula NaH2P04 + NaCl = Na2HPO4 + HC1. Other
theories have been proposed, but, as a matter of fact, no explanation
of the details of this reaction is satisfactory. We must be content
to say that in the acid-forming cells the neutral chlorids (NaCl) are
broken up with the formation of free HC1.

The Secretory Nerves of the Gastric Glands. — Although several
facts indicated to the older observers that the secretion of gastric
juice is under the control of nerve fibers, we owe the actual experi-
mental demonstration of this fact to Pawlow.* He demonstrated
that the secretion is under the control of the nervous system and that
the secretory fibers are contained in the vagus. Direct stimulation
of the peripheral end of the cut vagus causes a secretion of gastric
juice after a long latent period of several minutes. This long latency
may be due possibly to the presence in the vagus of inhibitory
fibers to the gland, which, being stimulated simultaneously with the
secretory fibers, delay the action of the latter. Very striking proof
of the general fact that the secretion is due to the action of vagus
fibers is furnished by such experiments as these : Pawlow divided the
esophagus in the neck and brought the two ends to the skin so as to
make separate fistulous openings to the exterior. Under these con-
ditions, when the animal ate and swallowed food it was discharged

* See Pawlow, " The Work of the Digestive Glands, " translated by
Thompson, 1902.

DIGESTION AND ABSORPTION IN THE STOMACH. 709

to the exterior instead of entering the stomach. The animal thus had
the enjoyment of eating without actually filling the stomach. Eating
in this style forms what the author called a fictitious meal (Schein-
jiitterung). It was found that it causes an abundant flow of gastric
juice as long as the vagi are intact, but has no effect on the secretion
when these nerves are cut. Evidently, therefore, the sensations of
taste, odor, etc., developed during the mastication and swallowing
of food set up reflexly a stinfulation of secretory fibers in the vagus.
Pawlow designates a secretion produced in this way as a psychical
secretion, — a term which implies that the reflex must be attended by
conscious sensations. In favorable cases the fictitious feeding has
been continued for five or six hours and a large amount of gastric
juice (700 c.c.) has been collected from a 'fistula, although no food
actually entered the stomach. It is important to note, also, that a
psychical secretion, once started, may continue for a long time after
the stimulus (the eating) has ceased. Experiments have been made
upon human beings under similar conditions. Thus, Hornborg*
reports the case of a boy with a stricture of the esophagus and a
fistula in the stomach. Food when chewed and swallowed did not
reach the stomach, but was regurgitated; it caused, nevertheless,
an active psychical secretion in the empty stomach.

Normal Mechanism of the Secretion of the Gastric Juice. —
During a meal the gastric juice is secreted, under normal conditions,
as long as the food remains in the stomach. The modern explana-
tion of the origin, maintenance, and regulation of this flow of secre-
tion is due chiefly to Pawlow. Contrary to a former general belief,
he showed that mechanical stimulation of the gastric mucous mem-
brane has no effect on the secretion of the tubules. This factor may
therefore be eliminated. In an ordinary meal the secretion first
started is due to the sensations of eating — that is, it is a psychical
secretion. The afferent stimuli originate in the mouth and nostrils;
the efferent path, the secretory fibers, is through the vagus nerve.
This reflex insures the beginning at least of gastric digestion, but its
effect is supplemented by a further action arising in the stomach
itself. It seems that some foods contain substances designated as
secretogogues, that are able to cause a secretion of gastric juice
when taken into the stomach. In other foods these ready-formed
secretogogues are lacking. Thus, meat extracts, meat juices,
soups, etc., are particularly effective in this respect; milk and water
cause less secretion. Certain common articles of food, such as
bread and white of eggs, have no effect of this kind at all. If
introduced into the stomach of a dog through a fistula so as not to
arouse a psychical secretion, — for instance, while the dog's attention
is diverted or while he is sleeping, — they cause no flow of gastric
* Hornborg, "Skandinavisches Archiv f. Physiologie," 15, 209, 1904.

710

PHYSIOLOGY OF DIGESTION AND SECRETION.

juice and are not digested. If such articles of food are eaten,
however, they cause a psychical secretion, and when this has acted
upon the foods some products of their digestion in turn become
capable of arousing a further flow of gastric juice. The steps in
the mechanism of secretion are, therefore, three: (1) The psychical
secretion; (2) the secretion from secretogogues contained in the

food; (3) the secretion
from secretogogues
contained in the
products of digestion.
The manner in which
the secretogogues act
cannot be stated posi-
tively. Since the gas-
tric glands possess
secretory nerve fibers
the first explanation
to suggest itself is
that the secreto-
gogues by acting on
sensory fibers in the
gastric mucous mem-
brane reflexly stimu-
late the secretory
fibers. This expla-
nation, however, is
rendered untenable
by the fact that the
effect of these sub-
stances is obtained
after complete sever-
ance of the nervous
connections of the
stomach. If, there-
fore, this so-called
chemical secretion is

.pi

Acidity in
percentage.

Quantity in
cubic centi-
meters.

MILK, MEAT, BREAD,
600 c.c. 100 gms. 100 gms.

10
8
6
4
2
0

0.576
0.528
0.480
0.432
0.384
0.336
0.288
0.240
0.192
0.144
0.096
0.048
0

18
16
14
12
10
8
6
4
2
0

s

^

\

ss

i

\

i

\

i

J

\

i

\

!

^^

\

\

\

\

\

-/

^

!=

f=

_ i

^5

>

r

^

j= —

v(

'

_\,

Hours .

/ 234-36789 WinZ

Quantity of secretion.

-___„ Acidity.

_— — — Digestive power.

Fig. 271. — Diagram showing the variation in quantity
of gastric secretion in the dog after a mixed meal ; also
the variations in acidity and in digestive power. — (After
K h igine.)

produced by a ner-
vous reflex the nerve centers concerned must lie in the stomach
itself, the reflex must take place through the peripheral ganglion
cells. Another more probable explanation has been offered.
Edkins * has shown that decoctions of the pyloric mucous mem-
brane, made by boiling in water, acid or peptone solutions,
when injected into the blood cause a marked secretion of gastric
juice. These substances when injected alone into the blood cause
* Edkins, " Journal of Physiology," 1906, xxxiv., p. 133.

DIGESTION AND ABSORPTION IN THE STOMACH. 711

no such effect, and decoctions of the mucous membrane of the
fundic end of the stomach are without action on the gastric secretion.
This author suggests, therefore, that the secretogogues, whether
preformed in the food or formed during digestion, act upon the
pyloric mucous membrane and form a substance which he designates
as gastrin or gastric secretin, and this substance after absorption
into the blood is carried to the gastric glands and stimulates them
to secretion. The effect is, therefore, not a usual nervous reflex, but
an instance of the stimulation of one organ by chemical products
formed in another. Starling * has emphasized the fact that this
mode of control is frequently employed in the body, as will be
described in the following pages in connection with the pancreatic
secretion and the internal secretions. He proposes to designate
such substances by the general term of hormones (from 6/y/*«w,
arouse or excite).

The researches of Pawlow and his co-workers seem also to in-
dicate that the quantity and properties of the secretion vary with
the character of the food. The quantity of the secretion varies,
also, other conditions being the same, with the amount of food to
be digested. The apparatus is adjusted in this respect to work
economically. Different kinds of food produce secretions varying
not only as regards quantity but also in their acidity and diges-
tive action. The secretion produced by bread, though less in
quantity than that caused by meat, possesses a greater digestive
action. On a given diet the secretion assumes certain characteris-
tics, and Pawlow is convinced that further work will disclose the fact
that the secretion of the stomach is not caused normally by general
stimuli all affecting it alike, but by specific stimuli contained in the
food or produced during digestion, whose action is of such a kind
as to arouse reflexly the secretion best adapted to the food ingested.

One of the curves, showing the effect of a mixed diet (milk, 600
c.c.; meat, 100 gms.; bread, 100 gms.) upon the gastric secretion,
as determined by Pawlow's method, is reproduced in Fig. 271. It will
be noticed that the secretion began shortly after the ingestion of the
food (seven minutes), and increased rapidly to a maximum that was
reached in two hours. After the second hour the flow decreased
rapidly and nearly uniformly to about the tenth hour. The acidity
rose slightly between the first ancl second hours, and then fell gradu-
ally. The digestive power showed an increase between the second
and third hours.

Nature and Properties of Pepsin. — Pepsin is a typical proteo-

lytic enzyme that exhibits the striking peculiarity of acting only in

acid media; hence peptic digestion in the stomach is the result of

the combined action of pepsin and hydrochloric acid. Pepsin is

* Starling, " Recent Advances in the Physiology of Digestion," 1906.

712 PHYSIOLOGY OF DIGESTION AND SECRETION.

influenced in its action by temperature, as is the case with the other
enzymes; low temperatures retard, and may even suspend its
activity, while high temperatures increase it. The optimum tem-
perature is stated to be from 37° to 40° C., while exposure for some
time to 80° C. results, when the pepsin is in a moist condition, in the
total destruction of the enzyme. Pepsin may be extracted from the
gastric mucous membrane by a variety of methods and in different
degrees of purity and strength. The commercial preparations of
pepsin consist usually of some form of extract of the gastric mucous
membrane to which starch or sugar of milk has been added. Labora-
tory preparations are made conveniently by mincing thoroughly
the mucous membrane and then extracting for a long time with
glycerin. Glycerin extracts, if not too much diluted with water or
blood, keep for an indefinite time. Purer preparations of pepsin
have been made by what is known as "Briicke's method," in which
the mucous membrane is minced and is then self-digested with a 5
per cent, solution of phosphoric acid. The phosphoric acid is pre-
cipitated by the addition of lime-water, and the pepsin is carried
down in the flocculent precipitate. This precipitate, after being
washed, is carried into solution by dilute hydrochloric acid, and a
solution of cholesterin in alcohol and ether is added. The cholesterin
is precipitated, and, as before, carries down with it the pepsin. This
precipitate is collected, carefully washed, and then treated repeatedly
with ether, which dissolves and removes the cholesterin, leaving the
pepsin in aqueous solution. This method is interesting not only
because it gives a pure form of pepsin, but also in that it illustrates
one of the properties of enzymes — namely, the readiness with which
they adhere to precipitates occurring in their solutions.

In spite of much work the chemical nature of pepsin is undeter-
mined. Most authors agree that it is a protein or protein-containing
body. Pekelharing* has prepared pepsin from gastric juice by
dialysis, the substance precipitating as the acid is dialyzed off. The
precipitate may be purified by repeated resolutions in acid followed
by dialysis. As prepared by this method pepsin is a substance of a
protein nature which contains sulphur and also some chlorin, but no
phosphorus. It does not belong, therefore, to the group of nucleo-
proteins.

Pepsin is supposed to be formed in the chief cells of the gastric
tubules, but as in other cases it is present in the cells as a zymogen
or propepsin which is not changed to the active pepsin until after
secretion. The propepsin may be extracted readily from the mucous
membrane, and, since it is known that the zymogen is converted
quickly to active pepsin by the action of acids, it is evident that in
the normal gastric juice the existence of the hydrochloric acid
* Pekelharing, "Zeitschrift f. physiol. Chemie," 35, 8, 1902.

DIGESTION AND ABSORPTION IN THE STOMACH. 713

Insures that all of the pepsin shall be present in active form. There
has been much discussion as to the nature of the secretion of the
pyloric glands. Heidenhain isolated this portion of the stomach and
collected its secretion. He found that it was alkaline and contained
pepsin. Later observers, however, still continue to doubt the secre-
tion of a true pepsin in this portion of the stomach. Glaessner*
states that propepsin can not be obtained from extracts of the pyloric
glands, and that the proteolytic enzyme that can be shown in this
portion of the stomach by self-digestion in acid or alkaline media is
not a true gastric pepsin. The possibility that a special secretin
(hormone) is formed in the pyloric mucous membrane has been
referred to above (p. 711). From the description of the events
in the stomach (p. 661) it would seem that the food material which
is churned and stirred by the contractions of the pyloric musculature
has already been charged with pepsin and hydrochloric acid by the
glands of the middle and fundic regions.

Artificial Gastric Juice. — In studying peptic digestion it is not
necessary for all purposes to establish a gastric fistula. The active
agents of the normal juice are pepsin and an acid of a proper strength ;
and, as the pepsin can be extracted and preserved in various ways
and the hydrochloric acid can easily be made of the proper strength,
an artificial juice can be obtained at any time and may be used in
place of the normal secretion for many purposes. In laboratory ex-
periments it is customary to employ a glycerin or commercial prep-
aration of the gastric mucous membrane, and to add a small portion
of this preparation to a large bulk of 0.2 per cent, hydrochloric acid.
The artificial juice thus made, when kept at a temperature of from
37° to 40° C., will digest proteins rapidly if the preparation of pepsin
is a good one. While the strength of the acid employed is generally
from 0.2 to 0.3 per cent., digestion will take place in solutions of
greater or less acidity. Too great or too small an acidity, however,
will retard the process; that is, there is for the action of the pepsin
an optimum acidity which lies somewhere between 0.2 and 0.5
per cent. Other acids may be used in place of the hydrochloric
acid — for example, nitric, phosphoric, or lactic — but they are not
so effective, and the optimum acidity is different for each; for
phosphoric acid it is given as 2 per cent.

The Pepsin-hydrochloric Digestion of Proteins. — It has
long been known that solid proteins, when exposed to the action of a
normal or an artificial gastric juice, swell up and eventually pass into
solution. The soluble protein thus formed was known not to be
coagulated by heat and was remarkable also for being more diffusible
than other forms of soluble proteins. This end-product of digestion
was formerly conceived as a soluble protein with properties fitting
* Glaessner, " Beitriige zur chem. Physiol. u. Pathol.," 1, 24 1901.

714 PHYSIOLOGY OF DIGESTION AND SECRETION.

it for rapid absorption, and the name of peptone was given to it. It
was quickly found, however, that the process is complicated — that in
the conversion to so-called "peptone" the protein under digestion
passes through a number of intermediate stages. The intermediate
products were partially isolated and were given specific names, such
as acid-albumin, parapeptone, and propetone. The present concep-
tion of the process we owe chiefly to Kiihne. This author believed
that the protein passes through three general stages before reaching
the final condition of peptone. This view is indicated briefly by the
following schema :

Native protein.

Acid albumin (syntonin).

Primary proteoses (protalbumoses).

Secondary proteoses (deutero-albumoses).

Peptone.

The first step is the conversion of the protein to an acid albumin.
This change may be considered as being chiefly an effect of the hy-
drochloric acid, although in some way the combined action of the
pepsin-hydrochloric acid compound is more effective than a solution
of the acid alone of the same strength. Like the acid albumins in
general (see appendix), the syntonin is readily precipitated on
neutralization. In the beginning of peptic digestion, therefore,
if the solution is neutralized with dilute alkali, an abundant precipi-
tate of syntonin occurs. Later on in the digestion neutralization
gives no such effect — the syntonin has all passed into a further stage
of digestion. Under the influence of the pepsin the syntonin under-
goes hydrolysis, with the production of a number of bodies which
as a group are designated as primary proteoses or protalbumoses.*
Although several members of this group have been isolated and given
separate names, so much doubt prevails as to the chemical individ-
uality of these substances that it is best perhaps to regard them as a
group of compounds which under the continued influence of the
pepsin undergo still further hydrolysis with the formation of secon-
dary proteoses or deutero-albumoses. As compared with the primary
proteoses, the secondary ones are distinguished by a greater solu-
bility ; they require a stronger saturation with neutral salts to precipi-
tate them. (See Appendix.) The secondary proteoses undergo still
further hydrolysis, with the production of peptone, or perhaps it
would be better to say peptones. The peptones show still greater
solubility, and, in fact, peptone, in Kiihne's sense, is that compound
or group of compounds formed in peptic digestion which, while still
showing protein reactions (biuret reaction), is not coagulated by

* The products intermediate between the original protein and the pep-
tone are described in general as albumoses or as proteoses, according as one
takes the term protein or albumin as the generic name for the original sub-
stance. The term protein is generally used in English ; hence, the intermedi-
ate products are more appropriately designated as proteoses.

DIGESTION AND ABSORPTION IN THE STOMACH. 715

heat nor precipitated when its solutions are completely saturated
with ammonium sulphate. According to the schema and descrip-
tion given above, the several stages in peptic digestion are repre-
sented as- following in sequence. It should be stated, however,
that many authors consider that even in the beginning of the
digestion the protein molecule may be split into several complexes,
and that some of the end-products may be formed in the very
beginning of the action. All that we can state very positively
is that the protein molecules undergo a series of hydrolytic cleav-
ages, the end-result of which is that in place of the originally very
large molecule with a weight of 5000 to 7000 there is obtained a
number of much smaller and much more soluble molecules wThose
molecular weights are perhaps only 250 to 400 or less.

It was formerly believed that pepsin was not able to split the complex
protein molecule into compounds of a simpler structure than the peptone.
But a number of recent authors have stated that if time enough is given
the breaking up of the protein molecule may be as complete as after the action
of trypsin, or after hydrolysis by acids (see Proteins in appendix). That
is, along with the peptone or in place of it are found certain simpler bodies
which no longer give the biuret reaction, but are precipitable by phospho-
tungstic acid and for which Hofmeister proposes the general name of pep-
toids. They would correspond, also, apparently, to the group of compounds
designated by Fischer as peptids or polypeptids. In addition, many of the
amino-acids and nitrogenous bases which constitute the final end-products
of the breaking up of the protein molecule may be found.*

In judging the digestive action of any given specimen of natural
or artificial gastric juice it is customary to measure the rapidity
with which an insoluble protein is converted into a soluble form.
The method most commonly employed is that devised in Pawlow's
laboratory by Mett. The Mett test is made by sucking white of egg
into a thin-walled glass tube having an internal diameter of 1 to 2
mms. The egg-albumin is coagulated in the tube by immersing it for
five minutes in water at 95° C. After some time the tube is cut into
lengths of 10 to 15 mms. and these are used to test the digestive action
or amount of pepsin. One or more of the tubes are placed in the
solution to be measured and kept for ten hours at body temperature.
The digestive power is measured in terms of the length in millimeters
of the column of egg-albumin that is dissolved. The relative amounts
of pepsin in solutions compared in this way are determined by the
law of Schiitz, according to which the digestive power is proportional
to the square root of the amount of pepsin. If in two specimens of
gastric juice the number of millimeters of egg albumin digested
was in one case two and in the other three, the digestive powers of the
two solutions would be as the squares of the numbers, as 4 to 9.

The Rennin Enzyme (Rennet, Chymosin). — The property
possessed by the mucous membrane of the calf's stomach of curdling

* See Hofmeister, " Ergebnisse der Physiologic," vol. i, part i, 796, 1902.

716 PHYSIOLOGY OF DIGESTION AND SECRETION.

milk has been known from remote times, and has been utilized in the
manufacture of cheese and curds. This action takes place with
remarkable rapidity under favorable conditions, a large mass of milk
setting to a firm coagulum within a very brief time. It .has been
shown that this effect is due to an enzyme — rennin or rennet. The
rennin. like the pepsin, is supposed to be formed in the chief cells of
the gastric tubules and to be present in the glands in a zymogen
form, the prorennin or prochymosin, which after secretion is con-
verted to the active enzyme. This conversion takes place very
readily under the influence of acid. Rennin (or its zymogen) may be
obtained easily from the mucous membrane of the stomach '(with
the exception of the pyloric end) by extracting with glycerin or water
or by digesting with dilute acid. Good extracts of rennin cause
the milk to clot with great rapidity at a temperature of 40° C.; the
milk (cows' milk), if undisturbed, sets at first into a solid clot, which
afterward shrinks and presses out a clear, yellowish liquid — the
whey. With human milk the curd is much less firm, and takes the
form of loose flocculi. The whole process resembles much the clotting
of blood. The rapidity of clotting is said to vary inversely as the
amount of rennin, or, in other words, the product of the amount of
rennin and the time necessary for clotting is a constant. The
curdling of the milk involves two apparently independent proc-
esses : First, the rennin acts upon the casein of the milk and converts
it into a substance known as paracasein. The paracasein then
reacts with the lime salts of the milk, forming an insoluble calcium
salt, which constitutes the curd or coagulum. According to this
view, the enzyme does not cause clotting directly. What takes place
when the casein is changed to paracasein is not understood. Ham-
marsten originally regarded the change as a cleavage process, but
this view has not been supported. Others have supposed that a
transformation or rearrangement of molecular structure occurs.
Indeed, the differences in properties between casein and paracasein
are not great, the most marked difference being that the calcium
salts of the latter are insoluble. If soluble calcium salts are removed
from milk by the addition of oxalate solutions it does not curdle upon
the addition of rennin. Addition of lime salts restores this property.
It should be added that casein is also precipitated from milk by the
addition of an excess of acid. The curdling of sour milk in the
formation of bonnyclabber is a well-known illustration of this fact.
When milk stands for some time the action of bacteria upon the milk-
sugar leads to the formation of lactic acid, and when this acid
reaches a certain concentration it causes the precipitation of the
casein.

So far as our positive knowledge goes, the action of rennin is
confined to milk. Casein is the chief protein constituent of milk,

DIGESTION AND ABSORPTION IN THE STOMACH. 717

and has therefore an important nutritive value. It is interesting
to find that before its peptic digestion begins the casein is acted
upon by an altogether different enzyme. The value of the curdling
action is not at once apparent, but we may suppose that casein is
more easily digested under the conditions that exist in the body after
it has been brought into a solid form. This has, however, been
doubted, and it has even been suggested that the process is a hin-
drance rather than an aid to the digestion of the casein. Until the
contrary is definitely demonstrated it is preferable to assume that
the process is of importance in the digestion of milk. The action of
rennin goes no further than the curdling; the digestion of the curd
is carried on by the pepsin, and later, in the intestines, by the
trypsin, with the formation of proteoses and peptones as in the
case of other proteins.*

Rennin is found elsewhere than in the gastric mucosa. It has been
described in the pancreatic juice, in the testis, and in many other organs
as well as in the tissues of many plants. In fact, wherever proteplytic enzymes
are found there also some evidence of a curdling action on milk may be ob-
tained. For this reason some observers f have taken the view that the milk coag-
ulation is not due to a specific ferment, but is an action of the pepsin itself.
That is, the proteolytic enzyme is capable of causing the change from casein
to paracasein as well as the hydrolysis of the proteid. This view is opposed to
the prevalent opinion regarding the specificity of enzyme actions.

Another interesting fact concerning rennin is that an animal may be im-
munized against it (see p. 399). If rennin be injected subcutanepusly in
an animal an antirennin will be formed in its blood. This antirennin added
to milk prevents its curdling by rennin, giving a result, therefore, similar
to the reaction between toxins and antitoxins.

The Digestive Changes Undergone by the Food in the
Stomach. — In addition to the pepsin and rennin various observers
have described other enzymes in the gastric juice or gastric mem-
brane— a lipase or fat-splitting enzyme (Volhard), an amylolytic
or starch-splitting enzyme (Friedenthal) , and an inverting enzyme
(Widdicombe) — but the normal existence or at least the normal
action of these latter enzymes in digestion is a matter about which
little is known. As was said above, it is probable that the ptyalin
swallowed with the food continues to exert its action upon the
starchy materials in the fundus for a long time, so that in this way
the starch digestion in the stomach may be important. Regarding
the fats, it is usually believed that they undergo no truly digestive
change in the stomach. They are set free from their intimate
mixture with other foodstuffs by the dissolving action of the gastric
juice upon proteins, they are liquefied by the heat of the body, and
they are disseminated through the chyme in a coarse emulsion by

* For references to the very abundant literature consult Oppenheimer,
loc. cit.

fSee Pawlow and Parastschuk, "Zeitschrift f. physiol. Chemie," 42, 415.

718 PHYSIOLOGY OF DIGESTION AND SECRETION.

the movements of the stomach. In this way they are mechanically
prepared so that the subsequent action of the pancreatic juice is
much favored. When, however, fats are ingested in emulsified
form, as in milk, for instance, the lipase of the stomach, according to
Volhard, may cause a marked hydrolysis. It is supposed that
this action may be important in the digestion of the milk-fat by
infants. Regarding the proteins, the practical point of interest
is as to how far they are digested during their stay in the stomach.
It seems probable that this question does not admit of a categorical
answer — that is, the extent of the digestion varies under different
circumstances; with the consistency of the food, the duration of
its stay in the stomach, etc. In the liquid material (chyme) forced
through the pylorus into the duodenum one may find unchanged
proteins, primary or secondary proteoses, peptones, or even the final
split products of proteolytic action. The true value of peptic diges-
tion is not so much in its own action as in its combined action with
the trypsin of the pancreatic juice. The digestion of the proteins
of the food is accomplished by both enzymes, and normally we are
justified in considering them together as effecting a peptic-tryptic
digestion. The preliminary digestion in the stomach is important
as regards the protein foods from several standpoints: First, in the
matter of mechanical preparation of the food and its discharge in
convenient quantities easily handled by the duodenum. Second,
in the more or less complete hydrolysis to peptones and proteoses
whereby the action of the pancreatic juice must be greatly acceler-
ated. Indeed, in some cases, this preliminary action of the pepsin-
hydrochloric acid may be absolutely necessary. Native proteins,
such as serum-albumin, are not acted upon by trypsin, but if sub-
mitted first to pepsin-hydrochloric acid they are quickly digested by
this enzyme. Third, for some as yet unknown reason proteins sub-
mitted to peptic digestion are split by the trypsin in a way different
from its action on proteins without this preliminary treatment.
These and other facts seem to indicate that the peptic digestion is not
so much an end in itself as a preparation for subsequent intestinal
digestion. The stomach, therefore, may be removed without a
fatal result. Several cases are on record in which the stomach was
practically removed by surgical operation, the esophagus being
stitched to the duodenum.* The animals did well and seemed
perfectly normal, although special precautions were necessary in
the matter of feeding.

Absorption in the Stomach. — In the stomach it is possible that
there may be absorption of the following substances : Water ; salts ;
sugars and dextrins that may have been formed in salivary digestion

*Ludwig and Ogata, "Archiv f. Physiologic," 1883, p. 89; Carvallo and
Pachon, "Archives de physiologie norm, et path.," 1894, p. 106.

DIGESTION AND ABSORPTION IN THE STOMACH. 719

from starch, or that may have been eaten as such; the proteoses and
peptones formed in the peptic digestion of proteins or albuminoids.
In addition, absorption of soluble or liquid substances — drugs,
alcohol, etc., that have been swallowed — may occur. It was formerly
assumed, without definite proof, that the stomach absorbs easily
such things as water, salts, sugars, and peptones. Actual experi-
ments, however, made, under'conditions as nearly normal as possible,
show, upon the whole, that absorption does not take place readily
in the stomach — certainly nothing like so easily as in the intestine.
The methods made use of in these experiments have varied, but the
most interesting results have been obtained by establishing a fistula
of the duodenum just beyond the pylorus.* After establishing this
fistula food may be given to the animal and the contents of the
stomach as they pass out through the pyloric opening may be
caught and examined.

Water. — Experiments of the character just described show that
water when taken alone is practically not absorbed at all in the
stomach. Von Mering's experiments especially show that as soon
as water is introduced into the stomach it begins to pass into the
intestine, being forced out in a series of spurts by the contractions of
the stomach. Within a comparatively short time practically all
the water can be recovered in this way, none or very little having
been absorbed in the stomach. For example, in a large dog with a
fistula in the duodenum, 500 c.c. of water were given through the
mouth. Within twenty-five minutes 495 c.c. had been forced out of
the stomach through the duodenal fistula. This result is not
true for all liquids; alcohol, for example, is absorbed readily.

Salts. — The absorption of salts from the stomach has not been
investigated thoroughly. According to Brandl, sodium iodid is
absorbed very slowly or not at all m dilute solutions. Not until its
solutions reach a concentration of 3 per cent, or more does its absorp-
tion become important. This result, if applicable to all the soluble
inorganic salts, would indicate that under ordinary conditions they
are practically not absorbed in the stomach, since it can not be sup-
posed that they are normally swallowed in solutions so concentrated
as 3 per cent. In the same direction Meltzer reports that solutions
of strychnin are absorbed with difficulty from the stomach as com-
pared with the intestines, rectum, or even the pharynx. It is said
that the absorption of sodium iodid is very much facilitated by
the use of condiments, such as mustard and pepper, or alcohol,
which act either by causing a greater congestion of the mucous
membrane or perhaps by directly stimulating the epithelial cells.

* Compare von Mering, " Verhandl. des Congresses f. innere Med.," 12,
471, 1893; Edkins, "Journal of Physiology," 13, 445, 1892; Brandl, "Zeit-
schrift f. Biologic," 29, 277, 1892.

720 PHYSIOLOGY OF DIGESTION AND SECRETION.

Sugars and Peptones. — Experiments by the newer methods leave
no doubt that sugars and peptones can be absorbed from the stomach.
In von Mering's work different forms of sugar — dextrose, lactose,
saccharose (cane-sugar), maltose, and also dextrin — were tested.
They were all absorbed, but it was found that absorption was more
marked the more concentrated were the solutions. Brandl reports
that sugar (dextrose) and peptone are not sensibly absorbed until
the concentration has reached 5 per cent. With these substances
also the ingestion of condiments or of alcohol increases distinctly the
absorptive processes in the stomach. Examination of the mucous
membrane of a stomach in full digestion shows that it contains
albumoses (Glaessner), — a fact that indicates some absorption.
Direct examination of the stomach contents* indicates that the
products of peptic action beyond the albumose stage — namely,
the peptones, peptids, and amido-bodies — are absorbed. On the
whole, however, it would seem that sugars and peptones are ab-
sorbed with some difficulty from the stomach.

Fats. — As we have seen, fats probably undergo no digestive
changes in the stomach, except when eaten in emulsified form.
The processes of saponification and emulsification -are supposed to
be preliminary steps to absorption, and these processes take place
usually after the fats have reached the small intestine. The fat that
is not acted upon at all in the stomach is, of course, not absorbed,
and even those fats in emulsified form which are partially saponified
in the stomach escape absorption until they reach the small intestine.
* Zunz, 'Beitrage zur chem. Physiol. u. Pathol.," 3, 339, 1903.

CHAPTER XLIII.
DIGESTION AND ABSORPTION IN THE INTESTINES.

The food undergoes its most profound digestive changes in the
intestines, and here also the products of digestion are mainly ab-
sorbed. The intestinal digestion begins in the duodenum, and is largely
completed by the time that the food arrives at the ileocecal valve.
It is effected through the combined action of three secretions, — the
pancreatic juice, the secretion from the intestinal glands (succus
entericus), and the bile. These secretions are mixed with the food
from the duodenum on, so that their action proceeds simultaneously.
For purposes of description it is necessary to speak of each more or
less separately.

The Pancreas. — The pancreas forms a long, narrow gland reach-
ing from the spleen to the curvature of the duodenum. Its main
duct in man (duct of Wirsung) opens into the duodenum, together
with the common bile-duct, about 8 to 10 cms. beyond the pylorus.
The points at which the duct or ducts of the pancreas enter the
intestine vary somewhat in different mammals. In the dog there are
two ducts, one opening, together with the bile-duct, about 3 to 5
cms. below the pylorus, while a second enters the duodenum some
3 to 5 cms. farther down. In rabbits the principal pancreatic duct
opens separately into the duodenum about 35 cms. below the opening
of the bile-duct. The pancreas is a compound tubular gland like
the salivary glands. The cells lining the secreting portion of the
tubules, the alveoli, belong to the serous or albuminous type. They
are characterized by the fact that the outer portion of each cell is
composed of a clear, non-granular material which stains readily,
while the inner portion, the portion facing the lumen, contains
numerous granules. Histological study of the gland after active
secretion, as compared with the resting state, has shown very con-
clusively that these granules represent a preparatory material for
secretion. As the secretion proceeds the granules are dissolved
and discharged into the lumen, while during the periods of rest new
granules are formed by metabolic processes at the expense, appar-
ently, of the non-granular material in the basal portion of the cell.
(Heidenhain, Kiihne, Lea). The histological picture of secretion
is in general the same in this as in the salivary and gastric glands,
only somewhat more distinctly shown. On the supposition that the
granules constitute an antecedent material from which the enzymes

721

722 PHYSIOLOGY OF DIGESTION AND SECRETION.

of the secretion are formed they are frequently designated as zymo-
gen granules. The pancreas contains also certain peculiar groups of
cells, the islands (or bodies) of Langerhans. These cells probably
have nothing to do with the digestive activity of the pancreas.
Their supposed function is referred to in the sections on Internal
Secretions and Nutrition.

Composition of the Secretion. — The pancreatic secretion is an
alkaline liquid which in some animals is thin and limpid, in others
thick and glairy. The secretion in man belongs to the former
type ; it is described as water-clear and as having a specific gravity of
1.0075. The secretion may be collected by opening the abdomen
and inserting a cannula directly into the duct, or a permanent
fistula may be made by the method of Pawlow. This method,
applicable to the dog, consists in cutting out a small portion of
the duodenum where the pancreatic duct opens and then suturing
this piece, the mucous membrane outward, into the abdominal
wall. The secretion in this case pours out upon the exterior and may
be collected. The animal, however, suffers nutritive disturbances
from the loss of the secretion, and requires careful dieting and atten-
tion. The secretion of the human pancreas has been collected in a
single case* in which for a few days it was necessary to drain off the
pancreatic juice to the exterior. From the observations made in this
case it appears that the secretion in man is quite abundant, amount-
ing to 500 to 800 c.c. per day. In the cow (Delezenne) from 1 J to 2
liters may be collected in the course of a day. The secretion possesses
a strong alkaline reaction, due to the presence of sodium carbonate;
it contains also a small amount of coagulable protein and a number
of organic substances in traces. The important constituents, how-
ever, are three enzymes or their zymogens, — namely, trypsin, a
proteolytic enzyme; pancreatic diastase (amylopsin), an amylolytic
enzyme; and lipase (steapsin), a lipolytic enzyme. Some authors
state, also, that the secretion contains a rennin enzyme. Glaessner
reports that he got no evidence of this last enzyme in human pan-
creatic juice.

Secretory Nerve Fibers to the Pancreas. — The pancreas
receives its nerve supply immediately from the celiac plexus, but
stimulation of the nerves going to this plexus — namely, the splanch-
nics and the vagi — have given negative results in the hands of most
observers so far as the pancreatic secretion is concerned. Pawlow f
and his coworkers claim to have been more successful. Mechanical
stimulation or electrical stimulation of the vagus or splanchnic gave
them a marked flow of pancreatic juice, but when the latter form of

* See Glaessner, " Zeitschrift f . physiol. Chemie, " 40, 465, 1903.

f For recent work upon the pancreas and the literature see Pawlow,
"The Work of the Digestive Glands," translation by Thompson, 1902; Bay-
liss and Starling, "Journal of Physiology," 30, 61, 1904; Walter, "Archives
des sciences biologiques, " 7, 1, ?899.

DIGESTION AND ABSORPTION IN THE INTESTINES.

723

stimulus was used it was necessary to cut the splanchnic some days
previously in order that the vasoconstrictor fibers might degenerate.
It seems that the secretory activity of the gland is prevented when
there is an interference with its blood supply. In this respect the
pancreas differs from the salivary glands. The secretion obtained
upon stimulation of the nerves is characterized, as in the case of the
gastric glands, by a long latent period of some minutes, — a fact that
is explained, although not satisfactorily, on the assumption that the
nerve trunks stimulated contain both secretory and inhibitory fibers
and that the antagonistic action of the latter delays the appearance

ko

32

U

'

V

7.

1.

Meat.

Fig. 272. — Four curves of the secretion of the pancreatic juice, the three in black,
from Walter, showing the secretion in dogs on different diets: (1) on 600 c.c. of milk; (2)
on 250 gms. bread; (3) on 100 gms. of meat. The curve in red, from Glaessner, shows
the secretion in man on a mixed diet, soup, meat, and bread. The figures, 1, 2, 3 etc.,
along the abscissa indicate hours after the beginning of the meal. The figures along the
ordinates indicate the quantity of the secretion in cubic centimeters.

of the secretion. These observations have been taken as proof of
the existence of secretory nerve fibers to the pancreas; but some
doubt has been thrown upon this conclusion. As is explained
below, all recent observers admit that the most effective stimulus
to the pancreas is a substance (secretin) formed in the duodenum
under the influence of the acid of the gastric juice. It seems possible,
therefore, that when the vagus is stimulated the movements of the
stomach that ensue may force out some acid secretion, and thus
indirectly lead to a stimulation of the pancreas.

The Curve of Secretion. — The rate of flow of the pancreatic
juice with reference to the period of digestion has been determined
by a number of observers. In the careful experiments reported by
Walter it is shown that the quantity of secretion is dependent to a
considerable extent upon the character of the food. Thus, the
flow is more abundant and reaches its maximum sooner after a

724 PHYSIOLOGY OF DIGESTION AND SECRETION.

meal of bread alone than after a meal of meat alone. It seems
possible that the latter point, the time at which the maximum flow
is reached, may depend upon the difference in rate at which these
foods are ejected from the stomach. Cannon (p. 664) has shown that
the carbohydrate foods leave the stomach sooner than the proteins or
fats. It is stated, however, that the composition of the secretion
varies also with the character of the food, and indeed shows an
adaptation to the character of the food. The secretion caused by
protein food is especially rich in trypsin, that caused by fatty food
in lipase, etc. The mechanism by which this adaptation is secured
is not understood. Glaessner* has measured the rate of flow in
man, and his curve for a mixed diet is represented also (in
red) in Fig. 272. These curves indicate in general that the secretion
of pancreatic juice begins very soon after food enters the stomach,
and increases rapidly to a maximum, which is reached somewhere
between the second and fourth hour. According to Glaessner's
case, there is a continuous small secretion of the juice during fast-
ing. The observations on dogs, on the contrary, indicate an
entire cessation of the flow when the stomach is empty.

Boldirefff has reported a very curious activity of the digestive organs
during fasting. It seems that (in dogs) when the stomach or even the small
intestine is empty the entire gastro-intestinal canal exhibits periodical out-
breaks of activity, which occur at intervals of two hours and last for twenty
to thirty minutes. During this stage the stomach and intestines exhibit
movements, and there is an abundant secretion of pancreatic juice, bile, and
intestinal juice, which is subsequently absorbed. Acids introduced into
the stomach or intestines prevent the occurrence of these periods, and they
are absent, therefore, as long as the stomach contains gastric juice. The
author's suggestion that the secretions thus formed furnish active enzymes
which are absorbed into the blood and utilized by the tissues in destroying
the newly absorbed food does not commend itself as probable.

Normal Mechanism of the Pancreatic Secretion — Secretin.

— Much light was thrown upon the mechanism of pancreatic secretion
by the discovery (Dolinsky, 1895) that acids brought into contact
with the mucous membrane of the duodenum set up promptly a
secretion of pancreatic juice. Since this discovery it has been be-
lieved that the acid gastric juice is the means that serves to inaugurate
the flow from the pancreas. As soon as any of the acid contents of
the stomach pass through the pylorus this action begins. Just as the
chewing and swallowing of the food initiate the gastric secretion, so
the acid of the latter starts the pancreatic secretion. Assuming
that the pancreatic gland possesses secretory fibers it was thought at
first that the acid acts reflexly through these fibers — that is, the acid
in the duodenum acting upon sensory endings causes a reflex stimu-
lation of the efferent secretory fibers. It has been shown, however,
that the same effect takes place after section of the va"gus and

* Glaessner, loc.cit.

t Boldireff, "Archives des sciences biologiques, " 11, 1, 1905.

DIGESTION AND ABSORPTION IN THE INTESTINES. 725

splanchnic nerves (Popielski), and Bayliss and Starling * have called
attention to another more probable explanation. These authors find
that if the mucous membrane of the duodenum (or jejunum) is
scraped off and treated with acid (0.4 per cent. HC1) the extract
thus made when injected into the blood sets up an active secretion of
pancreatic juice. They have shown that this effect is due to a special
substance, secretin, which is 'formed by the action of the acid upon
some substance (prosecretin) present in the mucous membrane.
Secretin is not an enzyme, since its activity is not destroyed by boil-
ing or by the action of alcohol. The experimental evidence at
present favors the view that the normal sequence of events is as
follows : The acid of the gastric juice upon reaching the duodenum
produces secretin; this in turn is absorbed by the blood, carried to
the pancreas, and stimulates this organ to activity. The pan-
creatic secretion furnishes, therefore, a second example of the group
of substances designated by Starling as hormones (p. 711). This
author calls attention to the fact that the salivary secretion is con-
trolled entirely by nerve reflexes; the gastric secretion partly by
a nerve reflex (psychical secretion) and partly by the action of a
hormone (chemical secretion), while the pancreatic secretion is
aroused mainly or entirely by the chemical method of stimulation.

Enter okinase. — It was discovered in Pawlow's laboratory
(Chepowalnikow) that the pancreatic juice obtained from a fistula
may have little or no digestive action on proteins, but if brought into
contact with the duodenal membrane or an extract of this membrane
it shows at once powerful proteolytic properties. This discovery has
been confirmed repeatedly. Evidently the proteolytic enzyme of the
juice is secreted in a zymogen or pro-enzyme form (typsinogen), which
is activated or converted to trypsin by something contained in the
mucous membrane of the small intestine (duodenum, jejunum).
This something Pawlow supposes is an enzyme, and since its action is
on another enzyme, "a ferment of ferments," he designated it as a
kinase or enterokinase. The action of the enterokinase seems to be
quite specific. According to Bayliss and Starling, trypsinogen is a
stable body which cannot be changed to trypsin otherwise than by
the action of the kinase; but a very small amount of the latter
suffices to convert a large quantity of trypsinogen. The active
trypsin itself, on the other hand, is very easily destroyed, especially
in alkaline solutions. The physiological value of this very interesting
relation is not clear, but it seems possible that it may serve to protect
the living tissues from the powerful digestive action of the trypsin.
The other enzymes of the pancreatic juice, the diastase and the lipase,
are secreted apparently in active form.

The Digestive Action of Pancreatic Juice. — The digestive
action of the secretion depends upon the three enzymes, trypsin,
* Bayliss and Starling, "Journal of Physiology," 28, 325, 1902.

726 PHYSIOLOGY OF DIGESTION AND SECRETION.

diastase (amylopsin), and lipase. The specific effects of each
may be considered separately.

Action of Trypsin. — The activated trypsinogen causes hydrolytic
cleavage of the protein molecule in a manner analogous to that
described for pepsin. Its action differs from that of pepsin, however,
in several respects. It attacks the protein in neutral as well as in
slightly acid or markedly alkaline solutions. Its effect upon the
protein is more rapid and powerful than that of pepsin and the
protein molecule is broken up more completely. As was said in
describing the action of pepsin, it and the trypsin really act to-
gether— the change begun by the pepsin is completed by the tryp-
sin. The preliminary action of the pepsin not only hastens that of
the trypsin, but to some extent alters it; a protein submitted first
to pepsin and then to trypsin is more completely broken up than if
the trypsin acted alone. The steps in the hydrolysis of the protein
molecule by trypsin have been the subject of a very great amount of
study, and views as to the details have changed somewhat rapidly
of recent years. Kiirme supposed that the protein molecule contains
two groups, the hemi and the anti. Under the influence of the tryp-
sin these are, on his theory, converted into corresponding proteoses,
primary and secondary, and then into peptones — hemipeptone and
antipeptone. As distinguished from the pepsin, the trypsin hy-
drolyzes the hemipeptone still further, splitting it up into a number
of much simpler crystalline bodies, such as leucin, tyrosin, etc.
Antipeptone, on the contrary, resists further hydrolysis, and among
the end-products of a prolonged pancreatic digestion some peptone
is always found. This view has not been supported by recent work.
After a prolonged pancreatic digestion no peptone or peptone-like
body can be found; in fact, no substance which gives a biuret reac-
tion. Under such conditions the protein molecule is broken up very
completely into a surprising number of smaller molecules, many
of which have been identified, while some have as yet escaped de-
tection so far as their chemical structure is concerned. The actual
products formed depend on the length of time the trypsin is allowed
to act and the conditions, favorable or unfavorable, under which it
acts. The end-products usually obtained most easily are tyrosin,
leucin, aspartic acid, glutaminic acid, tryptophan, lysin, arginin,
histidin. The first two of these substances have been known for a
long time and may be obtained easily in crystalline form from
pancreatic digestions. If the trypsin is allowed to exert its complete
action upon the protein the end-products are closely similar to those
obtained by boiling protein with acids. The hydrolysis caused
by the acids and by the trypsin seems to be nearly identical, although
that caused by the acids is probably more complete. The numerous
products obtained by this complete hydrolysis consist chiefly of
amino-acids — that is, organic acids containing one or more amino-

DIGESTION AND ABSORPTION IN THE INTESTINES. 727

groups (NH2) in direct union with carbon. The nitrogen of the
protein molecule appears in the split products in this form and also
partly as ammonia compounds. Some of these bodies are mon-
amino-acids, — that is, contain one NH2 group, such as leucin,
tyrosin, glycocoll — and include substances belonging to the fatty
acid series (aliphatic series), the benzene or carbocyclic series,
and the heterocyclic series.4' Others are diamino-acids, containing
two NH2 groups. These latter include lysin, histidin, and arginin,
which, on account of their basic properties, are frequently described
as nitrogenous bases, and sometimes as the hexon bases, since
they contain six carbon atoms.

The chemical formulas for the best known of these bodies are as follows.
For their properties and chemical relationships reference must be made to
the text-books on physiological chemistry (see also Appendix, Chemistry of
Proteins) :

I. MONAMINO-BODIES.
FATTY ACID SERIES.

Glycocoll or ammo-acetic acid: CH2NH2COOH. This product is ob-
tained in especially large quantities by hydrolysis of gelatin. Accord-
ing to Abderhalden,* it is split off with difficulty by trypsin.

Alanin or a-aminopropionic acid: CH3CHNH2COOH.

Ammovalerianic acid: ^3^CHCHNH2COOH.

Leucin or aminocaproic acid: £§3^CHCH2CHNH2COOH. As stated

above, this compound was one of the first end-products of protein
hydrolysis that was recognized. It may be obtained readily in
crystalline form.

CHNH2COOH
Aspartic or aminosuccinic acid :

CH2COOH.
Glutaminicacid: CH2(™NH2COOK

BENZENE OR AROMATIC SERIES.

Tyrosin (para-oxyphenylaminopropionic acid) : C6H4OH . CH2 . CHNH2-
COOH. This substance was also among the first recognized prod-
ucts of protein hydrolysis It occurs early in the process of pan-
creatic digestion, and is easily obtained in crystalline form from
the digested mixture. It is especially interesting because of the
presence of a benzene nucleus, thus giving proof that the benzene
grouping occurs normally in the protein molecule.

Phenylalanin (phenylaminopropionic acid) : C6H5CH2CHNH2COOH. This
benzene derivative is, according to Abderhalden, split off from the
protein with difficulty by the action of trypsin, although readily
produced by acid hydrolysis.

PYRROL AND INDOL SERIES.

CH2— CH2
o-Pyrrolidincarboxylicacid: CH2 CHCOOH. This substance, discovered

NH

* Abderhalden, " Zeitschrift f. physiol. Chemie," 44, 17, 1905. Consult
tor general description of the digestion of proteids.

728 PHYSIOLOGY OF DIGESTION AND SECRETION.

first by Fischer among the products of acid hydrolysis of proteins,
has since been shown to occur in tryptic digestion. Like the gly-
cocoll and phenylalanin, it is produced with difficulty by trypsin
acting alone, but more readily if the tryptic action follows upon
previous peptic digestion, as is the case in the body.

C . CH3

Tryptophan (skatolamino-acetic acid) : CCH4 C . CH(NH2)COOH. This

NH

substance has long been recognized among the products of tryptic
digestion by the reddish-violet color (Tiedemann and Gmelin, 1826)
observed upon the addition of chlorin or bromin. Its chemical struc-
ture was determined by Hopkins and Cole (1901). According to
Ellinger,* tryptophan is an indol-amino-propionic acid of the formula
C . CHCOOHCH2NH2. When fed to dogs it causes the appear-

NH
ance of kynurenic acid (Ci0H7NO3) in the urine.

It is interesting as showing the existence of an indol grouping
in the protein molecule.

II. THE DIAMINO-BODIES (HEXON BASES).

Lysin (a-s-diaminocaproic acid): C8H14N3O2 or CH2NH2(CH2)3CHNH2-

COOH.
Arginin (guanidin a-aminovalerianic acid) : C6H14N4O2 or NHCNH2NH-

CH2(CH2)2CHNH2COOH.

Histidin: C6H9N3O2 (imidazolaminopropionic acid?).

The Significance of Tryptic Digestion. — It was formerly
supposed that the object of peptic and tryptic digestion is to con-
vert the insoluble and non-dialyzable proteins into the simpler,
more soluble, and more diffusible peptones and proteoses. In this
way absorption of protein material was explained. This view,
however, is not sufficient. On the one hand, it has not been possible
to prove conclusively that peptones or proteoses are found in the
blood; on the other hand, a better knowledge of the processes of
tryptic or of peptic-tryptic digestion has shown that the hydrolysis
does not stop at the peptone stage; the protein molecule is split into
a number of simpler crystalline substances, the various ammo-
bodies. At present different views exist as to the extent of this
latter process. Some believe that the protein molecule is entirely
broken down into its so-called end-products, and that in order to
serve its nutritive function these products or some of them must be
synthetically combined again during or after absorption. This view
is supported, moreover, by the discovery of the existence of the
enzyme erepsin (see below) in the intestinal mucosa. The action of
this latter enzyme is exerted especially upon the albumoses and pep-
tones, breaking them down into the amino-acids, so that apparently
whatever peptone or albumose may escape the final action of the
* Ellinger, "Zeitschrift f. physiol. Chemie," 43, 325, 1904.

DIGESTION AND ABSORPTION IN THE INTESTINES. 729

trypsin before absorption is likely to be acted upon by the erepsin
before reaching the blood.* Another interesting view is that sug-
gested by Abderhalden.t According to this author, the hydrolysis
of the protein by pepsin and trypsin (and perhaps by erepsin) is not
complete. Many amino-bodies, such as tyrosin, leucin, arginin, etc.,
are split off from the protein molecule, but there remains behind
what one may call a nucleus of the original molecule, which serves as
the starting point for a synthesis. This nucleus is a substance or a
number of substances intermediate between the peptone and the
simpler end-products, and is spoken of as a peptid or peptoid (see
Appendix) . Since its structure is unknown and it is probably not
a simple body, it is designated as a polypeptid. Abderhalden has
shown that in tryptic digestion such substances are formed — that
is, substances which are not peptones, since they no longer give the
biuret reaction, but which have a certain complexity of structure,
since upon hydrolysis with acids they split into a number of mon-
amino- and diamino-bodies. A schema of peptic-tryptic digestion
from this standpoint may be given as follows:

Native protein.
Peptone.

Polypeptid. Tyrosin, leucin, glutaminic acid, aspartic acid,
a-pyrrolidin carbpxylic acid, tryptophan, etc.
Arginin, lysin, histidin.

From either of the points of view presented it may be suggested that
the value of this more or less complete splitting of the protein of the
food lies in the possibility that thereby the body is able to construct
its own peculiar type of protein. Many different kinds of proteins
are taken as food and many of them if introduced directly into the
blood act as foreign material incapable of nourishing the tissues.
If these proteins are broken down more or less completely during
digestion the tissue cells may reconstruct from the pieces a form of
protein adaptable to their needs. At present our knowledge of what
takes place during the absorption of protein is very incomplete, and
a satisfactory theory of protein nutrition is scarcely possible until
this portion of the subject is cleared up (see p. 737) .

Action of the Diastatic Enzyme (Amylopsin) of the Pan-
creatic Secretion. — This enzyme is found in the secretion of the
pancreas or it may be extracted from the gland. Its action upon

* Vernon ("Journal of Physiology," 30, 330, 1904) believes that the
pancreatic secretion contains two proteolytic enzymes — trypsin proper,
which converts the proteins to peptones, and pancreatic erepsin, which breaks
up the peptones into the simpler end-products, the amino-bodies.

f Abderhalden, loc. tit.

730 PHYSIOLOGY OF DIGESTION AND SECRETION.

starchy foods is closely similar to or identical with that of ptyalin.
It causes an hydrolysis of the starch with the production finally of
maltose and achroodextrin. Before absorption these substances are
further acted upon by the maltase of the intestinal secretion and
converted to dextrose. The starchy food that escapes digest-ion in
the mouth and stomach becomes mixed with this enzyme in the
duodenum, and from that time until it reaches the end of the large
intestine conditions are favorable for its conversion to maltose and
dextrin. Most of this digestion is probably completed, under normal
conditions, before the contents of the intestinal canal reach the ileo-
cecal valve.

Action of the Lipolytic Enzyme (Lipase, Steapsin). — The
importance of the pancreatic secretion in the digestion of fats was
first clearly stated by Bernard (1849). We know now that this secre-
tion contains an active enzyme capable of hydrolyzing or saponifying
the neutral fats. These latter bodies are chemically esters of the
trihydric alcohol glycerin. When hydrolyzed they break up into
glycerin and the constituent fatty acid. The action of lipase may
be represented, therefore, by the following reaction, in the case of
palmitin :

C3H5(C,5H31COO)3 + 3H2O = C3H5(OH)3 + 3(C15H31COOH)

Palmitin. Glycerin. Palmitic acid.

When lipase from any source is added to neutral oils its splitting
action is readily recognized by the development of an acid reaction
due to the formation of the fatty acid. If a bit of fresh pancreas
is added to butter, for example, and the mixture is kept at the body
temperature the hydrolysis of the fats is soon made evident by the
rancid odor due to the butyric acid produced. When pancreatic
juice is mixed with oils or liquid fats two phenomena may be
noticed: first, the splitting of the fat already referred to, and, second,
the emulsification of the fat. The latter process is very striking.
An oil is emulsified when it is broken up into minute globules that do
not coalesce. Artificial emulsions may be made by vigorous and
prolonged shaking of the oil in a viscous solution of soap, mucilage,
etc. Milk may be regarded as a natural emulsion that separates
slowly on standing, as the fat rises to the top to form the cream.
When a little pancreatic juice is added to oil at the body temperature
the mixture, after standing for some time, will emulsify readily with
very little shaking or even spontaneously. It is now known* that
the emulsification is due to the formation of soaps. The lipase splits
some of the fats, and the fatty acid liberated combines with the
alkaline salts present to form soaps. The emulsification produced

* See Ratchford, "Journal of Physiology," 12, 27, 1891.

DIGESTION AND ABSORPTION IN THE INTESTINES. 731

under these conditions is very fine and quite permanent, and it was
formerly believed that the formation of this emulsion is the main
function of the pancreatic juice so far as fats are concerned. It was
thought that in the form of fine droplets the fat may be taken up
directly by the epithelial cells of the villi, and this view was supported
by the histological fact that during the digestion of fats the epithelial
cells may be shown to contain fine oil drops in their interior. The
tendency of recent work, however, has been to indicate that the fats
are completely split into fatty acids and glycerin before absorption,
and that the emulsification may be regarded, from a physiological
standpoint, as a mechanical preparation for the action of the lipase
rather than as a direct preparation for the act of absorption. The
two products of the action of the lipase, the glycerin and the fatty
acid, are absorbed by the epithelium and again combined to form
neutral fat. In connection with this fact of a synthesis of the split
products to form neutral fat, the discovery by Kastle and Loeven-
hart (see p. 681) that the action of lipase is reversible assumes much
significance. It seems quite possible that the same enzyme may
cause both the splitting of the fat and the synthesis of the split
products, not only in the intestine during absorption, but in the
various tissues during the metabolism or the storage of fat. Lipase
is found in the blood and in many tissues, — muscle, liver, mammary
gland,* etc., — and during its nutritive history in the body the fat may
be split and synthesized a number of times. In this connection it is
interesting to note that the process of splitting does not involve much
work. Very little heat is liberated in the process, and a corre-
spondingly small amount of energy is needed for the synthesis. f

The lipase as formed in the pancreas is easily destroyed, especially
by acids. For this reason probably it is not found usually in simple
extracts of the gland made by laboratory methods. It should be
added, also, that the action of this enzyme is aided very materially
by the presence of bile. This latter secretion contains no lipase
itself, but mixtures of bile and pancreatic juice split the neutral
fats much more rapidly than the pancreatic juice alone.

The Intestinal Secretion (Succus Entericus). — The small
intestine is lined with tubular glands, the crypts of Lieberkiihn,
which in parts of the intestine at least give rise to a liquid secretion,
the so-called intestinal juice. To obtain this secretion recourse has
been had to the operation known as the Thiry-Vella fistula. In this
operation a given portion of the intestine is separated from the
remainder without injuring its blood-vessels or nerves and the two
ends are sutured into the abdominal wall. In the loop thus isolated
the secretions may be collected and experiments may be made upon

* See Loevenhart, " Amer. Journal of Physiology," 6, 331, 1902.

f Consult Herzog, " Zeitschrift f . physiol. Chemie, " 37, 383, 1903.

732 PHYSIOLOGY OF DIGESTION AND SECRETION.

the digestion and absorption of various substances. The secretion
from these loops is usually said to be small in quantity, especially in
the jejunum. Pregl estimates that as much as three liters may be
formed in the whole of the small intestine in the course of a day, but
this estimate does not rest upon very satisfactory data. The liquid
is distinctly alkaline, owing to the presence of sodium carbonate.
Experiments have shown that this liquid has little or no digestive
action except upon the starches, and it may perhaps be doubted
whether it is a true secretion. Extracts of the walls of the small
intestine or the juice squeezed from these walls have been found to
contain four or five different enzymes and to exert a most important
influence upon intestinal digestion. Whether these enzymes are
actually secreted into the lumen of the intestine is not satisfactorily
shown, but since they are contained in the intestinal wall we must
regard them as secretory products and consider them as the impor-
tant and characteristic feature of the intestinal secretion. These
enzymes and their actions are as follows :

1. Enterokinase (see p. 725), an enzyme which in some way activates the

proteolytic enzyme of the pancreatic juice, by converting the tryp-
sinogen to trypsin.

2. Erepsin. This enzyme, discovered by Cohnheim,* acts especially upon

the deutero-albumoses and peptones, causing further hydrolysis.
Whether its splitting action upon the peptones is complete is not
as yet known, but, as was said above (p. 728) the natural suggestion
regarding this enzyme is that it supplements the work begun by
the trypsin.

3. Inverting enzymes capable of converting the disaccharids into the

monosaccharids. These enzymes are three in number: maltase,
which acts upon maltose (and dextrin); invertase or invertin,
which acts upon cane-sugar; and lactase, which acts upon lactose.
The maltase acts upon the products formed in the digestion of
starches, the maltose and dextrin, converting them to dextrose
• according to the general formula:

C^H^A! + H20 = C6H1206 + C6H1206

Maltose. Dextrose. Dextrose.

In the same way invertase converts cane-sugar to dextrose and levu-
lose, and lactase changes milk-sugar to dextrose and galactose. This
inverting action is necessary to prepare the carbohydrate food for
nutritive purposes. Double sugars can not be used by the tissues
and would escape in the urine, but in the form of dextrose or
dextrose and levulose they are readily used by the tissues in their
normal metabolic processes.

4. Lastly, the substance secretin, which, as explained above, plays

such an important role in the control of the secretion of the pan-
creas, is formed in the walls of the small intestine. It is not an
enzyme, but a more stable and definite chemical substance which
is secreted or formed in the intestinal mucosa in a preliminary form,
prosecretin, and under the influence of acids is changed to secretin.
In this latter form it is absorbed, carried to the pancreas, and
causes a flow of pancreatic secretion.

* Cohnheim, " Zeitschrift f . physiol. Chemie, " 33, 451, 1901 ; also 35, 134
et seq.

DIGESTION AND ABSORPTION IN THE INTESTINES. 733

Absorption in the Small Intestine. — Absorption takes place
very readily in the small intestine. The general correctness of this
statement may be shown by the use of isolated loops of the intestine.
Salt solutions of varying strengths or even blood-serum nearly
identical in composition with the animals' own blood may be ab-
sorbed completely from these loops. Examination of the contents
of the intestine in the duodenum and at the ileocecal valve shows
that the products formed in digestion have largely disappeared in
traversing this distance. All the information that we possess in-
dicates, in fact, that the mucous membrane of the small intestine
absorbs readily, and it is one of the problems of this part of physiology
to explain the means by which this absorption is effected. Anatomi-
cally two paths are open to the products absorbed. They may enter
the blood directly by passing into the capillaries of the villi, or they
may enter the lacteals of the villi, pass into the lymph circulation,
and through the thoracic duct of the lymphatic system eventually
reach the blood vascular system. The older physiologists assumed
that absorption takes place exclusively through the central lacteals
of the villi, and hence these vessels were described as the absorbents.
We now know that the digested and resynthesized fats are absorbed
by way of the lacteals, but that the other products of digestion are
absorbed mainly through the blood-vessels and therefore enter the
portal system and pass through the liver before reaching the general
circulation. According to observations made upon a patient with a
fistula at the end of the small intestine,* food begins to pass into the
large intestine in from two to five and a quarter hours after eating,
and it requires from nine to twenty-three hours before the last of a
meal has passed the ileocecal valve ; this estimate includes, of course,
the time in the stomach. During this passage absorption of the
digested products takes place nearly completely. In the fistula case
referred to above it was found that 85 per cent, of the protein had
disappeared, and similar facts are known regarding the other food-
stuffs. The problems that have excited the greatest interest have
been, first, the exact form in which the digested products are ab-
sorbed, and, second, the means by which this absorption is effected.
With regard to the last question, much work has been done to
ascertain whether the known physical laws of diffusion, osmosis,
and imbibition are sufficient to account for the movements of the
absorbed substances or whether it is necessary to refer them in
part to some unknown activities of the living epithelial cells. It
would seem that diffusion and osmosis occur in the intestines.
Concentrated solutions of neutral salts, — sodium chlorid, for instance,
—if introduced into a Thiry-Vella loop, cause a flow of water into

* Macfadyen, Nencki, and Sieber, " Archiv f. experiment. Pathol. u.
Pharmakol.,"28, 311, 1891.

f
734 PHYSIOLOGY OF DIGESTION AND SECRETION.

the lumen in accordance with their high osmotic pressure, and, on
the other hand, some of the sodium chlorid diffuses into the blood
in accordance with the laws of diffusion. It seems equally clear,
however, that absorption as it actually takes place is not governed
simply by known physical laws. Thus, the animal's own serum,*
possessing presumably the same concentration and osmotic pres-
sure as the animal's blood, is absorbed completely from an isolated
intestinal loop. So also it has been shown that in the absorption of
salts from the intestine f the rapidity of absorption stands in no
direct relation to the diffusion velocity. The energy that controls
absorption resides, therefore, in the wall of the intestine, presumably
in the epithelial cells, and constitutes a special form of imbibition
which is not yet understood. That this particular form of energy
is connected with the living structure is shown by the fact that
when the walls are injured by the action of sodium fluorid, potas-
sium arsenate, etc., their absorptive power is diminished and
absorption then follows the laws of diffusion and osmosis. {

Absorption of the Carbohydrates. — Our carbohydrate food is
absorbed, for the most part, as simple sugars, — monosaccharids.
As has been said, there is reason to believe that but little sugar is
absorbed in the stomach. Cane-sugar and milk-sugar are inverted
in the small intestine by invertase and lactase, the first being con-
verted to dextrose and levulose, the second to dextrose and galactose.
If, however, these substances are fed in excess they are absorbed in
part without conversion to simple sugar, and in that case may be
eliminated in the urine. The bulk of our carbohydrate food is taken,
however, in the form of starch, and the conditions for absorption in
this case are more favorable. The time required for the digestion of
the starch to maltose and dextrin, and the subsequent inversion of
these substances to dextrose, insures a slower and more complete
absorption. Five hundred grams or more of starch may be digested
and absorbed in the course of the day and it all reaches the blood in
the form of dextrose. This dextrose enters the portal vein and is
distributed first to the liver. In this organ the excess of sugar is
withdrawn from the blood and stored as glycogen, so that the amount
of sugar in the general circulation is thereby kept quite constant, —
about 0.15 per cent. When a large amount of carbohydrate food is
eaten, however, it is possible that the liver may not be able to remove
the excess completely. In that case the amount of sugar in the gen-
eral circulation may be increased above normal, giving a condition
of hyperglycemia. In such cases the excess is likely to be excreted

* Heidenhain, "Archiv f. die gesammte Physiologie, " 56, 579, 1894.
f Wallace and Cushny, "Archiv f. die gesammte Physiologie," 77, 202,.
1899.

JCohnheim, " Zeitschrift f. Biologic," 37, 443, 1899.

DIGESTION AND ABSORPTION IN THE INTESTINES. 735

in the urine, giving the phenomenon known as " alimentary glyco-
suria." The amount of any carbohydrate that can be eaten without
producing a condition of alimentary glycosuria is designated by
Hofmeister* as the assimilation limit of that carbohydrate. If taken
beyond this limit it forms a physiological excess, and some is lost
in the urine. The assimilation limit varies with a great many
conditions; but, so far as the different forms of carbohydrates are
concerned, it is lowest for the milk-sugar and highest for starch. The
simple sugars dialyze easily, and it would be natural to suppose that
they are absorbed into the blood by a simple process of diffusion.
Experimental facts, however, do not support this view entirely. It
is stated that the absorption of sugars does not vary directly as their
velocity of diffusion, and in this case, as with the other products of
digestion, it is necessary to assume that work is done by the wall of
the intestine itself, probably the epithelial cells.

So far as the carbohydrates escape absorption as sugar they are
liable to undergo acid fermentation from the bacteria always present
in the intestine. As the result of this fermentation there may be
produced acetic acid, lactic acid, butyric acid, succinic acid, carbon
dioxid, alcohol, hydrogen, etc. This fermentation probably occurs
to some extent in the small intestines under normal conditions.
Macfadyen,f in the case already referred to, found that the contents
of the intestine at the ileocecal valve contained acid equivalent to
that of a 0.1 per cent, solution of acetic acid. Under less normal
conditions, such as excess of sugars in the diet or deficient absorp-
tion, the large production of acids may lead to irritation of the intes-
tines,— diarrhea, etc.

Absorption of Fats. — Numerous theories have been held in
regard to the mode of absorption of fats. It has been supposed that
the emulsified (neutral) fat is ingested directly by the epithelial cells,
that the fat droplets enter between the epithelial cells in the so-called
cement substance, that the fat droplets are ingested by leucocytes
that lie between the epithelial cells, or lastly that the fat is first split
into fatty acid and glycerin and is absorbed by the epithelial cells in
these forms. The tendency of recent work is to favor this last view.
During digestion the epithelial cells contain fat droplets without
doubt, but it seems probable that these droplets are formed in situ
by a synthesis of the absorbed glycerin and fatty acids. The border
of the cell is said to be free from fat globules, — a fact which would
indicate that the neutral fat is not mechanically ingested as oil drops.
But, granting that the fat is absorbed in solution, as fatty acids and
glycerin, the mechanism of absorption remains unexplained. It is

* Hofmeister, "Archiv f. exper. Pathol. u. Phannakol.," 25, 240, 1889,
and 26, 355, 1890.

f Macfadyen, Nencki, and Sieber, loc. cit.

736 PHYSIOLOGY OF DIGESTION AND SECRP7TION.

known that the bile as well as the pancreatic juice plays an important
part in the process. The pancreatic juice furnishes the lipase, the bile
furnishes the bile salts (glycocholate and taurocholate of sodium)
which aid the lipase in splitting the neutral fat, and moreover aid
greatly the absorption of the split fats. This latter function is due
probably to the fact that the bile (bile salts) dissolves the fatty acids
readily* and thus brings them into contact, in soluble form, with the
epithelial cells. When the bile is drained off from the intestine
by a fistula of the gall-bladder or duct, a large proportion of
the fatty foods escapes absorption and appears in the feces. Direct
observation shows that the fat after passing the epithelial lin-
ing and entering the stroma of the villus is taken up by the
lymphatic vessels, the so-called lacteals. This fact is beautifully
demonstrated by the mere appearance of the lymphatics of
the mesentery after a meal containing fats. These vessels are
injected with milky chyle during the period of absorption so that
their entire course is revealed. The chyle on microscopical exami-
nation is found to contain fat in the form of an extremely fine
emulsion. In this form it is carried to the thoracic duct and thence
to the venous circulation. For hours after a meal the blood contains
this chyle fat. If a specimen of blood is taken during this time and
centrifugalized in the usual way, the chyle fat may be collected at
the top in the form of a cream. It is an easy matter to insert a
cannula into the thoracic duct at the point at which it opens into the
subclavian and jugular veins and thus collect the entire amount of fat
absorbed from the intestines by way of the lacteals. Experiments
of this kind show that, after deducting the amount of fat that escapes
absorption and is lost in the feces, the amount that may be recovered
from the thoracic duct is less than that taken' in the food. It seems
probable, therefore, that some of the fat is absorbed directly by the
blood-vessels of the villi, probably in the form of fatty acids or soaps.
The portion thus absorbed enters the portal vein and passes through
the liver before reaching the general circulation. The liver holds
back more or less of the fat taking this route, as it is found that
during absorption the liver cells show an accumulation of fat droplets
in their interior.f The amount of fat that may be absorbed from
the intestines varies with the nature of the fat. Experiments show
that the more fluid fats, such as olive oil, are absorbed more com-
pletely,— that is, less is lost in the feces than in the case of the more
solid fats. Comparative experiments have given such results as the
following: Olive oil, — absorption, 97.7 per cent.; goose and pork fat,
97.5 per cent.; mutton fat, 90 to 92.5 percent.; spermaceti, 15 per

* See Moore and Rockwood, "Journal of Physiology," 21, 58, 1897;
also Moore and Parker, "Proceedings, Royal Society," London, 58, 64, 1901.
t See Frank, " Archiv f. Physiologic," 1892, 497, and 1894, 297.

DIGESTION AND ABSORPTION IN THE INTESTINES. 737

cent. The amount of fat that may be lost in the feces varies also
with other conditions. If, for instance, an excess is taken with the
food, or if the bile flow is diminished or suppressed, the percentage
in the feces is increased. The usual amount of fat allowed as a
maximum in dietaries is from 100 to 120 gms. daily.

Absorption of Proteins. — Most of the experimental work on
record shows that the digested proteins are absorbed by the blood-
vessels of the villi, although after excessive feeding of protein a
portion may be taken up also in the lymphatics.* This accepted
belief rests upon two facts: First (Schmidt-Mulheim), if the thoracic
duct (and right lymphatic duct) is ligated, so as to shut off the lym-
phatic circulation, an animal will absorb and metabolize the usual
amount of protein as is indicated by the urea excreted during the pe-
riod. Second (Munk), if a fistula of the thoracic duct is established
and the total lymph flow from the intestines is collected during
the period of absorption after a diet of protein, it is found that there
is no increase in the quantity of the lymph or in its protein contents.
The form in which protein is absorbed and circulates in the blood
is not satisfactorily determined. Under normal conditions the
protein food is digested by the successive actions of pepsin, trypsin,
and probably erepsin. During this digestion peptones and proteoses
are formed and may be absorbed as such, or they may be further
broken down by trypsin and erepsin to the amino-bodies, leucin,
tyrosin, arginin, etc., and the intermediate compounds, the poly-
peptids or peptoids (see p. 729), and be absorbed in the form of
these split products. Some observers claim to have found peptones
or proteoses as a normal constituent of the blood, but this claim
has not been satisfactorily established. Others have shown the
presence of traces of the amino-acids,f but much uncertainty exists
as to the precise form in which the protein nourishment for the body
exists normally in the blood. Several possibilities have been sug-
gested. It is conceivable that the peptones or the more simple
split products may be synthesized in* the wall of the intestine or in
the liver to the proteins of the blood, the serum-albumin or globulin;
it is possible that many of the end-products of the digestive splitting
may be further oxidized and converted to urea in the liver and only a
fractional part be really synthesized into the proteins of the bod}' ,
or it is possible that the absorbed protein exists in the blood in
some special form not as yet recognized. The whole question is
evidently one that cannot be discussed very profitably at present ;
it awaits the results of further investigation. In this connection
attention should be directed to the fact that many forms of protein
may be absorbed apparently without previous digestion. This fact

* See.Mendel, 'American Journal of Physiology," 2, 137, 1899.
t For references see Howell, 'American Journal of Physiology," 1906,
xvii., 273.

47

pin UO1 • KH OF I'i'.i S'l ION \\i> si nil i ION

1 1, 1 I XVI I .IrintMl:;! I'M If. I 1 1 H I .o I; i led loops ()f I he Mliall III I e -line Mild

:il :.o lor parts of (lie laryv mfesl inc. It is, in«>ivo\ er, home out. by
lli«- medical practice of ".mil", eiiemala nilo the rectum when (lie
conditions ;irr .Mich that the patient c:in nol he fed in (lie normal
\\;i\. I'liMl :il..-;orp(i«»ii :iml illlll alion .'!' (lie prolein (:ikc place
under Midi conditions is shown nol onlv h\ llic improved niih-ihvc
condition of (he mdmdnal. hnl also hv llic increased output of
nitrogen in the mine This phenomenon t.eenrs m purls of I he
inle .1 in: 1 1 canal in \\ liieli normally no proteoh he en \ nies occur, so
lh:tl I he whole |»roee,^s inns! he ivlenv.l |o ;m :ie| i\ i| \ • ,.f i
composing 1 1\0 walls of Ihe inleslme. Tlu^re Seems :il pn-vnl lil
.«•.!•« MUM 1:. !oi .1 .Mi !.i. I ..i \ e\|>l;in:ilion d' 1 he :tl .soi'pl ion o|' proteins,
\\ilh or \\ilhonl (h:M--lion, l>v ;i dnvcl ;i pplie;i I ion of 1 he Knouii
l:i\\.-. i«! OMIIOM,. diltn ion, :md mil ulul ion I '.\;imm;it ion of Ihe
conlenls of Ihe smnll mleslme :il its jnnehon \\ilh I he l:iri';t' shows
lh:it under norm:d conditions ItlOSt of the protein h;is hern ah-
sorhed luM'ore re:ichin!', this point. The process is cont inned intho
llirtfO intestine. modit'uMl some\\h:it h\ h:icteri:il .-iction, ;uul ihe
.Minount th:il liiKilly (>sc:ipes ;ihsoi-pl irn cin.l :ip|>»\-irs in tlu> l\>ces
\.MIC--. m |HM-fec(l\ normnl iiulix idiuils. \\ilh the chnnicter of (he
pnttein c;ilen. \ccordm;1; to Mnnk,^ the easily digest il>le :inini:il
loods snch ns milk, e!\:\s. ;md meal are ahsorhed lo ihe extent of
«>V to '.)'.) p(>r cent .\\lule \\ilh \e!-.e(:»hle foods the ut ili/.at ion is less
complete; from 17 to ,'U) per cent, of (he protein may he lost in (he
fcccs if (he ve^etahle food is m such form a.s im( to he attacked readily
h\ the di:',es|i\e secret ii»ns.

Digestion and Absorption in the Large Intestine. — Observa-

tions upon the secretions of the lar^e intestine have hecn made upon
human hcm;> m ca^es of anus prctcrnaturalis. in which the lower
portion of the intestine was practically isolated, and also upon
lower animals, in which an artificial anus was estahlished at the
end of the small intestine. These observations all indicate that
the secretion of the laiyv intestine, while it contains much mucus
and shows an alkaline reaction, is not character!. vd hy the presence
of distinctive en. 'vines. When the contents of the small intestine
pass the val\e they si ill contain a certain amount of unahsorhed
food material. As was stated in (he chapter on the movements of the
intestine, this material remains a lonj; time in the lar^e intestine, and
since it contains the digestive en -\ mes received in the duodenum the
digestive and absorptive- processes no doubt continue as in the small
intestine. Hu's general fact is well illustrated in experiments made
U{xm ilo^s most of whose small intestine (70 to S." per cent. "i had been
removed/)" These animals ctnild ili^est and absorb well, and formed

,- Miuik. •' rjxi'lmisso dor Tliysie': ', i, part i. l^O'J. an iclo.

wrption/1 ter littM-.-Uuro anil disoussiot\.
t 1 'danger aiul Moxxlou. " \uuM-u-au Journal of Physiology." o. 1. 100'J.

I.K.I I I- , ••IM'TION I . I III. I I I Ml . / /i

norin:il fen , provided care v,a: (ale,, vvith tin- diet An r •- .»•«•;••;., of

fa i or indi"e iiUe material caused dianhea and serious IOMH <>\ \'><><\

material in I he fece:-;. An infi-f tin." fealun in the lar-e mf< (me
i I lie m;irl.ed :di orplion of v.afer. In t he • mall mle I me no doubt,
water i:; ab orbed in la rye < pia nl il ie :, but it lo i evident:
gOOd by OSinoKlh or secretion ' mlo the nile | m, • mce the.

content : at tin ileoc<c;,| valve arc o/iite an fluid a^ at the pvlorui.
In the lar-'e mle I me t he ab orplion of v.ate/ j not compensated by
a. :ecrclion; tin- material become; mote and moje --olid 04 )! ap-
proache i he reel um, and i thn formed info the feeeH. The alkaline
reaetion of the content.; of the laiye mle lm<- makes a favorabl<:
environment ioi the vrowth of baclxtria, partieularl', t he putrefactive
bacteria that attad protein material I'nt j'efact ion i- a norm:. I
lirence in lh»- lai-e inl nd much mlejc t ha been I,-

in It e.x'ent and it po ible p -I'.,] i;'mf|c;,'

Bacterial Action in the Small Intestine. — Hocteria &rc

tantly prf ent in both the lar^e and the mall int<- tine I .-
normal condition i, howevi dd seem that in the mall intei-lme

only tho:e [Bacteria capable of fermenting Carbohydrate food hhow
any dr tin»-t activity. I'ul refarii YI- fe, ment at ion of protein mat.
i limited or ab'-ent in thi part of the inte-tin<- a,H long u* t|j(- proo'uctK
of protein di;re-iion arr; promptly abnorfxtd. rondilionii that pre-
vent or retard thi absorption favor the orriirronce of protein
putrefaction Opinion- amony if; if'fer a?- tr> the mean

by whieh the f>rotejn '-'^ntr-nf.--; are protecterj from the action of the
bacteria. It has been shown that the prf-en'-e of '-arhohydrate
material lias a restraining effect uf>on j>rotx?in put refaction The

irnfje t explanation of thr-: relation r that the fermentation of tfie
carl>o}jydratx*s ^ives ri-x- to a numfx^r of organic a'-ids laelie,
acetic, etc, — and these Mldf inhibit the action of the protein •
teria. 'J'o make tin.-; explanation -atHactory. hov/r-ve; j» j nece-
sar. that the contents Of the ma: e \XWMM an acid

oocermng this point opinioi ;:'' Tb "•» MO/IK

fie «mall intent ine are all alkaline and \ve hfjould | -,eir

bare thi-- PMU n that the '

tem mall intestine are -^<\ or • he indi»-.-

i. With pjjenolphthalein they may give a/i M, while

with litrnu-:, lakmoi' ;, a

result as t},; f - that, m in<- and;-;. Kurh I

and laetjc, are pre^mt. the phenolphthalein b' bly

be CO AH Munk ha^Kt, '-emx that \\>' ihe

small intestine throughout the duodenum and jejunum

nmiH Maifadyen. Ncricki, and Bieber, loc. cU.; Moore sad
merican JoomaJ of F
Phy^ologia/1 J'i, :u sad

Ncncki, and Sietjer, ^ c^.; Moora and Bendo.

"American Journal of iv»iok*y/' 3, 316, 1900; Munk, " Centrair>Utt7
146, 1W2.

740 PHYSIOLOGY OF DIGESTION AND SECRETION.

never alkaline, and when carbohydrates are used the reaction may
not only be acid to phenolphthalein but also to the stronger indica-
tors. On the whole, therefore, it would seem probable that the
small amount or total lack of protein putrefaction in the small intes-
tine is due in part to the rapid absorption of the digested protein
and in part to an unfavorable reaction. Some observers contend
that there is a struggle for existence or antagonism between the
bacteria acting upon carbohydrates and those living upon proteins.
When the former have conditions favorable for growth, their increase
in some way affects injuriously the protein bacteria.*

Bacterial Action in the Large Intestine. — In the large intestine
protein putrefaction is a constant and normal occurrence. The
reaction here is stated to be alkaline, and whatever protein may have
escaped digestion and absorption is in turn acted upon by the bac-
teria and undergoes so-called putrefactive fermentation. The split-
ting up of the protein molecule by this process is very complete, and
differs in some of its products from the results of hydrolytic cleavage
as caused by acids or by trypsin. The list of end-products of putre-
faction is a long one. Besides peptones, proteoses, ammonia, and
the various amino-acids, there may be produced such substances as
indol, skatol, phenol, phenylpropionic and phenylacetic acids, fatty
acids, carbon dioxid, hydrogen, marsh gas, hydrogen sulphid, etc.
Many of these products are given off in the feces, while others are
absorbed in part and excreted subsequently in the urine. In this
latter connection especial interest attaches to the phenol, indol, and
skatol. Phenol or carbolic acid, C6H5OH, after absorption is com-
bined with sulphuric acid, to form an ethereal sulphate (conjugated
sulphate) or phenolsulphonic acid, C6H5OSO2OH, and in this form
is found in the urine. So also with cresol. The indol, C8H7N, and
skatol (methyl-indol), C9H9N, are also absorbed, undergo oxidation to
indoxyl and skatoxyl, and are then combined or conjugated with
sulphuric acid, like the phenol, and in this form are found in the urine
— C8H6NOS02OH, or indoxyl-sulphuric acid, and C9H8NOSO2OH,
skatoxyl-sulphuric acid. These bodies have long been known to
occur in the urine, and the proof that they arise primarily from putre-
faction of protein material in the large intestine is so conclusive as
not to admit of any doubt. The amount to which they occur in
the urine is, therefore, an indication of the extent of the putrefaction
in the large intestine.

Is the Putrefactive Process of Physiological Importance? —
Recognizing that fermentation by means of bacteria is a normal
occurrence in the gastro-intestinal canal, the question has arisen
whether this process is in any way necessary to normal digestion and
nutrition. It is well known that excessive bacterial action may lead
* See Bienstock, " Archiv f. Hygiene," 39, 390, 1901.

DIGESTION AND ABSORPTION IN THE INTESTINES. 741

to intestinal troubles, such as diarrhea, or to more serious interference
with general nutrition owing to the formation of toxins. It is,
however, possible that some amount of bacterial action may be
necessary for completely normal digestion. As a special case it has
been pointed out that the gastro-intestinal tract is not provided with
enzymes capable of acting upon cellulose, a material that forms such
an important constituent of vegetable foods. Bacteria, on the other
hand, may hydrolyze the cellulose and render it useful in nutrition.
Leaving aside this special case, the question as to the necessity of
bacterial action has been investigated directly by attempting to
rear young animals under perfectly sterile conditions. Nuttall and
Thierf elder* report some very interesting experiments upon guinea
pigs in which the young animals from birth were kept sterile and fed
with perfectly sterile food. They found that the animals lived and
increased in weight, and concluded therefore that the intestinal
bacteria are not necessary to normal nutrition. This conclusion is
supported by the observations of Levin, f who finds that animals in
the Arctic regions in many cases have no bacteria in their intestines.
Schottelius t reports contrary results upon chickens. When kept
sterile they lost steadily in weight and showed normal growth only
when supplied with food containing bacteria. We may conclude,
however, that the evidence at present indicates that the bacterial
fermentation is not essential, although under the actual conditions
of life it plays a part in the digestive history of the food.

Composition of the Feces. — The feces differ widely in amount
and in composition with the character of the food. Upon a diet
composed exclusively of meats they are small in amount and dark
in color; with an ordinary mixed diet the amount is increased; and
it is largest with an exclusively vegetable diet, especially with vege-
tables containing a large amount of indigestible material. The
average weight of the feces in twenty-four hours upon a mixed diet
is given as 170 gms., while with a vegetable diet it may amount to as
much as 400 or 500 gms. The quantitative composition, therefore,
varies greatly with the diet. Qualitatively, we find in the feces
the following things : (1) Indigestible material, such as ligaments of
meat or cellulose from vegetables. (2) Undigested material, such as
fragments of meat, starch, or fats which have in some way escaped
digestion. Naturally, the quantity of this material present is slight
under normal conditions. Some fats, however, are almost always
found in feces, either as neutral fats or as fatty acids, and to a small
extent as calcium or magnesium soaps. The quantity of fat found is

* Nuttall and Thierfelder, " Zeitschrift f. physiol. Chemie," 21, 109,
1895; 22, 62, 1896; 23, 231, 1897.

t " Skandinavisches Archiv f. Physiologic," 16, 249, 1904.
j"Archiv f. Hygiene," 42, 48, 1902.

742 PHYSIOLOGY OF DIGESTION AND SECRETION.

increased by an increase of the fats in the food or by a deficient
secretion of bile. (3) Products of the intestinal secretions. Evi-
dence has accumulated in recent years* to show that the feces in
man on an average diet are composed in part of the material of the
intestinal secretion. The nitrogen of the feces, formerly supposed to
represent only undigested food, seems rather to have its origin largely
in these secretions, and, therefore, like the nitrogen of the urine,
represents so much metabolism in the body. (4) Products of bac-
terial decomposition. The most characteristic of these products are
indol and skatol. They are crystalline bodies possessing a disagree-
able, fecal odor; this is especially true of skatol, to which the odor
of the feces is mainly due. (5) Cholesterin, which is found always
in small amounts, and is probably derived from the bile. (6) Ex-
cretin, a crystallizable, non-nitrogenous substance to which the
formula C78H156SO2has been assigned, is found in minute quantities.

(7) Mucus and epithelial cells thrown off from the intestinal wall.

(8) Pigment. In addition to the color due to the undigested food
or to the metallic compounds contained in it, there is normally
present in the feces a pigment, urobilin or stercobilin, derived from
the pigments (bilirubin) of the bile. Urobilin is formed from the

' bilirubin by reduction in the large intestine. (9) Inorganic salts —
salts of sodium, potassium, calcium, magnesium, and iron. The
significance of the calcium and iron salts will be referred to in a subse-
quent chapter, when speaking of their nutritive importance. (10)
micro-organisms. Great quantities of bacteria of different kinds are
found in the feces.

In addition to the feces, there is found often in the large intestine
a quantity of gas that may also be eliminated through the rectum.
This gas varies in composition. The following substances have been
found at one time or another: CH4, CO2, H, N, H2S. They arise
mainly from the bacterial fermentation of the proteids, although
some of the N may be derived from air swallowed with the food.

* Prausnitz, " Zeitschrift f. Biologic," 35, 335, 1897; and Tsuboi, ibid.,
p. 68.

CHAPTER XLIV.
PHYSIOLOGY OF THE LIVER AND THE SPLEEN.

The liver plays an important part in the general nutrition of the
body. Its functions are manifold, but in the long run they depend
upon the properties of the liver cell, which constitutes the anatomical
and physiological unit of the organ. These cells are seemingly
uniform in structure throughout the whole substance of the liver, but
to understand clearly the different functions they fulfill one must
have a clear idea of their anatomical relations to one another and
to the blood-vessels, the lymphatics, and the bile-ducts. The histol-
ogy of the liver lobule, and the relationship of the portal vein, the
hepatic artery, and the bile-duct to the lobule, must be obtained from
the text-books upon histology and anatomy. It is sufficient here to
recall the fact that each lobule is supplied with blood coming in part
from the portal vein and in part from the hepatic artery. The blood
from the former source contains the soluble products absorbed from
the alimentary canal, such as sugar and protein, and these absorbed
products are submitted to the metabolic activity of the liver cells
before reaching the general circulation. The hepatic artery brings to
the liver cells the arterialized blood sent out to the systemic circu-
lation from the left ventricle. In addition, each lobule gives origin
to the bile capillaries which arise between the separate cells and which
carry off the bile formed within the cells. In accordance with these
facts, the physiology of the liver cell falls naturally into two parts, —
one treating of the formation, composition, and physiological signifi-
cance of bile, and the other dealing with the metabolic changes pro-
duced in the mixed blood of the portal vein and the hepatic artery
as it flows through the lobules. In this latter division the main
phenomena to be studied are the formation of urea and the formation
and significance of glycogen.

Bile. — From a physiological standpoint, bile is partly an excre-
tion carrying off certain waste products, and partly a digestive secre-
tion playing an important role in the absorption of fats, and possibly
in other ways. Bile is a continuous secretion, but in animals possess-
ing a gall-bladder its ejection into the duodenum is intermittent.
Bile is easily obtained from living animals by establishing a fistula
of the bile-duct or, as seems preferable, of the gall-bladder. The
latter operation has been performed a number of times on human
beings. In some cases the entire supply of bile has been diverted in

743

744 PHYSIOLOGY OF DIGESTION AND SECRETION.

this way to the exterior, and it is an interesting physiological fact
that such patients may continue to enjoy fair health, showing that,
whatever part the bile takes normally in digestion and absorption,
its passage into the intestine is not absolutely necessary to the nu-
trition of the body. The quantity of bile secreted during the day
has been estimated for human beings of average weight (43 to 73
kgms.) as varying between 500 and 800 c.c. This estimate is based
upon observations on cases of biliary fistula.* Chemical analyses
of the bile show that, in addition to the water and salts, it contains
bile pigments, bile acids, cholesterin, lecithin, neutral fats and soaps,
sometimes a trace of urea, and a mucilaginous nucleo-albumin for-
merly designated improperly as mucin. The last-mentioned sub-
stance is not formed in the liver cells, but is added to the bile by the
mucous membrane of the bile-ducts and gall-bladder. The quantity
of these substances present in the bile varies in different animals
and under different conditions. As an illustration of their relative
importance in human bile and of the limits of variation, the two
following analyses by Hammarstent may be quoted:

i. ii.

Solids ............................. 2.520 2.840

Water ............................. 97.480 97.160

Mucin and pigment ................. 0.529 0.910

Bile salts ............. ............. 0.931 0.814

Taurocholate ....................... 0.3034 0.053

Glycocholate ....................... 0.6276 0.761

Fatty acids from soap .............. 0.1230 0.024

Cholesterin ........................ 0.0630 0.096

......................... °-0220 °'1286

Soluble salts ................... 0.8070 0.8051

Insoluble salts ..................... 0.0250 0.0411

The color of bile varies in different animals according to the pre-
ponderance of one or the other of the main bile pigments, bilirubin
and biliverdin. The bile of carnivorous animals has usually a
golden color, owing to the presence of bilirubin, while that of the her-
bivora is a bright green from the biliverdin. The color of human bile
seems to vary : according to some authorities, it is yellow or golden
yellow, and this seems especially true of the bile as found in the gall-
bladder of the cadaver; according to others, it is of a dark-olive color
with the greenish tint predominating. Its reaction is feebly alkaline,
and its specific gravity varies in human bile from 1.050 or 1.040 to
1.010. Human bile does not give a distinctive absorption spectrum,
but the bile of some herbivora, after exposure to the air at least, gives
a characteristic spectrum.

*Copeman and Winston, " Journal of Physiology," 10, 213, 1889; Rob-
son, "Proceedings of the Royal Society," London, 47, 499, 1890; Pfaff and
Balch, "Journal of Experimental Medicine," 2, 49, 1897.

f Reported in " Centralblatt f. Physiologic," 1894, No. 8.

PHYSIOLOGY OF THE LIVER AND SPLEEN. 745

Bile Pigments. — Bile, according to the animal from which it is
obtained, contains one or the other, or a mixture, of the two pigments
bilirubin and bili verdin. Biliverdin is supposed to stand to bilirubin
in the relation of an oxidation product. Bilirubin is given the formula
C16H18N2O3, and biliverdin C16H18N2O4, the latter being prepared
readily from pure specimens of the former by oxidation. These
pigments give a characteristic reaction, known as" Gmelin's reaction,"
with nitric acid containing some nitrous acid (nitric acid with a
yellow color). If a drop of bile and a drop of nitric acid are brought
into contact, the former undergoes a succession of color changes, the
order being green, blue, violet, red, and reddish yellow. The play
of colors is due to successive oxidations of the bile pigments; starting
with bilirubin, the first stage (green) is due to the formation of bili-
verdin. The pigments formed in some of the other stages have been
isolated and named. The reaction is very delicate, and it is often
used to detect the presence of bile pigments in other liquids — urine,
for example. The bile pigments originate from hemoglobin. This
origin was first indicated by the fact that in old blood clots or in
extravasations there was found a crystalline product, the so-called
" hematoidin," which was undoubtedly derived from hemoglobin,
and which upon more careful examination was proved to be identical
with bilirubin. This origin, which has since been made probable by
other reactions, is now universally accepted. It is supposed that
when the blood-corpuscles disintegrate the hemoglobin is brought to
the liver, and there, under the influence of the liver cells, is converted
to an iron-free compound, bilirubin or biliverdin. It is very signifi-
cant that the iron separated by this means from the hemoglobin is,
for the most part, retained in the liver, a small portion only being
secreted in the bile. It seems probable that the iron held back in the
liver is again used in some way to make new hemoglobin in the
hematopoietic organs. The bile pigments are carried in the bile to
the duodenum and are mixed with the food in its long passage through
the intestine. Under normal conditions neither bilirubin nor bili-
verdin occurs in the feces, but in their place is found a reduction prod-
uct, urobilin or stercobilin, formed in the large intestine. More-
over, it is believed that some of the bile pigment is reabsorbed as it
passes along the intestine, is carried to the liver in the portal blood,
and is again eliminated. That this action occurs, or may occur, has
been made probable by experiments of Wertheimer* on dogs. It
happens that sheep's bile contains a pigment (cholohematin) that
gives a characteristic spectrum. If some of this pigment is injected
into the mesenteric veins of a dog it is eliminated while passing
through the liver, and can be recognized unchanged in the bile.

* " Archives de physiologie normale et pathologique," 1892, p. 577.

746 PHYSIOLOGY OF DIGESTION AND SECRETION.

The value of this " circulation of the bile/' so far as the pigments are
concerned, is not apparent.

Bile Acids. — " Bile acids" is the name given to two organic acids,
glycocholic and taurocholic, which are always present in bile, and,
indeed, form very important constituents of that secretion; they
occur in the form of their respective sodium salts. In human bile
both acids are usually found, but the proportion of taurocholate
is variable, and in some cases it may be absent altogether.
Among herbivora the glycocholate predominates, as a rule, although
there are some exceptions; among the carnivora, on the other hand,
taurocholate occurs usually in greater quantities, and in the dog's
bile it is present alone. Glycocholic acid has the formula C26H43NO6,
and taurocholic acid the formula C26H45NSO7. Each of them can
be obtained in the form of crystals. When boiled with acids or alka-
lies these acids take up water and undergo hydrolytic cleavage, the
reaction being represented by the following equations:

C^H.-NOe + H2O = CMH«OA + CH?(NH2)COOH.

Glycocholic acid. Cholic acid. Glycocoll (amino-acetic-acid).

C26H46NS07 + H20 = C.,H400. + C^NH^OH

Taurocholic acid. Cholic acid. Taurin (amino-ethyl-

sulphonic acid).

These reactions are interesting not only in that they throw light on
the structure of the acids, but also because similar reactions doubtless
take place in the intestine, cholic acid having been detected in the
intestinal contents. As the formulas show, cholic acid is formed in
the decomposition of each acid, and we may regard the bile acids as
compounds produced by the synthetic union of cholic acid with
glycocoll in the one case and with taurin in the other. Cholic acid
or its compounds, the bile acids, are usually detected in suspected
liquids by the well-known Pettenkofer reaction. As usually per-
formed, the test is made by adding to the liquid a few drops of a 10
per cent, solution of cane-sugar and then strong sulphuric acid. The
latter must be added carefully and the temperature be kept below
70° C. If bile acids are present, the liquid assumes a red-violet
color. It is now known that the reaction consists in the formation
of a substance (furfurol) by the action of the acid on sugar, which
then reacts with the bile acids. The bile acids are formed directly
in the liver cells. This fact, which was for a long time the subject of
discussion, has been demonstrated in recent years by an important
series of researches made upon birds. It has been shown that if the
bile-duct is ligated in these animals, the bile formed is reabsorbed and
bile acids and pigments may be detected in the urine and the blood.
If, however, the liver is completely extirpated, then no trace of either
bile acids or bile pigments can be found in the blood or the urine,
showing that these substances are not formed elsewhere in the body

PHYSIOLOGY OF THE LIVER AND SPLEEN. 747

than in the liver. It is more difficult to ascertain from what sub-
stances they are formed. The fact that glycocoll and taurin contain
nitrogen, and that the latter contains sulphur, indicates that some
protein or albuminoid constituent is broken down during their pro-
duction.

From the standpoint of nutrition the taurocholate is interesting as giving
one of the forms in which the sulphur of protein material is eliminated. Some
light has been thrown upon the origin of taurin by the discovery (Friedmann*)
that it may be formed from cystin. This latter body, C6H12N2S2O4, or its
reduction product cystein, is known to occur as one of the end-products in the
acid hydrolysis of proteins, and it is possible that it occurs also in the tryptic-
erepsin hydrolysis in the small intestine, representing the end-product in which
the sulphur of the protein molecule is found. Cystin may be oxidized to
cysteinic acid (COOHC2H3NH,SO.2OH) and from this taurin (C2H4NH2SO2OH)
may be obtained. It is probable, therefore, that the taurin is formed nor-
mally from cystin in the body and that the latter represents one of the split
products of protein, f Some of the sulphur of the cystin appears also in the
urine in oxidized form as sulphate. Under certain pathological conditions
the cystin itself appears in the urine, giving the phenomenon of cystinuria.

A circumstance of considerable physiological significance is that
these acids or their decomposition products are absorbed in part from
the intestine and are again secreted by the liver; as in the case of the
pigments, there is an intestinal-hepatic circulation. The value of this
reabsorption may lie in the fact that the bile acids constitute a very
efficient stimulus to the bile-secreting activity of the cells, being one
•of the best of cholagogues, or it may be that it economizes material.
From what we know of the history of the bile acids it is evident that
they are not to be considered solely as excreta: they have some
important function to fulfill. The following suggestions as to their
value have been made: In the first place, they serve as a menstruum
for dissolving the cholesterin which is constantly present in the bile
and which is an excretion to be removed; secondly, they facilitate
greatly the splitting and the absorption of fats in the intestine. It
is an undoubted fact that when bile is shut off from the intestine the
absorption of fats is very much diminished, and it has been shown
that this action of the bile in fat absorption is due to the presence
of the bile acids, and in the same way the known augmenting
influence of bile upon the activity of pancreatic lipase has been
traced to the bile acids.

Cholesterin. — Cholesterin is a non-nitrogenous substance of the
formula C27H46O. It is a constant constituent of the bile, although
it occurs in variable quantities. Cholesterin is very widely distrib-
uted in the body, being found especially in the white matter (medul-
lary substance) of nerve fibers. It seems, moreover, to be a constant
constituent of all animal and plant cells. It is assumed that choles-
terin is not formed in the liver, but that it is eliminated by the liver
cells from the blood, which collects it from the various tissues of the

* Friedmann, " Hofmeister's Beitrage," 3, 1, 1902.

fSee Simon, "Johns Hopkins Hospital Bulletin," 15,365, 1904.

748 PHYSIOLOGY OF DIGESTION AND SECRETION.

body. According to Naunyn, however, the cholesterin is not secreted
by the liver cells proper, but is added to the secretion while in the bile
passages — the gall-ducts and gall-bladder. That it is an excretion
is indicated by the fact that it is eliminated unchanged in the feces.
Cholesterin is insoluble in water or in dilute saline liquids, and is held
in solution in the bile by means of the bile acids. We must regard
it as a waste product of cell life, formed probably in minute quantities,
and excreted mainly through the liver. It is partly eliminated
through the skin, in the sebaceous and sweat secretions, and in the
milk.

Lecithin, Fats, and Nucleo-albumin. — Lecithin, C44H90NPO9
is a compound of glycerophosphoric acid with fatty acid radicals
(stearic, oleic, or palmitic) and a nitrogenous base, cholin. When
hydrolyzed by boiling with alkali it splits up into these three sub-
stances. It is found generally as such, or in combination, in all cells,
and evidently plays some as yet unknown part in cell metabolism.
It occurs in largest quantity in the white matter of the nervous
system. In the liver it occurs to a considerable extent both as lecithin
and in a more complex combination with a carbohydrate residue, a-
compound designated as jecorin. So far as it is found in the bile it
represents possibly a waste product derived from the liver or from
the body at large. Little is known of its precise physiological sig-
nificance.

The special importance, if any, of the small proportion of fats
and fatty acids in the bile is unknown. The ropy, mucilaginous
character of bile is due to the presence of a body formed in the bile-
ducts and gall-bladder. This substance was formerly designated
as mucin, but it is now known that in ox bile at least it is not a true
mucin, but a nucleo-albumin (see appendix). Hammarsten reports
that in human bile some true mucin is found. Outside the fact that
it makes the bile viscous, this constituent is not known to possess any
especial physiological significance.

The Secretion of the Bile. — Numerous experiments have been
made to ascertain whether or not the secretion of bile is controlled
by a special set of secretory fibers. The secretion itself is continuous,
but varies in amount under different conditions. These conditions
may be controlled experimentally in part. It has been shown, for
example, that stimulation of the spinal cord or splanchnic nerve
diminishes the flow of bile, while section of the splanchnic branches
may cause an increased flow. These and similar actions are ex-
plained, however, by their effect on the blood-flow through the liver.
The splanchnics carry vasomotor nerves to the liver, and section or
stimulation of these nerves will therefore alter the circulation in the
organ. Since the secretion increases when the blood-flow is increased
and vice versa, it is believed that in this case no special secretory
nerve fibers exist. The metabolic processes in the liver cells which

PHYSIOLOGY OF THE LIVER AND SPLEEN. 749

produce the secretion probably go on at all times, but they are
increased when the blood-flow is increased. We may believe, there-
fore, that the quantity of the bile secretion varies with the quantity
and composition of the blood- flowing through the liver. On the
physiological and pharmacological side efforts have been made to
discover what substances stimulate especially the formation of bile.
Such substances are designated as cholagogues. The therapeutical
agents capable of giving this action are still a subject of controversy.
On the physiological side the following facts are accepted : Any agent
that causes an hemolysis of red corpuscles increases the flow of bile,
or the same effect is produced if a solution of hemoglobin is injected
directly into the blood. This result is in harmony with the views
already stated regarding the significance of the bile pigments as an
excretory product of hemoglobin. The cholagogue whose action is
most distinct and prolonged is bile itself. When fed or injected
directly into the circulation bile causes an undoubted increase in the
secretion. This effect is due both to the bile acids and bile pigments.
Since the bile acids have a hemolytic effect on red corpuscles, it
might at first be assumed that their action as cholagogues is due
indirectly to this circumstance. The action of the bile acids is,
however, much more pronounced than that of other hemolytic agents,
and it seems certain, therefore, that they exert a specific effect on the
liver cells. Lastly, there is evidence that the secretin, whose action
upon the pancreatic secretion has been described, exerts a similar
effect upon the secretion of bile. Statements differ somewhat in
regard to the extent of this action, but it seems to be certain that,
when acids (0.5 per cent. HC1) are injected into the duodenum or upper
part of the jejunum, the secretion of bile is increased; and, since
this effect takes place when the nervous connections are severed, the
effect, as in the case of the pancreatic secretion, is explained by as-
suming that the acid converts prosecretin to secretin, and this
latter after absorption into the blood acts upon the liver cells.*
A similar effect may be obtained by injecting secretin directly into
the blood. Since during a meal the stomach normally ejects acid
chyme into the duodenum, the importance of this secretin reaction
in adapting the secretion of bile to the period of digestion is evident.
The Ejection of Bile into the Duodenum — Function of the
Gall-bladder. — Although the bile is formed more or less continu-
ously, it enters the duodenum periodically during the time of digestion.
The secretion during the intervening periods is prevented from enter-
ing the duodenum apparently by the fact that the opening of the
common bile-duct is closed by a sphincter. The secretion, therefore,
backs up into the gall-bladder. According to Bruns,t no bile appears

* See Falloise, quoted in Maly's " Jahres-bericht der Thier-chemie, " 33,
611, 1904. t" Archives des sciences biologiques, " 7,87, 1899.

750

PHYSIOLOGY OF DIGESTION AND SECRETION.

in the duodenum as long as the stomach is empty. When, however,
a meal is taken the ejection of the chyme into the duodenum is fol-
lowed by an ejection of bile.* It would seem, therefore, that each
gush of chyme into the duodenum excites, probably by reflex action, a
contraction of the gall-bladder. The substances in the chyme that
are responsible for the stimulation have been investigated by Bruns.
He finds that acids, alkalies, and starches are ineffective, and con-
cludes that the reflex is due to the proteins and fats or some of the
products of their digestion. The gall-bladder has a muscular coat

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Fig. 273. — Curves showing the velocity of secretion of bile into the duodenum on
(1) a diet of milk, uppermost curve; (2) a diet of meat, middle curve; (3) a diet of bread,
lowest curve. The divisions on the abscissa represent intervals of thirty minutes; the
figures on the ordinates represent the volume of secretion in cubic centimeters. — (Bruns.)

of plain muscle, and records made of its contractions show that the
force exerted is quite small. According to Freese,f the maximal con-
traction does not exceed that necessary to overcome the hydrostatic
pressure of a column of water 220 mms. in height, — a force, therefore,
which is about equivalent to the secretion pressure of bile as deter-
mined by Heidenhain. The innervation Of the gall-bladder and gall-
ducts has been studied especially by Doyon.f It would seem, from

* See also Klodnizki, quoted from Maly's " Jahres-bericht der Thier-
chemie," 33, 617, 1904.

t "Johns Hopkins Hospital Bulletin," June, 1905.
J Doyon, " Archives de physiologic, " 1894, p. 19.

PHYSIOLOGY OF THE LIVER AND SPLEEN. 751

the experiments made by, this author together with later experiments
reported by others,* that the bladder receives both motor and in-
hibitory fibers by way of the splanchnic nerves. These fibers emerge
from the spinal cord in the roots of the sixth thoracic to the first
lumbar spinal nerve, and pass to the celiac plexus by way of the
splanchnic nerves. Motor fibers may occur also in the vagi. Sensory
fibers capable of causing a reflex constriction or dilatation of the
bladder are found in both the vagus and splanchnic nerves. Stim-
ulation of the central end of the cut splanchnic causes a dilatation
of the bladder (reflex stimulation of the inhibitory fibers), while
stimulation of the central end of the vagus causes a contraction
of the bladder and a dilatation (inhibition) of the sphincter muscle
at the opening of the common duct into the intestine. Since these
last movements are the ones that occur during normal digestion,
it is probable that the afferent fibers from the duodenum, which
are concerned in this reflex, run in the vagus.

Effect of Complete Occlusion of the Bile-duct. — When the
flow of bile is prevented by ligation of the bile-duct, or when this
duct is occluded by pathological changes the bile eventually gets
into the blood, producing. a condition of jaundice (icterus). There
has been much discussion as to whether the bile is absorbed directly
into the blood from the liver cells or the liver lymph-spaces, or
whether it is carried to the blood by way of the lymph-vessels and
thoracic duct.f Experimental evidence points to both possibili-
ties. The increased pressure in the bile system leads possibly to a
rupture of the delicate bile capillaries, and the bile thus escapes
into the lymph-spaces. From these spaces it may be absorbed
directly by the blood-vessels of the liver, or it may be carried off
in the lymph-stream toward the thoracic duct.

General Physiological Importance of Bile. — The physiological
value of bile has been referred to in speaking of its several constitu-
ents. Bile is of importance as an excretion in that it removes from
the body waste products of metabolism, such as cholesterin, lecithin,
and bile pigments. With reference to the pigments, there is evidence
to show that a part at least may be reabsorbed while passing through
the intestine, and be used again in some way in the body. The bile
acids represent end-products of metabolism involving the proteins
of the liver cells, but they are undoubtedly reabsorbed in part, and
can not be regarded merely as excreta. As a digestive secretion, the
most important function attributed to the bile is the part it takes in
the digestion and absorption of fats. It accelerates greatly the action
of the lipase of pancreatic juice in splitting the fats to fatty acids and
glycerin, and it aids materially in the absorption of the products

* Bainbridge and Dale, "Journal of Physiology," 1905, xxxiii., 138.
t See Mendel and Underbill for literature, "American Journal of Phys-
iology," 1905, xiv., 252.

752 PHYSIOLOGY OF DIGESTION AND SECRETION.

of this hydrolysis. A number of observers have shown that when a
permanent biliary fistula is made, and the bile is thus prevented from
reaching the intestinal canal, a large proportion of the fat of the food
escapes absorption and is found in the feces. This action of the
bile may be referred directly to the fact that the bile acids serve as a
solvent for the fats and fatty acids. It was formerly believed that
bile is also of great importance in restraining the processes of putre-
faction in the intestine. It was asserted that bile is an efficient
antiseptic, and that this property comes into use normally in prevent-
ing excessive putrefaction. Bacteriological experiments made by a
number of observers have shown, however, that bile itself has very
feeble antiseptic properties, as is indicated by the fact that it putrefies
readily. The free bile acids and cholalic acid do have a direct retard-
ing effect upon putrefactions outside the body ; but this action is not
very pronounced, and has not been demonstrated satisfactorily for
bile itself. It seems to be generally true that in cases of biliary fistula
the feces have a very fetid odor when meat and fat are taken in the
food. But the increased putrefaction in these cases may possibly be
an indirect result of the withdrawal of bile. It has been suggested,
for instance, that the deficient absorption of fat that follows upon the
removal of the bile results in the protein and carbohydrate material
becoming coated with an insoluble layer of fat, so that the penetration
of the digestive enzymes is retarded and greater opportunity is given
for the action of bacteria. We may conclude, therefore, that, while
there does not seem to be sufficient warrant at present for believing
that the bile exerts a direct antiseptic action upon the intestinal
contents, nevertheless its presence limits in some way the extent of
putrefaction.

Glycogen. — One of the most important functions of the liver is
the formation of glycogen. This substance was found in the liver in
1857 by Claude Bernard, and is one of several brilliant discoveries
made by him. Glycogen has the formula (C6H10O5)n, which is also
the general formula given to vegetable starch ; glycogen is therefore
frequently spoken of as "animal starch." It gives, however, a port-
wine-red color with iodin solutions, instead of the familiar deep blue
of vegetable starch, and this reaction serves to detect glycogen not
only in its solutions, but also in the liver cells. Glycogen is readily
soluble in water, and the solutions have a characteristic opalescent
appearance. Like starch, glycogen is acted upon by ptyalin and
other diastatic enzymes, and the end-products are apparently the
same — namely, maltose, or maltose and some dextrin, or else dex-
trose, depending upon the enzyme used. Under the influence of
acids it may be hydrolyzed at once to dextrose.*

* The extensive literature of glyccgen is collected and reviewed by Cre-
;ner in the " Ergebnisse der Physiologic, " vol. i, part i, 1902; and by Pfliiger,
f. die gesammte Physiologic," 96, 1, 1903.

PHYSIOLOGY OF THE LIVER AND SPLEEN. 753

Occurrence of Glycogen in the Liver. — Glycogen can be
detected in the liver cells microscopically. If the liver of a dog is
removed twelve or fourteen hours after a hearty meal, hardened in
alcohol, and sectioned, the liver cells are found to contain clumps
of clear material which give the iodin reaction for glycogen. Even
when distinct aggregations of the glycogen can not be made out, its
presence in the cells is shown by the red reaction with iodin. By
this simple method one can demonstrate the important fact that the
amount of glycogen in the liver increases after meals and decreases
again during the fasting hours, and if the fast is sufficiently prolonged
it may disappear altogether. This fact is, however, shown more
satisfactorily by quantitative determinations, by chemical means,
of the total glycogen present. The amount of glycogen in the
liver is quite variable, being influenced by such conditions as the
character and amount of the food, muscular exercise, body tem-
perature, drugs, etc. From determinations made upon various
animals it may be said that the average amount lies between 1 .5 and
4 per cent, of the weight of the liver. But this amount may be in-
creased greatly by feeding upon a diet largely made up of carbohy-
drates. It is said that in the dog the total amount of liver glycogen
may be raised to 17 per cent., and in the rabbit to 27 per cent., by
this means, while it is estimated for man (Neumeister) that the quan-
tity may be increased to at least 10 per cent. It is usually believed
that glycogen exists as such in the liver cells, being deposited in the
substance of the cytoplasm. Reasons have been brought forward
to show that this is not strictly true, and that the glycogen is prob-
ably held in some sort of weak chemical combination. It has been
shown, for instance, that although glycogen is easily soluble in cold
water, it can not be extracted readily from the liver cells by this agent.
One must use hot water, salts of the heavy metals, and other similar
agents that may be supposed to break up the combination in which
the glycogen exists. For practical purposes, however, we may speak
of the glycogen as lying free in the liver-cells, just as we speak of
hemoglobin existing as such in the red corpuscles, although it is
probably held in some sort of combination.

Origin of Glycogen. — To understand clearly the views held as
to the origin of liver glycogen, it is necessary to describe briefly the
effect of the different foodstuffs upon its formation.

Effect of Carbohydrates on the Amount of Glycogen. — The amount
of glycogen in the liver is affected very quickly by the quantity of car-
bohydrates in the food. If the carbohydrates are given in excess, the
supply of glycogen may be increased largely beyond the average
amount present, as has been stated above. Investigation of the differ-
ent sugars has shown that dextrose, levulose, saccharose (cane-sugar),
and maltose are unquestionably direct glycogen-formers, — that is,

48

754 PHYSIOLOGY OF DIGESTION AND SECRETION.

glycogen is formed directly from them or from the products into
which they are converted during digestion. The bulk of our car-
bohydrate food reaches the liver as dextrose, or as dextrose and levu-
lose, and these forms of sugar may be converted into glycogen in the
liver cells by a simple process of dehydration, such as may be repre-
sented in substance by the formula C6H12O6 — H20 = C6H1005.
There is no doubt that both dextrose and levulose increase markedly
the amount of glycogen in the liver; and, since cane-sugar is inverted
in the intestine before absorption, it also must be a true glycogen-
former, — a fact that has been abundantly demonstrated by direct
experiment. Lusk* has shown, however, that, if cane-sugar is in-
jected under the skin, it has a very feeble effect in the way of increas-
ing the amount of glycogen in the liver, since under these conditions
it is probably absorbed into the blood without undergoing inversion.
Experiments with subcutaneous injection of lactose gave similar
results, and it is generally believed that the liver cells can not convert
the double sugars to glycogen, at least not readily; hence the value
of the hydrolysis of these sugars in the alimentary canal before
absorption. We may assume, therefore, that dextrose, levulose, and
galactose are the true glycogen-formers that occur normally in the
blood, and that the disaccharids (cane-sugar, milk-sugar, etc.) and
the polysaccharids (starches) are true glycogen-formers to the ex-
tent that they are converted into dextrose, levulose, or galactose.

Effect of Protein on Glycogen Formation. — In his first studies
upon glycogen Bernard asserted that it may be formed from protein
material. Since that time there have been much discussion and
experimentation upon this point. The usual view is that protein
must be counted among the true glycogen-formers in the sense that
some of the material of the protein molecule is directly converted to
glycogen. The protein in digestion undergoes, it will be remem-
bered, a splitting process, the limits of which are not definitely settled.
It is assumed, however, that the nitrogenous split products are
acted upon in the liver, the nitrogen being converted first to an
ammonia compound and then to urea, while the non-nitrogenous
residue is converted to sugar by a synthetic process. Among
the split products of protein that have been especially investigated
in this relation the results with leucin and glucosamin have been
chiefly negative. f Experimentally observers find for the warm-
blooded animals, at least, that feeding with proteins, even in the
case of those proteins, such as casein, that contain no carbohydrate
grouping, causes an increased production of glycogen. J The con-
clusion to be drawn from these experiments is strengthened by

*Voit, "Zeitschrift f. Biologie," 28, 285, 1891.

f Halsey, "American Journal of Physiology," 10, 229, 1904.

j See Stookey, "American Journal of Physiology," 9, 138, 1903.

PHYSIOLOGY OF THE LIVER AND SPLEEN. 755

clinical experience upon human beings suffering from diabetes.
In severe forms of this disease the carbohydrate material of the
food escapes oxidation in the body and is secreted unchanged in
the urine. If under these conditions the individual is given an
exclusively protein diet sugar still continues to appear in the urine,
and it would seem that this sugar can only arise from the protein
food. In the similar condition of severe glycosuria that may be
produced by the use of phld'ridzin it has been shown that the animal
continues to excrete sugar even when fed on protein alone or when
starved. Under such conditions the amount of dextrose in the
urine bears a definite ratio to the amount of nitrogen excreted
D : N : : 3.65 : 1 (Lusk), which would indicate that both arise from
the breaking down of the protein molecule. On this supposition
58.4 per cent, of the protein may be converted to sugar. So also
the fact that during prolonged starvation, lasting for forty or even
ninety days, the blood retains a practically constant composition
in sugar indicates that this material is being formed from either
the protein or fat supply of the body. Other considerations tend
to exclude the fat, and we are, therefore, led to the belief that the
protein can give rise to sugar in the body. If this change is part
of the normal metabolism of the body it would make protein a gly-
cogen-former, since the sugar formed from the protein may, of course,
be converted to glycogen. Whether or not all proteins yield gly-
cogen or sugar in the body is not entirely determined. Some
authors have thought that only those proteins that contain a
carbohydrate residue have this property; but, as stated above,
casein and other proteins that do not possess this grouping seem
also to increase the glycogen supply when fed alone.

Effect of Fats upon Glycogen Formation. — A large number of
substances have been found by some observers to increase the store
of glycogen in the liver. In some of these cases at least it is evident
that the substance is not a direct glycogen-former in the sense that
the material is itself converted to glycogen. It may increase the
supply of liver glycogen in some indirect way, — for example, by
diminishing the consumption of glycogen in the body. The most
important substance in this connection from a practical standpoint
is fat. Whether or not the body can convert fats into sugar or
glycogen is a question about which at present there is much
difference of opinion, and much evidence might be cited on each side.
Cremer, however, has furnished apparent proof that glycerin acts
as a direct glycogen or sugar-former. When fed, especially in the
diabetic condition, it causes an increase in the sugar which can not
be explained as a result of protein metabolism. Since in the body
neutral fats are normally split into glycerin and fatty acid, the fact
that glycerin can be converted to sugar seems to carry with it the

756 PHYSIOLOGY OF DIGESTION AND SECRETION.

admission that fats may contribute directly to sugar production.
Whether the synthesis of sugar (or glycogen) from glycerin is,
so to speak, a normal process or occurs only under especial condi-
tions, can not be decided at present.

The Function of Glycogen — Glycogenic Theory. — The mean-
ing of the formation of glycogen in the liver has been, and still is,
the subject of discussion. The view advanced first by Bernard is
perhaps most generally accepted. According to Bernard, glycogen
forms a temporary reserve supply of carbohydrate material that is
laid up in the liver during digestion and is gradually made use of in
the intervals between meals. During digestion the carbohydrate
food is absorbed into the blood of the portal system as dextrose or as
dextrose, levulose, and galactose. If these sugars passed through
the liver unchanged, the contents of the systemic blood in sugar
would be increased perceptibly. It is 'now known that when the
percentage of sugar in the blood rises above a certain normal limit
(condition of hyperglycemia), the excess is excreted through the
kidney and is lost. But as the blood from the digestive organs
passes through the liver the excess of sugar is abstracted by the
liver cells, is dehydrated to make glycogen, and is retained in
the cells in this form for a short period. From time to time
the glycogen is reconverted into sugar (dextrose) and is given off to
the blood. By this means the percentage of sugar in the systemic
blood is kept nearly constant (0.1 to 0.2 per cent.) and within limits
best adapted to the use of the tissues. The great importance of the
formation of glycogen and the consequent conservation of the sugar
supply of the tissues is evident when we consider the nutritive value
of carbohydrate food. Carbohydrates form the bulk of our usual
diet, and the proper regulation of the supply to the tissues is, there-
fore, of vital importance in the maintenance of a normal, healthy
condition. The second part of this theory, which holds that the
glycogen is reconverted to dextrose, is supported by observations
upon livers removed from the body. It has been found that shortly
after the removal of the liver the supply of glycogen begins to dis-
appear and a corresponding increase in dextrose occurs. Within a
comparatively short tune all the glycogen is gone and only dextrose
is found. It is for this reason that in the estimation of glycogen in the
liver it is necessary to mince the organ and to throw it into boiling
water as quickly as possible, since by this means the liver cells are
killed and the conversion of the glycogen is stopped. How the gly-
cogen is changed to dextrose by the liver is a matter not fully ex-
plained. According to most authors, the conversion is due to an
enzyme produced in the liver. Extracts of liver, as of some other
tissues, yield a diastatic enzyme that changes glycogen to dextrose.*
*Tebb, "Journal of Physiology," 22, 423, 1897-98.

PHYSIOLOGY OF THE LIVER AND SPLEEN. 757

It is probable, therefore, that the normal conversion of glycogen to
dextrose is effected by a special enzyme produced in the liver cells.
In this description of the origin and meaning of the liver glycogen
reference has been made only to the glycogen derived directly from
digested carbohydrates. The glycogen derived from protein foods,
once it is formed in the liver, has, of course, the same functions to
fulfill. It is converted into sugar, and eventually is oxidized in
the tissues. For the sake of completeness it may be well to add
that some of the sugar of the blood formed from the glycogen may
under certain conditions be converted into fat in the adipose tissues,
instead of being burnt, and in this way it may be retained in the
body as a reserve supply of food of a more stable character.

Glycogen in the Muscles and other Tissues. — The history of
glycogen is not complete without some reference to its occurrence in
the muscles. Glycogen is, in fact, found in various places in the body,
and is widely distributed throughout the animal kingdom. It occurs,
for example, in leucocytes, in the placenta, in the rapidly growing
tissues of the embryo, and in considerable abundance in the oyster
and other molluscs. But in our bodies and in those of the mammals
generally the most significant occurrence of glycogen, outside the
liver, is in the voluntary muscles, of which glycogen forms a normal
constituent. It has been estimated that the percentage of glycogen
in resting muscle varies from 0.5 to 0.9 per cent., and that in the
musculature of the whole body there may be contained an amount
of glycogen equal to that in the liver itself. Muscular tissue, as
well as liver tissue, has a glycogenetic function — that is, it is cap-
able of laying up a supply of glycogen from the sugar brought
to it by the blood. The glycogenetic function of muscle has been
demonstrated directly by Kulz,* who has shown that an isolated
muscle irrigated with an artificial supply of blood to which dextrose
is added is capable of changing the dextrose to glycogen, as shown
by the increase in the latter substance in the muscle after irriga-
tion. Muscle glycogen is to be looked upon as a temporary and
local reserve supply of material; so that, while we have in the
liver a large general depot for the temporary storage of glycogen for
the use of the body at large, the muscular tissue, which, considering
its bulk, is the most active tissue of the body from the standpoint
of energy production, is also capable of laying up in the form of
glycogen any excess of sugar brought to it. The fact that glycogen
occurs so widely in the rapidly growing cells of embryos indicates
that this glycogenetic function may at times be exercised by any
tissue.

Conditions Affecting the Supply of Glycogen in Muscle and
Liver. — In accordance with the view given above of the general value
* "Zeitschrift f. Biologie," 27, 237, 1890.

758 PHYSIOLOGY OF DIGESTION AND SECRETION.

of glycogen — namely, that it is a temporary reserve supply of
carbohydrate material that may be rapidly converted to sugar and
oxidized with the liberation of energy— it is found that the supply
of glycogen is greatly affected by conditions calling for increased
metabolism in the body. Muscular exercise quickly exhausts the
supply of muscle and liver glycogen, provided it is not renewed
by new food. Observations on isolated muscles have shown
definitely that the local supply of glycogen is diminished when the
muscle is made to contract (see p. 60). In a starving animal
glycogen finally disappears, except perhaps in traces, but this
disappearance occurs much sooner if the animal is made to use its
muscles at the same time. It has been shown also by Morat and
Dufourt that if a muscle has been made to contract vigorously
it takes up much more sugar from an artificial supply of blood sent
through it than a similar muscle which has been resting ; on the
other hand, it has been found that if the nerve of one leg is cut
so as to paralyze the muscles of that side of the body, the amount
of glycogen is greater in these muscles than in those of the other
leg that have been contracting meantime and using up their gly-
cogen. The further history of glycogen is considered in the section
on Nutrition.

Formation of Urea in the Liver. — The nitrogen contained in
the protein material of our food is finally eliminated, mainly in the
form of urea. It has been definitely proved that the urea is not
formed in the kidneys, the organs that eliminate it. It has long been
considered a matter of the greatest importance to ascertain in what
organ or tissues urea is formed. Investigations have gone so far as
to demonstrate that it arises in part at least in the liver; hence the
property of forming urea must be added to the other important func-
tions of the liver cell. Schroder * performed a number of experi-
ments in which the liver was taken from a freshly killed dog and
irrigated through its blood-vessels with a supply of blood obtained
from another dog. If the supply of blood was taken from a fasting
animal, then circulating it through the isolated liver was not followed
by any increase in the amount of urea contained in it. If, on the
contrary, the blood was obtained from a well-fed dog, the amount
of urea contained in it was distinctly increased by passing it through
the liver, thus indicating that the blood of an animal after digestion
contains something that the liver can convert to urea. It is to be
noted, moreover, that this power is not possessed by all the organs,
since blood from well-fed animals showed no increase in urea after
being circulated through an isolated kidney or muscle. As further
proof of the urea-forming power of the liver Schroder found that

* " Archiv f. experimentelle Pathologie und Pharmakologie," 15, 364,
1882, and 19, 373, 1885.

PHYSIOLOGY OF THE LIVER AND SPLEEN. 759

if ammonium carbonate was added to the blood circulating through
the liver — to that from the fasting as well as from the well-nourished
animal — a very decided increase in the urea was always obtained.
It follows from the last experiment that the liver cells are able to
convert carbonate of ammonium into urea. The reaction may be
expressed by the equation (NH4)2CO3-2H2O = CON2H4. Schon-
dorff * in some later work showed that if the blood of a fasting dog
is irrigated through the ru'nd legs of a well-nourished animal, no
increase in urea in the blood can be detected; but if the blood, after
irrigation through the hind legs, is subsequently passed through the
liver, a marked increase in urea results. Obviously, the blood in this
experiment derives something from the tissues of the leg which the
tissues themselves cannot convert to urea, but which the liver cells
can. Finally, in some remarkable experiments upon dogs made by
four investigators (Hahn, Massen, Nencki, and Pawlow), which are
described more fully in the next chapter, it was shown that when the
liver is practically destroyed there is a distinct diminution in the
urea of the urine. In birds uric acid takes the place of urea as the
main nitrogenous excretion of the body, and Minkowski has shown
that in them removal of the liver is followed by an important
diminution in the amount of uric acid excreted. From experiments
such as these it is safe to conclude that urea is formed in the liver
and is then given to the blood and excreted by the kidney. In
treating of the physiological history of urea an account will be given
of the views proposed with regard to the antecedent substance or
substances from which the liver produces urea.

Physiology of the Spleen. — Much has been said and written
about the spleen, but we are yet in the dark as to the distinctive
function or functions of this organ. The few facts that are known
may be stated briefly without going into the details of theories that
have been offered at one time or another. The older experimenters
demonstrated that this organ may be removed from the body without
serious injury to the animal. An increase in the size of the lymph-
glands and of the bone-marrow has been stated to occur after ex-
tirpation; but this is denied by others, and, whether true or not, it
gives but little clue to the normal functions of the spleen. Some
observers f find that the removal of the spleen causes a marked
diminution in the number of red corpuscles and the quantity of
hemoglobin. They infer, therefore, that the spleen is normally
concerned in some way in the formation of red corpuscles. Others,
however, report with equal positiveness that removal of the spleen
has no effect upon the number of red corpuscles or upon the power of
the animal to regenerate its corpuscles after hemorrhage. { The

760 PHYSIOLOGY OF DIGESTION AND SECRETION.

most definite facts known about the spleen are in connection with its
movements. It has been shown that there is a slow expansion and
contraction of the organ synchronous with the digestion periods.
After a meal the spleen begins to increase in size, reaching a maximum
at about the fifth hour, and then slowly returns to its previous size.
This movement, the meaning of which is not known, is probably due
to a slow vasodilatation, together, perhaps, with a relaxation of the
tonic contraction of the musculature of the trabeculae. In addition
to this slow movement, Roy* has shown that there is a rhythmical
contraction and relaxation of the organ, occurring in cats and dogs
at intervals of about one minute. Roy supposes that these con-
tractions are effected through the intrinsic musculature of the organ,
— that is, the plain muscle tissue present in the capsule and trabeculse,
— and he believes that the contractions serve to keep up a circulation
through the spleen and to make its vascular supply more or less
independent of variations in general arterial pressure. The fact
that there is a special local arrangement for maintaining its cir-
culation makes the spleen unique among the organs of the body, but
no light is thrown upon the nature of the function fulfilled. The
spleen is supplied richly with motor nerve fibers which when stimu-
lated either directly or reflexly cause the organ to diminish in
volume. According to Schaefer,f these fibers are contained in the
splanchnic nerves, which carry also inhibitory fibers whose stimu-
lation produces a dilatation of the spleen.

The chemical composition of the spleen is complicated, but sug-
gestive. Its mineral constituents are characterized by a large
percentage of iron, which seems to be present as an organic compound
of some kind. Analysis shows also the presence of a number of fatty
acids, fats, cholesterin, and, what is perhaps more noteworthy, a
number of nitrogenous extractives belonging to the group of purin
bases, such as xanthin, hypoxanthin, adenin, guanin, and uric acid.
The presence of these bodies seems to indicate that active metabolic
changes of some kind occur in the spleen. As to the theories of the
splenic functions, the following may be mentioned: (1) The spleen
has been supposed to give rise to new red corpuscles. This it un-
doubtedly does during fetal life and shortly after birth, and in some
animals throughout life, but there is no reliable evidence that the
function is retained in adult life in man or in most of the mammals.
(2) It has been supposed to be an organ for the destruction of red
corpuscles. This view is founded chiefly on microscopical evidence
according to which certain large ameboid cells in the spleen ingest
and destroy the old red corpuscles, and partly upon the fact that the
spleen tissue seems to be rich in an iron-containing compound. This

* "Journal of Physiology/' 3, 203, 1881.
t/6id., 20, 1, 1896.

PHYSIOLOGY OF THE LIVER AXD SPLEEN. 761

theory cannot be considered at present as satisfactorily demon-
strated. (3) It has been suggested that the spleen is concerned in
the production of uric acid. This substance is found in the spleen,
as stated above, and it was shown by Horbaczewsky that the
spleen contains substances from which uric acid or xanthin may
readily be formed by the action of the spleen-tissue itself. More
recent investigations * hate shown that the spleen, like the liver
and some other organs, contains special enzymes (adenase, guanase,
and xanthin oxydase), by whose action the split products of the
nucleins may be converted to uric acid, and it is probable, therefore,
that this latter substance is constantly formed in the spleen. (4)
Lastly, a theory has been supported by Schiff and Herzen, according
to which the spleen produces something (an enzyme) which, when
carried in the blood to the pancreas, acts upon the trypsinogen con-
tained in this gland, converting it into trypsin. This view has been
corroborated by a number of observers, but it is difficult at present
to decide whether such an action occurs normally during digestion.
As already stated, the general testimony at present indicates that
the pancreatic juice when secreted contains its trypsin in inactive
form. It is activated only after reaching the duodenum under the
influence of the enterokinass.

* Consult Jones and Austrian. " Zeitschrift f. physiol. Chem." 1906,
xlviii., 110.

CHAPTER XLV.

THE KIDNEY AND SKIN AS EXCRETORY ORGANS.

Structure of the Kidney. — The kidney is a compound tubular
gland. The uriniferous tubules composing it may be roughly
separated into a secreting part comprising the capsule, convoluted
tubes, and loo'p of Henle, and a collecting part, the so-called straight
or collecting tube, the epithelium of which is assumed not to
have any secretory function. Within the secreting part the epithe-
lium differs greatly in character in different regions; its peculiarities
may be referred to briefly here so far as they seem to have a physio-

E F

G

Fig. 274. — Portions of the various divisions of the uriniferous tubules drawn from
sections of human kidney: A, Malpighian body; x, squamous epithelium lining the cap-
sule and reflected over the glomerulus; y, z, afferent and efferent vessels of the tuft; et
nuclei of capillaries; n, constricted neck marking passage of capsule into convoluted tu-
bule; B, proximal convoluted tubule; C, irregular tubule; D and F, spiral tubules; Et
ascending limb of Henle's loop; G, straight collecting tubule. — (Piersol.)

logical bearing, although for a complete description reference must
be made to works on histology.

The arrangement of the glandular epithelium in the capsule with
reference to the blood-vessels of the glomerulus is worthy of special
attention. It will be remembered that each Malpighian corpuscle con-
sists of two principal parts, a tuft of blood-vessels, the glomerulus, and
an enveloping expansion of the uriniferous tubule, the capsule. The
glomerulus is an interesting structure (see Fig. 274, A). It consists

762

KIDNEY AND SKIN AS EXCRETORY ORGANS. 763

of a small afferent artery which after entering the glomerulus, breaks
up into a number of capillaries. These capillaries, although twisted
together, do not anastomose, and they unite to form a single efferent
vein of a smaller diameter than the afferent artery. The whole
structure, therefore, is not an ordinary, capillary area, but a rete
mirabile, and the physical factors are such that within the capil-
laries of the rete there must be a greatly diminished velocity of the
blood-stream, owing to the'' great increase in the width of the stream
bed, and a high blood-pressure as compared with ordinary capil-
laries. Surrounding this glomerulus is the double-walled capsule.
One wall of the capsule is closely adherent to the capillaries of the
glomerulus; it not only covers the structure closely, but dips into
the interior between the small lobules into which the glomerulus is
divided. This layer of the capsule is composed of flattened, endo-
thelial-like cells, the glomerular epithelium, to which great impor-
tance is attached in the formation of the secretion. It will be no-
ticed that between the interior of the blood-vessels of the glomerulus
and the cavity of the capsule, which is the beginning of the urin-
iferous tubule, there are interposed only two very thin layers, —
namely, the epithelium of the capillary wall and the glomerular
epithelium. The apparatus would seem to afford most favorable
conditions for filtration of the liquid parts of the blood. The epi-
thelium clothing the convoluted portions of the tubule, including
under this designation the so-called irregular and spiral portions
and the loop of Henle, is of a character quite different from that of
the glomerular epithelium (Fig. 274, B, C, D, E, F, G). The cells,
speaking generally, are cuboidal or cylindrical, protoplasmic, and
granular in appearance; on the side toward the basement mem-
brane they often show a peculiar striation, while on the lumen side
the extreme periphery presents a compact border which in some
cases shows a cilia-like striation. These cells have the general
appearance of an active secretory epithelium, and one theory of
urinary secretion attributes this function to them.

The Secretion of Urine. — The kidneys receive a rich supply
of nerve fibers, but most histologists have been unable to trace any
connection between these fibers and the epithelial cells of the kidney
tubules.

The majority of purely physiological experiments upon direct
stimulation of the nerves going to the kidney are adverse to the
theory of secretory fibers, the marked effects obtained in these ex-
periments being all explicable by the changes produced in the blood-
flow through the organ. Two general theories of urinary secretion
have been proposed. Ludwig held that the urine is formed by the
simple physical processes of filtration and diffusion. In the glom-
eruli the conditions are most favorable to filtration, and he sup-

764 PHYSIOLOGY OF DIGESTION AND SECRETION.

posed that in these structures water filtered through from the blood,
carrying with it not only the inorganic salts, but also the specific
elements (urea, etc.) of the secretion. There was thus formed at
the beginning of the uriniferous tubules a complete but diluted
urine, and in the subsequent passage of this liquid along the con-
voluted tubes it became concentrated by diffusion with the more
concentrated lymph surrounding the outside of the tubules.

Bowman's theory of urinary secretion, which has since been
vigorously supported and extended by Heidenhain, was based orig-
inally mainly on histological grounds. It assumes that in the
glomeruli water and inorganic salts are produced, while the urea
and related bodies are eliminated through the activity of the epi-
thelial cells in the convoluted tubes.

The first of these theories (Ludwig) is sometimes spoken of as
the mechanical theory, since as originally proposed it attempted
to explain the formation and composition of the urine by reference
only to the physical forces of filtration and diffusion. Adherents
of this view in recent years have modified it, however, to the extent
that the absorption supposed to take place in the convoluted tubules
is designated as a selective absorption, or selective diffusion, the
characteristics of which depend upon unknown peculiarities of struc-
ture in the epithelial cell, so that it is no longer a purely mechanical
theory. The difference between the Ludwig and the Bowman
theories may be stated briefly in this way. The former assumes that
in the glomerulus all of the constituents of the urine are produced
from the blood, probably by filtration, and that the function of the
epithelium lining the convoluted tubules is absorptive, like the
epithelium of the intestines, and not secretory. The Bowman view
as formulated by Heidenhain teaches that the glomerular epithe-
lium forms the water and salts of the urine by an act of secretion,
the ultimate chemistry or physics of which is not known. The
theory asserts that the epithelial cells participate actively in the
process of secretion and do not serve simply as a passive membrane.
The cells of the convoluted tubules are also secretory, their special
activity being limited mainly to the organic constituents, urea, etc.,
although, in this respect, — namely, in the precise distinction be-
tween the secretory products of the glomerular epithelium and those
of the convoluted tubules, — the theory is not very explicit. Much
interest and a large literature have been stimulated by controver-
sies based on these theories, and to-day the facts accumulated are
not such as to demonstrate conclusively one view or the other,
although, on the whole, perhaps, it may be said that the majority of
physiologists adhere to the more conservative view of Bowman-
Heidenhain to the extent at least of recognizing that the physical
laws of filtration, diffusion, and imbibition, so far as they are known,

KIDNHY AND SKIN AS EXCRETORY ORGANS. 765

do not suffice for a satisfactory explanation of the facts.* As in
other similar cases, our knowledge of the physical structure and
chemical properties of the walls of the living cells is still very de-
ficient, and it seems necessary to designate these activities by the
indefinite term secretion.

Function of the Glomerulus. — As stated above, the structure
of the glomerulus is peculiar and suggestive of a special adaptation.
Ludwig's theory looks upon it as a filter, the pressure of the blood
in the glomerular capillaries driving the water and salts through
the endothelium of the capillaries and the glomerular epithe-
lium into the cavity of the urinary tubule. If we consider
only the water and assume that the membranes traversed are freely
permeable to its molecules, then it is evident that, upon this theory,
the quantity of urine formed will depend upon the filtration pres-
sure, and that this filtration pressure can be expressed by the formula
F=P — p, in which P represents the blood-pressure in the glom-
erular capillaries and p the pressure of the urine in the capsular
end of the uriniferous tubules. Some of the interesting facts de-
veloped by experiment may be presented in connection with this
formula. According to the mechanical theory, the amount of urine
formed should vary directly with P and inversely with p. The
factor P may be increased in two general ways: First, by those
changes which raise general arterial pressure and therefore the
pressure in the renal arteries, — such changes, for instance, as are
brought about by an increased force of heart beat or a large vaso-
constriction. Second, by obstructing or occluding the renal veins.
Experiments have been made along these lines. With regard to
the first possibility »it has been found in general, although not invar-
iably, that raising arterial pressure increases the quantity of urine
if the means used are such as may be assumed to raise the pressure
in the glomerular capillaries.

The reverse experiment, however, of raising P by blocking the
venous outflow fails entirely to support the theory. When the renal
veins are compressed the capillary pressure in the glomemli must
be increased, and, if the veins are blocked entirely, we may suppose
that the capillary pressure is raised to the level of that of the renal
arteries. In such experiments, however, the flow of urine is di-
minished instead of being increased, and indeed may be stopped
altogether when the veins are completely blocked. The adherents of
the Ludwig theory have attempted to explain this unfavorable
result by assuming that the swollen interlobular veins press upon
and block the uriniferous tubules. According to the antagonistic
theory of Heidenhain, blocking the veins suppresses the secretory
activity of the glomerular epithelium by depriving it of oxygen and

* For discussion and literature see Magnus, "Miinchener med. Wochen-
schrift," 1906, Nos. 28 and 29.

766 PHYSIOLOGY OF DIGESTION AND SECRETION.

the chance for removal of CO2, — that is, by producing local as-
phyxia. The latter explanation seems the simpler of the two, and it
is very strongly supported by the opposite experiment of clamping
the renal artery. When this is done the blood-flow through the
kidney ceases and the secretion of urine also stops, as would be
expected. But when after a few minutes' closure the artery is un-
clamped, the secretion is not restored with the return of the cir-
culation. On the contrary, a long time (as much as an hour or more)
may elapse before the secretion begins. This fact is quite in harmony
with the Heidenhain theory, since complete removal of their blood
supply might well result in a long-continued injury to the delicate
epithelial cells. On the mechanical theory, however, we should
expect the contrary. Injury to the cells should be followed by
greater permeability and an increased filtration, as is found to be
the case with the production of lymph. These two experiments,
blocking the renal artery and the renal vein, seem at present to dis-
credit the filtration theory and to support the secretion theory.
If we accept this latter theory it may be asked how it agrees with
the experiments mentioned above upon the variations in capillary
pressure brought about otherwise than by obstructing the venous
outflow. Heidenhain has emphasized the fact that all of these ex-
periments involve not only a variation in capillary pressure, but also
in the blood-flow, and that it is open to us to suppose that the
effect upon the secretion of urine is dependent upon the rate of flow
rather than upon the capillary pressure. If we adopt this expla-
nation we are led again to the secretion hypothesis. Mere rate of
flow should not influence filtration, but might affect secretion, since
it would alter the composition of the blood flowing through the
glomeruli and also the amount of oxygen and carbon dioxid. An
important fact, which seems at first sight to show a direct influence
of pressure, is that when general arterial pressure falls below a cer-
tain point, about 40 mms. of mercury, the secretion of urine ceases
altogether. Such a condition may be brought about by surgical
shock, by hemorrhage, or by section of the spinal cord in the cer-
vical or thoracic region. But here again the great vascular dila-
tation causing this fall of pressure is associated with a feeble cir-
culation, and the effect upon the kidney secretion may well be due
to this latter factor.

In addition to varying the factor P in the formula given above,
it is possible also to increase the factor p. Normally the pressure
of the urine in the capsule must be very low, owing to the fact that
the secretion drains away as rapidly as it is formed. If the ureter
is occluded, however, the pressure of the urine will increase, and the
filtration pressure P — p will diminish. When this experiment is
performed and the pressure in the ureter is measured by a manom-

KIDNEY AND SKIN AS EXCRETORY ORGANS. 767

eter, it is found to rise to 50 or 60 mms. of mercury and then to
remain stationary. This fact might be explained by supposing
that when p = P the secretion stops on account of the failure of
the nitration pressure. Little weight, however, can be given to
this argument, since it is quite possible that under these condi-
tions the urine may still continue to form, but be reabsorbed under
the high tension reached. 'The experiment simply serves to show
the secretion pressure of the urine, and the fact that this pressure
rises as high as 50 to 60 mms. mercury, while the capillary pressure
is probably somewhat lower, would rather serve as an argument
against the nitration theory. Moreover, experiments show * that
when a certain moderate resistance is established in the ureters
(p = 10 cms. e. g.} the flow of urine is actually increased instead
of falling off, a fact entirely opposed to the mechanical theory, but
explicable on the secretion theory on the assumption that the
resistance acts as a stimulus.

Function of the Convoluted Tubule. — By the term convoluted
tubule is meant here the entire stretch from the glomerulus to the
straight tubules. Its epithelium varies in character; its cells are
distinguished in general, as contrasted with the glomerular epithe-
lium, by a relatively large amount of granular protoplasm. The
question of interest at present in regard to this epithelium is whether
it is secretory or absorptive. The original view of Ludwig that
diffusion takes place in these tubules between the urine and the
blood (lymph) in accordance with simple physical laws and that
by this action alone the dilute urine is brought to its normal concen-
tration must be abandoned. The mere fact that the urine may be
more concentrated in certain constituents than the blood is suffi-
'cient evidence that other factors must co-operate. Those who be-
lieve that the main function of the tubules is absorptive are obliged
to regard this process as physiological, as a selective absorption
depending upon the living structure and properties of the epithelial
cells. The kind of evidence upon which this view is based is some-
what indirect; a single example may suffice. Cushny statesf that
if certain diuretics — for example, sodium chlorid and sodium sul-
phate— are injected simultaneously into the blood and in such
amounts that an equal number of the anions (Cl and SO4) are pres-
ent, the quantities that are excreted in the urine during the next
hour or two follow different curves and vary independently of their
concentration in the plasma. While this independence might be
referred to a specific secretory action, the author finds a simpler
explanation in variations in absorption, the epithelium of the con-
voluted tubule, like that of the intestine, absorbing the sulphate

* Brodie and Cullis, "Journal of Physiology," 1906, xxxiv., 224.
f "Journal of Physiology," 27, 429, 1902.

768 PHYSIOLOGY OF DIGESTION AND SECRETION.

with more difficulty. On the other side, the facts that have been
urged in favor of the secretory hypothesis are more numerous and
varied, but none is entirely convincing. Some of these facts are
as follows: (1) It is stated that if the ureters are ligated in birds
the urates will be found deposited in the uriniferous tubules, but
never at the capsular end. (2) Heidenhain has given proof that
the convoluted tubules are capable of excreting indigo-carmin after
this substance is injected into the blood. His experiment consisted
essentially in injecting the material into the blood, after dividing
the cord so as to reduce the rapidity of secretion. After a certain
interval the kidney was removed and irrigated with alcohol to pre-
cipitate the indigo-carmin in situ in the organ. Microscopical ex-
amination showed that after this treatment the granules of the
indigo-carmin are found in the convoluted tubules, but not in the
capsules around the glomeruli. (3) Several observers (Van der
Stricht, Disse, Trambasti, Gurwitsch*) have described microscopical
appearances in the cells lining the tubules indicative of an active
secretion. They picture the formation of vesicles in the cells and
appearances which indicate the discharge of these vesicles into the
cavity of the tubules. (4) Nussbaum made use of the fact that in
the frog the glomeruli are supplied by branches of the renal artery,
while the rest of the tubes is supplied by the renal portal vein.
He stated that if the renal artery is ligated the glomeruli are de-
prived completely of blood, and that as a result the flow of urine
ceases. If under these conditions urea is injected into the circulation
it is excreted together with some water, thus proving the secretory
activity of the tubules with regard to urea. These results, although
denied at one time, have recently been confirmed and extended. f
(5) Dreser has shown that the acidity of the urine is due to an action «
of the epithelium of the tubules. If an acid indicator, such as acid
fuchsin, is injected into the dorsal lymph sac of a frog, and an hour
or so later the kidneys are examined, it will be found that the con-
voluted tubules are colored red, while the capsular end is colorless,
indicating that the secretion at the latter point has an alkaline
reaction. The experiment shows that the acid substances in the
urine are produced in the convoluted tubules. The simplest
explanation is that they are formed by a secretory activity of the
epithelial cells. . (6) Study of the gaseous exchanges in the kidney
during diuresis, t and of the sugar output during the glycosuria
caused by phlorhizin § tend to support the secretion hypothesis
to the extent that they prove an increased metabolism during

* See Gurwitsch, 'Archiv f. die gesammte Physiologic, " 91, 71, 1902.
t Bainbridge and Beddard, "Journal of Physiology," 1906, xxxiv. (Proc.
Physiol. Soc.); also Cullis, Ibid., p. 250.

J Barcroft and Brodie, 'Journal of Physiology," 1906, xxxiii., 52.
§ Pavy, Brodie, and Siam, ibid., 1903, xxix., 467.

KIDNEY AND SKIN AS EXCRETORY ORGANS. 769

functional activity. (7) The action of diuretics (see below).
On the whole, it must be admitted that the weight of evidence is
in favor of the Bowman-Heidenhain theory of secretion, and it
remains for future investigations to explain more definitely what
is meant by the obscure term secretory activity.

Under pathological conditions it has been shown satisfactorily
that the albumin and sugar which may be present in the urine are
secreted or eliminated at the glomerular end of the tubule.

Action of Diuretics. — An important side of the theories of
secretion of urine is their application to the action of diuretics.
Water; various soluble substances, such as salts, urea, and dextrose;
and certain special drugs, such as caffein or digitalis, exert a diuretic
action on the kidneys. Much experimental work has been done
to ascertain whether the action of these substances can be explained
mechanically by their influence on the blood-flow or the blood-
pressure in the kidney capillaries, or whether it is necessary to fall
back upon a specific stimulating effect exerted by them upon the
epithelial cells of the tubules. Adherents of the original Ludwig
theory are forced to explain their action by the effect they pro-
duce upon the pressure in the kidney capillaries, and, indeed, it
has been shown with reference to the saline diuretics that their
effect upon the secretion is in proportion to the osmotic pressure
they exert. It has been suggested, therefore, that the action of
these diuretics lies in the fact that they attract water from the tis-
tues into the blood and thus cause a condition of hydremic plethora.
But whether the elimination of this excess of water is due to filtra-
tion or to an active secretion by the glomerular epithelium is a
question that revives the discussion that has been presented briefly
above. Most observers find that the vascular changes in the kid-
ney, particularly after the administration of caffein and digitalis,
do not explain satisfactorily the phenomenon of diuresis, and al-
though it is necessary to admit that the diuretics, or some of them,
act in part by the changes which they cause in the circulation in
the kidney, it is not possible to demonstrate that all the phenomena
under this head can be thus explained. The bulk of the work
published indicates that some at least of the known diuretics act as
stimulants to the secreting cells. In the case of the inorganic salts
it may be said (Magnus) that there is for each salt a "secretion
threshold." An increase in concentration above this level leads
to the elimination of the excess of salt and an increased secretion
of water.

The Blood-flow through the Kidneys. — It will be inferred
from the discussion above that, other conditions remaining the same,
the secretion of the kidney varies with the quantity of blood flowing
through it. It is, therefore, important to refer briefly to the nature

49

770 PHYSIOLOGY OF DIGESTION AND SECRETION.

and especially the regulation of the blood-flow through this organ,
although the same subject is referred to in connection with the
general description of vasomotor regulation (see Circulation). It
has been shown by Landergren* and Tigerstedt that the kidney
is a very vascular organ, at least when it is in strong functional activ-
ity such as may be produced by the action of diuretics. They esti-
mate that in a minute's time, under the action of diuretics, an amount
of blood flows through the kidney equal to the weight of the organ;
this is an amount from four to nineteen times as great as occurs in
the average supply of the other organs in the systemic circulation.
Taking both kidneys into account, their figures show that (in strong
diuresis) 5.6 per cent, of the total quantity of blood sent out of the
left heart in a minute may pass through the kidneys, although the
combined weight of these organs makes only 0.56 per cent, of that
of the body.

The nature of the supply of vasomotor nerves to the kidney and
the conditions which bring them into activity are fairly well known,
owing to the useful invention of the oncometer by Roy. This in-
strument is, in principle, a plethysmograph especially modified
for use upon the kidney of the living animal. It is a kidney-shaped
box of thin brass made in two parts, hinged at the back, and with
a clasp in front to hold them together. In the interior of the box
thin peritoneal membrane is so fastened to each half that a layer
of olive oil may be placed between it and the brass walls. There
is thus formed in each half a soft pad of oil upon which the kidney
rests. When the kidney, freed as far as possible from fat and sur-
rounding connective tissue, but with the blood-vessels and nerves
entering at the hilus entirely uninjured, is laid in one-half of the on-
cometer, and the other half is shut down upon it and tightly fas-
tened, the organ is surrounded by oil in a box which is liquid-tight
at every point except one, from which a tube is led off to some suitable
recorder such as a tambour. Under these conditions every increase
in the volume of the kidney causes a proportional outflow of oil
from the oncometer, which is measured by the recorder, and
every diminution in volume is accompanied by a reverse change.
At the same time the flow of urine during these changes can be
determined by inserting a cannula into the ureter and measuring
directly the outflow of urine. By this and other means it has
been shown that the kidney receives a rich supply of vasoconstrictor
nerve fibers that reach it between and around the entering blood-
vessels. These fibers emerge from the spinal cord chiefly in the
lower thoracic spinal nerves (tenth to thirteenth in the dog), pass
through the sympathetic system, and reach the organ as postgan-
glionic fibers. Stimulation of these nerves causes a contraction of

* " Skandinavisches Archiv f. Physiologie, " 4, 241, 1892.

KIDNEY AND SKIN AS EXCRETORY ORGANS. 771

the small arteries of the kidney, a shrinkage in volume of the whole
organ as measured by the oncometer (see Fig. 231), and a dimin-
ished secretion of urine. When, on the other hand, these con-
strictor fibers are cut as they enter the hilus of the kidney, the ar-
teries are dilated on account of the removal of the tonic action of
the constrictor fibers, the organ enlarges, and a greater quantity
of blood passes through it, since the resistance to the blood-flow is
diminished while the general arterial pressure in the aorta remains
practically the same. Along with this greater flow of blood there
is a marked increase in the secretion of urine.

Under normal conditions we must suppose that these fibers are
brought into play to a greater or less extent by reflex stimulation,
and thus serve to control the blood-flow through the kidney and
thereby influence its functional activity. It has been shown, too,
that the kidney receives vasodilator nerve-fibers, — that is, fibers
which when stimulated directly or reflexly cause a dilatation of
the arteries, and therefore a greater flow of blood through the or-
gan. According to Bradford, these fibers emerge from the spinal
cord mainly in the anterior roots of the eleventh, twelfth, and thir-
teenth spinal nerves. Under normal conditions these fibers are
probably thrown into action by reflex stimulation and lead to an
increased functional activity. It will be seen, therefore, that the
kidneys possess a local nervous mechanism through which their
secretory activity may be increased or diminished by correspond-
ing alterations in the blood-supply. So far as is known, this is the
only way in which the secretion in the kidneys can be directly af-
fected by the central nervous system. It should be borne in mind,
also, that the blood-flow through the kidneys, and therefore their
secretory activity, may be affected by conditions influencing general
arterial pressure. Conditions such as asphyxia, strychnin poison-
ing, or painful stimulation of sensory nerves, which cause a general
vasoconstriction, influence the kidney in the same way, and tend,
therefore, to diminish the flow of blood through it ; while conditions
which lower general arterial pressure, such as general vascular dila-
tation of the skin vessels, may also depress the secretory action of
the kidney by diminishing the amount of blood flowing through it.

In what way any given change in the vascular conditions of the
body will influence the secretion of the kidney depends upon a num-
ber of factors and their relations to one another, but any change
which will increase the difference in pressure between the blood in
the renal artery and the renal vein will tend to augment the flow
of blood unless it is antagonized by a simultaneous constriction in
the small arteries of the kidney itself. On the contrary, any vas-
cular dilatation of the vessels in the kidney will tend to increase
the blood-flow through it unless there is at the same time such a

772 PHYSIOLOGY OF DIGESTION AND SECRETION.

general fall of blood-pressure as is sufficient to lower the pressure
in the renal artery and reduce the driving force of the blood to an
extent that more than counteracts the favorable influence of dimin-
ished resistance in its small arteries. Although the kidney does
not possess specific secretory nerve fibers it is possible that there
may be formed in the body specific chemical excitants or diuretics
belonging to the general group of hormones (p. 711). Schafer * has
recently shown that such a substance occurs normally in the infun-
dibular lobe of the pituitary gland, and it is possible that the
internal secretion of this lobe may play toward kidney activity a
role similar to that of the adrenalin in muscular metabolism.

The Composition of Urine. — The urine of man is a yellowish
liquid that varies greatly in depth of color. It has an average
specific gravity of 1.020 and usually an acid reaction. This acid
reaction is attributed generally to the presence of acid phosphates,
particularly acid sodium phosphate (NaH2PO4); but, according to
Folin,f the acidity is due partially and indeed in larger part to or-
ganic acids. When tested by the usual indicators (litmus) human
urine may show an alkaline reaction, and, in fact, observations
indicate that the reaction may vary in accordance with the
character of the food. Among carnivora the urine is uniformly
acid, and among herbivora it is alkaline so long as they use a veg-
etable diet. During starvation, however, or when living upon the
mothers' milk, — that is, whenever they are existing upon a purely
animal diet — the urine becomes acid. The general explanation of
this effect of food that has been suggested (Drechsel) is that upon
an animal diet more acids are formed (from the oxidation of the
sulphur and phosphorus of the proteids) than in the case of the
vegetable foods in which the alkaline salts of the vegetable acids
give rise on oxidation in the body to alkaline carbonates. The
kidney separates from the alkaline (neutral) blood and lymph the
excess of salts and thus maintains a normal balance between the
acid and basic equivalents in the blood.

The composition of the urine is very complex. In addition to
the water and inorganic salts the following elements are important,
namely, urea, the purin bodies (uric acid, xanthin, hypoxanthin),
creatinin, hippuric acid, oxalic acid (calcium oxalate), several
conjugated sulphates and conjugated glycuronates, several aromatic
oxyacids and nitrogenous acids, fatty acids, dissolved gases ( N and
CO2), and the urinary pigments urochrome and urobilin. This list
is not complete; a number of additional substances have been de-
scribed as occurring constantly or. occasionally in traces within the
limits of health. Under pathological conditions the composition
may be still further modified. The complexity of the composition
*Schiifer and Herring. "Phil. Trans. " 1906, B. cxcix., 1.
t "American Journal of Physiology," 9, 265, 1903.

KIDNEY AND SKIN AS EXCRETORY ORGANS. 773

may be understood when it is recalled that through this organ are
eliminated some of all the end-products formed in the various tis-
sues, together with products arising from bacterial fermentation
in the gastro-intestinal canal and various more or less foreign sub-
stances taken with the food. It is not possible to describe all the
numerous constituents that f have been observed. Attention may
be directed to those that quantitatively or otherwise are of chief
physiological interest.

The Nitrogen Elimination in the Urine. — Nearly all of the ex-
cretion of nitrogen occurs in the urine. In the metabolism of the
usual foodstuffs — carbohydrates, fats, and proteins — the end-prod-
ucts of their destruction or physiological oxidation in the body are
water, carbon dioxid, and nitrogenous waste products (and sulphates
and phosphates from the sulphur and phosphorus in the proteins).
The water is eliminated in the urine, the sweat, saliva, etc., and the
expired air. The CO2 is eliminated in the expired air, and in smaller
part in dissolved form in the secretions (sweat, urine). The nitrog-
enous excretion, representing the breaking down of protein material,
is found in minute part in the sweat, to a larger extent in the fecesr
but in by far the main amount in the urine. In all problems con-
cerning protein metabolism in the body, both as regards its char-
acter and extent, the quantitative study of this excretion is of par-
amount importance. In order to determine the total amount of
protein metabolism it is customary to determine the total nitrogen
eliminated in the urine, without regard to its specific form. This
determination is made usually by the method of Kjeldahl. The
total weight of nitrogen multiplied by 6.25 gives the amount of pro-
tein broken down, since nitrogen forms, on the average, 16 per
cent, of the weight of the protein molecule. In an average-sized
man the total nitrogen eliminated in a day varies, let us say, between
14 and 18 gms., which would correspond to 88 and 117 gms. of pro-
tein. It being often necessary to distinguish between the forms in
which this nitrogen is eliminated, the following distinctions are made:
(1) The urea nitrogen, — that is, the nitrogen eliminated as urea.
According to some recent analyses by Folin,* the urea nitrogen in
man averages 87.5 per cent, of the total nitrogen. (2) The am-
monia nitrogen, — that is, the nitrogen found in the form of am-
monia salts which liberate free ammonia on the addition of a fixed
alkali. The proportion of this ammonia nitrogen often varies,
especially under pathological conditions affecting the liver. Its
quantitative determination is a matter of importance. The aver-
age amount in health may be stated (Folin) as 4.3 per cent, of the
total nitrogen. (3) The creatinin nitrogen, — that is, the amount
excreted as creatinin and indicative of a special (muscular) metab-
* " American Physiological Journal, " 13, 45, 1905.

774 PHYSIOLOGY OF DIGESTION AND SECRETION.

olism (3.6 per cent, of total nitrogen). (4) The purin body nitrogen
(uric acid, xanthin, hypoxanthin), also indicative of a special metab-
olism.

Origin and Significance of Urea. — Urea has the formula, CO-
N2H4. It may be considered as an amid of carbonic acid, and

has, therefore, the structural formula of CO<^NH2. It occurs in the
urine in relatively large quantities (2 per cent.). As the total quan-
tity of urine secreted in twenty-four hours by an adult male may
be placed at from 1500 to 1700 c.c., it follows that from 30 to 34
gms. of urea are eliminated from the body during this period. It
is the most important of the nitrogenous excreta of the body, the
chief end-product, so far as the nitrogen is concerned, of the phys-
iological metabolism of the proteins and the albuminoids of the
foods arid the tissues. If we know how much urea is secreted in a
given period, we know approximately how much protein has been
broken down in the body in the same time. In round numbers,
1 gm. of protein will yield J gm. of urea, as may be calculated easily
from the amount of nitrogen contained in each. Since, however,
some of the nitrogen of protein is eliminated in other forms — uric
acid, creatinin, etc. — even an exact determination of all the urea
is not sufficient to determine with accuracy the total amount of
protein of all kinds that has been metabolized. This fact is arrived
at more perfectly, as stated above, by a determination of the total
nitrogen of the urine and other excretions. In addition to the urine,
urea is found in slight quantities in other secretions — in milk (in
traces) and in sweat. In the latter liquid the quantity of urea in
twenty-four hours may be quite appreciable — as much, for instance,
as 0.8 gm. — although such a large amount is found only after active
exercise. It has been ascertained definitely that urea is not formed
by the kidneys; it is brought to the kidneys by the blood for elimi-
nation. That urea is not made in the kidneys is demonstrated
by such facts as these : If blood, on the one hand, is irrigated through
an isolated kidney, no urea is formed, even though substances (such
as ammomium carbonate) from which urea is readily produced are
added to the blood; on the other hand, urea is constantly present
in the blood (0.0348 to 0.1529 per cent.), and if the two kidneys
are removed, it continues to accumulate steadily in the blood as
long as the animal survives. It has been ascertained that the urea
is produced in part in the liver. The most important questions
to be decided are: Through what steps is the protein molecule
metabolized to the form of urea? and What is the antecedent
substance brought to the liver, from which it makes urea? It is
impossible to. answer these questions perfectly, but recent investi-
gations have thrown a great deal of light on the whole process,
and they give hope that before long the entire history of the deriva-

KIDNEY AND SKIN AS EXCRETORY ORGANS. 775

tion of urea from proteins and albuminoids will be known. The
results of this work may be stated briefly as follows:

1 . Urea arises from ammonia salts which in the liver are converted
to urea by a process equivalent to dehydration. It has long been
known that when ammonium carbonate is added to blood perfused
through a liver it is concerted to urea.* The reaction may be
represented as follows:

Ammonium carbonate. Urea.

Moreover, the experiments made by Harm, Pawlow, Massen, and
Nencki f show that in dogs removal of the liver is followed by a
decrease in the amount of urea in the urine and an increase in the
ammonia contents. In these remarkable experiments a fistula
(Eck fistula) was made between the portal vein and the inferior
vena cava, the result of which was that the whole portal circulation of
the liver was abolished, the organ receiving blood only by way of
the hepatic artery. If now the latter artery was ligated and the
liver was cut away as far as possible, the result was practically a
complete extirpation of the organ. Later investigations J showed
that in normal animals the ammonia contents of the blood of the
portal vein may be three to four times as great as in arterial blood,
but that after removal of the liver the ammonia in the general
circulation increases to a point equal to that observed for the
portal blood and produces symptoms of poisoning which may
result fatally. It would seem, therefore, that the liver protects the
body from the poisonous action of the ammonia compounds by
converting them to urea. Now in the normal digestive hydrol/sis
of proteins brought about by the successive action of pepsin, trypsin,
and erepsin the evidence at present indicates that the protein
material is split largely or entirely into its constituent elements
and its nitrogen appears mainly in three forms — as ammonia, as
monamino-acids, and as diamino-bodies. The ammonia produced
is probably carried to the liver and there converted to urea. In
what form the ammonia exists in the blood is not positively known ;
it may be present as a carbonate or possibly, as some observers
have thought, as a carbamate. Ammonium carbamate might be
changed to urea according to the following reaction :

m .

NH

Ammonia salts may arise similarly in the other protein tissues

* Schroeder, "Archiv f. exp. Pathol. u. Pharmakol./' vols. xv. andxix.,
1882, 1885.

t See "Archiv f. exp. Pathol. u. Pharmakol.," 1893, xxxii., 161.
j See Nencki and Pawlow, "Archives des sciences biologiques, " v.,

213.

776 PHYSIOLOGY OF DIGESTION AND SECRETION.

of the body. It is known, for instance, that the percentage of
ammonia compounds in the tissues is greater than in the blood.
Since the cells of many of the protein tissues of the body contain
intracellular enzymes capable of causing hydrolytic cleavage of the
protein molecule it is probable that some ammonia may be thus
formed in various parts of the body; and so far as it is produced
it will be converted to urea by the action of the liver and possibly
by a similar action in other tissues.

2. Urea arises from the monamino-acids by a process of deami-
dization, whereby the NH2 group is converted to ammonia and
then probably to urea. It is known, for example, that when a
monamino-acid such as glycocoll or leucin is given to an animal the
nitrogen of the compound is promptly eliminated as urea. Since,
as stated above, these monamino-acids form the chief constituent
of the end-products formed in the digestion of proteins, it is very
probable that in passing through the liver their nitrogen is removed
by a process of deamidization and eliminated as urea. The organic
acid radicle that remains may suffer oxidation and thereby furnish
heat energy to the body, or it may possibly be stored after synthesis
as carbohydrate (glycogen) or as fat. Doubtless also in the met-
abolism of the proteins of the tissues, as in the digestion of the
food proteins, monamino-acids are likewise formed and suffer a
similar fate, -so far as the nitrogen is concerned.

3. Urea arises from the diamino bodies (arginin), formed in the
cleavage of the protein molecule, by conversion of the contained
guanidin radicle. Kossel and Dakin * have demonstrated the
existence of a ferment, arginase, which is capable of splitting
arginin into urea and ornithin. The reaction may be represented
by the following equation:

NHC<^2(CH2)3CHNH2COOH + H2O - CO<*Jg2 + NH2(CH2)3CHNH2COOH

Arginin (guanidin diamino-valerianic acid. Urea. Diamino-valerianic acid.

Unlike cases 1 and 2 the urea in this instance is formed directly
from the guanidin residue contained in the arginin. Since this
latter substance constitutes one of the split-products of the protein
during digestion and probably also one of the split-products in
the metabolism of the proteins of the tissues, there is reason to
believe that part of the urea actually formed in the body arises
by this method.

4. Urea arises from a further metabolism of uric acid. As is
stated below in describing the history of the origin of uric acid
there is positive evidence that not all of the uric acid produced
in the body is excreted as such. A portion is further acted upon
by a uricolytic enzyme and converted to urea. The portion so

* 'Zeitschrift f. Physiol. Chemie," 1904, xlii., 181.

KIDNEY AND SKIN AS EXCRETORY ORGANS. 777

affected varies in different animals. In man it is estimated that
about one-half of the uric acid arising in the body metabolism
proper (endogeneous uric acid) suffers this fate.

It is a very significant fact that the relative and absolute amount
of urea nitrogen in the urine varies directly with the amount of
protein taken as food, while other nitrogenous constituents of the
urine (creatinin, purin bases) are practically not affected by the
food, if care is taken to have the food free of these substances to
begin with. Folin has laid emphasis upon this fact,* and suggests
that most of the urea may come directly from protein of the
food which is hydrolyzed during digestion and absorption (action
of trypsin and erepsin) into simpler amino-acids. These amino-
bodies by further hydrolysis and oxidation may be converted, so
far as their nitrogen is concerned, into ammonia compounds and
eliminated at once as urea by the liver without entering into tissue
formation at all.

Even after the removal of the liver some urea is still found in
the urine. It seems as though the urea-forming power of the liver
is shared by some of the other tissues, just as its glycogenic functions
are.

Origin and Significance of the Purin Bodies (Uric Acid,
Xanthin, Hypoxanthin, Adenin, Guanin). — These bodies are
related chemically, and appear also to have a common physiological
significance. Their chemical relations have been described by
Emil Fischer, to whom we owe the term purin bodies. Fischer
pointed out that these and other substances belonging to this
group have a common nucleus:
N — C

C C — Nv which he named the purin nucleus. The

hydrogen compound of this nucleus would be designated as purin,

N = CH

: HC C—

and would have the formula: HC C— NH , C5H4N4. Addi-

N — C — N^CH

tion of an atom of oxygen gives hypoxanthin, C5H4N40:
HN — CO

HC C — NH

II _ II _ NXCH* Addition of two atoms of oxygen gives xan-
HN — CO

thin, C5H4N402: CO C — NH

H'N — C — NXCH- An(* addition of three atoms
* Folin, 'American Journal of Physiology," 13, 117, 1905.

778 PHYSIOLOGY OF DIGESTION AND SECRETION.

HN — CO

of oxygen gives uric acid, C5H4N4O3: CO C — NH , which

HN — C — NH

from this standpoint might be named trioxypurin. If one of the H
atoms in the purin is substituted by an amino-group, NH2, the com-
pound, adenin (C5H5N5), is obtained, and the substitution of an
NH2 group in hypoxanthin gives the compound guanin (C5H.N5O).
Moreover, caffein, the active principle of coffee and tea, and theo-
bromin, the active principle of cocoa, are respectively trimethyl
and dimethyl compounds of xanthin. We have to distinguish,
therefore, three classes of purin compounds, namely, the oxypurins,
comprising monoxypurin or hypoxanthin, dioxypurin or xanthin,
and trioxypurin or uric acid; the aminopurins, comprising adenin or
aminopurin and guanin or aminohypoxanthin, and the methyl-
purins, comprising caffein or trimethyl xanthin (C8H10N4O2 or C5H-
(CH3)3N4O2) and theobromin or dimethyl xanthin (C7H8N4O2 or
C5H2(CH3)2N4O2). Uric acid, xanthin, and hypoxanthin are found
constantly in the urine and in the feces small amounts of xanthin,
hypoxanthin, adinin, and guanin may also occur. It has been
pointed out * that these substances come partly from purin bodies
taken as food. If materials containing the purin bodies, such as
meat, are fed, these bodies are excreted in part in the urine. It is
proposed to designate the uric acid, etc., that has this origin as the
exogenous purin material. A portion of the amount daily secreted
comes, however, from a metabolism of the protein material of the
body, and this portion may be distinguished as the endogenous purin
bodies. This latter amount is found to be practically constant,
0.15 to 0.20 gm. per day for any one individual, and the amount is
not affected by changes in the quantity or character of the food,
but varies within certain limits with the manner of life. Evidently
the endogenous purin nitrogen represents a special metabolism,
probably of the living tissues, that goes on independently, in great
measure, of the mere oxidation of food. Since the purin bodies
may be obtained readily by hydrolytic cleavage of the nuclein or
nucleic acid constituent of the nucleoproteins, and since nucleo-
protein material or nucleins when fed to animals cause an increase
in the amount of purin nitrogen eliminated in the urine, it is most
probable that in the body these purin bases represent the end-
products of the metabolism of nuclein material. The intermediate
processes in this metabolism, whether it affects the nuclein taken as
food or the nuclein contained within the tissues of the body, are
supposed to take place according to the following general schema:

* See Burian and Schur, "Archiv f. die gesammte Physiologic/' 94, 273,
1903.

KIDNEY AND SKIN AS EXCRETORY ORGANS. 779

The nucleins that are split off from the nucleoprotein are acted
upon first by an enzyme, nuclease, which has been demonstrated to
exist in various tissues, e. g., in the spleen, liver, lungs, and kidneys.
By the action of this enzyme the nuclein is split with the formation
of some of the purin bodies, adenin, guanin, xanthin, or hypoxan-
thin. The adenin and guanin are then deamidized and converted
respectively to hypoxanthin and xanthin. Jones * has given reasons
to believe that two specific deamidizing enzymes of this character
may exist in the body, namely, adenase and guanase. Their action
may be represented by the following equations :
C5H5N5 4- H2O = C5H4N4O + NH3

Adenin. Hypoxanthin.

C5H5N5O + H2O = C6H4N4O2 + NH3

Guanin. Xanthin.

The hypoxanthin and xanthin thus formed are in turn oxidized
to uric acid by the action of an oxidase to which the specific nair»e
of xanthinoxidase has been given. Its action upon the hypoxanthin
or xanthin is represented by the series:

C5H4N4O + O = C5HtN4O2

Hypoxanthin. Xanthin.

C5H4N402 f O = C5H4N40S

Xanthin. Uric acid.

Finally, as stated above, it can be shown that a portion of the uric
acid may be further metabolized by the action of a specific urico-
lytic enzyme and give rise to urea. The portion of the uric acid under-
going this last change varies in different animals, as may be demon-
strated by giving definite amounts of uric acid in the food. Ex-
periments of this kind have shown that in man about one-half
of the uric acid formed gives rise to urea, while in dogs and cats
only about -^V suffers this change. In rabbits the proportion is J.
According to a former view (Horbaczewsky) it was supposed that
the endogenous purin nitrogen represents an end-product of the
metabolism of the nuclein found in the nuclei of ceils, especially
in the nuclei of the leucocytes. But Burian has shown, on the
contrary, that most of this nitrogen in the excreta arises from a
metabolism in the muscular tissues. f Increased muscular activity
is followed within an hour or two by an increased output of uric
acid, and when an isolated muscle is perfused with a mixture of
defibrinated blood and Ringer's solution, uric acid is given off to
the circulating liquid. When the muscle under these last-mentioned
conditions is made to work a distinct increase in the hypoxanthin
and uric acid can be determined. It would seem, therefore, that
under normal conditions the uric acid and other purin bases are

* Jones and Austrian, ' Zeitschrif t f. physioh Chem.," 1906, xlviii., 110.
t Burian, 'Zeitschrift f. physiol. Chemie., xliii., p. 532.

780 PHYSIOLOGY OF DIGESTION AND SECRETION.

derived mainly from a metabolism of the muscular substance
whereby hypoxanthin is produced. This substance is then oxidized
to uric acid and a part of the uric acid is further changed to urea.*

Origin and Significance of the Creatinin. — Creatinin
(C4H7N3O) occurs in the urine and it has been assumed that
it is derived from the creatin (C4H9N3O2) found in muscle. Its

/NH — CO
structural formula is given as NHC/ I and its chemical re-

XN(CH3)CH2

lations are indicated by the fact that it may be prepared synthetically
from methyl-glycocoll and cyanamid, — that is, the union of these
two substances gives creatin, from which in turn creatinin may be
obtained.

N=C-NH, + NH(CH,)CH,COOH ==

Cyanamid. Methyl-glycocoll. Creatin.

Creatinin occurs in the urine constantly and in amounts equal to
1 to 2 gms. per day. Next to the urea and the ammonia com-
pounds it forms the most important nitrogenous constituent of the
urine. Its physiological history, is imperfectly known. Under
constant conditions of life the amount of creatinin is independent
of the quantity of protein eaten, and this fact indicates (Folin) that
it represents an end-product of the metabolism of living or organized
protein tissue rather than one of the results of the metabolism of the
food protein. Everything would indicate also that this substance
originates in the muscular tissue. Creatin is a constant and consid-
erable constituent of muscle, and a fair inference, therefore, is that
it originates in this tissue from the catabolism of the muscle sub-
stance, and is subsequently given to the blood and excreted as crea-
tinin. A difficulty in regard to this last hypothesis is found in the
fact that the mass of muscular tissue in the body contains a relatively
large amount of creatin (90 gms.) and yet only 1 to 2 gms. are
excreted in the urine during the day. On account of this dis-
proportion it has been suggested that some of the creatin may
be converted to urea, but no proof has been furnished as yet that
the body can accomplish this transformation. Creatin given in
the food is, according to some observers, eliminated as creatinin.
Folin, however, finds that when creatin in not too large amounts is
given to an individual living on a low protein diet none of it appears
in the urine as creatinin. On the contrary, when creatinin is fed
most of it may be recovered as creatinin in the urine. This observer
finds that the conversion of creatin to creatinin is a matter of
some difficulty. According to his experiments this conversion is

* For a review of the extensive literature see Block, "Biochemisches
Centralblatt, " 1906, v., Nos. 12-14.

KIDNEY AND SKIN AS EXCRETORY ORGANS. 781

not made by the body and hence muscular creatin is probably not
an antecedent substance to the urinary creatinin.* As is described
in the section on Nutrition, it is known that increased muscular
work may or may not increase the nitrogen output in the urine
according to the diet used. Several observers have claimed that
muscular activity increases the amount of creatinin in the urine, f
but the increase is not so distinct nor so invariable that one may
conclude satisfactorily that it is due to actual increase in production
in the muscle. Others state that the increase is observable only
after excessive muscular activity.

Hippuric Acid. — This substance has the formula C9H9NO3. Its
molecular structure is known, since upon decomposition it yields
benzoic acid and glycocoll, and, moreover, it may be produced syn-
thetically by the union of these two substances. Hippuric acid
may be described, therefore, as a benzoyl-amino-acetic acid (CH2-
NH[C6H5CO]COOH). It is found in considerable quantities in the
urine of herbivorous animals (1.5 to 2.5 per cent.), and in much
smaller amounts in the urine of man and of the carnivora. In
human urine, on an average diet, about 0.7 gm. are excreted in
twenty-four hours. If the diet is largely vegetable, this amount may
be much increased. This last fact is readily explained, for it has been
found that if benzoic acid or substances containing this grouping
are fed to animals they appear in the urine as hippuric acid. Evi-
dently a synthesis occurs in the body, and Bunge and Schmie-
deberg proved conclusively that in dogs the union of benzoic acid
and glycocoll to form hippuric acid takes place in the kidney
itself. Later it was discovered:}: that the same synthesis may be
effected by ground-up kidney tissue, mixed with blood and kept
under oxygen pressure. It seems possible, therefore, that the
synthesis is due to some specific constituent of the kidney cells,
possibly an enzyme. Vegetable foods contain benzoic acid com-
pounds, and we can understand, therefore, why when fed they in-
crease the hippuric acid output of the urine. Since, however, in
starving animals or animals fed upon meat hippuric acid is still
present in the urine, although reduced in amount, it is evident that
it arises in part as a result of the body metabolism. It should be
added finally that some of the hippuric acid may be derived from
the process of protein putrefaction that occurs in the large intestine.

The Conjugated Sulphates and the Sulphur Excretion. —
The sulphur excretion of the urine possesses an importance similar

* Folin, "Festschrift fur Olof Hammarsten," Upsala, 1906.

t Gregor, "Zeitschrift f. physiol. Chemie," 31, 98, 1900.

j Bashford and Cramer, 'Zeitschrift f. physiolog. Chemie," 35, 324, 1902.

782 PHYSIOLOGY OF DIGESTION AND SECRETION.

to that of nitrogen. Sulphur constitutes an element in most of the
proteins, and in some form, therefore, it will be represented in the
end-products of protein metabolism. The sulphur elimination in
the urine, like the nitrogen elimination, has been taken as a measure
of the amount of protein destruction. In the urine the sulphur
occurs in three forms: (1) In an oxidized form as inorganic sul-
phates. Some of the sulphates are undoubtedly derived or may be
derived from the mineral sulphates ingested with the food, but the
larger part arises from the oxidation of the sulphur of the proteins.
(2) The so-called conjugated or ethereal sulphates are combinations
between sulphuric acid and indoxyl, skatoxyl, phenol, and cresol,
giving us phenolsulphuric acid (C6H5OSO2OH) , cresolsulphuric acid
(C7H7OSO2OH), indoxylsulphuric acid or indican (C8H6NOSO2OH),
and skatoxylsulphuric acid (C9H8NOSO2OH) . The indol, skatol,
phenol, and cresol are formed in the large intestine as a result of bac-
terial putrefaction. They are eliminated in part in the feces, but
in part are absorbed into the blood, and after oxidation are
conjugated with sulphuric acid and eliminated in the urine. The
process of conjugation is valuable from a physiological standpoint,
as it converts substances having an injurious action into harmless
compounds. It should be added, also, that to a small extent the
phenol, indoxyl, and skatoxyl may be secreted in the urine as con-
jugated glucuronates, — that is, in combination with glycuronic acid
(C6H1007), a reducing substance closely connected with dextrose.
From a nutritional standpoint the amount of these substances pres-
ent furnishes a measure of the extent of protein putrefaction in the
intestine, by virtue of the indol and phenol constituents. All con-
ditions that increase the putrefactive processes in the intestine
are accompanied by a parallel increase in the ethereal sulphates.
By virtue of the sulphuric acid component these bodies represent
also one of the forms in which sulphur is excreted from the
body. (3) Some of the sulphur in the urine may occur in unoxid-
ized form as sulphocyanid or as ethyl-sulphide (Abel) ([C2H5]2S).
Under certain pathological conditions (cystinuria) some sulphur may
be excreted in the form of cystin, but this is not a normal con-
stituent of the urine. For other most interesting and significant
changes in the composition of the urine under pathological condi-
tions reference must be made to special works upon the urine or
upon pathological chemistry.

Water and Inorganic Salts. — Water is lost from the body
through three main channels, — namely, the lungs, the skin, and
the kidney, the last of these being the most important. The quan-
tity of water lost through the lungs probably varies within small
limits only. The quantity lost through the sweat varies, of course,
with the temperature, with exercise, etc., and it may be said that

KIDNEY AND SKIN AS EXCRETORY ORGANS. 783

the amounts of water secreted through kidney and skin stand in
something of an inverse proportion to each other; that is, the greater
the quantity lost through the skin, the less will be secreted by the
kidneys. Through these three organs, but mainly through the
kidneys, the blood is being continually depleted of water, and the
loss must be made up by the ingestion of new water. When water
is swallowed in excess the superfluous amount is rapidly eliminated
through the kidneys. The* amount of water secreted may be in-
creased by the action of diuretics, such as potassium nitrate and
caffein.

The inorganic salts of urine consist chiefly of the chlorids, phos-
phates, and sulphates of the alkalies and the alkaline earths. It
may be said, in general, that they arise partly from the salts ingested
with the food, and are eliminated from the blood by the kidney
in the water secretion; and in part they are formed in the destruc-
tive metabolism that takes place in the body, particularly that
involving the proteins and related bodies. Sodium chlorid occurs
in the largest quantities, averaging about 15 gms. per day, of
which the larger part, doubtless, is derived directly from the salt
taken in the food. The phosphates occur in combination with cal-
cium and magnesium, but chiefly as the acid phosphates of sodium
or potassium. The acid reaction of the urine is usually attributed
to these latter substances. The phosphates result in part from the
destruction of phosphorus-containing tissues in the body, but
chiefly from the phosphates of the food. The sulphates of urine
are found partly in an oxidized form as simple sulphates or con-
jugated with organic compounds, as described above.

Micturition. — The urine is secreted continuously by the kid-
neys, is carried to the bladder through the ureters, and is then at
intervals finally ejected from the bladder through the urethra by
the act of micturition.

Movements of the Ureters. — The ureters possess a muscular coat
consisting of an internal longitudinal and external circular layer.
The contractions of this muscular coat form the means by which
the urine is driven from the pelvis of the kidney into the bladder.
The movements of the ureter have been carefully studied by Engel-
mann.* According to his description, the musculature of the ureter
contracts spontaneously at intervals of ten to twenty seconds (rab-
bit), the contraction beginning at the kidney and progressing
toward the bladder in the form of a peristaltic wave and with a
velocity of about 20 to 30 mms. per second. The result of this
movement should be the forcing of the urine into the bladder in a
series of gentle, rhythmical spurts, and this method of filling the

* " Pfluger's Archiv f . die gesammte Physiologic, " 2, 243, 1869, and 4, 33.

784 PHYSIOLOGY OF DIGESTION AND SECRETION.

bladder has been observed in the human being. Suter and Mayer*
report some observations upon a boy in whom there was ectopia
of the bladder, with exposure of the orifices of the ureters. The
flow into the bladder was intermittent and was about equal upon the
two sides for the time the child was under observation (three and
a half days).

The causation of the contractions of the ureter musculature is
not easily explained. Engelmann finds that artificial stimulation
of the ureter or of a piece of the ureter may start peristaltic con-
tractions which move in both directions from the point stimulated.
He was not able to find ganglion cells in the upper two-thirds of the
ureter and was led to believe, therefore, that the contraction orig-
inates in the muscular tissue independently of extrinsic or intrinsic
nerves, and that the contraction wave propagates itself directly
from muscle cell to muscle cell, the entire musculature behaving
as though it were a single, colossal, hollow muscle fiber. The liber-
ation of the stimulus which inaugurates the normal peristalsis
of the ureter seems to be connected with the accumulation of urine
in its upper or kidney portion. It may be supposed that the urine
that collects at this point as it flows from the kidney stimulates
the muscular tissue to contraction, either by its pressure or in some
other way, and thus leads to an orderly sequence of contraction
waves. It is possible, however, that the muscle of the ureter, like that
of the heart, is spontaneously contractile under normal conditions,
and does not depend upon the stimulation of the urine. Thus,
according to Engelmann, section of the ureter near the kidney does
not materially affect the nature of the contractions of the stump
attached to the kidney, although in this case the pressure of the
urine could scarcely act as a stimulus. Moreover, in the case of
the rat, in which the ureter is highly contractile, the tube may be
cut into several pieces and each piece will continue to exhibit period-
ical peristaltic contractions. It does not seem possible at present
to decide between these two views as to the cause of the contrac-
tions. The nature of the contractions, their mode of progression,
and the way in which they force the urine through the ureter seem,
however, to be clearly established. Efforts to show a regulatory
action upon these movements through the central nervous system
have so far given negative results.

Movements of the Bladder. — The bladder contains a muscular coat
of plain muscle tissue, which, according to the usual description,
is arranged so as to make an external longitudinal coat and an
internal circular or oblique coat. A thin, longitudinal layer of
muscle tissue lying to the interior of the circular coat is also de-
scribed. The separation between the longitudinal and circular
* "Archiv f. exper. Pathologie und Pharmakologie," 32, 241, 1893.

KIDNEY AND SKIN AS EXCRETORY ORGANS. 785

layers is not so definite as in the case of the intestine; they seem,
in fact, to form a continuous layer, one passing gradually into the
other by a change in the direction of the fibers. At the cervix the
circular layer is strengthened, and has been supposed to act as a
sphincter with regard to the urethral orifice — the so-called sphinc-
ter vesicse internus. Around the urethra just outside the blad-
der is a circular layer of striated muscle that is frequently desig-
nated as the external sphincter or sphincter urethrae. The urine
brought into the bladder accumulates within its cavity to a certain
limit. It is prevented from escaping through the urethra at first
by the mere elasticity of the parts at the urethral orifice, aided per-
haps by tonic contraction of the internal sphincter, although this
function of the circular layer is disputed by some observers. When
the accumulation becomes greater the external sphincter is brought
into action. If the desire to urinate is strong the external sphincter
seems undoubtedly to be controlled by voluntary effort, but whether
or not, in moderate filling of the bladder, it is brought into play
by an involuntary reflex is not definitely determined. Backflow
of urine from the bladder into the ureters is effectually prevented
by the oblique course of the ureters through the wall of the blad-
der. Owing to this circumstance, pressure within the bladder
serves to close the mouths of the ureters, and, indeed, the more
completely, the higher the pressure. At some point in the filling
of the bladder the pressure is sufficient to arouse a conscious sen-
sation of fullness and a desire to micturate. Under normal condi-
tions the act of micturition follows. It consists essentially in a
strong contraction of the bladder, with a simultaneous relaxation
of the external sphincter, if this muscle is in action, the effect of
which is to obliterate more or less completely the cavity of the blad-
der and drive the urine out through the urethra.

The force of this contraction is considerable, as is evidenced by
the height to which the urine may spurt from the end of the urethra.
According to Mosso, the contraction may support, in the dog, a
column of liquid two meters high. The contractions of the blad-
der may be and usually are assisted by contractions of the walls
of the abdomen, especially toward the end of the act. As in defeca-
tion and vomiting, the contraction of the abdominal muscles, when
the glottis is closed so as to keep the diaphragm fixed, serves to in-
crease the pressure in the abdominal and pelvic cavities, and thus
assists in or completes the emptying of the bladder. It is,
however, not an essential part of the act of micturition. The last
portions of the urine escaping into the urethra are ejected, in the
male, in spurts produced by the rhythmical contractions of the
bulbocavernosus muscle.

Considerable uncertainty and difference of opinion exists as to

50

786 PHYSIOLOGY OF DIGESTION AND SECRETION.

the physiological mechanism by which this series of muscular con-
tractions, and especially the contractions of the bladder itself, are
produced. According to the frequently quoted description given
by Goltz,* the series of events is as follows: The distention of the
bladder by the urine causes finally a stimulation of the sensory
fibers of the organ and produces a reflex contraction of the blad-
der musculature which squeezes some urine into the urethra. The
first drops, however, that enter the urethra stimulate the sensory
nerves there and give rise to a conscious desire to urinate. If no
obstacle is presented the bladder then empties itself, assisted per-
haps by the contractions of the abdominal muscles. The emptying
of the bladder may, however, be prevented, if desirable, by a volun-
tary contraction of the sphincter urethrae, which opposes the effect
of the contraction of the bladder. If the bladder is not too full
and the sphincter is kept in action for some time, the contractions
of the bladder may cease and the desire to micturate pass off. Ac-
cording to this view, the voluntary control of the process is limited
to the action of the external sphincter and the abdominal muscles;
the contraction of the bladder itself is purely an unconscious reflex
taking place through a lumbar center.

The experiments of Goltz and others, upon dogs in which the
spinal cord was severed at the junction of the lumbar and the tho-
racic regions, indicate that micturition is essentially a reflex act,
with its center in the lumbar cord, although the same observer has
shown that in dogs whose spinal cord has been entirely destroyed,
except in the cervical and upper thoracic region, the bladder emp-
ties itself normally without the aid of external stimulation. Mosso
and Pellacanif have made experiments upon women in which a
catheter was introduced into the bladder and connected with a record-
ing apparatus to measure the volume of the bladder. Their ex-
periments indicate that the sensation of fullness and desire to
micturate come from sensory stimulation, in the bladder itself,
caused by the pressure of the urine. They point out that the
bladder is very sensitive to reflex stimulation; that every psychical
act and every sensory stimulus is apt to cause a contraction or in-
creased tone of the bladder. The bladder is therefore subject to
continual changes in size from reflex stimulation, and the pressure
within it will depend not simply on the quantity of urine, but on
the condition of tone of its muscles. At a certain pressure the
sensory nerves are stimulated and under normal conditions mictu-
rition ensues. We may understand, from this point of view, how it
happens that we have sometimes a strong desire to micturate when
the bladder contains but little urine, — for example, under emotional

* " Archiv f . die gesammte Physiologie, " 8, 478, 1874.
t" Archives italiennes de biologic," 1, 1882.

KIDNEY AND SKIN AS EXCRETORY ORGANS. 787

excitement. In such cases if the micturition is prevented, probably
by the action of the external sphincter, the bladder may sub-
sequently relax and the sensation of fullness and desire to micturate
pass away until the urine accumulates in sufficient quantity, or the
pressure is again raised by some circumstance which causes a reflex
contraction of the bladder.

Nervous Mechanism. — According to Langley and Anderson,* the
bladder in cats, dogs, and rabbits receives motor fibers from two
sources: (1) From the lumbar nerves, the fibers' passing out in the
second to the fifth lumbar nerves and reaching the bladder through
the sympathetic chain and the inferior mesenteric ganglion and
hypogastric nerves. Stimulation of these nerves causes a compara-
tively feeble contraction of the bladder. (2) From the sacral
spinal nerves, the fibers originating in the second and third sacral
spinal nerves, or in the rabbit in the third and fourth, and taking their
course through the so-called nervus erigens. Stimulation of these
nerves, or some of them, causes strong contractions of the blad-
der, sufficient to empty its contents. Little evidence was obtained
of the presence of vasomotor fibers. According to Nawrocki and
Skabitschewsky,t the spinal sensory fibers to the bladder are found
in part in the posterior roots of the first, second, third, and fourth
sacral spinal nerves, particularly the second and third. When these
fibers are stimulated they excite reflexly the motor fibers to the
bladder found in the anterior roots of the second and third sacral
spinal nerves. Some sensory fibers to the bladder may pass by
way of the hypogastric nerves. When the central stump of one
hypogastric nerve is stimulated it produces, according to these
authors, a reflex effect upon the motor fibers in the other hypo-
gastric nerve, causing a contraction of the bladder, the reflex oc-
curring through the inferior mesenteric ganglion. This observa-
tion has been confirmed by several authorities, but has been ex-
plained by Langley and Anderson as a pseudoreflex or axon reflex
(see p. 144).

The immediate spinal center through which the contractions
of the bladder may be reflexly stimulated or inhibited lies, accord-
ing to the experiments of Goltz, in the lumbar portion of the cord,
probably between the second and fifth lumbar spinal nerves. In
dogs in which this portion of the cord was isolated by a cross-section
at the junction of the thoracic and lumbar regions, micturition still
ensued when the bladder was sufficiently full, and it could be called
forth reflexly by sensory stimuli, especially by slight irritation of
the anal region. This localization has been confirmed by others,}:

*" Journal of Physiology," 19, 71, 1895.

t"Archiv f. die gesammte Physiologie, " 49, 141, 1891.

j See Stewart, "American Journal of Physiolog^, " 2, 182, 1899.

788 PHYSIOLOGY OF DIGESTION AND SECRETION.

Excretory Functions of the Skin. — The physiological activi-
ties of the skin are varied. It forms, in the first place, a sensory
surface covering the body, and interposed, as it were, between the
external world and the inner mechanism. Nerve fibers of pressure,
temperature, and pain are distributed over its surface, and by means
of these fibers reflexes of various kinds are effected which keep the
body adapted to changes in its environment. The physiology of
the skin from this standpoint is discussed in the section on special
senses. Again, the skin plays a part of immense value to the body
in regulating the body temperature. This regulation, which is
effected by variations in the blood supply or the sweat secretion,
is described at appropriate places in the sections on Nutrition and
Circulation. In the female, during the period of lactation, the mam-
mary glands, which must be reckoned among the organs of the
skin, form an important secretion, the milk; the physiology of this
gland is referred to in the section on Reproduction. In this section
we are concerned with the physiology of the skin from a different
standpoint, — namely, as an excretory organ. The excretions of
the skin are formed in the sweat-glands and the sebaceous glands.

Sweat. — The sweat or perspiration is a secretion of the sweat
glands. These latter structures are found over the entire cutaneous
surface except in the deeper portions of the external auditory meatus,
the prepuce, and the glans penis. They are particularly abundant
upon the palms of the hands and the soles of the feet. Krause
estimates that their total number for the whole cutaneous surface
is about two millions. In man they are formed on the type of
simple tubular glands; the terminal portion contains the secretory
cells, and at this part the tube is usually coiled to make a more or
less compact knot, thus increasing the extent of the secreting sur-
face. The larger ducts have a thin, muscular coat of involuntary
tissue that may possibly be concerned in the ejection of the secre-
tion. The secretory cells in the terminal portion are columnar in
shape, possess a granular cytoplasm, ancl are arranged in a single
layer. The amount of secretion formed by these glands varies
greatly, being influenced by the condition of the atmosphere as re-
gards temperature and moisture, as well as by various physical and
psychical states, such as exercise and emotions. The average quan-
tity for twenty-four hours is said to vary between 700 and 900 gms.,
although this amount may be doubled under certain conditions.

According to an interesting paper by Schierbeck,* the average
quantity of sweat in twenty-four hours may amount to 2 to 3 liters
in a person clothed, and therefore with an average temperature
of 32° C. surrounding the skin. This author states that the amount

*"Archiv f. Physiologic," 1893, 116; see also Willebrand, "Skandi-
navisches Archiv f. Physiologic," 13, 337, 1902.

KIDNEY AND SKIN AS EXCRETORY ORGANS. 789

of sweat given off from the skin in the form of insensible perspira-
tion increases proportionately with the temperature until a certain
critical point is reached (about 33° C. in the person investigated),
when there is a marked increase in the water eliminated, the in-
crease being simultaneous with the formation of visible sweat. At
the same time there is a sudden increase in the CO2 eliminated from
the skin. It is possible that the sudden increase in CO2 is an in-
dication of greater metabolism in the sweat glands in connection
with the formation of visible sweat.

Composition of the Secretion. — The precise chemical composition
of sweat is difficult to determine, owing to the fact that as usually
obtained it is liable to be mixed with the sebaceous secretion. Nor-
mally it is a very thin secretion of low specific gravity (1.004) and
an alkaline reaction, although when first secreted the reaction may
be acid owing to admixture with the sebaceous material. The
larger part of the inorganic salts consists of sodium chlorid. Small
quantities of the alkaline sulphates and phosphates are also pres-
ent. The organic constituents, though present in mere traces, are
quite varied in number. Urea, uric acid, creatinin, aromatic oxy-
acids, ethereal sulphates of phenol and skatol, and albumin, are
said to occur when the sweating is profuse. Argutinsky has shown
that after the action of vapor baths, and as the result of muscular
work, the amount of urea eliminated in this secretion may be con-
siderable. Under pathological conditions involving a diminished
elimination of urea through the kidneys it has been observed that
the amount found in the sweat is markedly increased, so that crys-
tals of it may be deposited upon the skin. Under perfectly nor-
mal conditions, however, it is obvious that the organic constituents
are of minor importance. The main fact to be considered in the
secretion of sweat is the formation of water.

Secretory Fibers to the Sweat Glands. — Definite experimental
proof of the existence of sweat nerves was first obtained by Goltz *
in some experiments upon stimulation of the sciatic nerve in cats.
In the cat and dog, in which sweat glands occur on the balls of the
feet, the presence of sweat nerves may be demonstrated with great
ease. Electrical stimulation of the peripheral end of the divided
sciatic nerve, if sufficiently strong, will cause visible drops of sweat
to form on the hairless skin of the balls of the feet. When the
electrodes are kept at the same spot on the nerve and the stimula-
tion is maintained the secretion soon ceases; but this effect seems
to be due to a temporary injury of some kind to the nerve fibers
at the point of stimulation, and not to a genuine fatigue of the
sweat glands or the sweat fibers, since moving the electrodes to a
new point on the nerve farther toward the periphery calls forth a
*"Archiv f. die gesammte Physiologie, " 11, 71, 1875.

790 PHYSIOLOGY OF DIGESTION AND SECRETION.

new secretion. The secretion so formed is thin and limpid, and has
a marked alkaline reaction. The anatomical course of these fibers
has been worked out in the cat with great care by Langley.* He
finds that for the hind feet they leave the spinal cord chiefly in the
first and second lumbar nerves, enter the sympathetic chain, and
emerge from this as postganglionic fibers in the gray rami which
pass from the sixth lumbar to the second sacral ganglion, but chiefly
in the seventh lumbar and first sacral, and then join the nerves of
the sciatic plexus. For the forefeet the fibers leave the spinal cord
in the fourth to the tenth thoracic nerves, enter the sympathetic
chain, pass upward to the first thoracic ganglion, whence they are
continued as postganglionic fibers that pass out of this ganglion by
the gray rami communicating with the nerves forming the brachial
plexus. The action of the nerve fibers upon the sweat glands can
not be explained as an indirect effect, — for instance, as a result of
a variation in the blood-flow. Experiments have repeatedly shown
that, in the cat, stimulation of the sciatic still calls forth a secre-
tion after the blood has been shut off from the leg by ligation of
the aorta, or indeed after the leg has been amputated for as long
as twenty minutes. So in human beings it is known that profuse
sweating may often accompany a pallid skin, as in terror or
nausea, while, on the other hand, the flushed skin of fever is char-
acterized by the absence of perspiration. There seems to be no
doubt that the sweat nerves are genuine secretory fibers, causing
a secretion in consequence of a direct action on the cells of the sweat
glands. In accordance with this physiological fact histological
work has demonstrated that special nerve fibers are supplied to
the glandular epithelium. According to Arnstein, the terminal
fibers form a small, branching, varicose ending in contact with the
epithelial cells. The sweat gland may be made to secrete in many
ways other than by direct artificial excitation of the sweat fibers, —
for example, by external heat, dyspnea, muscular exercise, strong
emotions, and by the action of various drugs, such as pilocarpin,
muscarin, strychnin, nicotin, picrotoxin, and physostigmin. In all
such cases the effect is supposed to result from an action on the
sweat fibers, either directly on their terminations or indirectly upon
their cells of origin in the central nervous system. In ordinary
life the usual cause of profuse sweating is a high external temper-
ature or muscular exercise. With regard to the former it is known
that the high temperature does not excite the sweat glands im-
mediately, but through the intervention of the central nervous
system. If the nerves going to a limb be cut, exposure of that
limb to a high temperature does not cause a secretion, showing
that the temperature change alone is not sufficient to excite the

*" Journal of Physiology," 12, 347, 1891.

KIDNEY AND SKIN AS EXCRETORY ORGANS. 791

gland or its terminal nerve fibers. We must suppose, therefore,
that the high temperature acts upon the sensory cutaneous nerves,
possibly the heat fibers, and reflexly stimulates the sweat fibers.
Although external temperature does not directly excite the glands,
it should be stated that it affects their irritability either by direct
action on the gland cells or upon the terminal nerve fibers. At a
sufficiently low temperature the cat's paw does not secrete at all,
and the irritability of the glands is increased by a rise of temper-
ature up to about 45° C.

Dyspnea, muscular exercise, emotions, and many drugs affect
the secretion, probably by action on the nerve centers. Pilocarpin,
on the contrary, is known to stimulate the endings of the nerve
fibers in the glands, while atropin has the opposite effect, com-
pletely paralyzing the secretory fibers.

Sweat Centers in the Central Nervous System. — The fact that
secretion of sweat may be occasioned by stimulation of afferent
nerves or by direct action upon the central nervous system, as in
the case of dyspnea, implies the existence of physiological centers
controlling the secretory fibers. The precise location of the sweat
center or centers has not, however, been satisfactorily determined.
Histologically and anatomically the arrangement of the sweat
fibers resembles that of the vasoconstrictor fibers, and, reasoning
from analogy, one might suppose the existence of a general sweat
center in the medulla comparable to the vasoconstrictor center,
but positive evidence of the existence of such an arrangement is
lacking. It has been shown that when the medulla is separated
from the cord by a section in the cervical or thoracic region the
action of dyspnea, or of various sudorific drugs supposed to act on
the central nervous system, may still cause a secretion. On the
evidence of results of this character it is assumed that there are spinal
sweat centers; but whether these are few in number or represent
simply the various nuclei of origin of the fibers to different regions
is not definitely known. It is possible that in addition to these
spinal centers there is a general regulating center in the medulla.

Sebaceous Secretion. — The sebaceous glands are simple or
compound alveolar glands found over the cutaneous surface, usually
in association with the hairs, although in some cases they occur
separately, as, for instance, on the prepuce and glans penis, and
on the lips. When they occur with the hairs the short duct opens
into the hair follicle, so that the secretion is passed out upon the
hair near the point at which it projects from the skin. The alveoli are
filled with cuboidal or polygonal epithelial cells, which are arranged
in several layers. Those nearest the lumen of the gland are filled
with fatty material. These cells are supposed to be cast off bodily,
their detritus going to form the secretion. New cells are formed

792 PHYSIOLOGY OF DIGESTION AND SECRETION.

from the layer nearest the basement membrane, and thus the glands
continue to produce a slow but continuous secretion. The sebaceous
secretion, or sebum, is an oily, semiliquid material that sets, upon
exposure to the air, to a cheesy mass, as is seen in the comedones
or pimples which so frequently occur upon the skin from occlusion
of the opening of the ducts. The exact composition of the secretion
is not known. It contains fats and soaps, some cholesterin, albu-
minous material (part of which is a nucleo-albumin often described
as a casein), remnants of epithelial cells, and inorganic salts. The
cholesterin occurs in combination with a fatty acid, and is found in
especially large quantities in sheep's wool, from which it is extracted
and used commercially under the name of lanolin. The sebaceous
secretion from different places, or in different animals, is probably
somewhat variable in composition as well as in quantity. The
secretion of the prepuce is known as the smegma proeputii; that of
the external auditory meatus, mixed with the secretion of the neigh-
boring sweat glands or ceruminous glands, forms the well-known
earwax or cerumen. The secretion in this place contains a reddish
pigment of a bitterish-sweet taste, the composition of which has
not been investigated. Upon the skin of the newly born the se-
baceous material is accumulated to form the vernix caseosa. The
well-known uropygal gland of birds is homologous with the mam-
malian sebaceous glands, and its secretion has been obtained in
sufficient quantities for chemical analysis. Physiologically it is
believed that the sebaceous secretion affords a protection to the
skin and hairs. Its oily character doubtless serves to protect the
hairs from becoming too brittle, or, on the other hand, from being
too easily saturated with external moisture. In this way it prob-
ably aids in making the hairy coat a more perfect protection against
the effect of external changes of temperature. Upon the surface of
the skin, also, it forms a thin, protective layer that tends to prevent
undue loss of heat from evaporation of the sweat and possibly is
important in other ways in maintaining the physiological integrity
of the external surface.

Excretion of C02. — In some of the lower animals — the frog,
for example — the skin takes an important part in the respiratory
exchanges, eliminating CO2 and absorbing O. In man, and pre-
sumably in the mammalia generally, it has been ascertained that
changes of this kind are very slight. Estimates of the amount of
CO 2 given off from the skin of man during twenty-four hours vary
greatly, but the amount is small, about 7 to 8 gms. in twenty-four
hours, unless there is marked sweating, in which case the amount is
noticeably increased.

CHAPTER XLVI.

SECRETION OF THE DUCTLESS GLANDS-INTERNAL

SECRETION.

The term "internal secretion" is used to designate those secre-
tions of glandular tissues which, instead of being carried off to the
exterior by a duct, are eliminated in the blood or lymph. The idea
that secretory products may be given off in this way has long been
held in reference to the ductless glands, such as the thyroid, pitui-
tary body, etc., the absence of a duct suggesting naturally such a
possibility. The term, however, seems to have been employed
first by Claude Bernard, who emphasized the distinction between
the ordinary secretions, or external secretions, and this group of
internal secretions. Modern interest in the latter is due largely to
work done by Brown-Sequard (1889) upon testicular extracts, work
which itself was of doubtful value. This author was led to amplify
the conception of an internal secretion by the assumption that all
tissues give off a something to the blood which is characteristic,
and is of importance in general nutrition. This idea led in turn to
a revival of some old notions regarding the treatment of diseases
of the different organs by extracts of the corresponding tissue,
a therapeutical method usually designated as opotherapy. Brown-
Sequard's extension of the idea of internal secretion has not been
justified by subsequent work, and to-day we must limit the term
to definitely glandular tissues. Experience has shown, however,
that not only the ductless glands, but some at least of the typical
glands provided with ducts may give rise to internal secretions,
the pancreas, for example. In some of the ductless glands, on the
contrary, the existence or non-existence of an internal secretion
is still an open question. The work done since 1889 has, however,
demonstrated fully that some of the ductless glands play a role
of the very greatest importance in general nutrition, and this
knowledge has proved useful in widening our conception of the
nutritional relations in the organism and besides has found a valuable
application in practical medicine. The conception that certain
glandular organs may give rise to chemical products which on
entering the circulation influence the activity of one or more other
organs has recently found a fruitful application in the study of the
digestive secretions. The gastric and pancreatic secretins may

793

794 PHYSIOLOGY OF DIGESTION AND SECRETION.

be regarded as examples of internal secretions. Chemical products
of this kind which stimulate the activity of special organs Starling
designates as hormones* From this point of view the active
substances formed in the thyroids, adrenal glands, etc., may all
be classified as specific hormones. Starling makes the suggestive
remark that this means of coordinating the activities of the various
parts of a complex organism may be regarded as the most primitive,
while the better known coordination through the medium of a
nervous system is of later development. In the mammalian body
both methods, as we have seen, are employed.

Liver. — We do not usually regard the liver as furnishing an
internal secretion. As a matter of fact, it does form two products
within its cells — glycogen (sugar) and urea — which are subsequently
given off to the blood for purposes of general nutrition or for elim-
ination. The processes in this case fall under the general defini-
tion of internal secretion, and, in fact, may be used to illustrate
specifically the meaning of this term. The history of glycogen and
urea has been considered.

Internal Secretion of the Thyroid Tissues. — The most im-
portant and definite outcome of the work on internal secretions has
been obtained with the thyroids. Recent experimental work on
this organ makes it necessary for us now to distinguish between the
thyroid and the parathyroid tissues. The thyroids proper form
two oval bodies lying on the sides of the trachea at its junction with
the larynx. They have no ducts, and are composed of vesicles of
different sizes, which are lined by a single layer of cuboidal epithe-
lium and contain in their interior a material known as colloid. A
number of histologists have traced the formation of this colloid to
the lining epithelial cells, and have stated, moreover, that the vesicles
finally rupture and discharge the colloid into the surrounding lym-
phatic spaces. Accessory thyroids varying in size and number may
be found along the trachea as far down as the heart. They possess
a vesicular structure and no doubt have a function similar to that
of the thyroid body.

The parathyroids are, according to most authors, quite different
structures. Four of these bodies are usually described, two on each
side, and their positions vary somewhat in different animals. In
man the superior (or internal) parathyroids are found upon the
posterior surface of the thyroid at the level of the junction of its
upper with its middle third. This portion of the organ may be
imbedded in the thyroid. The inferior (or external) parathyroids
lie near the lower margin of the thyroid on its posterior surface,
and in some cases lower down on the sides of the trachea. The

* For general discussion consult Starling, "Recent Advances in the
Physiology of Digestion," Chicago, 1906.

SECRETION OF THE DUCTLESS GLANDS. 795

tissue has a structure quite different from that of the thyroids,
being composed of solid masses or columns of epithelial cells which
are not arranged in vesicles and contain no colloid.

Extirpation of the Thyroids and Parathyroids. — In 1856
Schiff showed that extirpation of the thyroids (complete thyroi-
dectomy) in dogs is followed usually by the death of the animal in
one to four weeks. The aninial exhibits certain characteristic symp-
toms, such as muscular tremors, which may pass into convulsions,
cachexia, emaciation, and a condition of apathy. This result was
confirmed by subsequent observers, but many exceptions were noted.
Great interest was shown in these results, because on the surgical
side reports were made showing that after complete removal of the
thyroids in cases of goiter evil consequences might ensue, either
acute convulsive attacks or chonic malnutrition. On the other
hand, it became known that atrophy of the thyroids in the young
is responsible for the condition of arrested growth and deficient
mental development designated as cretinism, and in the adult the
same cause gives rise to the peculiar disease of myxedema, character-
ized by distressing mental deterioration, an edema tous condition
of the skin, loss of hair, etc. SchifT and others found that the evil
results of complete thyroidectomy in dogs might be obviated by
grafting pieces of the thyroid in the body, and this knowledge was
quickly applied to human beings in cases of myxedema and cretinism
with astonishingly successful results. Instead of grafting thyroid
tissue it was found, in fact, that injection of extracts under the
skin or better still simple feeding of thyroid material gave similar
favorable results: the individuals recovered their normal appear-
ance and mental powers.* Later Baumannf succeeded in isolating
from the glands a substance designated as iodothyrin, which shows
in large measure the beneficial influence exerted by thyroid extracts
in cases of myxedema and parenchymatous goiter. This substance
is characterized by containing a large amount of iodin (9.3 per
cent, of the dry weight). It is contained in the gland in combina-
tion with protein bodies, from which it may be separated by diges-
tion with gastric juice or by boiling with acids.

The Function of the Parathyroids. — Most of the results des-
cribed above were obtained before the existence of the parathy-
roids was recognized. Early in the history of the subject it was
recognized that complete removal of the thyroids proper in herbiv-
orous animals (rats, rabbits) is not attended by a fatal result.
Gley and others, however, proved that if the parathyroids also are

* For a general account of the development of the subject and the liter-
ature see "Transactions of the Congress of American Physicians and Sur-
geons" (Howell, Chittenden, Adami, Putnam, Kinnicutt, Osier), 1897, and
Jeandelize, 'Insuffisance thyroidienne et parathyroidienne, " Nancy, 1902 ;
also Vincent, 'Internal Secretions," etc., Lancet, Aug. 11 and 18, 1906.

fZeitschrift f. physiolog. Chemie," 21, 319, and 481, 1896.

796 PHYSIOLOGY OF DIGESTION AND SECRETION.

removed these animals die with the symptoms described in the
case of dogs, cats, and other carnivorous animals. This result at-
tracted attention to the parathyroids. Numerous experiments,
especially by Moussu,* Gley,f and Vassale and Generate, t have
seemed to show a marked difference between the results of thyroi-
dectomy and parathyroidectomy. When the parathyroids alone are
removed the animal dies quickly with acute symptoms, muscular
convulsions (tetany), etc.; when the thyroids alone are removed
the animal may survive for a long period, but develops a condition
of chronic malnutrition, — a slowly increasing cachexia which may
exhibit itself in a condition resembling myxedema in man. This
distinction has been generally accepted, and it throws much light
upon the discrepancy in the results obtained by some of the earlier
observers. Complete thyroidectomy with the acutely fatal results
usually described includes those cases in which both thyroids and
parathyroids were removed, while probably many of the apparently
negative results obtained after excision of the thyroids are expli-
cable on the supposition that one or more of the parathyroids were
left in the animal. It should be stated, however, that two recent
observers, Vincent and Jolly, as the result of numerous experi-
ments made upon different varieties of animals, throw some doubt
upon these conclusions. They contend that in herbivorous animals
fully half of those operated upon survive complete removal of all
thyroid tissue, showing no evil symptoms except perhaps a di-
minished resistance to infection. Carnivorous animals, on the con-
trary, usually die after such an operation. In spite of such con-
tradictory results in the hands of some observers the general opinion
prevails that complete removal of the parathyroids is followed by
acutely toxic results which develop rapidly and the most prom-
inent symptom of which is muscular tetany. Several observers
have reported that injections of extract of the parathyroids cause
this last-named symptom to disappear without, however, protecting
the animal from a fatal outcome. The experimental evidence in
the case of the parathyroids tends to support the view that their
function consists in neutralizing in some way toxic substances
formed elsewhere in the body, and that therefore after removal of
these glands death occurs from the accumulation of such toxic
bodies in the blood and tissues. Thus Macallum § states that in
animals in which tetany had developed as a consequence of extir-
pation of the parathyroids, bleeding and infusion of salt solution
caused the tetany to disappear. In a^ interesting case of tetany

* Moussu, 'Proc. Fourth International Physiolog. Congress," 1898.
fGley, " Pfluger's Archiv," 66, 308, 1897.

j Vassale and Generale, "Archives italiennes de biologie," 33, 1900.
^Macallum, ' ' Centralblatt f. allg. Pathol. u. patholog. Anat. ." 1905,
xvi.,'385.

SECRETION OF THE DUCTLESS GLANDS. 797

in man following upon a greatly dilated stomach histological ex-
amination of the parathyroids snowed evidences of active cell mul-
tiplication. The inference in this case would seem to be that the
toxins resulting from the gastric conditions had aroused a com-
pensatory increase in parathyroid activity. No precise statement,
however, can be made regarding the physiology of the parathy-
roids. The old view that they represent follicles of undeveloped
or embryonic thyroid tissu'e is not supported by experiments. We
must believe rather that the parathyroids and the thyroids are
different structures ; their histology is different, they have different
embryological origins, and physiologically they subserve different
functions. Chemically also there is perhaps a distinction in that
the iodin compounds so characteristic of the thyroid tissue are said
by some observers to be absent from the parathyroids. Some
observers contend that there is a correlation of functions between
the thyroids and parathyroids, but the proofs for this view are not
convincing.

The General Nature of the Functions of the Thyroids and
Parathyroids. — Disregarding the difference in function between
these two bodies, it is quite evident from the facts given that they
exercise an important control over the processes of nutrition of the
body, and especially perhaps over those of the central nervous
system. How is this control exerted? Two general points of view
have been advocated. According to one theory, the thyroid tis-
sues elaborate a special internal secretion, characterized by its
contents in iodin. This secretion is given off to the lymph or blood,
is carried to the tissues, and there exercises a regulating action of
an important or indeed essential character. Excision or atrophy
of these bodies results in a loss of this secretion and a consequent
malnutrition or perverted metabolism in other tissues of the organ-
ism. This view prevails for the case of the thyroids. According
to another point of view the function of these bodies is to neu-
tralize or destroy toxic substances formed in the metabolism of
the rest of the body, as the liver, for instance, destroys the toxic
character of the ammonia compounds by converting them to urea.
On this theory the removal of the thyroid tissues results in the
accumulation of toxic substances in the blood and the animal dies
by a process of auto-intoxication. As stated above there is some
evidence for this view in the case of the parathyroids.

Cyon's View of the Function of the Thyroid. — Cyon in numerous
publications has advocated a different view of the function of the thyroids.
These bodies have a very large vascular supply, and this author assumes that
this area serves as a vascular shunt or flood-gate to protect mechanically
the circulation in the brain. The dilatation of the thyroid area under con-

798 PHYSIOLOGY OF DIGESTION AND SECRETION.

ditions that threaten congestion of the brain is effected reflexly by means
of the hypophysis cerebri and the vagi. For details of this mechanism and
also of the supposed effect of the thyroid secretion on the irritability of the
centers innervating the heart and blood-vessels see " Archives de physiologic, "
1898, p. 618.

Thy mus. — The physiology of the thymus gland is very obscure,
indeed, practically nothing is known about its functions. Its prox-
imity to the thyroids and parathyroids and its general similarity
in origin would indicate that like them it may have some impor-
tant specific influence upon metabolism, but physiological experi-
ments so far have failed to discover what this influence is. Ac-
cording to Verdun the thymus arises from the endothelial pouches
belonging to the branchial clefts, chiefly from that of the third
cleft. Formerly it was supposed to reach its maximal develop-
ment at birth and subsequently to atrophy, being replaced by a
growth of lymphoid and fatty tissues. More recently doubt has
been thrown upon this belief. Several observers have stated that
it continues to increase in size after birth until the appearance of
puberty, and that true thymus tissue may persist throughout life.
Stohr, in fact, insists that what has usually been taken as lymphoid
tissue in the adult thymus is, in reality, epithelial or endothelial
tissue which presumably has some specific function. On the
physiological side Abelous and Billard have stated that extirpation
of these glands in the frog is followed by the death of the animal,
but later observers have failed to confirm this result either upon
frogs or mammals (guinea-pigs), so that we must believe that
whatever their function may be it is not absolutely essential to
the life of the organism. Injections of extract of the gland
(Svehla) cause a fall of blood-pressure and some quickening of the
heart-beat, but these effects are not specific. Unlike the thyroid
and parathyroid glands, the thymus contains no iodin (Mendel).
The only definite suggestion made regarding its influence is that
there is some sort of reciprocal relationship between it and the re-
productive glands. Castration (Henderson) causes a persistent
growth and retarded atrophy of the thymus, while removal of the
thymus (Paton) hastens the development of the testes.*

Adrenal Bodies. — The adrenal bodies — or, as they are frequently
called in human anatomy, the suprarenal capsules — belong to the
group of ductless glands. It was shown first by Brown-Sequard
(1856) that removal of these bodies is followed rapidly by death.
This result has been confirmed by many experimenters, and so far

* References: — Friedleben, "Die Physiologic der Thymusdriise," 1858;
Verdun, " Derives branchiaux chez les vertebras," 1898; Hammar, " Pfliiger's
Archiv," ex., and " Anatom. Anzeiger," xxvii.; Henderson, "Journal of Phys-
iology," 1904, xxxi., 222; Stohr, " Beit. z. Anat. u. Entwick," Anatom.
Hefte, 1906, xxxi., 409.

SECRETION OF THE DUCTLESS GLANDS. 799

as the observations go the effect of complete removal is the same
in all animals. The fatal effect is more rapid than in the case of
removal of the thyroids, death following the operation usually in
two to three days, or, according to some accounts, within a few
hours. The symptoms preceding death are great prostration, mus-
cular weakness, and marked diminution in vascular tone. These
symptoms resemble those occurring in Addison's disease in man, —
a disease which clinical evidence has shown to be associated with
pathological lesions in the suprarenal capsules. It has been ex-
pected, therefore, that the results obtained from thyroid treatment
of myxedema might be paralleled in cases of Addison's disease by
the use of adrenal extracts, but so far these expectations have not
been completely realized. Oliver* and Schaefer, and, about the
same time, Cybulski and Szymonowicz,t discovered that this organ
forms a peculiar substance that has a very definite physiological
action, especially upon the circulatory system. They found that
aqueous extracts of the medulla of the gland when injected into the
blood of a living animal have a remarkable influence upon the heart
and blood-vessels. If the vagi are intact, the adrenal extracts cause
a very marked slowing of the heart beat together with a rise of blood-
pressure. When the inhibitory fibers of the vagus are thrown out
of action by section or by the use of atropin the heart rate is ac-
celerated, while the blood-pressure is increased sometimes to an
extraordinary extent. These results are obtained with very small
doses of the extracts. Schaefer states that as little as 5£ mgms.
of the dried gland may produce a maximal effect upon a dog weigh-
ing 10 kgms. The effects produced by such extracts are quite tem-
porary in character. In the course of a few minutes the blood-
pressure returns to normal, as also the heart beat, showing that the
substance has been destroyed in some way in the body, although
where or how this destruction occurs is not known. According to
Schaefer, the kidneys and the adrenals themselves are not respon-
sible for this prompt elimination or destruction of the active sub-
stance. Several observers have shown satisfactorily that the ma-
terial producing this effect is present in perceptible quantities in
the blood of the adrenal vein, so that there can be but little doubt
that it is a distinct internal secretion of the adrenal. J Dreyer has
shown, moreover, that the amount of this substance in the adrenal
blood is increased, judging from the physiological effects of its in-
jection, by stimulation of the splanchnic nerve. Since this result
was obtained independently of the amount of blood-flow through
the gland, Dreyer makes the justifiable assumption that the adrenals

*" Journal of Physiology," 18,230, 1895.

t"Archiv f. die gesammte Physiologic, " 64, 97, 1896.

j" American Journal of Physiology," 2, 203, 1899.

800 PHYSIOLOGY OF DIGESTION AND SECRETION.

possess secretory nerve fibers. Abel * has succeeded in isolating a
substance from the gland that produces the effect on blood-pressure
and heart rate, and proposes for it the name epinephrin hydrate.
He assigns to it the formula C10H13NO3 • £H2O and describes it as
a peculiar, unstable, basic body. Salts of epinephrin may be ob-
tained which when injected into the circulation cause the typical
effects produced by injection of extracts of the gland.

The active principle of the gland has been prepared in crystalline
form and named adrenalin (Takamine, Aldrich); its formula is
given as C9H13NO3. This substance is much used practically in
minor surgical operations as a hemostatic to check the flow of blood.
The constriction of the blood-vessels seems to be due to a direct
effect upon the walls of the vessels, either upon the musculature
itself or upon the endings of the peripheral nerve fibers distributed
to these muscles. That the effect is not entirely central is indicated
by the fact that after destruction of the vasoconstrictor center and
removal of the spinal cord injection of the extracts causes a rise
of blood-pressure of 100 per cent, or more. Langley has called
attention to the peculiar fact that the action of adrenal extracts
or solutions of adrenalin on plain muscle resembles always the
effect of stimulating the sympathetic nerves supplying the same
tissue. It has been proposed, therefore, to use these solutions to
determine whether or not given vascular areas, such as those of the
brain or lungs, are provided with vasoconstrictor nerve fibers.
When adrenalin is injected into a normal animal it may have an
influence upon the nerve centers of the vasomotor nerves as well
as upon the peripheral endings. Meltzer f has shown that mod-
erate doses under such conditions may cause a dilatation, while
in parts whose connection with the nerve center is destroyed only
a constriction is obtained. Under normal conditions at least
these extracts when injected into the circulation soon lose their
effect. This fact may explain why injection of the extracts has
failed to give permanent relief in animals from whom the adrenals
had been removed or in human beings suffering from Addison's
disease. Bearing in mind the results obtained in the case of thy-
roidectomy, it has been suggested that grafts of the adrenals under
the skin or into the peritoneal cavity may prove more effective.
Results by this method have been chiefly negative, owing apparently
to the fact that in such grafts the medullary substance, which con-
tains the material that causes constriction of the blood-vessels,
readily undergoes atrophy and absorption, but Busch and Van
Bergen J report at least one successful transplantation of the adrenal

*Abel, "Berichte d. deut. chem. Gesellschaft," 37, 368, 1904.

t S. J. and Clara Meltzer, "American Journal of Physiology, " 9. 252,
1903.

J Busch and Van Bergen. "American Journal of Physiology," 1906, xv.,
444.

SECRETION OF THE DUCTLESS GLANDS. 801

(rabbit) in which the medulla persisted, and in which the grafted
gland preserved the animal from the usual fatal result following
total extirpation. It seems probable that if the method of grafting
is perfected the procedure may prove effective as a therapeutical
means in the treatment of Addison's disease.

The Physiological R61e of the Adrenals. — There seems to be
no question that the medullary substance forms epinephrin or adre-
nalin or some related compound which has a marked stimulating
effect upon the tone of the blood-vessels and upon the heart, and
that this material passes into the blood. The general view, there-
fore, has* been that one at least of the functions of the adrenals is
the internal secretion of this material. It is assumed that its con-
tinued formation is necessary to the maintenance of the normal
metabolism of the muscular tissues either by a direct effect or
indirectly by influencing the activity of the nerve centers. Removal
of this secretion results in a marked loss of muscular tone and vigor,
exhibited by the blood-vessels, the heart, and the skeletal muscles, and
death follows rapidly. This general view is in accord with the
facts so far as they are known, but it must be confessed that it goes
somewhat beyond the facts. Another permissible, although less
probable view is that the adrenals produce an antitoxic substance
whose function is to neutralize or destroy certain (unknown) poi-
sonous products of body metabolism. Removal or disease of the
adrenals, on this theory, causes death because it allows these
toxic products to accumulate. It should be noted that this sug-
gestion regarding the functions of the adrenal glands refers only
to the medullary portion, in which alone the substance caus-
ing a rise of blood-pressure is found. Regarding the functions of
the relatively large cortical portion of the gland we have no
definite information, although some comparative observations
indicate that it may have important specific relations to the growth
of the body, particularly of the genital organs.

Pituitary Body. — This body is usually described as consisting
of two parts, — a large anterior lobe of distinct glandular structure
and a much smaller posterior lobe whose structure is not clearly
known. The cells are said to form follicles which contain some
colloid material.* Embryologically the two lobes are entirely dis-
tinct. The anterior lobe, which may be designated as the hypoph-
ysis cerebri, arises from the epithelium of the mouth, while the
posterior lobe, or the infundibular body, develops as an outgrowth
from the infundibulum of the brain, and in the adult remains con-
nected with this portion of the brain by a long stalk. Ho well f and

* Thorn, 'Archiv f. mik. Anat ," 57, 632, 1901.

f "Journal of Experimental Medicine," 3, 245, 1898; also Schaefer and
Vincent, "Journal of Physiology," 25, 87, 1899.
51

802 PHYSIOLOGY OF DIGESTION AND SECRETION.

others have shown that extracts of the hypophysis when injected
intravenously have little or no physiological effect, while extracts
of the infundibular body, on the contrary, cause a marked rise of
blopd-pressure and slowing of the heart beat. These effects resemble
in general those obtained from adrenal extracts, but differ in some
details. They seem to warrant the conclusion that the infundib-
ular body is not a mere rudimentary organ, as had been generally
assumed, but produces a peculiar substance, an internal secretion,
that may have a distinct physiological value. The most signifi-
cant observation made in regard to the probable functional signifi-
cance of the internal secretion of the infundibular lobe is found
in the experiments of Schafer and Herring.* These observers
report that this part of the gland yields a substance soluble in
water and not destroyed by boiling, which acts specifically upon the
kidney, producing a dilatation of the renal vessels and an increased
secretion of urine. A number of observers, especially Vassale and
Sacchi, have succeeded in removing the entire pituitary body.
They report that the operation results eventually in the death of
the animal with a certain group of symptoms, such as muscular
tremors and spasms, apathy and dyspnea, that resemble the results
of thyroidectomy. It has been suggested, therefore, that the pit-
uitary body may be related in function to the thyroids and may be
able to assume vicariously the functions of the latter after thy-
roidectomy. There is no satisfactory evidence, however, in support
of this view. On the pathological side it has been shown that
usually lesions of the pituitary body, particularly of the hypophysis,-
are associated with a peculiar disease known as acromegaly, the
most prominent symptom of which is a marked hypertrophy of the
bones of the extremities and of the face. The conclusion sometimes
drawn from this fact that acromegaly is caused by a disturbance
of the functions of the pituitary body is, however, very uncertain,
and is not supported by any definite clinical or experimental facts.

Organs of Reproduction. — Some of the earliest work upon the
effect of the internal secretions of the glands was done upon the
reproductive glands, especially the testis, by Brown-Sequard.f Ac-
cording to this observer, extracts of the fresh testis when injected
under the skin or into the blood may have a remarkable influence
upon the nervous system. Mental and physical vigor, and the
activity of the spinal centers, are greatly improved, not only
in cases of general prostration and neurasthenia, but also in the
case of the aged. Brown-Sequard maintained that this general
dynamogenic effect is due to some unknown substance formed
in the testis and subsequently passed into the blood, although he

* Schiifer and Herring, "Philosophical Transactions, Royal Society,"
London, 1906, B. cxcix., 1.

f " Archives de physiologic normale et pathologique, 1889-92.

SECRETION OF THE DUCTLESS GLANDS. 803

admitted that some of the same substance may be found in the ex-
ternal secretion of the testis — i. e., the spermatic liquid. Poehl*
asserts that he has prepared a substance, spermin, to which he gives
the formula C5HUN2, which has a very beneficial effect upon the
metabolism of the body. He believes that this spermin is the sub-
stance that gives to the testicular extracts prepared by Brown-Se"-
quard their stimulating effect. He claims for this substance an
extraordinary action as a physiological tonic. Zothf and also
PregelJ seem to have obtained exact objective proof, by means
of ergographic records, of the stimulating action of the testicular
extracts upon the neuromuscular apparatus in man. They find
that injections of the testicular extracts cause not only a diminu-
tion in the muscular and nervous fatigue resulting from muscular
work, but also lessen the subjective fatigue sensations. The fact
that the internal secretion of the testis, if it exists at all, is not ab-
solutely essential to the life of the body as a whole, as in the case
of the thyroids, adrenals, and pancreas, naturally makes the satis-
factory determination of its existence and action a more difficult
task.

Similar ideas in general prevail as to the possibility of the ovaries
furnishing an internal secretion that plays an important part in
general nutrition. In gynecological practice it has been observed
that complete ovariotomy with its resulting premature menopause
is often followed by distressing symptoms, mental and physical.
In such cases many observers have reported that these symptoms
may be alleviated by the use of ovarian extracts. Morris § reports
a number of cases in which, after complete removal of the ovaries,
a piece of ovary from the same or a different person was grafted
into the fundus of the uterus or into the broad ligament. In all
cases menstruation persisted, showing, therefore, that the presence
of the ovaries is necessary for this function. A similar operation
in cases of amenorrhea or dysmenorrhea brought on free and easy
menstruation and an improvement in general nutrition and well-
being. Glass || also reports a case in which the entire ovary from
one woman was transplanted into another patient upon whom com-
plete ovariotomy had been performed two years before. The result
of the operation was a return of menstruation and sexual desire,
and a marked alleviation of the disagreeable symptoms following the
artificial menopause. Similar results have been reported upon
the lower animals. After complete ovariotomy a condition of

* "Zeitschrift f. klinische Medicin," 26, 133, 1894.

t"Pfliiger's Archiv f. die gesammte Physiologic," 62, 335, 1896; also
69, 386, 1897.

t Ibid., p. 379. § Morris, " Medical Record," 1901, p. 83.

|| Glass, " Medical News," 1899, p. 523.

804 PHYSIOLOGY OF DIGESTION AND SECRETION.

"heat" may be reproduced by grafting ovarian tissue * (see section
on Reproduction). In the natural menopause, as well as in the
premature menopause following operations, it is a frequent, though
not invariable, result for the individual to gain noticeably in weight.
An effect of the ovaries on general nutrition is indicated also by
the interesting fact that in cases of osteomalacia, a disease char-
acterized by softening of the bones, removal of the ovaries may
exert a favorable influence upon the course of the disease. These
indications have found some experimental verification in a research
by Loewy and Richter f made upon dogs. These observers found
that complete removal of the ovaries, although at first apparently
without effect, resulted in the course of two to three months in a
marked diminution in the consumption of oxygen by the animal,
measured per kilogram of body- weight. If now the animal in this
condition was given ovarian extracts (oophorin tablets) , the amount
of oxygen consumed was not only brought to its former amount,
but considerably increased beyond it. A similar result was obtained
when the extracts were used upon castrated males. The authors
believe that their experiments show that the ovaries form a specific
substance which is capable of increasing the oxidations of the body.
In addition to the internal secretion of the ovaries which is respon-
sible for the phenomenon of menstruation, other similar secretions
have been assumed to account for changes connected with the
process of reproduction. Thus the implantation of the fertilized
ovum in the uterine mucous membrane and the development of
the placenta have been supposed to be effected through the agency
of some chemical stimulus arising in the cells of the corpus luteum.
So also the development of the mammary glands during pregnancy
is attributed to the action of a hormone formed in the tissues of
the fetus itself (see section on Reproduction).

Pancreas. — The importance of the external secretion, the pan-
creatic juice, of the pancreas has long been recognized, but it was
not until 1889 that von Mering and Minkowski J proved that it fur-
nishes also an equally important internal secretion. These observers
succeeded in extirpating the entire pancreas without causing the
immediate death of the animal, and found that in all cases this
operation was followed by the appearance of sugar in the urine in
considerable quantities. Further observations of their own and of
other experimenters have corroborated this result and added a num-
ber of interesting facts to our knowledge of this side of the activity
of the pancreas. It has been shown that when the pancreas is com-
pletely removed a condition of glycosuria inevitably follows, even

* Marshall and Jolly, "Philosoph. Transactions," B. cxcviii., 99, 1905.
t Loewy and Richter, " Archiv f. Physiologie, " 1899, suppl. volume, p. 174.
J Minkowski, "Archiv f. exper. Pathologic u. Pharmakologie, " 31, 85,
1893.

SECRETION OF THE DUCTLESS GLANDS. 805

if carbohydrate food is excluded from the diet. Moreover, as in
the similar pathological condition of glycosuria or diabetes mel-
litus in man, there is an increase in the quantity of urine (polyuria)
and of urea, and an abnormal thirst and hunger. Acetone also is
present in the urine. These symptoms in cases of complete extir-
pation of the pancreas are followed by emaciation and muscular
weakness, which finally end in death in two to four weeks. If the
pancreas is incompletely removed, the glycosuria may be serious,
or slight and transient, or absent altogether, depending upon the
amount of pancreatic tissue left. According to the experiments
of von Mering and Minkowski on dogs, a residue of one-fourth to
one-fifth of the gland is sufficient to prevent the appearance of sugar
in the urine, although a smaller fragment may suffice apparently
if its physiological condition is favorable. The portion of pancreas
left in the body may suffice to prevent glycosuria, partly or com-
pletely, even though its connection with the duodenum is entirely
interrupted, thus indicating that the suppression of the pancreatic
juice is not responsible for the glycosuria. The same fact is shown
more conclusively by the following experiments: Glycosuria after
complete removal of the pancreas from its normal connections may
be prevented partially or completely by grafting a portion of the
pancreas elsewhere in the abdominal cavity or even under the skin.
So also the ducts of the gland may be completely occluded by liga-
ture or by injection of paraffin without causing a condition of per-
manent glycosuria.

On the basis of these and similar results it is believed that the
pancreas forms an internal secretion which passes into the blood
and plays an important, indeed, an essential part in the metabolism
of sugar in the body. Moreover, considerable evidence has been
accumulated to show that the tissue concerned hi this important
function is not the pancreatic tissue proper, but that composing the
so-called islands of Langerhans. In man these islands are scattered
through the pancreas, forming spherical or oval bodies that ma.y
reach a diameter of as much as one millimeter. The cells in these
bodies are polygonal; their cytoplasm is pale, finely granular, and
small in amount. The nuclei possess a thick chromatin network
which stains deeply. Each island possesses a rich capillary network
that resembles somewhat the glomerulus of the kidney.

According to Ssbolew,* ligation of the pancreatic duct is followed
by a complete atrophy of the pancreatic cells proper, while those
of the islands of Langerhans are not affected. Since under these
conditions no glycosuria occurs, while removal of the whole organ
including the islands is followed by pancreatic diabetes, the obvious
conclusion is that the diabetes is due to the loss of the islands.
*"Virchow's Archiv," 168, 91, 1902.

806 PHYSIOLOGY OF DIGESTION AND SECRETION.

This conclusion is strengthened by reports from the pathological
side. A number of recent observers (Opie, Ssbolew, Herzog, et a/.)
find that in diabetes mellitus in man the islands may be markedly
affected. They show signs of hyaline degeneration or atrophy or in
severe cases may be absent altogether. It should be added that
this connection of the islands of Langerhans with the internal
secretion of the pancreas is by no means a demonstrated fact.
Several observers * contend that the islands represent a stage in the
development of the ordinary secreting alveoli of the pancreas.
When the pancreas is subjected to prolonged and excessive activity,
by the injection of secretin, for example, the number of islands is
greatly increased, and the same result follows periods of prolonged
inactivity, as in fasting.

Several theories have been advanced to explain the action of
the internal secretion of the pancreas. It has been suggested that
the secretion contains an enzyme which is necessary for the hydrol-
ysis or oxidation of the sugar of the body and in the absence of
this enzyme the sugar accumulates in the blood and is drained off
through the kidney. Cohnheimf states that, while the juices ex-
pressed from muscle and from pancreas have little effect upon sugar
when taken separately, yet when combined they cause a marked
disappearance (glycolysis) of sugar added to the mixture. The
inference from this result is that the pancreas furnishes a substance
which activates the glycolytic enzyme or enzymes of the muscle
and thus makes possible the physiological consumption of sugars
in the body. Since the pancreas extracts do not lose this property,
upon boiling it is evident that the activating substance is not an
enzyme, but a body of a more stable character. Other investigators
adopt an entirely different view of the relation of the pancreas to
carbohydrate metabolism. They believe that the internal secre-
tion of the pancreas regulates in some way the output of sugar
from the liver (and other sugar-producing organs). In the absence
of this secretion the liver gives off its glycogen as sugar too rapidly,
the sugar contents of the blood are thereby increased (hypergly-
cemia) above normal, and the excess passes out in the urine.

Kidney. — Tigerstedt and Bergman t state that a substance
may be extracted from the kidneys of rabbits which when injected
into the body of a living animal causes a rise of blood-pressure.
They get the same effect from the blood of the renal vein. They
conclude, therefore, that a substance, for which they suggest the

* Dale, "Philosophical Transactions," B. cxcyii., 1904 ; also Vincent and
Thompson, "Journal of Physiology," 1906, xxvii., xxxiv.

fCohnheim, "Zeitschrift f. physiolog. Chemie," 39, 336, 1903; also 1904.

J " Skandinavisches Archiv f. Physiologic," 8, 223, 1898; see also Brad-
ford, 'Proceedings of the Royal Society," 1892.

SECRETION OF THE DUCTLESS GLANDS. 807

name " rennin," is normally secreted by the kidney into the renal
blood, and that this substance causes a vasoconstriction. Other
observers claim that the kidneys furnish an important internal
secretion that affects the metabolism. The absence of this secretion
after complete nephrectomy leads to the production of uremia.*

* Suner, " Zentralblatt f. d. ges. Physiol. u. Path, des Stofferechsel, "
1907, ii., 3.

SECTION VIII.

NUTRITION AND HEAT PRODUCTION AND
REGULATION.

CHAPTER XLVII.
GENERAL METHODS— HISTORY OF THE PROTEIN FOOD.

Under the head of nutrition or general metabolism we include
usually all those changes that occur in our foodstuffs from the time
that they are absorbed from the alimentary canal until they are
eliminated in the excretions. In many of these processes the oxygen
absorbed from the lungs takes a most important part, and the
changes directly due to this element, the physiological oxidations
of the body, can not be separated from the general metabolic phe-
nomena of the tissues. As was said in another place, the respiratory
history of oxygen ceases after this element has reached the tissues;
its subsequent participation in the chemical changes of the organ-
ism forms an integral part of the nutritional processes. These latter
processes are varied and complex and only partially understood.
For the sake of simplicity in presentation it is convenient to con-
sider separately each of the so-called foodstuffs, — the proteins,
albuminoids, carbohydrates, fats, water, and inorganic salts, — and
attempt to trace its nutritive history from the time it is absorbed
into the blood until it is eliminated from the body in the form of
excretory products. Before undertaking this description it is desir-
able to call attention to certain general methods and conceptions
that have been developed in connection with this part of physiology.

Nitrogen Equilibrium. — Among our main foodstuffs the pro-
teins (and albuminoids) are characterized by containing nitrogen.
After this material is metabolized in the body the nitrogen is elim-
inated in various forms, chiefly in the urine, but to a smaller ex-
tent in the feces and sweat. In the feces, moreover, there may be
present some undigested protein which, although taken with the
food, has never really entered the body. It is evident that the
urine, feces (and sweat) may be collected during a given period and
analyzed to determine their contents in nitrogen. The sweat i?

808

GENERAL METHODS — HISTORY OF PROTEIN FOOD. 809

usually neglected except in observations upon conditions in which
muscular activity has been a prominent feature. As a rule, the
amount of nitrogen is determined by some modification of the Kjel-
dahl method. In principle this method consists in heating the
material to be analyzed with strong sulphuric acid. The nitrogen
is thereby converted to ammonia, which is distilled off and caught
in a standardized solution of sulphuric acid. By titration the
amount of ammonia can be'determined, and from this the amount of
nitrogen is estimated. Nitrogen forms a definite percentage of the
protein molecule (about 16 per cent.) ; so that if the weight of nitro-
gen is multiplied by 6.25 the weight of protein from which it is de-
rived is obtained. If, on the other hand, the nitrogen is determined
in the food eaten during the period of the experiment it is evident
that a balance may be struck which will determine whether the
body is receiving or losing nitrogen. If the balance is even the body
is in nitrogen equilibrium — that is, it is receiving in the food as
much nitrogen (or protein) as it is metabolizing and eliminating in
the excreta. If there is a plus balance in favor of the food it is
evident that the body is laying on or storing protein tissue, while
if the balance is minus, the body must be losing protein. During
the period of growth, in convalescence, etc., the body does store
protein, and under these conditions the balance is in favor of the
food nitrogen. But throughout adult life under normal conditions
our diet is so regulated by the appetite that a nitrogen equilibrium
is maintained through long periods. Under experimental condi-
tions, involving, for instance, a special diet, it often becomes neces-
sary to make the analyses for nitrogen in order to determine whether
or not the individual is losing or gaining protein or is in equilibrium.
It is important also to bear in mind that nitrogen or protein
equilibrium may be established at different levels. If, for instance,
a man is in nitrogen equilibrium on a diet containing 10 gms. of
nitrogen, what will happen if the protein in this diet is doubled ?
Our experience teaches us that the extra 10 gms. of nitrogen or
62.5 gms. of protein is not stored in the body indefinitely. As a
matter of fact, the extra protein is metabolized in the body and
nitrogen equilibrium becomes established at a higher level. Where-
as under the first condition 62.5 gms. of protein were eaten and 62.5
gms. of protein were lost from the body, either in the form of nitrog-
enous excreta or in the feces as undigested protein, under the
second condition 125 gms. of protein are eaten and 125 gms. of pro-
tein are lost. The total mass of protein tissue in the body may
remain the same, or if any increase takes place at the beginning of
the change in diet it soon ceases. Experimentally it is found that
there is a certain low limit of protein which just suffices to maintain
nitrogen equilibrium, and between this level and the capacity of

810 NUTRITION AND HEAT REGULATION.

the body to digest and absorb protein food nitrogen equilibrium
may be maintained upon any given amount of protein.

Carbon Equilibrium and Body Equilibrium.— The term car-
bon equilibrium is sometimes used to describe the condition in which
the total carbon of the excreta (in the carbon dioxid, urea, etc.) is
balanced by the carbon of the food. It is possible that an individual
may be in nitrogen equilibrium and yet be losing or gaining in
weight, since, although the consumption of proteins may just be
covered by the proteins of the food, the comsumption of non-protein
material, particularly the fats of the body, may be greater than the
supply furnished by or manufactured from the food. An animal
may lose or gain in carbon when his nitrogen supply is in equilib-
rium. In the same way under special circumstances we may
speak of a water equilibrium or a salts equilibrium, although these
terms are not generally used. An adult under normal conditions
lives so as to maintain a general body equilibrium; his ingesta of
all kinds are balanced by the corresponding excretions, and the
individual maintains a practically constant body-weight.

Complete Balance Experiments — Respiration Chamber. —
According to the statements made in the last paragraph, it is obvious
that if the analytical work is properly done, an exact balance may
be drawn between the proteins, fats, and carbohydrates eaten as
food and the proteins, fats, and carbohydrates destroyed in the
body as represented by the nitrogen and carbon contained in the
excreta. Complete experiments of this kind were attempted first
by Voit * and Pettenkofer, to whose work much of our fundamental
knowledge is due. In the experiments of these authors, made upon
men as well as animals, the total nitrogen of the urine and feces was
determined and the total quantity of CO2 given off from the lungs
was estimated. This last determination was made possible by
placing the individual in a specially constructed chamber or respi-
ration apparatus. Air was drawn through this room by means of
a pump. The total quantity of air passing through the room was
measured by a gasometer and definite fractions were drawn off
from time to time for analysis of its CO2. From the figures thus
obtained it was possible to estimate the entire CO2 given off during
the period of observation. Knowing the total nitrogen and carbon
eliminated, it is possible to estimate the amount of protein and
fat or carbohydrate destroyed in the body. If the carbon belong-
ing to the amount of protein metabolized is deducted from the total
carbon excreta, what is left represents either fat or carbohydrate
burnt in the body, and, knowing the amount of these materials
taken in the diet, it is possible to ascertain whether the correspond-
ing amount of carbon has all been excreted. By experiments of
* See Hermann's "Handbuch der Physiologic, " vol. vi., 1881.

GENERAL METHODS — HISTORY OF PROTEIN FOOD. 811

this kind a nearly perfect balance may be struck between the in-
come and the outgo of the body. Absolute accuracy is not sought
for, since the materials eaten vary somewhat in composition and
some little of the carbon or nitrogen excreted is found in the secre-
tions from the skin, the saliva, etc., which are not usually examined.

More recent experiments made in this country under the direc-
tion of Atwater* have attempted to balance not only the material
income and outgo of the body during a given period, but also the
income and outgo of energy. For this purpose the individuals ex-
perimented upon were placed in a very carefully constructed respi-
ration chamber so that their expired air could be analyzed as well
as the urine and feces. The chamber, however, was also arranged
to act as a calorimeter (see p. 855) by means of which the heat given
off by the person could be measured. The heat value of the diet
being known, it is possible in this way to ascertain whether or not
this theoretical amount of heat is actually given off from the body.
Atwater's respiration chamber is described as a respiration calorim-
eter; some of the results obtained from its use are referred to later on.

The Effect of Non-protein Food on Nitrogen Equilibrium. —
By use of the methods referred to above the general influence of
the non-protein foods (fats, carbohydrates, albuminoids) upon the
protein consumption of the body has been made evident. An ani-
mal may be brought into nitrogen equilibrium on protein food alone,
the amount of protein required being relatively large. If now
non-protein foodstuffs are added to the diet it is found that the
amount of protein necessary to maintain nitrogen equilibrium may
be reduced correspondingly. With reference to the consumption
of protein in the body the non-protein foods are all protein-spar ers,
and herein lies one great peculiarity of their nutritional value.
On a mixed diet of protein and non-protein food the proportion of
the latter may be increased and that of the former decreased to a
marked extent without breaking down nitrogen equilibrium —
that is, without causing a loss of protein tissue from the body.
This fact is explained by the consideration that the protein of our
food fulfills two general functions : Its oxidation furnishes energy,
especially heat energy to the body, and, moreover, a portion of it
is used to reconstruct the living protoplasm which breaks down in
the functional activity of the tissues. The non-protein food also
furnishes heat energy and work energy, and can replace this part
of the function fulfilled by the protein.

The Nutritive History of the Protein Food. — The digestive
changes undergone by protein and its subsequent absorption have
been described in the section on Digestion. It will be remembered
* Atwater, Bulletins 45, 63, 69, United States Department of Agriculture.

812 NUTRITION AND HEAT REGULATION.

that the products of protein digestion are absorbed mainly into the
blood-vessels of the intestine, and therefore must pass through the
liver before reaching the general circulation. It will also be remem-
bered that we are as yet ignorant of the precise form in which these
products enter the portal blood. This deficiency in our knowledge
constitutes a serious obstacle to a satisfactory explanation of the
nutritional history of the protein. Three general views have been
advanced concerning the ultimate fate of the absorbed material.
In two of these theories it is assumed that the digested material is
synthesized into a new protein, before or after absorption, being
converted into what we might call a body protein characteristic of
the animal. Although it is not specifically stated, the assumption
seems to be that this body protein is the serum-albumin of the
animal's blood.

Accepting this general assumption, one theory, advocated by
Pfliiger, supposes that before undergoing physiological oxidation
all of this absorbed material is built up into the living protoplasm
of the various tissues and then undergoes the characteristic metab-
olism (catabolism or disassimilation) of that tissue.

The second theory, advanced by Voit, assumes that some of the
absorbed material is assimilated to form living protoplasm, so far
as this is necessary to replace the wastes of the tissue or to provide
new material for growth. The portion of the absorbed protein
that subserves this function is designated as tissue protein. It is
obvious that this function cannot be replaced by the non-protein —
that is, the non-nitrogenous — foodstuffs. The larger portion of the
absorbed material, however, after distribution to the tissues is
destroyed, with liberation of heat, under the influence of the activity
of the living cells, but without actually becoming transformed into
living matter. The cells act toward this material as the yeast
cells do toward the sugar that they decompose into alcohol and
carbon dioxid. The portion of the protein that undergoes this fate
is designated as the circulating protein, on the hypothesis that it
enters the circulating liquids of the body, the blood, and lymph.

The third general point of view has not been formulated very
definitely, but represents perhaps the trend of modern investigation.
According to this theory, the split products of protein digestion,
the monamino- and diamino-bodies — leucin, tyrosin, arginin, etc. —
are not wholly built up into a new body protein. Some of the ma-
terial must be so synthesized, either in the intestine or in the tis-
sues, to provide material for the regeneration of the wastes of the
body, and it will be remembered that, as stated by Abderhalden
p. 729), there is some evidence that a portion of the protein mole-
cule during digestion is not broken up into the ultimate split prod-

GENERAL METHODS HISTORY OF PROTEIN FOOD. 813

ucts, but remains in the more or less complex form indicated by the
term polypeptid. This portion may serve as a nucleus for the
reconstruction of a body protein suitable for assimilation into the
living structure of the cells. On the other hand, it is known that
some of the split products of the digestion of protein — the am-
monia, the leucin, etc. — when circulated through the liver, give
rise to urea. Since the splk products of protein digestion are car-
ried at once to the liver, it is possible that this fate overtakes them,
and that the nitrogen contained in them is at once converted to urea
and prepared for elimination (see paragraph below on " The Inter-
mediate Stages in Protein Metabolism"), while the rest of the mole-
cule from which the nitrogen is thus removed is retained in the
body to be subsequently oxidized and to furnish heat energy. This
non-nitrogenous residue may first be converted to sugar or fat before
its final oxidation. The characteristic feature of this view is the
belief that a large part of the nitrogen of the protein food is promptly
converted to urea and is eliminated before becoming a part either
of the living protein or the circulating protein of the body. This
view is in harmony with the fact that the digestive enzymes are
adapted to split the protein molecule into what we may call its
ultimate products, the relatively simple amino-bodies, and moreover
that most of the protein food taken into our bodies reappears, so
far as its nitrogen is concerned, in a few hours as urea in the urine.

Folin * has called attention to the fact that the proportions
of the different nitrogen compounds in the urine vary with the
amount of protein food. Upon an average diet containing 16 to
17 gms. of nitrogen (100 to 106 gms. of usable protein) the urea
forms 87 to 88 per cent, of the total nitrogen of the urine, while when
the protein intake is reduced to 3 or 4 gms. of nitrogen the urea
forms only 61 to 62 per cent, of the total nitrogen of the urine. On
the other hand, the creatinin and the purin bodies (uric acid, xanthin,
etc.) are not diminished in amount with a decrease in the protein
food. He suggests, therefore, that the latter bodies, creatinin and
purin bases and perhaps a part of the other nitrogenous waste prod-
ucts, represent the waste of the breaking down of the living tissues,
the catabolism or wear and tear of the living machinery. The urea,
on the other hand, represents in large part that portion of the
protein food which, from the present point of view, is hydrolyzed
during digestion into split products and whose nitrogen is converted
to urea in the liver.

The Amount of Protein Necessary for Normal Nutrition —
Luxus Consumption. — As was stated above, nitrogen equilibrium
may be maintained on different amounts of protein food. It is
important, from a scientific and from an economic standpoint, to

* Folin, " American Journal of Physiology," xiii., 45, 66, and 117, 1905.

814 NUTRITION AND HEAT REGULATION.

determine the low limit for this equilibrium and to ascertain whether,
for the purposes of the best as well as the most economical nutrition,
this low limit is as good as or preferable to a higher amount of pro-
tein in the diet. Examination of the dietaries of civilized races
shows that, on the average, 100 to 120 gms. of protein are used
daily by an adult man. Voit gives 1 18 gms. of protein as the average
daily consumption. A variable portion of this amount passes into
the feces in undigested form, but we may assume that about 105
gms. are absorbed and actually metabolized in the body. Experi-
ments show, however, that a man may exist in good health upon
a much smaller amount per day, as little as 20 to 40 gms.,* provided
the non-protein portion of the diet is increased. The question is
whether the large excess of protein above what is actually necessary
for nitrogen equilibrium is beneficial to the body or is harmful, or
lastly is merely a waste, or, as the older physiologists called it, a
luxus consumption. The facts at our command at present are in-
sufficient to give a final answer to this question. On the pne side
we have the following facts: Some observers (Munk, Rosenheim),
from experiments made upon dogs, state that when a low protein
diet is maintained for some time the animals show a marked dis-
turbance in digestion and absorption, which may terminate in
death. The fact that mankind universally under the guidance of
the self-regulating appetite has adopted a high level of protein food
must also be given considerable weight. With our imperfect
knowledge of all the conditions it is dangerous to assert that this
outcome of the processes of natural selection is without important
significance. There is also the fact that in the modern treatment
of tuberculosis high feeding with proteins constitutes a factor to
which much importance is attributed. The inference seems to
be that such a diet increases the power of resistance of the tissues
toward invading micro-organisms. On the other side, we have the
evidence of numerous investigators, who have experimented upon
themselves, showing that a protein diet much smaller than that
ordinarily used suffices to maintain normal nutrition. Chittenden,
especially, in the careful work already referred to, has shown that
men in various walks in life, students, athletes, soldiers, may be
well nourished, without loss of strength or impairment of the feeling
of well-being, on a diet containing 30 to 50 gms. of protein instead
of 118 gms. These observers believe that the excess of protein
usually employed is undesirable in that it increases the amount of
injurious nitrogenous waste products, that it throws an unnecessary
amount of labor upon the excretory organs, and that it increases
the possibility of the formation of toxic products in the intestines
* Consult Chittenden, "Physiological Economy in Nutrition," New York,
1905, for discussion and literature.

GENERAL METHODS - HISTORY OF PROTEIN FOOD. 815

from putrefactive processes, etc. It may be said, however, that
although these experimenters have shown that normal conditions
may be maintained for six months to a year or longer upon a low
protein diet, they do not demonstrate satisfactorily that a larger
protein diet is actually attended by evil consequences.

The Intermediate Stages in Protein Metabolism. — The urea
found in the urine and in lesser amounts in the sweat and other
secretions may arise in two general ways: 1. As an end-product
of the digestive hydrolysis of the protein food. That is to say,
the protein material is split by the successive actions of the pepsin,
trypsin, and erepsin into products similar to those obtained by
the action of acids at high temperatures (acid hydrolysis). As a
result of this process the nitrogen appears in the form of ammonia,
monamino-acids, and the so-called diamino-bodies, such as arginin,
and we may suppose that in these forms it is carried to the liver.
In this organ the ammonia, as ammonia salts, is transformed into
urea. The monamino-acids, some of them, at least, are deamidized,
that is, their NH2 group is split off as ammonia which then is like-
wise converted to urea. The organic acid radicles left after removal
of the NH2 group may subsequently be oxidized through various
stages to carbon dioxid and water, or they may be synthesized to
form a carbohydrate body or possibly a fat, and thus be kept
temporarily as storage, although their eventual fate is to suffer
oxidation to carbon dioxid and water. Regarding the diamino-
compounds like arginin it is known that when this substance is
injected subcutaneously its nitrogen is excreted for the most part
if not entirely as urea. Since Kossel and Dakin have shown that
the liver especially contains a hydrolytic enzyme, arginase, which
is capable of splitting off the guanidin residue of arginin to form
urea, we may assume that the arginin formed during protein diges-
tion actually undergoes this fate. The process is represented by
the following equation :

NHC<NHCHCHNHCOOH + H*° " CO<2 + NH2(CH,),CHNH2COOH

NH(CH2)3CHNH2COOH 2

Arginin or guanidin diamino-valerianic acid. Urea. Ornithin or diamino-valerianic

acid.

The ornithin, in turn, may suffer deamidization, its (NH,) groups
being converted to ammonia and urea.

By these possible processes it is evident that much of the nitrogen
of the food may be excreted promptly as urea without entering at
any time into the formation of living protoplasmic tissue. It seems
clear also that so far as the protein undergoes these intermediary
changes its nitrogen constituent is without value to the body.
The body gets rid of the nitrogen and utilizes the balance of the
protein molecule as a source of heat energy or as material for the

816 NUTRITION AND HEAT REGULATION.

synthesis of its non-nitrogenous storage fuel. Fclin's estimations,
quoted above, showing that the urea of the urine rises and falls
promptly with the amounts of protein in the food, indicate that a
large part of the protein food undergoes this series of changes.
Since some of the nitrogenous food material must be actually
synthesized into living protoplasm, acting as a " tissue protein" in
Voit's sense, to make new tissue or to repair tissue waste, it follows
that a portion of the absorbed split products of digested protein
must undergo an entirely different process, but concerning the
intermediary steps of this process we have little or no knowledge.
From a quantitative standpoint it is probable that most of the
protein food in an average diet follows the history first described
and takes no part in the formation of tissue. 2. The urea of the
excretion may arise in the tissues at large from the breaking down
of the organized or living protein or of the protein material included
in the cell liquids. As has been stated in another vplace most of
the living tissues contain intracellular enzymes capable of causing
hydrolysis of the proteins. When the excised tissues are kept warm
but protected from the action of the bacteria they undergo self
digestion or autolysis. As a result of this process the protein
molecule is split into its constituent parts, which in general are the
same as those formed during digestion. Assuming that these
intracellular enzymes act in this way during life it is evident that
the fate of the split products may be the same as that described
above. The ammonia compounds are converted to urea by the
liver and quite probably by other tissues; the monamino-bodies
lose their NH2 group by a process of deamidization and the am-
monia compounds thus produced are in turn changed to urea, and
such compounds as arginin will probably under the influence of
arginase yield their nitrogen as urea. In the protein that undergoes
metabolism in the tissues, as well as in the protein of the food that
is metabolized before reaching the tissues at large, the urea is formed
by two general methods at least, by the intermediate production
of ammonia compounds and by the conversion of a guanidin residue.
For the sake of completeness a third method of producing urea in
the body may be added, namely, by being split off from uric acid.
This mode of origin is considered in the following paragraph.

The Intermediary Metabolism of the Nucleoproteins. — Nucleo-
proteins are taken in our food and likewise are found in the tissues
of the body. Their metabolism so far as the nuclein portion is
concerned gives rise to the formation of uric acid and the purin
bases. It will be remembered that in the urine we find some uric
acid and some xanthin and hypoxanthin. In the feces small
amounts may be detected of xanthin, hypoxanthin, adenin, and
guanin. These bodies all contain the purin group or radicle (see

GENERAL METHODS — HISTORY OF PROTEIN FOOD. 817

p. 777) and are closely related chemically. By hydrolytic processes
outside the body one may obtain their purin bases from nucleins
or nuclein acids, and inside the body the metabolic processes give
similar products. The histoiy of the intermediary metabolism
may be outlined as follows: When nucleoprotein is eaten the
nuclein is split off apparently by the action of the pepsin, the
protein portion then undergoing the digestive and metabolic changes
already described. The nuclein is not acted upon further by the
pepsin or trypsin, except that under the influence of the latter it is
rendered soluble possibly by an act of hydration.* Once within
the body the nuclein is submitted to the action of a series of enzymes
as follows: Under the influence of nuclease it is split with the
production of some of the purin bases, adenin, guanin. The amino-
purins so far as they are formed are converted to the corresponding
oxypurins by the action of a deamidizing enzyme. According
to Jones two such enzymes may occur in the body, namely, adenase
and guanase. Their action takes place as follows:

C6H5N5 + H,0 = C5H4N40 + NH3

Adenin. Hypoxanthin.

C6H5N50 + H20 = QH4NA •{-• NH,

Guanin. Xanthin.

The xanthin and hypoxanthin in turn are converted to uric acid
by the action of an oxidase, known as xanthinoxydase, and finally
the uric acid formed may in turn be partly split under the influence
of a special uricolytic enzyme so that part of its nitrogen is elimi-
nated as urea. Eventually, therefore, we may believe that the
nitrogen of the nuclein is excreted largely as uric acid and urea,
and to a smaller amount as xanthin, hypoxanthin, adenin, or guanin.
The proportion of the uric acid which is further split to form urea
varies in different animals (see p. 779). In man the proportion is
estimated at about one-half. Burian has given reasons for be-
lieving (see p. 779) that most of the purin nitrogen excreted arises
in the metabolism of the muscle, and represents presumably the
break down of organized structure. The action of the series of
enzymes just described seems adapted simply to remove the waste
nuclein with little corresponding profit to the body from the stand-
point of liberated heat energy. It is to be borne in mind, however,
that the activity of some of these enzymes, the nuclease, for example,
may be concerned in the synthesis of nucleins and nucleoproteins
within the body, a process about which at present little or nothing
is known.

It is usually believed that the creatinin of the urine is formed
from the creatin found in muscular tissue and that the latter is

*See Abderhalden and Schittenhelm, "Zeit. f. physiol. Chem.," 1906,
xlvii., 452.
52

818 NUTRITION AND HEAT REGULATION.

derived from a metabolism of the living muscular tissue, but no
entirely satisfactory demonstration of the correctness of these
views has been obtained (see p. 780). There is evidence to show
that increased muscular activity may be associated with an increased
formation of creatin.

The Specific Dynamic Action of Proteins. — This somewhat
indefinite term is used by Rubner to designate the fact that protein
foods seem to stimulate the metabolic processes of the body to a
greater extent than the fats or carbohydrates. This peculiarity
may be demonstrated, for instance, in the case of a starving animal
living upon its own substance and metabolizing a certain amount
of its tissues daily. The amount thus metabolized may be expressed
in terms of the heat production and it represents the minimal con-
sumption of material requisite for the maintenance of body-tempera-
ture. If this minimal daily consumption is expressed in calories
and the animal is given food containing the same amount of avail-
able energy the consumption of body material is not completely
covered, since the food leads to an increased total metabolism
which is especially marked in the case of proteins. Expressing the
minimal daily metabolism during starvation by 100, Rubner esti-
mates that the minimal amounts of the three foodstuffs requisite
to give a heat equilibrium would be for proteins 140.2, for fat 114.5,
and for sugar 106.4. The fact that protein food tends to increase
the total metabolism of the body has been explained by some
authors on the assumption that a greater amount of secreting and
muscular work is required for its digestion. The proteins are
retained for a longer time, for instance, in the stomach, and the
continued muscular movements of the organ involve, of course, a
consumption of tissue material. This explanation does not seem
to be entirely satisfactory and the term "specific dynamic action1'
expresses the view that the protein food actually stimulates the
tissues to a greater metabolism, in somewhat the same way as in
the case of increased muscular work. On the general basis of the
theory of protein metabolism given above, its specific dynamic
action would mean simply that the body stores protein with rela-
tive difficulty, either as so-called circulating protein or in the form
of glycogen or fat, so that in cases of abundant protein feeding a
greater portion of the material is promptly consumed. With abun-
dant feeding of fats or carbohydrates, on the contrary, a larger por-
tion of these substances is retained as storage in the form of body
fat or glycogen.*

Nutritive Value of Albuminoids. — The albuminoid most fre-
quently occurring in food is gelatin. It is derived from collagen

* For further discussion see Rubner, " Gesetze des Energieverbrauchs, 1902,
or Lusk, "Elements of the Science of Nutrition, Philadelphia, 1906.

GENERAL METHODS — HISTORY OF PROTEIN FOOD. 819

of the connective tissue. Collagen of bones or of connective tissue
takes up water when boiled and becomes converted into gelatin.
We eat gelatin, therefore, in boiled meats, soups, etc., and, besides,
it is frequently employed directly as a food in the form of table
gelatin. Collagen has the following percentage composition: C,
50.75 per cent.; H, 6.47; N, 17.86; O, 24.32; S, 0.6. It resembles
the protein molecule closely ih percentage composition, and it would
seem that the tissues might use it as they do protein for the for-
mation of new protoplasm. Experiments, however, have demon-
strated clearly that this is not the case. Animals fed upon albu-
minoids together with fats and carbohydrates do not maintain
nitrogen equilibrium. The final result of such a diet would be
continued loss of weight and malnutrition and death. Some light
is thrown upon the inability of the gelatin to act as a tissue fcrmer
from a consideration of the split products formed from it in hydro-
lytic cleavage. While it yields a number of the products usually
given by the proteins, there are others which are lacking, such as
cystein (thioaminopropionic acid), tyrosin (oxyphenylaminopro-
pionic acid), serin (oxyaminopropionic acid), and tryptophan (indol-
aminopropionic acid). On the hypothesis that proteins during
digestion are normally split more or less completely into their
constituent parts, and that the characteristic body-protein of the
animal is reconstructed synthetically by a new arrangement of these
groups, it is apparent that the gelatin, when used without protein,
may fail to furnish some of the groupings necessary to such a
synthesis. Gelatin is readily digested, gelatoses and gelatin
peptones and eventually some split products being formed; these
are absorbed and oxidized in the body, with the formation of
C02, H2O, and urea. Gelatin serves, then, as a source of energy
to the body in the same sense as do carbohydrates and fats. When
any one of these three substances is used in a diet, the proportion of
protein necessary for the maintenance of nitrogen equilibrium may
be reduced greatly. Actual experiments have shown that gelatin
is more efficacious than either fats or carbohydrates in protecting
the protein in the body. The relative value of fats, carbohydrates,
and gelatin in protecting protein from destruction in the body is
illustrated by an experiment reported by Voit: A dog weighing
32 kgms. was fed alternately upon protein and sugar, protein and
fat, and protein and gelatin, with the following result:

NOURISHMENT (GMS.) CALCULATED DESTRUCTION OF

MEAT. GELATIN. FAT. SUGAR. FLESH IN BODY (GMS.).

400 200 450

400 250 439

400 200 356

Practically, however, the use of gelatin in diets is restricted by its
unpalatableness when employed in large quantities. Whatever

820 NUTRITION AND HEAT REGULATION.

may be the physiological cause of this peculiarity, there seems to be
no doubt that when used largely in the diet both animals and
men soon develop such an aversion to it that it is necessary to dis-
continue its use. A number of observers have attempted to de-
termine experimentally just how far the protein of the food may
be replaced by gelatin without causing a loss of body-protein.
Munk states, from experiments upon dogs, that when about six-
sevenths of the nitrogen necessary to maintain equilibrium was given
in the form of gelatin, the animal could be kept in nitrogen equilib-
rium for a few days at least. Kaufmann * kept himself in nitrogen
equilibrium for a short time upon a diet in which no protein was
contained, all the nitrogen being supplied in the form of gelatin
together with small amounts of the amino-acids which are lacking
in the gelatin molecule (cystin, tyrosin, tryptophan).

* Kaufmann, "Pfliiger's Archiv f. d. ges. Physiol." 1905, cix., 440.

CHAPTER XL VIII.
NUTRITIVE HISTORY OF CARBOHYDRATES AND FATS.

The Carbohydrate Supply of the Body. — The available carbo-
hydrate material of the body consists of the glycogen found in the
tissues, especially in the liver (1 to 4 per cent, or more) and mus-
cles (0.5 per cent.), and the sugar formed from this glycogen and
present constantly in the blood to the amount of 0.1 to 0.15 per
cent. In addition it is believed that during starvation glycogen
or sugar may be made from the protein tissues of the body, and
possibly also from the body fat, although this latter source is
disputed. The supply of glycogen under normal conditions is
maintained chiefly 'by the carbohydrate food. As was explained
in the section on Digestion, the starches, sugars, gums, etc.,
which constitute the carbohydrate foodstuffs are eventually
absorbed into the blood as simple sugars, chiefly dextrose, but
probably also some levulose and galactose. These simple sugars
constitute the important glycogen formers. There is still some
difference of opinion as to whether all proteins are capable of
yielding glycogen to the body. Some physiologists believe that
after the nitrogen is split off to form urea, the non-nitrogenous
portion of the molecule may be converted to glycogen in the
liver. Others hold that only those proteins, such as egg-albu-
min, which contain a carbohydrate grouping in the molecule
are capable of yielding glycogen in the body.* The store of glyco-
gen in the body is about equally divided between the liver and the
muscular tissues, and it is estimated that in man each of these
depots may contain, at a maximum, about 150 gms. The regula-
tion of the supply of sugar to the blood is usually attributed to
the liver. This regulation is adjusted so that the percentage of
sugar in the blood is kept astonishingly constant, not only during
the conditions of ordinary living, but under such an abnormal con-
dition as prolonged starvation. It is assumed that this regulation
is effected mainly by an enzyme formed in the liver cells which
converts the glycogen to dextrose in proportion as the sugar of the
blood is used up by the tissues.

Regulation of the Sugar-supply of the Body. — This regula-

* See Pfliiger. in "Archiv f. die gesammte Physiologic," 96, 1, 1903, for
literature and discussion.

821

822 NUTRITION AND HEAT REGULATION.

tion is of the greatest importance to the body, since any distinct
increase in the percentage of dextrose in the blood, a condition
known as hyperglycemia, is followed promptly by glycosuria, that
is, the appearance of sugar in the urine. It has been suggested
that the regulation of the output of sugar from the liver is con-
trolled reflexly through the nervous system. Some evidence for
this view is found in the following facts: Bernard discovered (1855)
that a puncture of the medulla, made between the levels of origin
of the vagus and auditory nerves, causes the development of a
condition of glycosuria. This puncture, known as the "piqure"
or "sugar puncture," fails to cause glycosuria if the animal has been
starved previously so as to remove most of the glycogen from the
liver or if the splanchnic nerves have been cut. Moreover, stimula-
tion of various sensory nerve trunks, the vagus, for example, causes
the same phenomenon, and in human beings lesions of the central
nervous system may likewise develop a condition of glycosuria.
These results have been explained in two ways. The puncture or
sensory stimulation may act upon the vasomotor center of the
medulla, cause a dilatation of the blood-vessels in the liver, and
thus indirectly accelerate the output of sugar; or these stimuli may
act upon a distinct sugar-regulating center and through it augment
directly the conversion of glycogen to sugar in the liver. According
to this latter view the efferent fibers for the center reach the liver
via the splanchnic nerves. If such a nervous mechanism exists
it affords a suitable means for the adjustment of the supply of
sugar to the needs of the tissues, particularly the muscles. The
contractions of the muscles and the heart by exciting their contained
sensory fibers might be supposed to stimulate reflexly the sugar
center and thus provide an increased output of sugar in proportion
to the extent of the contractions (Pfluger). While this theory is
attractive, it has not yet received definite experimental proof.
It is certain, however, that by some means, chemical or nervous,
the supply of sugar from the liver is regulated, and that under
various unusual and pathological conditions this regulation is
broken down with the production of conditions of hyperglycemia
and glycosuria. It is interesting, from a physiological standpoint,
to recall that glycosuria may result temporarily from too great
an ingestion of carbohydrate food (see Alimentary Glycosuria,
p. 735). The liver in this case gets more sugar than it can convert
to glycogen, and an excess gets through into the general circulation.
From a medical standpoint most interest attaches to the cases of
glycosuria occurring under pathological and experimental con-
ditions.

Pancreatic Diabetes. — Some of the facts regarding this form
of diabetes are described on p. 755. The immediate cause of

CARBOHYDRATES AND FATS. 823

the diabetes is the increased percentage of sugar in the blood
(hypergly cemia) . This result finds its most probable explanation
in the view that the loss of the internal secretion of the pancreas
robs the tissues of their power to metabolize the sugar.

Diabetes Mellitus. — In this severe and usually fatal disease the
amount of sugar lost daily in the urine may be very large. In severe
forms of the disease practically all the carbohydrate of the food may
be eliminated in the urine in the form of sugar, and even when the
diet contains no carbohydrate, or during complete starvation, sugar
continues to be secreted in the urine in considerable amounts. In
these latter cases the sugar is supposed usually to have its source
in the proteins of the food or of the body, a view which is supported
by the fact that the amount of nitrogen and dextrose excreted in
the urine may exhibit a constant proportion to each other. The
ratio of dextrose to nitrogen (D : N) is given as 3.65 to 1.*
Special cases have been reported, however, in which the ratio
exceeded these figures. The general and specific symptoms observed
in diabetes mellitus closely resemble those observed upon dogs
suffering from pancreatic diabetes. It seems probable, therefore,
that in man the condition of diabetes may also be due in the first
place to some trouble in the pancreas which prevents it from giving
off its normal internal secretion. In addition to the sugar found
in the urine in diabetes this secretion may also contain considerable
amounts of the acetone bodies, namely, /2-oxybutyric acid, aceto-
acetic acid, and acetone. It is probable that these bodies rep-
resent intermediary products in the metabolism of the fats of the
body which escape oxidation.

Phlorhizin Diabetes. — Phlorhizin is a vegetable glucoside ob-
tained from the roots of certain trees — e. g., apple, pear. When
injected into an animal it causes a glycosuria which is temporary,
but which may be renewed by repeated injections. Examination
of the blood in this case reveals the fact that the percentage of
sugar is not increased, so that the immediate cause of the glycosuria
is different from that responsible for the diabetes of man or of
animals without the pancreas. A satisfactory explanation of the
action of the phlorhizin has not yet been obtained, but it would
seem that the drug acts in some way upon the kidney itself — that
is, the tissues of the body are probably still able to metabolize the
sugar, but the blood is continually depleted of this substance
through the kidney ; it leaks off through the kidney faster than it
can be utilized by the tissues. The evidence at hand seems to indi-
cate that the sugar (in part at least) exists in the blood in some
form of colloidal combination, and that under the influence of the
phlorhizin the kidney breaks up this combination and eliminates
* Lusk, "Elements of the Science of Nutrition," Philadelphia, 1906.

824 NUTRITION AND HEAT REGULATION.

the sugar.* From the above description one may conclude (Mac-
leod) that the sugar-regulating mechanism of the body may be
broken down in one of three general ways:

1. By an accelerated production of sugar in the liver (piqure
reflex stimulation).

2. By a loss of the power to metabolize the sugar on the part
of the tissues of the body (pancreatic diabetes — diabetes mellitus).

3. By the elimination of the sugar of the blood through the
kidney (phlorhizin diabetes).

The Intermediary Metabolism of the Carbohydrate in the
Body. — Eventually the carbohydrate of the body is oxidized in the
tissues with the formation of carbon dioxid and water. Much
uncertainty prevails, however, as to the steps and means by which
this oxidation is effected. * Reference has already been made to the
important fact that the internal secretion of the pancreas is neces-
sary to this process (p. 804). According to Cohnheim's experiments,
this secretion furnishes an activating substance which enables the
enzymes of the muscles and other tissues to attack the sugar. The
sugar is probably broken down and oxidized by the successive
action of a number of enzymes, with the formation, therefore, of
a number of intermediate products. Our knowledge at present
is not sufficient to warrant positive statements concerning the
exact nature of these intermediate processes. Two general points
of view have been advocated. According to some observers the
sugar molecule first undergoes a splitting process, and the split
products are subsequently acted upon by oxidases and converted
to carbon dioxid and water. The following steps have been sug-
gested, f First a cleavage to form lactic acid:

C6H1206 = 2(Q,H80S)

Dextrose. Lactic acid.

Then a second cleavage to form alcohol and carbon dioxid :
C3H6O? = CO2 + C,H5OH

Lactic acid. Ethyl alcohol.

The alcohol is then oxidized successively to acetic and formic acid
and finally to carbon dioxid and water. Others have assumed that
the sugar undergoes a series of oxidations, without preliminary cleav-
age, with the formation of such intermediate products as glycuronic
acid and oxalic acid, both of which are undoubtedly formed in the
body, since they are found in small quantities in the urine. A

* For more complete details and the literature see Macleod, "The Metab-
olism of the Carbohydrates " in "Recent Advances in Physiology/' London
and New York, 1906, and Lusk, loc. tit.'

t See Biichner and Meisenheimer, "Berichte d. deutsch. chem. Gesell-
schaft," 38, 620, 1905; and Stoklase, ibid., p. 664.

CARBOHYDRATES AND FATS. 825

series of oxidations may occur such as is represented in the following
formulas:

CH2OH COOH COOH COOH

(CHOH)4 (CHOH)4 (CHOH)4 COOH

COH COH COOH

Dextrose. Glycuronic acid. Saccharic acid. Oxalic acid.

We are certain at present only of the fact that the final products
are carbon dioxid and water — that is, complete oxidation products
— and that in some way the internal secretion of the pancreas is
essential to the process.

Functions of the Carbohydrate Food. — The general value of
the carbohydrate food to the organism may be considered under
three heads: (1) It furnishes a source of energy for muscular
work. It will be remembered that the glycogen of a muscle dis-
appears in proportion to the work done by the muscle, and indeed
prolonged muscular work, especially during starvation, may wipe
out quickly the entire store of glycogen in the body, in the liver as
well as in the muscles. It is usually believed, therefore, that the
oxidation of the sugar furnishes energy which by the machinery
of the muscles is utilized to do work, — that is, to cause muscular
contractions. It seems probable that under normal conditions this
material furnishes the main, if not the sole source of energy for
muscular work. (2) The oxidation of the sugar furnishes an im-
portant part of the constant supply of heat needed by the body.
Each gram of sugar on oxidation yields 4 Calories of heat, and,
since the carbohydrates form the largest part of our diet and are
easily oxidized in the body, they must be regarded as an especially
available material for keeping up the supply of animal heat. The
largest part of the energy liberated by the oxidation of sugar in the
muscles during contraction takes the form of heat, and even dur-
ing muscular rest the condition of tone is probably attended by a
constant oxidation of this material. (3) The oxidation of the sugar
protects the protein of the body. Attention has already been
called to the fact that an animal may be kept in nitrogen equilibrium
on a relatively small protein diet provided carbohydrates (or fats)
are also eaten. One may say, in fact, that as the carbohydrate food
is increased the protein food may be diminished, down to a certain
irreducible minimum. From the chemical composition of carbo-
hydrates it is evident that they alone cannot serve to build up
protoplasm. An animal fed on carbohydrate food alone, no
matter how abundant the supply, would eventually starve to death.
Within certain limits, however, the carbohydrates are protein
sparers; the energy provided by their oxidation keeps up the supply
of heat and enables the muscles and probably the other tissues to
function normally, and to this extent protects the living protein

826 NUTRITION AND HEAT REGULATION.

from consumption and enables us to reduce the protein material
in our diet. Experiments show, in fact, that carbohydrate is
more efficient as a sparer of protein than fat. An animal fed
on carbohydrates alone loses less protein from the body than when
kept on a fat diet containing the same amount of heat energy.
It would seem that the body must always have sugar to oxidize.
If this material is not furnished in the food it is obtained by breaking
down the body protein itself, as is indicated by the facts of diabetes
and also by the fact that even in prolonged starvation the sugar
contents of the blood are kept at a normal level. (4) Any excess
of carbohydrate, taken as food, beyond the power of the tissues
to store as glycogen may be synthesized to form fat. Nutritional
experiments, described below, leave no doubt that the fat of the
body may be formed from carbohydrate food. It is stated that the
fat of the body having this origin, so-called carbohydrate fat, is
of a more solid consistency than the fat derived from other sources.

Nutritive Value of Fats. — The fats of food are absorbed into
the lacteals chiefly as neutral fats, — the so-called chyle fat. They
eventually reach the blood in this condition, and are afterward in
some way oxidized by the tissues. The final products of their
oxidation are the same as when burnt outside the body —
namely, CO2 and H2O — and a corresponding amount of energy must
be liberated. Speaking generally, then, the essential nutritive
value of the fats is that they furnish energy to the body, and, from
a chemical standpoint, they must contain more available energy,
weight for weight, than the proteins or the carbohydrates. In a
well-nourished animal a large amount of fat is found normally in
adipose tissues, particularly in the so-called "panniculus adiposus"
beneath the skin, in the folds of the peritoneum, etc. Physi-
ologically, this body fat is to be regarded as a reserve supply of
nourishment. When food is eaten and absorbed in excess of the
actual metabolic processes of the body, the excess is stored in the
adipose tissue as fat, to be drawn upon in case of need — as, for
instance, during partial or complete starvation. A starving animal,
after its small supply of glycogen is exhausted, lives entirely upon
body proteins and fats; the larger the supply of fat, the more
effectively will the protein tissues be protected from destruction.
In accordance with this fact, it has been shown that when subjected
to complete starvation a fat animal survives longer than a lean
one. Our supply of fat is called upon not only during complete
abstention from food, but also whenever the diet is insufficient to
cover the oxidations of the body, as in deficient food, sickness, etc.

The Fate of the Fat in the Tissues.— The fat absorbed as
food may temporarily subserve several different purposes: (1) It

CARBOHYDRATES AND FATS. 827

may be oxidized with the formation of heat energy. (2) It may
be stored in the tissues as part of the body fat. (3) It may be
synthesized with other substances to form some more complex
constituent of the body, such as lecithin. (4) According to some
authors, it may serve under certain conditions as a source of sugar.
This latter suggestion is nof supported by convincing experiments.
The final fate of the fat in the body is, however, to be oxidized to
water and carbon dioxid. The nature of the processes involved
is not understood. It is generally believed, however, that the
first step is the splitting of the fat into fatty acid and glycerin
under the influence of the lipase found in so many of the tissues
of the body. The fat that lies in the storage tissues — skin, peri-
toneum, etc. — probably does not undergo oxidation in these places.
In times of need it is absorbed and distributed to the more active
tissues, and in this initial process of solution it is probable that a
regulative influence is exerted by the lipase as suggested by Loeven-
hart (see p. 681). That is, by its reversible action this enzyme
may control the output of fat to the blood, as the supply of sugar
in the blood is kept constant by the diastatic enzyme of the liver.
After the action of the lipase we can only say that oxidation
takes place, but through how many stages is not known. It seems
probable that the long carbon chain of the fats (stearic acid = CH3-
(CH.,)16COOH) is deprived in succession of its carbon atoms by
oxidation, with the formation of simple fatty acids, but little
positive evidence has been obtained of intermediate products.
Perhaps the most significant fact known bearing upon this point
is that under conditions which involve a large destruction of fat
in the body, as in starvation, fevers, and especially in diabetes,
/9-oxybutyric acid together with aceto-acetic acid and acetone are
excreted in the urine. These three substances are designated as
the acetone bodies, and their appearance in the urine makes the
condition known as acetonuria. The oxybutyric acid may be
regarded as the source of the other two, as may be inferred from
their formulas, ^-oxybutyric acid = CH3CHOHCH2COOH. By
oxidation this yields aceto-acetic acid, CH3COCH2COOH, and
this by loss of CO2 is converted to acetone, CH3COCH3. The
evidence seems to show that the oxybutyric acid arises from the
fats, and it represents possibly one of the simpler fatty acids formed
in the intermediate metabolism of the fats.

Origin of the Body Fat. — The views upon the origin of body
fat have undergone a number of changes in the last fifty or sixty
years, illustrating in an interesting way how development of our
experimental methods leads often at first to half-truths which are
corrected later by more extensive work. Dumas and others (1840)
held to the natural view that the fat of the body originates directly

828 NUTRITION AND HEAT REGULATION.

from the fat of the food. Liebig, applying his more exact methods,
demonstrated that in some cases at least this source is insufficient
to account for all the fat. The fat yielded by the milk of a cow
for instance, may be greater in quantity than the fat contained
in the food. He also pointed out that the fat of each species of
animal is more or less peculiar, the fat of the sheep having a higher
melting point than pork fat, and both differing in composition from
the fat taken as food. "In hay or the other fodder of oxen no
beef suet exists, and no hog's lard can be found in the potato refuse
given to swine." He was led to attribute the source of body fat
chiefly to the carbohydrate food, and this belief agreed well with
the experience of agriculturists as to the use of such foods in fatten-
ing animals for market. This view, in turn, was displaced by the
theory of Voit, supported by elaborate feeding experiments. Voit
believed that the fat of the body is formed mainly or entirely from
the protein of the food, the carbohydrate and the fat of the diet
being useful only to protect a part of this protein from oxidation.
Voit's experiments have been shown by Pfliiger to have been based
upon erroneous analyses of the meat used in his experiments. Voit
assumed that in this meat the ratio -Q- is equal to 1.34 to 1.37, while
Pfliiger showed that it is lower,* 1.33. The modern point of view
is that the fat of the body originates partly from the fat of the food,
particularly in carnivora, and partly from the carbohydrate of the
food, especially in herbivora, in whose diet this foodstuff forms
such a large part. Whether under any circumstances the pro-
tein food may also serve as a source of body fat is still an open
question, decisive experiments being lacking.

Origin of Body Fat from Food Fat. — The first proofs that
the food fats may be deposited as such in the fat tissues of the
body were obtained by feeding foreign fats to dogs and demon-
strating that these fats can afterward be recognized in the
tissues of the animals, t Linseed oil, rape-seed oil, and mutton-fat
were used in these experiments. Secondly, it has been made
probable by feeding experiments that the normal fat of the food
undergoes a similar fate. Thus, Hofmann used a dog weighing
26 kgms. and allowed it to starve until its weight was reduced to
16 kgms. It was then fed for five days on a little meat and large
quantities of fat. At the end of that time it was killed and analyzed.
The body contained 1353 gms. of fat, of which only 131 gms. could
have come from the protein used, assuming that this material
can serve as a fat former. Much of the fat found, therefore, was
probably derived from the fat of the food.

* Pfliiger, " Archiv f. die gesammte Physiologic," 51, 229, 1892, and 77,
521, 1899.

t Lebedeff, " Centralblatt f. die med. Wiss.," 8, 1881, and Munk, "Vir-
chow's Archiv, " 95, 407, 1884.

CARBOHYDRATES AND FATS. 829

Origin of Body Fat from Carbohydrates. — That the body
fat may have this origin has been made probable or certain by
feeding experiments. Thus, Rubner fed a dog (5.89 kgms.) for
two days on a diet of sugar, starch, and fat whose total carbon
content was equal to 176.6 gms. During this period the animal
excreted 87.1 gms. of carbon. There were retained in the body,
therefore, 89.5 gms. carbon. The fat fed, 4.7 gms., contained
(4.7 X 0.77) 3.6 gms. C. The total nitrogen excreted during this
period was 2.55 gms., which indicated a metabolism, therefore, of
16 gms. (2.55 X 6.25) of body protein. Making the improbable
assumption that all of the carbon of this protein was retained in
the body, this would account for 8.32 gms. C (16 X 0.52); so that
3.6 -r 8.32 or 12 gms. C might have originated from sources other
than the carbohydrate of the food, leaving, therefore, 89.5 — 12
or 77.5 gms. of C, which could have arisen only from the carbohy-
drate. This quantity of carbon could have been retained only as
glycogen or fat. Allowing for the greatest possible storage of
glycogen, 78 gms. or 34.6 gms. C, there would still remain 42.9 gms.
of C, which could have been retained only as fat. Numerous other
fattening experiments of different kinds have been made in which
it has been shown that the fat laid on by the animal could not be
accounted for by the fat of the food, nor by assuming with Voit that
it originated from the protein. The combined testimony of these
experiments have satisfied physiologists that the tissues can pro-
duce fat from sugar. The chemistry of the change is not understood
and cannot be imitated in the laboratory.

The Source of Body Fat in Ordinary Diets. — For the pur-
poses of demonstration the experiments made to prove the origin
of body fat from carbohydrate or the fat of food have made use
of abnormal diets and conditions. It would be a matter of practical
interest to ascertain whether upon normal diets the fat of the
body arises more easily from the fat or from the carbohydrate of
the food. While the question is one to which a positive answer
cannot be given, it seems to be probable that the result varies with
conditions and the nature of the animal. Experience seems to
show that carnivorous animals can be fattened more easily on a
fat diet, herbivora on a carbohydrate diet. In animals, like our-
selves, there is reason to believe that the carbohydrates are more
easily and more quickly destroyed in the body than the fats, and
that, therefore, the latter may be more readily deposited in the tis-
sues, although an excess of carbohydrate beyond the actual needs
of the body will also be preserved in the form of fat or glycogen.*

The Cause of the Deposit of Body Fat — Obesity. — Our
experience shows that individuals differ greatly in the ease with

* Consult Rosenfeld, 'Ergebnisse der Physiologic, " vol. i, part i, 1902.
Complete literature.

830 NUTRITION AND HEAT REGULATION.

which they form fat. Some upon relatively small diets form much
fat, while others remain thin in spite of the ingestion of large amounts
of food. Voit has indicated the general reason for this difference —
namely, that it depends upon the capacity of the body to destroy
food material. When food is supplied and absorbed in excess
of this capacity the excess is stored mainly as fat, and to a small
extent as glycogen or as new protein. A diet which will give such
an excess to one individual may in the body of another of the same
weight be all consumed. The oxidizing capacity of the body
differs in different individuals and some will lay on fat more readily
than others, because for them an excess of material is provided by
a relatively small diet. Fundamental differences of this character
in the properties of the protoplasm are frequently transmitted by
heredity through many generations. Those individuals who show
little tendency to lay on fat may be made to do so by largely in-
creasing the amount of food, or more certainly by altering the mode
of life. A sedentary life, absence of worry, etc., may lead to a
tendency of this kind, while a very active muscular life has the
opposite effect. Men who lead a very muscular life — farmers,
fishermen, etc. — are rarely disposed to accumulate fat to a notice-
able degree. So also the use of alcoholic beverages may indirectly
favor accumulation of fat, partly because the oxidation of the
alcohol protects the fats and carbohydrates from oxidation, and
partly also, perhaps, because long-continued use of alcohol may
depress the oxidizing capacity of the tissues. The tendency to
form fat may exhibit itself in some cases to such an extent as to con-
stitute an almost pathological condition. Obesity may be coun-
teracted by altering the mode of life, especially by taking much
muscular exercise, and by reducing the diet, so that the total amount
of calories represented do not exceed one-half to three-fifths that
recognized as the usual average (see p. 849). The diet for such
purposes should not only be reduced in amount, but should be as
free as possible from excess of fats and carbohydrates, consisting of
such material as eggs, fish, lean meat, salads, fruits, etc.*

Summary of the General Functions of Fat. — The general
functions fulfilled by the fats may be summarized briefly under
the following heads: (1) It provides a store of reserve food which
is used by the body in case of deficiency of food or complete starva-
tion. The fattening of hibernating animals before their winter
sleep and the humps of the camel give conspicuous examples of this
peculiarity. (2) By its oxidation in the body it furnishes a part
of the heat energy necessary to maintain the body temperature.
On account of its high combustion equivalent (1 gm. of fat yields
9.3 Calories) fat is very effective in this respect. Inhabitants

* For practical directions concerning the treatment of obesity by dieting
see Gautier, " L'alimentation et les regimes." Paris, 1904.

CARBOHYDRATES AND FATS. 831

of cold regions choose a diet rich in fat. (3) It is a protein saver.
Like the carbohydrate food, its oxidation protects the protein from
consumption. In starvation, therefore, the amount of protein
destroyed daily is smaller as long as any fat remains, and, under
ordinary conditions of life, the larger the amount of fat in the diet,
the less the amount of protein necessary to maintain the body
in nitrogen equilibrium. Experiments show that in this respect
the fat is not so effective as an equivalent amount of carbohydrate
food. The difference is referable to the greater difficulty of oxida-
tion of the fatty material, and, perhaps, also to the fact that the
necessary sugar which the body requires, even in starvation, is
obtained largely from the proteins when carbohydrates are lacking
in the diet.

CHAPTER XLIX.

NUTRITIVE VALUE OF THE INORGANIC SALTS AND
THE ACCESSORY ARTICLES OF DIET.

The Inorganic Salts. — The body contains in its tissues and
liquids a considerable amount of inorganic material. When any
organ is incinerated this material remains as the ash. If we omit
the bones, which are rich in mineral material, the average amount
of ash in the body amounts to about 0.1 per cent, of its weight.
It consists of chlorids, phosphates, sulphates, carbonates, fluorids,
or silicates of potassium, sodium, calcium, magnesium, and iron;
iodin occurs also, especially in the thyroid tissues. In the liquids
of the body the main salts are sodium chlorid, sodium carbonate,
sodium phosphate, potassium and calcium chlorid or phosphate.
In considering the organic foodstuffs weight was laid upon their
value as sources of energy, as well as upon their function in con-
structing tissue. The salts have no importance from the former
standpoint. Whatever chemical changes they undergo are not
attended by any liberation of heat energy — none at least of suffi-
cient importance to be considered. They have, however, most
important functions. They maintain a normal composition and
osmotic pressure in the liquids and tissues of the body, and by
virtue of their osmotic pressure they play an 'important part in
controlling the flow of water to and from the tissues. Moreover,
these salts constitute an essential part of the composition of living
matter. In some way they are bound up in the structure of the
living molecule and are necessary to its normal reactions or irrita-
bility. Even the proteins of the body liquids contain definite
amounts of ash, and if this ash is removed their properties are
seriously altered, as is shown by the fact that ash-free native pro-
teins lose their property of coagulation by heat. The globulins
are precipitated from their solutions when the salts are removed.
The special importance of the calcium salts in the coagulation of
blood and the curdling of milk has been referred to, as also the
peculiar part played by the calcium, potassium, and sodium salts
in the rhythmical contractions of heart muscle and the irritability
of muscular and nervous tissues. The special importance of the
iron salts for the production of hemoglobin is also evident without
comment. The nutritive importance of the salts in the diet has
been demonstrated by direct experiment.

832

INORGANIC SALTS, STIMULANTS, AND CONDIMENTS. 833

Fatal Effects of Ash-free or Ash-poor Diets. — Dogs have
been fed (Forster) upon a diet composed of ash-free fats and carbo-
hydrates, and meats which had been extracted with water until
the salts had been much reduced. The animals were in a moribund
condition at the end of 26 to 36 days. It is probable that they
would have lived longer if deprived of food entirely, with the excep-
tion of water, since the metabolism of the abundant diet provided
aided in increasing the loss of salts from the body. Lunin has
described experiments which indicate that some at least of our
salts must be provided for us in organic combinations such as are
found in plant and animal foods. In his experiments he found
that mice lived well on a diet of dried cows' milk. If fed, however,
on a diet containing the organic but ash-free constituents of milk,
• — namely, sugar, fat, and casein, — together with the extracted
salts of cows' milk, they died in 20 to 30 days.

The Special Importance of Sodium Chlorid, Calcium, and
Iron Salts. — Sodium chlorid occupies a peculiar position among
the inorganic constituents of our diet, in that it is the only one
which we deliberately add to our food. The other inorganic
material is taken unconsciously in our diet, but although sodium
chlorid exists also in our food in relatively large quantities we
purposely add more. It is estimated that the average man in-
gests from 20 to 30 gms. a day. This peculiarity is exhibited
also by many animals. The farmer provides salt for his stock and
wild animals visit the salt-licks constantly. Bunge has called
attention to the fact that among men and animals this desire for
salt is limited, for the most part at least, to those that use vege-
table food. From the accounts of travelers he shows that when
a purely animal diet is used there is no desire for salt ; but on a vege-
table diet there is a craving for it which may become very intense
and unpleasant when circumstances prevent its being obtained.
He offers an ingenious explanation for this relation. Most vege-
tables contain a large amount of potassium salts, and in the blood
these salts react with the sodium chlorid. Thus, if potassium
sulphate were added to the blood it would react with sodium
chlorid, giving some potassium chlorid and some sodium sulphate.
Both of these salts will be removed by the kidneys, since, except
in minute amounts, they are, so to speak, foreign to the blood.
This latter liquid will thereby lose some of its supply of sodium
salt, whence the craving for more in the food.* Whether or not
this explanation is correct, the fact which it seeks to account for
seems to be well established. It can not be doubted, however, that
under ordinary conditions we use salt in quantities much larger than

* For an interesting discussion, see Bunge, " Physiologic des Menschen, "
vol. ii, p. 103, 1901.
53

834 NUTRITION AND HEAT REGULATION.

is necessary to maintain the sodium chlorid content of the blood.
It is employed as a condiment for its pleasant flavor, and it is
possible that its use is often carried to excess. This is a matter of
practical dietetics concerning which at present we have no satisfac-
tory experimental data to base a judgment upon.

The calcium salts of the body play a most important role in
connection with the irritability of muscle and nerve (p. 520).
They are also of obvious importance in furnishing material for
the growth of the skeleton. Their importance in this regard has
been demonstrated by feeding experiments. Young dogs when
given a diet poor in calcium salts fall into a condition resembling
rickets in children, owing to a deficient growth of the bones. Pig-
eons also, when fed upon a similar diet, exhibit an atrophy and
fragility of the bones due doubtless to the lack of calcium salts.
As in the case of the other food materials, there must be a definite
calcium metabolism in the body. It is probable, indeed certain,
that most of the calcium salts ingested simply pass through the
body without entering into its structure. They are eliminated
unchanged or unused in the feces or urine. A small portion, how-
ever, must be absorbed and used and a corresponding amount must-
be eliminated as a true waste product of tissue metabolism. Voit,
by experiments upon isolated loops of the intestine, has shown
that some calcium is constantly eliminated from the inner surface
of the intestine. The amount is small, not exceeding perhaps 0.15
to 0.16 grams per day. There is some evidence that the amount
of calcium in the tissues increases with age. This is certainly
true of the bones, which become exceedingly brittle in advanced
life.

The iron salts that are constantly necessary for the production
of new hemoglobin are provided in our food, in which they exist
in organic combination. The value of the food in this respect
varies greatly, as may be seen from the following table selected
from Bunge's analysis :

100 grns. of dry substance contain iron in milligrams, as follows :

White of egg trace Apples 13

Rice 1 to 2 Cabbage (green leaves) ... 17

Wheat flour (bolted) . . 1.6 Beef 17

Cows' milk 2.3 Asparagus 20

Potatoes 6.4 Yolk of egg 10 to 24

Peas 6.2 to 6.6 Spinach 33 to 39

Carrots 8.6

In conditions of malnutrition, particularly in the simple anemias,
it becomes necessary to select a diet with reference to its contents
in iron or to add iron deliberately to the diet. Therapeutically
iron may be given in the form of simple salts with organic or mineral
acids or in more complex organic combination. There has been
much controversy as to whether the body is capable of taking

INORGANIC SALTS, STIMULANTS, AND CONDIMENTS. 835

the iron in inorganic form and synthesizing it into a molecule so
complex as that of hemoglobin. Experience, however, seem to
show that this is possible, although under normal conditions at
least our iron is used in organic form. Bunge first isolated such a
compound, a nucleo-albumin containing iron, which he prepared
from the egg yolk and called hematogen. This compound must
serve as the source of the hemoglobin in the developing chick.
When the diet is directed especially toward increasing the iron
food it would seem to be wiser to choose these compounds, or, better
still, the iron-rich foods, rather than medicinal preparations of
the inorganic salts. The daily excretion of iron from the body
takes place in the feces rather than in the urine. The experiments
of Voit upon isolated loops of the intestine, referred to above, show
that iron is eliminated from the walls of the intestine. The whole
history of the metabolism of iron in the body is surrounded by
much uncertainty. After absorption its synthesis to hemoglobin
takes place, as to its final stages, in the red marrow, but it is possible
that other organs may take part in the formation of intermediate
products. As regards its elimination, we know that the breaking
down of the hemoglobin (formation of bile pigments) occurs prob-
ably in the liver, but the final excretion of the iron takes place
mainly through the walls of the intestine.

Accessory Articles of Diet. — Under this general term we may
include all those bodies classed as condiments, flavors, and stimu-
lants, which we habitually take in our diet in order to enhance the
attractiveness of the food. These substances may or may not
have some heat value to the body — that is, they may undergo
oxidation with the liberation of heat energy; but, in general, their
value in nutrition is due to other properties.

The Flavors and Condiments. — Perhaps the most important
influence exerted by these bodies is that by making the food appe-
tizing they increase the secretion of gastric juice. The origin of
the so-called psychical secretion has been described (p. 689), and
there can be little doubt that the palatableness of food influences
greatly the facility with which its gastric digestion is accomplished.
It is said, in fact, that dogs will refuse to eat food that has been
deprived entirely of its sapidity and flavor, preferring rather to
starve. Some of these substances (pepper), as also the stimulants
(alcohol), may have an additional value in that they increase the
rapidity of absorption from the stomach. Gautier divides the
condiments into the following classes: (1) Aromatics, comprising
vanilla, anise, cinnamon, nutmeg, and other similar essential oils.
(2) Peppers. (3) The alliaceous condiments, — garlic, mustard,
etc. (4) The add condiments, — vinegar, citron, pickles, etc. (5)
The salty condiments, such as table salt. (6) The sugar condiments.

836 NUTRITION AND HEAT REGULATION.

The Stimulants. — Under this head we include alcohol, tea, coffee,
chocolate, or cocoa, and meat extracts (beef tea, etc.). Regarding
the last mentioned substance, its physiological value has been made
clear by the work of Pawlow (p. 709). Meat extracts of various
kinds contain secretogogues which stimulate the gastric glands to
secretion. In themselves they may contain very little actual
foodstuff. Liebig's extract contains some protein, gelatin, and gly-
cogen, which form an actual nourishment, but its specific value
as a gastric stimulant depends upon other constituents, possibly the
nitrogenous extractives, — creatin, xanthin, carnin, etc. Coffee
and tea owe their well-known stimulating action to the presence
of an alkaloid, caffein or trimethyl-xanthin. It may be considered
as xanthin in which three of the hydrogen atoms have been re-
placed by methyl (CH3) groups, as is indicated in the following
structural formulas:

HN— CO CH3N— CO

CO C— NH CO C— N<CH3

\PTT I || ^CH

//^' CH3N— C— N

HN-C— N

Xanthin. Caffein.

This alkaloid has a diuretic action on the kidneys and a stimulating
effect on the nerve centers, as is illustrated by its effect in raising
blood-pressure by an action on the vasoconstrictor center. The
influence of tea and coffee in preventing sleepiness may be referred,
to this action on blood-pressure. The use of these substances,
according to general experience, augments muscular energy and
diminishes the sense of fatigue. Cocoa, or the chocolate made
from it by the addition of sugar, contains considerable nourish-
ment in the form of fats, carbohydrates, and proteins, but its stimu-
lating effect is referred to the alkaloid theobromin or dimethyl-
xanthin, and to some extent possibly to the essential oils developed
in roasting. The theobromin exerts stimulating effects similar to
those of the caffein. The methylxanthins are in part oxidized in
the body and in part (one-third) excreted in the urine.

Alcohol. — The physiological effects of alcohol are of peculiar
interest to mankind, owing to its widespread use, and especially
to the disastrous results following its intemperate consumption.
Those who employ it in excess are in danger of acquiring an alco-
holic thirst or habit toward which the body possesses no counter-
acting regulation. When food is eaten in excess we experience a
feeling of satiety which destroys the desire for more food, and the
same regulation prevails in the case of water. With alcoholic
drinks, however, the desire may continue long after the alcohol
taken has begun to exert an injurious action upon the tissues.
The evil effects of excessive use of alcohol are so continually demon-

INORGANIC SALTS, STIMULANTS, AND CONDIMENTS. 837

strated upon man that there is no need for experimental investi-
gations to establish this fact. Pathological examination of the
tissues in the case of confirmed drunkards has demonstrated the
existence of definite lesions in many of the organs, — stomach,
liver, heart, nervous system, — and have shown that under these
conditions it acts as a tissue poison.* This result is exhibited
not only in cases of chronic alcoholism in which these lesions
have developed gradually, but also in cases of acute alcoholism
resulting from excessive doses. On the other hand, it is known
that many individuals use alcohol in moderate doses throughout
life with no noticeably evil result, but, on the contrary, with possible
benefit, particularly in advanced life. The matter of practical
importance and interest is to determine the physiological role of
moderate doses of alcohol. Does it serve a useful purpose, acting
as a food or stimulant, or is it a poison in all doses to a greater or
less extent ? The literature upon the subject is very large and
in many respects conflicting. Only a brief summary can be
attempted here. Regarding its stimulating action the general
experience of mankind attributes a result of this kind to its use
in small quantities. It confers a sense of well-being and an in-
crease in mental and muscular activity, although these good effects
may be quickly overstepped by too great a dose. Specific researches
have been made to show that the alcohol may decrease the reaction
time and increase the rapidity and amount of the muscular
contractions. On the heart and blood-vessels alcohol in small
quantities appears to have no positive effect of a stimulating
character. It is known that even in small doses it causes a dilata-
tion of the skin vessels, giving a feeling of warmth and leading to
increased loss of heat ; but whether this effect is due to a stimula-
tion of the vasodilator centers or, as seems more probable, to a
narcotic or depressing action upon the vasoconstrictor centers has
not been definitely demonstrated. Some observers obtain results
which indicate that alcohol decreases the efficiency of the neuro-
muscular apparatus and acts in all doses as a sedative or paralyzant
rather thanf as a stimulant. It has been suggested that as regards
the higher nerve centers its apparent stimulating effect may be due
in reality to a paralysis of inhibitory centers, thus removing control
and restraint and leading to freer mental action. The experience
of explorers bears out the general view that under conditions of
stress and excitement alcohol is of little value as a stimulant. What-
ever action it has in this direction is temporary. After the day's

* See Welch, "The Pathological Effects of Alcohol," in "Physiological
Aspects of the Liquor Problem," vol. ii, 1903.

t For literature and discussion see Abel, " The Pharmacological Action of
Alcohol," in "Physiological Aspects of the Liquor Problem," vol. ii, 1903.

838 NUTRITION AND HEAT REGULATION.

work is done, however, or in conditions of mental depression the
use of alcohol may remove the sense of fatigue and exhaustion
and lead to a sense of well-being. The most important work of
recent years has been directed toward determining the nutritive
value of alcohol. Does it function under any circumstances as a
food? Much depends in such a discussion upon the meaning of
the terms used. In the present brief statement it is to be under-
stood that by food is meant material which can be oxidized in
the body with the production of usable energy, but without in-
jurious effect upon the tissues, and moreover a material whose
consumption protects some of the other foodstuffs — fats, carbo-
hydrates, and protein — from destruction. In the first place, there
is no doubt that alcohol is oxidized in the body. Various observers
estimate that as much as 90 to 98 per cent, of the alcohol absorbed
is destroyed.* Since 1 gm. of alcohol, when burnt, yields 7 calories
of heat, it is evident that its oxidation in the body must yield a
large supply of heat energy. The question arises whether this
oxidation of the alcohol occurs in addition to the normal metab-
olism of the protein and non-protein foodstuffs, or whether it pro-
tects and takes the place of these foodstuffs. With regard to the
non-proteins a number of observers have attempted to determine
the point by ascertaining the total carbon excretion during an
alcohol period. If the usual amount of material is burnt, and the
alcohol in addition, it is evident that the carbon excretion should be
markedly increased. Most observers, however, find that it re-
mains practically the same. Such results as the following have
been obtained:

, , ,. , f Alcohol-free days. . 251.9 ems. carbon.

Atwater and Benedict ( Alcohol dayg > ^3^ * „

— 13.4 "

-P • / Alcohol-free days . . 212.58 gms. carbon.
^jerie \Alcoholdays 220.84 "

-f 8.26 "

n, f Alcohol-free days. . 214.83 gms. carbon.
C1°Patt -\Alcoholdays 220.87 "

+ 6.04 "

These results indicate that the alcohol is used by the body in place
of the other carbon-containing foodstuffs. Geppert and Zuntz have
also found that on alcohol days there is no material increase in
the carbon dioxid eliminated or the oxygen absorbed.

Theoretically if the alcohol takes the place of the other material the
amount of carbon dioxid excreted should be diminished. One gram of
alcohol when oxidized furnishes as much heat as 1.7 gms. of sugar or 0.75 gm.
of fat. But 1 gm. of alcohol when burnt yields only 1.91 gms. of CO2, while
1.7 gms. of sugar yield 2.77 gms. CO2, and 0.75 gm. of fat, 2.13 gms. of CO2.

* See Atwater and Benedict, Bulletin 69, United States Department of
Agriculture, 1899.

INORGANIC SALTS, STIMULANTS, AND CONDIMENTS. 839

If fat were replaced by the alcohol the amount of CO2 should be reduced
about 10 per cent., while if the sugar were replaced the reduction should
amount to 31 per cent. That such a reduction is not actually observed is
explained by the fact that the alcohol leads to more muscular activity and
a greater loss of heat from the congested skin, thus indirectly augmenting
the oxidations of the body.

To determine whether the combustion of the alcohol protects the
protein material from metabolism to the same extent as is done by
carbohydrates and fats, experiments have been made in which the
individual was brought into nitrogen equilibrium on a mixed diet.
Then for a given period a portion of the carbohydrate was omitted
and alcohol in isodynamic amounts was substituted. The result
was an increase in the nitrogen excretion, showing that the alcohol
did not protect fully the protein tissue. In a third period the
first diet was resumed, and after nitrogen equilibrium had again
been established the same proportion of carbohydrate was omitted
from the diet, but this time alcohol was not substituted. If the
diet was poor in protein it was found that less protein was lost from
the body when the alcohol was omitted than when it was used.
Hence alcohol not only did not take the place of the carbohydrate
in protecting the protein, but it actually caused an increased pro-
tein consumption.* Other observers (Neumann, Rosemann f) have
found that, although the effect just described may occur in the first
few days, yet if the alcohol diet is maintained the injurious effect
exercised by it disappears, the body ceases to lose its protein tissue,
and may even lay on protein. These results, taken with those
given above, indicate, therefore, that the alcohol may actually
take the place physiologically of fat or carbohydrates as a source
of energy and as a protector of protein metabolism. J Under these
circumstances, therefore, it acts as a true foodstuff. It is perhaps
scarcely necessary to emphasize the fact that this scientific con-
clusion does not mean that alcohol can be regarded as a prac-
tical food. Its expensiveness, its dangers when the dose is too
large, etc., prevent us from regarding it in this light. As Rosemann
says, however, it is possible that on account of its ready absorption
and palatableness it may form a useful substitute for the solid,
non-nitrogenous foodstuffs in sickness. This suggestion seems
to be supported by many reports of cases in which alcohol has served
as the sole or main nutriment during the critical periods of fevers
and in other conditions, but it needs to be tested more carefully by
direct experiments before it can be accepted generally for prac-
tical purposes.

*See Miura, " Zeitschrift fur klin. Medicin," 20, 1892.

t See Rosemann, " Archiv f. die gesammte Physiologic, " 86, 307, 1901,
and 100, 348, 1903, for discussion and literature.

t See also At water and Benedict, " Memoirs of National Academy of
Sciences," 1902; and Atwater, "The Nutritive Value of Alcohol, " in " Physi-
ological Aspects of the Liquor Problem," vol. ii, 1903.

CHAPTER L.

EFFECT OF MUSCULAR WORK AND TEMPERATURE ON

BODY METABOLISM— HEAT ENERGY OF

FOODS— DIETETICS.

The Effect of Muscular Work. — It is a matter of common
knowledge that muscular exercise increases the food consumed,
and scientific experiments have shown that it greatly augments
the consumption of material in the body. Physiologists have
attempted to determine which of our energy-yielding foodstuffs
is directly affected by muscular activity. A brief statement of
the development of our knowledge upon this point will make clear
our present theories. According to Liebig, our foods fulfill two
general purposes in the body : they are burnt to supply heat, respira-
tory foods — fats, and carbohydrates, or they are used to construct
tissue, plastic foods — proteins. It seemed to follow, from this
generalization, that muscular tissue in activity should use protein
material, and it was believed at that time that the metabolism of
protein furnished the source of muscular energy. That it is not
the sole source was demonstrated by the interesting experiments
of Fick and Wislicenus. These physiologists ascended the Faul-
horn to a height of 1956 meters. Knowing the weight of his body,
each could estimate how much work was done in ascending such
a height. Fick's weight, for example, was 66 kilograms; therefore
in climbing the mountain he performed 66X1956=129,096 kilo-
grammeters of work. In addition, the work of the heart and the
respiratory muscles, which could not be determined accurately,
was estimated at 30,000 kilogrammeters. There was, moreover,
a certain amount of muscular work performed in the move-
ments of the arms and in walking upon level ground that was
omitted entirely from their calculations. For seventeen hours
before the ascent, during the climb of eight hours, and for six
hours afterward their food was entirely non-nitrogenous, so that
the urea eliminated came entirely from the protein of the body.
Nevertheless, when the urine was collected and the urea estimated,
it was found that the energy contained in the protein destroyed,
reckoned as heat energy, was entirely insufficient to account for
the work done. Although later estimates would modify somewhat
the actual figures of their calculation, the margin was so great that

840

EFFECT OF MUSCULAR WORK AND TEMPERATURE. 841

the experiment has been accepted as showing conclusively that the
total energy of muscular work does not come necessarily from the
oxidation of protein. Later experiments made by Voit upon a
dog working in a tread-wheel and upon a man performing work
while in the respiratory chamber gave the surprising result that
not only may the energy of muscular work be far greater than the
heat energy of the protein simultaneously oxidized, but that the
performance of muscular^ work within certain limits does not
affect at all the amount of protein metabolized in the body, since
the output of urea is the same on working days as during days of
rest. Careful experiments by an English physiologist, Parkes, made
upon soldiers, while resting and after performing long marches,
showed also that there is no distinct increase in the secretion of urea
after muscular exercise. It followed from these latter experiments
that Liebig's theory as to the source of the energy of muscular
work is incorrect, and that the increase in the oxidations in the
body, which undoubtedly occurs during muscular activity, must affect
only the non-protein material — that is, the fats and carbohydrates.
Subsequently the question was reopened by experiments made
under Pfliiger by Argutinsky.* In these experiments the total
nitrogen excreted was determined with especial care in the sweat
as well as in the urine and the feces. The muscular work done
consisted in long walks and mountain climbs. Argutinsky found
that work caused a marked increase in the elimination of nitrogen,
the increase extending over a period of three days, and he estimated
that the additional protein metabolized in consequence of the work
was sufficient to account for most of the energy expended in per-
forming the walks and climbs. A number of objections have been
made to Argutinsky's work. It has been asserted that during his
experiment he kept himself upon a diet deficient in non-protein
material, and that if the supply of this material had been sufficient
there would not have been an increase in protein metabolism.
These experiments were repeated in various forms by many ob-
servers (Zuntz, Speck, et a/.), and the general result has been
the abandonment of both the former views — the Liebig theory,
that the energy comes only from the consumption of protein, and
the Voit theory, that it comes only from the oxidation of non-pro-
tein material. It has been found that in muscular work carried to
the ordinary extent protein material, in excess of that destroyed in
conditions of rest, may or may not be used according to the amount
of fats and carbohydrates contained in the diet. If these latter
elements are in sufficient quantity they furnish the energy required,
and the protein metabolism is not increased by work. If, however,

* Argutinsky, "Pfliiger's Archiv f. die gesammte Physiologie, " 46, 552,
1890.

842 NUTRITION AND HEAT REGULATION.

the non-proteins are not sufficient in quantity some of the energy
is obtained at the expense of the protein of the body, and there is
an increase in the nitrogen excretion. We may believe, in fact,
that the energy necessary for muscular work may be obtained from
any of the heat-yielding foodstuff — carbohydrates, fat, or proteins.
It seems probable that the sugar (glycogen) of the muscle is, so to
speak, the easiest source; but, when the carbohydrates are deficient
or absent altogether in the diet, muscular exercise is accompanied
by an increase in the consumption of proteins or fats or both. The
Voit theory is correct to the extent that on an abundant non-protein
diet much muscular work may be done without any increase in the
consumption of protein tissue. The muscle is a protein machine
for the accomplishment of work, and the fuel supplied may be pro-
tein or non-protein, but in the accomplishment of moderate work
there is apparently no greater wear and tear of the machinery, no
greater tissue waste, than under resting conditions. If, however,
the muscular work is excessive, the tissue waste may be increased.
Argutinsky found an increased nitrogen elimination lasting two or
three days after the cessation of the work. It is probable that this
result indicates a greater waste of the protein apparatus itself, and
this idea is borne out by the fact that under similar conditions
other observers have detected an increase in the creatinin and
uric acid excretion, nitrogenous wastes that are derived from
muscle. The effect of muscular work on the carbon excretion, car-
bon dioxid, is, of course, marked and invariable. Some extra ma-
terial must be oxidized to furnish the energy, and since this material
is usually sugar, or sugar and fat, or the non-nitrogenous portion
of the protein of the diet, the effect, so far as the excretions are con-
cerned, will be most manifest in the amount of carbon dioxid
given off. Pettenkofer and Voit found that the carbon dioxid
eliminated by a man during a day of work was nearly double that
excreted during a day of rest. Along with this rise in the carbon
dioxid excretion there is a corresponding increase in the absorption
of oxygen.

Metabolism during Sleep.— It has been shown that during
sleep there is no marked diminution of the nitrogen excreted, and
therefore no distinct decrease in the protein metabolism; on the
contrary, the carbon dioxid eliminated and the oxygen absorbed
are unquestionably diminished. This latter fact finds its simplest
explanation in the supposition that the muscles are less active
during sleep. The muscles do less work in the way of contractions,
and, in addition, probably suffer a diminution in tonicity, which
also affects their total metabolism.

Effect of Variations in Temperature. — In warm-blooded
animals variations of outside temperature within ordinary limits

EFFECT OF MUSCULAR WORK AND TEMPERATURE. 843

do not affect the body temperature. An account of the means by
which this regulation is effected will be found in the chapter upon
Animal Heat. So long as the temperature of the body remains con-
stant, it has been found that a fall of outside temperature may
increase the oxidation of non-protein material in the body, the in-
crease being in a general way proportional to the fall in tempera-
ture. That the increased oxidation affects the non-protein con-
stituents is shown by the fact that the urea remains unchanged in
quantity, other conditions being the same, while the oxygen con-
sumption and the carbon dioxid elimination are increased. This
effect of temperature upon the body metabolism is due mainly to a
reflex stimulation of the motor nerves to the muscles. The tem-
perature nerves of the skin are affected by a fall in outside tempera-
ture, and bring about reflexly an increased innervation of the
muscles of the body. Indeed, it is stated * that unless the lowering
of the temperature is sufficient to cause shivering or muscular
tension no increase in the excretion of CO2 results. This fact suf-
fices to explain, therefore, the physiological value of shivering and
muscular restlessness when the outside temperature is low. The
fact that variations in outside temperature affect only the con-
sumption of non-protein material falls in, therefore, with the concep-
tion of the nature of the metabolism of muscle in activity, given
above. When the means of regulating the body temperature
break down from too long an exposure to excessively low or ex-
cessively high temperatures, the total body metabolism, protein
as well as non-protein, increases with a rise in body temperature
and decreases with a fall in temperature. In fevers arising from
pathological causes it has been shown that there is an increased
excretion of nitrogen as well as of carbon dioxid.

Effect of Starvation. — A starving animal must live upon the
material present in its body. This material consists of the fat
stored up, the circulating and tissue protein, and the glycogen.
The latter, which is present in comparatively small quantities, is
quickly used, disappearing more or less rapidly according to the
extent of muscular movements made. Thereafter the animal lives
on its own protein and fat, and if the starvation is continued to a
fatal termination the body becomes correspondingly emaciated.
Examination of the several tissues in animals starved to death has
brought out some interesting facts. Voit took two cats of nearly
equal weight, fed them equally for ten days, and then killed one to
serve as a standard for comparison and starved the other for thirteen
days; the latter animal lost 1017 gms. in weight, and the loss was
divided as follows among the different organs:

* Johannson, " Skandinavisches Archiv f. Physiologic," 7, 123, 1897.

844 NUTRITION AND HEAT REGULATION.

Loss TO

SUPPOSED WEIGHT ACTUAL Loss EACH 100 GMS.
OP ORGANS BEFORE OF ORGANS OF FRESH ORGAN
STARVATION. IN GMS. (PERCENTAGE Loss)

Bone 393.4 54.7 13.9

Muscle 1408.4 429.4 30.5

Liver 91.9 49.4 53.7

Kidney . . .' 25.1 6.5 25.9

Spleen 8.7 5.8 66.7

Pancreas 6.5 1.1 17.0

Testes 2.5 1.0 40.0

Lungs 15.8 2.8 17.7

Heart 11.5 0.3 2.6

Intestines 118.0 20.9 18.0

Brain and cord 40.7 1.3 3.2

Skin and hair 432.8 89.3 20.6

Fat 275.4 267.2 97.0

Blood 138.5 37.3 27.0

Remainder 136.0 50.0 36.8

According to these results, the greatest absolute loss was in the
muscles (429gms.), while the greatest percentage loss was in the fat
(97 per cent.), which had practically disappeared from the body.
It is very significant that the central nervous system and the heart,
organs which we may suppose were in continual activity, suffered
practically no loss of weight : they had lived at the expense of the
other tissues. We must suppose that in a starving animal the fat
and the protein materials, particularly in the voluntary muscles,
pass into solution in the blood, and are then used to nourish the
tissues generally and to supply the heat necessary to maintain the
body temperature. Examination of the excreta in starving ani-
mals has shown that a greater quantity of protein is destroyed dur-
ing the first day or two than in the subsequent days. This fact
is explained on the supposition that the body is at first richly sup-
plied with "circulating protein" derived from its previous food, and
that after this is metabolized the animal lives entirely, so far as
protein consumption is concerned, upon its "tissue protein." If
the animal remains quiet during starvation, the amount of nitrogen
excreted daily soon reaches a nearly constant minimum, showing
that a practically constant amount of protein (together with fat)
is consumed daily to furnish body heat, and probably to repair
tissue waste in the active organs, such as the heart. Shortly before
death from starvation the daily amount of protein consumed may in-
crease, as shown by the larger amount of nitrogen eliminated. This
fact is explained by assuming that the body fat is then exhausted
and the animal's metabolism is confined to the tissue proteins
alone. The general fact that the loss of protein is greatest during
the first one or two days of starvation has been confirmed upon men,
in a number of interesting experiments made upon professional
f asters. For the numerous details as to loss of weight, variations
of temperature, etc., carefully recorded in these latter experiments,

POTENTIAL ENERGY OF FOOD. 845

reference must be made to original sources.* It may be added, in
conclusion, that the fatter the body is to begin with, the longer will
starvation be endured, and if water is consumed freely the evil
effects of starvation, as well as the disagreeable sensations of hun-
ger, are very much reduced.

The Potential Energy of Food. — The food material during
digestion and after absorption undergoes numerous chemical changes
in the body. Some of these changes are not attended by the libera-
tion of heat to any marked extent. Such is the case, for instance,
with the hydrolytic cleavages of the molecule which have been
described especially in connection with the digestive processes.
Similar hydrolytic cleavages occur doubtless within the tissues,
and other changes connected with muscular, nervous, and glandular
activity, and the building up and breaking down of the living sub-
stance, take place constantly as a part of general nutritional metab-
olism. On the other hand, many of the chemical processes occur-
ring in the body are especially valuable on account of the heat
liberated. These reactions, for the most part, at least, are oxida-
tions ; they are effected under the influence of oxidizing enzymes or
by some other means of activating the oxygen. The various stages
in the process are not explained, but we know that oxygen is neces-
sary and that the carbon and the hydrogen contained in the sub-
stances acted upon appear eventually in the form of oxidation prod-
ucts— namely, carbon dioxid and water — Liebig designated the
fats and carbohydrates as respiratory foods on the hypothesis
that their fate in the body is to be oxidized and furnish heat. While
this view is, in the main, correct, it is evident now that a portion at
least of the protein molecule, after the splitting off of the nitrogen,
may also undergo oxidation and furnish heat. In Liebig' s sense,
therefore, the proteins play the part of respiratory or heat-producing
foods as well as acting as tissue formers. On the other hand, fats
and carbohydrate material may enter to some extent, together with
the protein, into the synthesis of living material, and thus play the
role of a plastic or tissue-forming as well as of a respiratory food.
We cannot divide the foodstuffs, therefore, strictly into two such
classes, but we may perhaps consider the chemical processes in
the body under the two heads mentioned above — namely, the oxi-
dation or heat-producing changes and those due to hydrolytic
cleavages, synthesis, etc., which are attended by a small liberation
of heat energy, or, indeed, may cause a loss of heat (synthesis).
The great supply of heat energy needed by the body to maintain its
temperature comes from the oxidation processes. This classifica-
tion is employed by some physiologists, and is helpful in empha-
sizing the fact that many chemical changes occur in the body that

* " Virchow's Archiv," vol. 131, supplement, 1893; and Luciani, "Das Hun-
gern," 1890. See also Weber, " Ergebmsse der Physiologic," vol. i, part i, 1902.

846 MJTRITION AND HEAT REGULATION.

are of no importance from the standpoint of heat production, and
that the changes that do give rise mainly to heat form, as it were,
a special group, which is not connected with the building up or
breaking down of the living matter, but furnishes the energy by
means of which these latter changes and perhaps other functions,
such as muscular work, are made possible. Roughly speaking, an
adult man forms in his body and gives off to the surrounding air
about 2,400,000 calories of heat per day. By calorie or small
calorie (c) is meant the quantity of heat necessary to raise 1
gm. of water 1° in temperature. This great supply of heat is derived
from the physiological oxidation of the carbohydrate, fat, and
protein material of the food. These same materials may be oxi-
dized outside the body by burning them at a high temperature or
under a high pressure of oxygen, and the heat that they give off in
the process can be measured directly. So far as the fats and carbo-
hydrates are concerned, the end-products of the oxidation in the
body are the same as in their combustion out of the body, and we
may believe, therefore, that the amount of heat produced is the
same in both cases. Consequently the heat value of a gram of fat
or carbohydrate burnt outside the body is spoken of as its combus-
tion equivalent, and it measures the amount of potential energy
of these foodstuffs with regard to their capacity for the production
of heat or of muscular work in the body. With regard to the pro-
tein, the case is somewhat different. Its end-products in the body
are carbon dioxid, water, and urea or some other of the nitrogenous
waste products. These nitrogenous wastes are capable of further
oxidation with liberation of heat, so that, as far as they are elimi-
nated, the body loses a possible supply of heat energy, which must .
be subtracted from the total heat energy that the protein gives upon
oxidation outside the body, in order to determine the available heat
energy yielded within the body. The figures obtained for the heat
equivalents of the foodstuffs by burning them outside the body in
some form of calorimeter are as follows : 1 gm. of fat yields an aver-
age of 9300 calories, or 9.3 large calories (C), 1 gm. of carbohydrate
yields an average of 4100 calories (4.1 C.). These figures may be
taken, therefore, to express the quantity of heat given to the body
by the oxidation within its tissues of these elements of our food.
A gram of protein when burnt outside of the body yields on the aver-
age 5778 calories. The heat value of the urea is estimated as 1
gm. = 2523 calories. If we assume that all the nitrogen of the pro-
tein appears as urea and that 1 gm. of protein yields J gm. of urea,
then the available heat energy of a gram of protein should be equal
to 5778—841 (or J of 2523) = 4937 calories. Later workers, however,
have given reasons for believing that this last figure is too high.
All of the nitrogen is not eliminated as urea, and, moreover, all of
the nitrogenous waste is not excreted in the urine; a distinct pro-

POTENTIAL ENERGY OF FOOD.

847

portion is given off in the feces. Rubner has calculated the avail-
able heat energy of proteins by direct experiments upon animals.
In these experiments the heat value of the protein fed was directly
determined by burning a sample in a calorimeter. Then after feed-
ing a known amount of the protein the urine and feces were col-
lected and their heat value was determined in the same way. The
difference between the total heat value of the protein fed and the
heat value lost in its excreted products in the feces and urine gave
the actual heat energy obtained from the protein by the animal
body. Results obtained by this method give an average value
for 1 gm. protein of 4100 calories (4.1 C.), or, since protein contains
an average of 16 per cent, of nitrogen, we may say that 1 gm. of ni-
trogen ingested as protein has a heat value of 4.1 X 6.25 = 25.6 C.
The figures that are used, therefore, in estimating the heat value
of our foodstuffs are:

1 gm. proteid = 4100 calories (4.1 C.).

1 gm. carbohydrate = 4100 calories (4.1 C.).
1 gm. fat = 9305 calories (9.3 C.).

Making use of these values, it is obvious that we can calculate the
total heat value of any given diet. If we analyze the food for its
composition in the three principal foodstuffs we may determine how
many calories will be furnished to the body. In many of the tables
published to show the composition of the different foods figures are
given also to express their heat value or potential energy, on the
belief that, for the most part, our food is used as fuel to supply
energy to the body. These values for some of our ordinary foods
are as follows : *

PROTEID. FAT.

Beefsteak, porterhouse 19.1 17.9

Beefsteak, round (lean) 20.2 2.4

Corned beef (canned) 26.3 18.7

Veal, leg (lean) 19.4 3.7

Veal liver 19.0 5.3

Mutton, leg (lean) 16.5 10.3

Pork, ham (fresh, lean) 24.8 14.2

Pork chops, medium fat 13.4 24.2

Chicken (fowl) 13.7 12.3

Shad 9.4 4.8

Shad roe 20.9 3.8

Eggs 11.7 10.7

Milk 3.3 4.0

Oatmeal 16.1 7.2

Rice 8.0 0.3

Wheat flour (entire wheat) 13.8 1.9

Green peas 7.0 0.5

Potatoes (raw) 2.2 0.1

Spinach . 2.1 0.3

Tomatoes 0.9 0.4

Apples 0.4 0.5

Bananas 1.3 0.6

CARBOHY-
DRATE.

2.6

*5.0

67.5

79.0

71.9

16.9

18.4

3.2

3.9

14.2

22.0

ASH.

0.8
1.2
4.0
1.1
1.3
0.9
1.3
0.8
0.7
0.7
1.5
0.7
0.7
1.9
0.4
1.0
1.0
1.0
2.1
0.5
0.3
0.8

HEAT VALUE
IN CALORIES
PER POUND.

1110

475
1280

520

575

740
1060
1270

775

380

600

680

325
1860
1630
1675

465

385

110

105

290

460

* Selected from Atwater and Bryant, Bulletin 28 (revised edition),
United States Department of Agriculture, 1899.

848 NUTRITION AND HEAT REGULATION.

It must be borne in mind, however, that the entire nutritional value
of a food is not expressed in its heat value — some of our food mate-
rial— the green foods and fruits, for example — are useful and in a
measure essential because of their salts and organic acids. In a
general way, however, the heat energy of a food expresses its value
as a means for maintaining the body in a normal condition.

Dietetics. — The subject of the proper nourishment of individ-
uals or collection of individuals in health and in sickness is treated
usually in works upon hygiene or dietetics. The practical details
of the preparation and composition of diets must be obtained from
such sources.* The general principles upon which practical diet-
ing depends have been obtained, however, from experimental work
upon the nutrition of man and the lower animals, some account of
which has been given in the foregoing pages. In a healthy adult the
main objects of a diet are to furnish sufficient nitrogenous and non-
nitrogenous foodstuffs, salts, and water to maintain the body in an
equilibrium of material and of energy — that is, the diet must furnish
the material for the regeneration of tissue and the material for the
heat produced and the muscular work done. Nutritional experi-
ments prove that this object may be accomplished by protein food
alone, together with salts and water. It is doubtful, however,
whether, in the case of man, such a diet could be continued for long
periods without causing some nutritional disturbance, directly or
indirectly. It will be remembered that a pure meat diet is not
entirely protein, since all flesh contains some fats and carbohydrates
(glycogen). The functions of a diet are accomplished more easily
and more economically when it is composed of proteins and fats, or
proteins and carbohydrates, or, as is almost universally the case, of
proteins, fats, and carbohydrates. The experience of mankind
shows that such a mixed diet is most beneficial to the body and
most satisfying to that valuable regulating mechanism of nutrition,
the appetite. The proportions in which the proteins, fats, and
carbohydrates are mixed in a diet vary greatly among different
nations and individuals. So far as the fats and carbohydrates are
concerned, their use is mainly that of fuel to supply energy, and
from this standpoint we ought to be able to exchange them in the
diet in the ratio of their heat values.

This ratio, or as it is frequently called, the isodynamic equiva-
lent, is as 9.3 to 4.1 or 2.3 to 1, and within the limits permitted by
the appetite we should be able to substitute 1 part of fat for 2.3
parts of sugar or starch. Experiments upon animals as well as
the experience of mankind show that this substitution can be made,

* For practical directions see Gautier, " L 'alimentation et les regimes, "
1904; Blyth, "Foods: their Composition and Analysis."

DIETETICS. 849

although it is not advisable to eliminate either of these foodstuffs
entirely from the diet. The fact that within certain limits fats
and carbohydrates may be substituted for each other is illustrated
in a general way by the different diets recommended by various
physiologists, as follows:

AVERAGE DIETS AND THEIR HEAT VALUES.

MOLESCHOTT. RANKE. VoiT.

CALORIES. CALORIES. CALORIES.

Protein.. ..130 gms. .. 533,(X)6 100 gms, ... 410,000 118 gms. . . 483,000

Fats 40 " ... 372,000 100 " ... 930,000 56 " ... 520,800

Carbohydrates. 550 " ...2,275,000 240 ' . . . 984,000 500 ' ...2,050,000

2,980,000 2,324,000 3,053,800

FORSTER. ATWATER.

CALORIES. CALORIES.

Proteid 131 gins. . . . 567,100 125 gms. . . 512,500

Fats 68 " ... 632,400 125 " ...1,172,500

Carbohydrates. 494 " ...1,825,400 400 ' . ..1,640,000

2,024,900 3,325,000

The average heat value of these diets is equal to 2,741,540 calo-
ries. In round numbers it is usually estimated that the diet should
furnish daily 2,400,000 calories for an individual weighing 60 kgms.,
or about 40,000 calories per kgm. of body -weight. It will be noticed
that in all cases the greatest portion of this energy is obtained from
the carbohydrate food, which, on account of its economy, its abun-
dance, and its ease of digestion and oxidation in the body, consti-
tutes the bulk of our diet. In cases of excessive muscular work
the food eaten may supply more than twice the average heat value
given above. Thus, Atwater and Sherman * estimate that in a six-
day bicycle race by professionals the heat value of the food for the
different participants varied from 4,770,000 to 6,095,000 calories.
Chittenden, in the work previously referred to,f has raised the
question whether the heat value of the diet ordinarily employed
is unnecessarily high. In his own case he found that the body
could be well nourished on a diet containing a total heat value of
only 1,600,000 calories or 28,000 calories per kgm. of body -weight
instead of 40,000 calories. The diet in this case, it will be remem-
bered, contained only 36 to 40 gms. of protein in place of the 100 to
130 gms. recommended in the diets mentioned above. The ques-
tion thus raised is one that must be decided by actual experience.
Mankind is guided and has been guided in all times by the control
of the appetite, using this term in a general sense to designate the
conscious desire for food, and also the desire, more or less clearly

* Bulletin 98, United States Department of Agriculture, 1901.
t Chittenden, u Physiological Economy in Nutrition, " 1905.
54

850 NUTRITION AND HEAT REGULATION.

recognized, for special kinds of food. If scientific experiments
indicate that this regulatory apparatus leads us to ingest more food
than is actually required for the machinery of the body, it remains
for observation and experiment to determine whether this excess
is beneficial or useless or, perhaps, even harmful.

Munk gives an interesting table showing how much of certain
familiar articles of food would be necessary, if taken alone, to supply
the requisite daily amount of protein or non-protein material; his
estimates are based upon the percentage composition of the foods
and upon experimental data showing the extent of absorption of the
foodstuffs in each food. In this table he supposes that the daily
diet should contain 110 gms. of protein = 17.5 gins, of N, and non-
proteins sufficient to contain 270 gms. of C:

FOR 110 GMS. PROTEIN ,-, 0_A „

(17.5 GMS. N). FOR 27° GMS- u

Milk 2900 gms. 3800 gms.

Meat (lean) 540 " 2000 "

Hen's eggs 18 eggs. 37 eggs.

Wheat flour 800 gms. 670 gms.

Wheat bread 1650

Rye bread 1900

Rice 1870

Corn 990

Peas 520

Potatoes'. . 4500

1000

1100

750

660

750

2550

As Munk points out, this table shows that any single food, if taken
in quantities sufficient to supply the nitrogen, would give too much
or too little carbon and the reverse; those animal foods which, in
certain amounts, supply the nitrogen needed furnish only from one-
fourth to two-thirds of the necessary amount of carbon. To live
for a stated period upon a single article of food — a diet sometimes
recommended to reduce obesity — means, then, an insufficient quan-
tity of either nitrogen or carbon and a consequent loss of body
weight. Such a method of dieting amounts practically to a partial
starvation. In practical dieting we are accustomed to get our
supply of proteins, fats, and carbohydrates from both vegetable
and animal foods. To illustrate this fact by an actual case, in
which the food was carefully analyzed, an experimenter weighing
67 kgms. records that he kept himself in nitrogen equilibrium upon
a diet in which the protein was distributed as follows:

300 gms. meat = 63.08 gms. protein = 9.78 gms. N.

666.3 c.c. milk = 18.74 " " = 2.905 " "

100 gms. rice = 7.74 " " = 1.2 " "

100 " bread = 11.32 " " = 1.755 " "

500 c.c. wine = 1.17 " " = 0.182 gm. "

102.05 " = 15.868 gms.

DIETETICS. 851

For a person in health and leading an active, normal life, appetite
and experience seem to be safe and sufficient guides by which to
control the diet ; but in conditions of disease, in regulating the diet
of children and of collections of individuals, scientific dieting, if one
may use the phrase, has accomplished much, and will be of greater
service as our knowledge of the physiology of nutrition increases.

CHAPTER LI.

THE PRODUCTION OF HEAT IN THE BODY— ITS MEAS-
UREMENT AND REGULATION— BODY TEMPERA-
TURE— CALORIMETRY— PHYSIOLOGICAL
OXIDATIONS.

It is customary to date our modern ideas of the origin of
animal heat from the time of Lavoisier (1774-77). To the older
physiologists it was a most difficult problem. The animal's body
produces heat continually and maintains a temperature higher, as
a rule, than that of the surrounding air. Since oxygen and the
nature of ordinary combustions were unknown, they naturally
explained this heat formation by reference to causes which the
science of the- day had shown to be capable of producing warmth,
such as friction and fermentation. Haller (1757), for instance,
taught that the body heat arises mainly from the friction of the
circulating blood and the movements of the heart and blood-vessels,
and this view found currency in text-books well into the nine-
teenth century. Lavoisier first gave to the physiologist the con-
ception that the heat produced in the body is due to a combustion or
oxidation, and that therein lies the significance of our respiration
of oxygen. He believed himself that this oxidation takes place in
the lungs, — that is, the blood brings to the lungs a hydrocarbon-
ous material which is attacked by the oxygen and burnt with
the formation of water and carbon dioxid and the liberation of
heat. Later experimenters demonstrated that the heat production
does not occur in the lungs, at least not exclusively, but over the
whole of the body. After a long and interesting controversy it was
also shown satisfactorily that the oxidations of the body do not
occur in the blood, but in the tissues themselves. The oxygen is
transported to the cells and there does its work of effecting oxi-
dations and giving rise to heat. This heat is equalized more or
less over the whole body, chiefly by the circulation of the blood,
which absorbs heat from the warmer organs and distributes it to
the cooler ones. The body temperature is maintained at a nearly
constant level by an intricate adjustment of physiological reflexes
which together constitute the heat-regulating mechanism. Such
in brief is the general theory of our time regarding heat production
in the body. Many of the problems that interested the older phys-

852

BODY TEMPERATURE. 853

iologists have been solved satisfactorily, but there remain, of course,
many more to interest this and succeeding generations. Investi-
gations in this field at present are directed mainly to an effort to
understand the details of the heat-regulating apparatus, on the one
hand, and, on the other, to comprehend more satisfactorily the
nature of the process of oxidation. This latter problem is one of
common interest at present in chemistry and in physiology.

The Body Temperature. — We divide animals into the two
great classes of warm blooded and cold blooded, according as their
temperature is or is not above that of the surrounding air. In
this sense, birds and mammals are warm blooded and reptiles,
amphibia, and fishes are cold blooded. The names, however, are
badly chosen. The difference of deepest significance between the
mammals and birds, on the one hand, and the fishes, amphibia, and
reptiles, on the other, is that in the former the body temperature
is, within wide limits, independent of the outside temperature; it
remains practically constant during winter and summer, whether,
the surrounding air is hotter or cooler than the body. They are,
therefore, constant-temperature animals (homoiothermous). The
reptiles, amphibia, and fishes, on the contrary, have a body tem-
perature that changes with the environment. On winter days
their temperature is low, approximately that of the surrounding
air or water, and in summer their body temperature rises to cor-
respond with that of the outside. Strictly speaking, they are cold
blooded only in cold surroundings. This group may be designated
as the changeable-temperature animals (poikilothermous). The
warm-blooded animals maintain a constant high body temperature
on account of their relatively active oxidations and the existence
of a heat-regulating mechanism. In the cold-blooded animals the
oxidations are not so intense and a heat-regulating mechanism is
absent or poorly developed. The hibernating animals form a group
intermediate in many ways between these two classes. They possess
a heat-regulating apparatus that maintains a constant body tem-
perature under most conditions, but breaks down in very cold
weather; so that during the period of winter sleep their tem-
perature is but little above that of the surrounding air. In
some of the cold-blooded animals the production of heat is more
rapid during warm weather than its loss; so that they exhibit
a body temperature slightly higher than the surrounding me-
dium. A hive of bees in activity may raise the temperature
within the hive through a number of degrees and snakes and
many reptiles show a temperature of 2° to 8° C. above that of
the air. So also some reptiles possess a rudimentary means of
protecting their bodies from too great a rise of temperature, — •
for instance, by accelerated breathing whereby more water is evap-

854 NUTRITION AND HEAT REGULATION.

orated from the lungs and thus more heat is lost.* The distinc-
tion between the two great groups of animals is not entirely abso-
lute, but it is sufficiently marked to constitute a striking physio-
logical characteristic.

The temperature of the human body is measured usually by
thermometers placed in the mouth, in the axilla, or in the rectum.
Measurements made in this way show that in general the tempera-
ture in the interior of the body (rectal) is slightly higher than on the
surface of the skin. The average temperature in the rectum is 37. 2 c
C. (98.96° F.); in the axilla, 36.9° C. (98.45° F.); in the mouth,
36.87° C. (98.36° F.). We may speak of the body temperature,
therefore, in the places in which it can be conveniently measured, as
varying between 36.87° C. and 37.2° C. Some of the internal or-
gans have a higher temperature, particularly during their period of
greatest activity. The temperature of man, measured in the places
mentioned, shows also a distinct variation during the day, a diurnal
rhythm. This daily variation has been measured by many ob-
servers, and shows individual peculiarities that depend largely upon
the manner of living, time of meals, etc. In general it may be said
that the lowest temperature is shown early in the morning, — 6 to
7 A.M. ; that it rises slowly during the day to reach its maximum
in the evening, 5 to 7 P.M. ; and falls again during the night. The
difference between early morning and late afternoon or evening
may amount to a degree or more centigrade, and this fact must be
borne in mind by physicians when observing the temperature of
patients. Muscular activity and food appear to be the factors that
are mainly responsible for the rise in temperature during the day.
Most observers state that when the habits of life are reversed for.
some time — that is, when work is performed and meals are eaten
during the night, and the day is given up to sleep and rest — the daily
variation of temperature is inverted to correspond, — that is, the
highest temperature is observed in the early morning and the lowest
in the late afternoon. Age also has a slight influence. Newly born
infants and young children have a somewhat higher temperature
than adults. The difference may amount to half a degree or
a degree centigrade, — 37.6° C. in infants as compared with
36 . 6° C. or 37 . 1° C. in the adult. It is known, also, that the heat-
regulating mechanism in infants and young children is not so
efficient as in adults, and that therefore febrile disturbances are more
easily excited in the former than in the latter. In the matter of body
temperature, as in so many other characteristics, aged people show
a tendency to revert to infantile conditions. Their temperature,
according to most observers, is slightly higher than in middle life.

* See Langlois, " Journal de physiologic et de pathol. generate, " 1902,
249.

CALORIMETRY. 855

Among physiological conditions that influence the body tempera-
ture, muscular work and meals, as stated above, have the most posi-
tive effect. Marked muscular activity implies a great increase in
the production of heat in the body and most observers find that
the initial result at least is a small rise in body temperature, — a fact
which indicates that the heat regulation is not perfect; the excess
of heat produced is not dissipated promptly. In the period of rest
following upon work, on the contrary, the body temperature may
fall, owing probably to the«fact that more heat is lost through the
flushed skin than is produced within the body. In this matter of
the effect of muscular work individual variations are to be expected,
since the perfection of the heat-regulating mechanisms may vary
somewhat in different persons. Meals also cause a slight rise in
body temperature, which reaches its maximum about an hour and
a half after the ingestion of the food. The explanation in this case
also is to be found doubtless in a greater production of heat, due to
the increased metabolism in the secreting glands, the liver, and the
musculature of the gastro-intestinal canal. The excessive production
of heat is not compensated completely by a corresponding increase in
the heat dissipated.* It is sufficiently obvious, perhaps, from these
facts that the temperature as measured by the thermometer is a
balance between the amount of heat produced and the amount of
heat lost or dissipated. The thermometer alone gives us no cer-
tain indication of the quanity of heat produced in the body. A
temperature higher than normal, fever temperature, may be due
either to an excessive production of heat or to a deficient dissipa-
tion. To understand and control the processes by which the body
temperature is kept normal it is necessary to discover a means for
ascertaining at any time the actual quantities of heat produced
and dissipated, and the effect upon each factor of different normal
and pathological conditions. The method used for determining
the quantity of heat is designated as calorimetry. It is necessary,
therefore, to describe the principle and construction of calorimeters
and the methods of calorimetry before attempting to explain the
mechanism of heat regulation.

Calorimetry. — A calorimeter is an instrument for measuring
the quantity of heat given off from a body. The unit employed in
these determinations is the calorie, — that is, the amount of heat
necessary to raise 1 gm. of water 1° C.,or more accurately the amount
of heat required to raise 1 gm. of water from 15° to 16° C. This
unit is sometimes designated as a small calorie to distinguish it
from the large calorie (C), — that is, the quantity of heat necessary
to raise 1 kgm. of water 1° C. The large calorie is equal to 1000

* For further details see Richet, "La chaleur animate, " 1889; and Pem-
brey, "Animal Heat," Schaefer's "Text-book of Physiology," vol. i, 1898.

856

NUTRITION AND HEAT REGULATION.

small calories. In physiology calorimeters have been used for two
main purposes: to determine the heat equivalent of foods, — that is,
the amount of heat given off when the various foodstuffs are burned,
— and, secondly, to determine the heat produced and the heat dissi-
pated by living animals during a given period. For the first pur-
pose the apparatus that is most frequently employed at present is
the bomb calorimeter devised by Berthelot. The bomb consists
of a strong steel cylinder in which the food to be burned is placed

Fig. 275. — Reichert's water calorimeter.

and which is filled with oxygen. The combustion of the foodstuff
is initiated by means of a spiral of platinum wire heated by an
electrical current. The bomb is immersed in water and the heat
given off raises the water to a measured extent of temperature.
The weight of water being known, the amount of heat is easily
expressed in calories. For the purpose of measuring the heat
given off by living animals two principal forms of calorimeter are
used, each form having a number of modifications. These two
forms are the water calorimeter and the air calorimeter. The
water calorimeter was the form used in the first experiments on rec-
ord (Crawford, 1779). In principle it consists of a double-walled
box with a known weight of water between the walls. The animal
is placed in the inner box and the heat given off is absorbed by the

CALORIMETRY. 857

water. Knowing the weight of the water and how much its tem-
perature is raised, the data are at hand for determining the number
of calories given off during the experiment. One form of this
variety of calorimeter, used in this country by Reichert, is shown
in Fig. 275. It consists of two concentric boxes of metal with a
space between them of about 1J inches. The animal is placed
in the inner box (A). The two boxes are inclosed in a large wooden
box, the space between the metal and wooden boxes being filled
with shavings (SH). The" object of this outer box is to prevent
radiation of heat from the metal boxes. The tubes EN and EX,
which lead into the interior chamber containing the animal, are for
the entrance and exit of the ventilating air. A thermometer is
placed in each to determine the heat- carried off by the air. The
thermometer, CT, measures the temperature of the water, and S is
a stirrer to keep the water well mixed and thus insure a uniform
temperature. When the animal is placed in the apparatus the
heat given off warms not only the water, but also the metal; so
that to determine the total heat the weight of metal must be re-
duced to an equivalent amount of water by multiplying its weight
by its specific heat, or, a more simple method, the calorimetric equiv-
alent of the apparatus is determined, — that is, the actual amount of
heat necessary to raise the temperature of the apparatus, water and
metal, one degree. This value is obtained by burning in the appa-
ratus a known weight of some substance (alcohol, hydrogen) whose
heat of combustion is known. Knowing how much heat is given
off by this combustion and how much the temperature of the
apparatus is raised, the calorimetric equivalent is easily calcu-
lated and may be used subsequently in estimating the results ob-
tained from animals. In the use of the apparatus many precau-
tions must be observed. These practical details need not be des-
cribed here except to say that account must be taken of the warm-
ing of the air used to ventilate the apparatus and of any changes
in the amount of its moisture. The calorimeter used in this way
measures directly the amount of heat given off from the animal
during the period of observation. The amount of heat produced in
the animal's body during this time may be the same, or may be
more or less. To arrive at a knowledge of this factor observations
must be made upon the animal's body temperature by means of a
thermometer in the rectum. If this body temperature is the same
at the end as at the beginning of the experiment then it is obvious
that the heat produced must have been equal to the heat lost. If
the animaPs body temperature has fallen, then it is evident that
less heat has been produced than was lost. To ascertain how much
less, the weight of the animal is multiplied by its specific heat (0.8)
to reduce it to so much water, and this product is multiplied by the
difference in body temperature at the beginning and the end of the

858

NUTRITION AND HEAT REGULATION.

experiment. The product is obtained in calories and is subtracted
from the amount of heat lost, as determined by the calorimeter, to
obtain the amount of heat produced. If, on the contrary, the ani-
mal's temperature has risen during the experiment the body has
produced more heat than it has dissipated. The increase may be
determined as above by multiplying the weight of the animal, the
specific heat of the body, and the difference in temperature. This
amount added to the heat lost gives the heat produced.

Most recent investigators have used some form of air calorimeter.
An air calorimeter consists essentially of a double-walled chamber
or box with air between the walls. The animal is placed in the
inner box and the heat given off is measured by the expansion of
the air between the walls. Many different forms are used, prefer-

276. — D' Arson val's differential calorimeter.

ence being given to some modification of the differential air calo-
rimeter. In this last-named instrument two exactly similar chambers
are constructed ; one contains the animal while the other serves as a
dummy. These two chambers are balanced against each other,
the air space in the dummy being heated by immersion in a bath or
by burning hydrogen in the interior. As these sources of heat are
known and can be controlled, it is evident that if the dummy is
made to balance exactly the chamber containing the animal the
amount of heat given off in each is the same. The principle of the
differential calorimeter is represented in Fig. 276, which gives a
schema of the form originally employed by d'Arsonval; 8 and 8'
represent the two calorimeters, in one of which the animal is placed
while the other acts as dummy. Each is double walled and the
air spaces are connected by tubes, 10 and 10', to small gasometers,
4, 4', suspended in water and hung on opposite sides of a balance.
The movements of these gasometers antagonize each other, and the
resultant may be recorded upon smoked paper, as indicated in the
figure.*

* For detailed accounts of special forms of air calorimeters see Rubner,
" Calorimetrische Methodik," 1891; and Rosenthal, "Archiv f. Physiologie,"
1897, p. 170.

CALORIMETRY. 859

The Respiration Calorimeter. — When a calorimeter is so arranged
that the composition of the air drawn through the apparatus for
ventilation can be determined as well as the amount of heat pro-
duced, the apparatus becomes a respiration calorimeter. In such
an apparatus, if proper provision is made for analyzing the urine,
the feces, and the food, the total carbon and nitrogen excretion may
be obtained simultaneously with the heat loss. Since we may
calculate from the carbon and nitrogen excretion how much pro-
tein, fat, and carbohydrate, have been burnt in the body, and since
the heat values of these constituents are known, it is evident that
we may reckon indirectly how much heat ought to be produced
from the combustion of so much material. This method of arriv-
ing at the heat production is designated indirect calorimetry. With
an adequate respiration calorimeter it is possible to ascertain
whether the results calculated by the method of indirect calorim-
etry really correspond with the heat obtained by direct measure-
ment. In the hands of good observers the correspondence is
very close, and gives substantial proof of the scientific belief
that in the living body the energy liberated as heat or as heat
and work is all contained in potential form in the foodstuffs
eaten. By means of the respiration calorimeter we can obtain a
balance between the energy income and outgo of the body as well
as between the material income and outgo, — that is, the carbon and
nitrogen equilibrium. The most complete and elaborate form of
respiration calorimeter used is that devised by Atwater and Rosa for
experiments upon man.* Considered as a calorimeter the appara-
tus used by these investigators belongs to the type of water cal-
orimeters. Instead, however, of having a stationary stratum of
water to be warmed by the heat given off from the body, the appara-
tus is arranged so that a stream of water may be circulated between
the walls, and this stream is so regulated, as to quantity and
temperature, as to keep the temperature of the calorimeter as a
constant point. In other words, the heat given off from the body
is carried away by the circulating water, and the quantity of the
heat may be calculated when the temperature and amount of the
water are known. By means of this apparatus many interesting
and important experiments have been made upon the nutrition
of man under special conditions. Such results as the following
have been obtained (Atwater and Benedict) in the case of a man
who, while in the apparatus, did much muscular work on a bicycle
ergometer:

* See Atwater and Rosa, Bulletin 63, United States Department of Agri-
culture, 1899; and for recent improvements, Atwater and Benedict, ''A Respira-
tion Calorimeter," Carnegie Institution, Washington, 1905.

860 NUTRITION AND HEAT REGULATION.

Outgo |

Income : Potential energy of material metabolized in body = 5459 Cal.
Energy given off from the body as heat .... 4833 Cal.
Heat equivalent of muscular work 602 Cal.

5435 Cal. 5435 Cal.

Experimental error 24 Cal.

Results of Calorimetric Measurements. — The actual results
obtained from direct calorimetric measurements corroborate those
deduced from the study of the energy given off in the oxidation of
the foodstuffs of the daily diet. They show that man gives off heat
from his body to the amount of 40,000 to 50,000 calories per kgm.
of weight during 24 hours under conditions of ordinary life, — a
total, therefore, of 2,400,000 to 3,000,000 calories per day for an
individual weighing 60 kgms. This amount is increased greatly
under conditions demanding much muscular work. This loss of
heat is, of course, made good by the production of an equal amount
within the body by the oxidation of the food material. Actual
experiments upon different animals* show that small animals
produce more heat in proportion to their weight than larger animals
of the same species, owing to their relatively larger surface and
therefore greater loss of heat. Birds produce and lose more heat
for a unit of surface than mammals, — a fact which indicates that
their physiological oxidations are more intense. According to
Richet, a sparrow gives off per unit of surface five times as much
heat as a rabbit. According to Rubner, the sparrow produces
thirteen times as much heat as man for the same amount of tissue.
In infants, owing to their larger surface relative to the mass of the
body, the loss of heat is greater than in the adult.

HEAT REGULATION.

From a general standpoint the most important problem that the
physiologist has to study is the means by which the heat production
and heat loss are so regulated as to maintain a practically constant
body temperature. Experiments show that the mechanism of
heat regulation is very complex and is two-sided, — that is, the body
possesses means of controlling the loss of heat as well as the produc-
tion of heat, and under the conditions of normal life both means
are used.

Regulation of the Heat Loss. — Heat is regularly lost from our
bodies in a number of different ways, which may be classified as
follows :

1. Through the excreta, urine, feces, saliva, which are at the temperature
of the body when voided.

*See Eubner, " Zeitschrift. f. Biologic," 19, 535, 1883; and Richet, "La
chaleur animate," 1889, p. 224.

REGULATION OF HEAT LOSS.

861

2. Through the expired air. This air is warmer than the inspired air,

and moreover is nearly saturated with water-vapor. The vaporiza-
tion of water requires heat, which is, of course, taken from the body
supply. Each gram of water requires for its vaporization about 582
calories.

3. By evaporation of the sweat from the skin. The amount lost in this

way increases naturally with the amount of sweat secreted.

4. By conduction and especially by radiation of heat from the skin.

The relative values of these different means of heat loss are
estimated as follows by Vierordt:

1. By urine and feces 1.8 per cent, or 47,500 calories.

2. By expired air: Warming of air 3.5 " " 84,500 "

Vaporization of water from lungs 7.2 " " 182,120 "

3. By evaporation from skin 14.5 " " 364,120 "

4. By radiation and conduction from skin .73.0 " " 1,791,820 "

Total daily loss = 2,500,000 "

It is obvious that the relative importance of these factors will vary
with conditions. Thus, high external temperatures will tend to
diminish the loss from radiation while increasing that from evapora-
tion, owing to the greater production of sweat. The variation
in this respect is well illustrated by the following table, compiled
by Rubner, from experiments made upon a starving dog:*

Temperature.

Calories lost by radia-
tion and conduction.

Calories lost by
evaporation.

Total calories of
metabolism.

7° C.

78.5

7.9

86.4

15°

55.3

7.7

63.0

20°

45.3

10.6

55.9

25°

41.0

13.2

54.2

30°

33.2

23.0

56.2

It will be noted that between 25° and 30° C. there was a marked
increase in the loss of heat through evaporation.

In man loss of heat is regulated chiefly by controlling the impor-
tant factors of evaporation and radiation. We accomplish this end in
part deliberately or voluntarily by the use of appropriate clothing.
Clothing of any kind captures a layer of warm and moist air between
it and the skin and thus diminishes greatly the loss by evaporation
and by radiation. In cold weather the amount and character of the
clothing is changed in order to diminish the heat loss. The ideal
clothing for this purpose is made of material, such as wool, which,
while porous enough to permit adequate ventilation of the air next
to the skin, is at the same time a poor conductor of heat and thus
diminishes the main factor of loss by radiation. The most impor-
tant means of controlling the heat loss, however, is by automatic
reflex control through the sweat nerves and the vasomotor nerves.

* Taken from Lusk, "Elements of the Science of Nutrition," Philadel-
phia, 1906.

862 NUTRITION AND HEAT REGULATION.

In warm weather the secretion of sweat is greatly increased 'by re-
flex stimulation of the sweat nerves. The greater amount of water
requires a greater amount of heat to vaporize it, and thus the heat
loss is increased. The value of this control is illustrated by a case
recorded by Zuntz * of a man who possessed no sweat glands. In
summer this individual was incapacitated for work, since even a
small degree of muscular activity would cause an increase in his
body temperature to 40° or 41° C. .

The control through the vasomotor nerves is doubtless even
more important. The blood-vessels bring the warm blood to the
skin, where it loses its heat by conduction and especially by radia-
tion to the cooler air. When the surrounding air is much below the
temperature of the body the vasoconstrictor center is stimulated,
the blood-vessels in the skin are constricted, the supply of warm
blood to the skin is diminished, and therefore the amount of heat lost
is less. The reflex in this case may be attributed primarily to the
action of the cool air on the cold nerves of the skin. The impulses
carried by these fibers to the nerve centers stimulate the vasocon-
strictor center or that part of it controlling the vasomotor fibers
to the skin. On warm days, on the contrary, the blood-vessels
in the skin are dilated sometimes to an extreme extent, the
supply of warm blood is therefore increased, and more heat
is lost if the air is lower in temperature than the blood. The
reflex in this case may be regarded possibly as an inhibition of the
vasoconstrictor center through the warm nerves of the skin. Sub-
stances, such as alcohol, which cause a dilatation of the skin ves-
sels also increase the loss of body heat, in some cases to a sufficient
extent to lower the body temperature. To a smaller extent our
heat loss is controlled through an acceleration of the breathing
movements. The greatly increased respirations in muscular ac-
tivity must aid somewhat in eliminating the excess of heat produced,
although this factor must be much less important than the sweating
and the flushing of the skin which are produced reflexly during
muscular work. In some of the lower animals — the dog, for in-
stance— in which the sweat nerves are absent over most of the body
and in which the coat of hair interferes with the free loss by
radiation, it is found that the loss through the respiratory channel is
relatively more important. The panting of the dog is a familiar
phenomenon. Richet has studied this reflex upon dogs and has
designated the greatly accelerated breathing in warm weather or
after muscular exercise as thermic polypnea (according to Gad,
tachypnea). He assumes a special center for the reflex situated in
the medulla and acting through the respiratory center. It is a
curious fact, as shown by Langlois, that some reptiles exhibit a
similar reflex; when their body temperature is raised to 39° C. they
* Zuntz, "Deutsche medizinai-Zeitung, " 1903, No. 25.

REGULATION OF HEAT PRODUCTION.

863

show a condition of marked polypnea (rapid breathing) the ap-
parent object of which is to augment the loss of heat from the
body.

Regulation of Heat Production. — Heat production is varied
in the body by increasing or decreasing the physiological oxida-
tions. This end is effected in part voluntarily by muscular exercise
or by taking more food. Muscular contractions are attended by
a marked liberation of heat and it is a part of everyone's experience
that by work or muscular activity the effect of outside cold may be
counteracted. In the case of food the body burns promptly most
of the material of a daily diet. By increasing the diet in cold
weather provision is made for the greater supply of heat required.
In normal individuals this regulation is not, strictly speaking,
voluntary. Outside cold is most effective in stimulating the appe-
tite and thus leading us to increase the diet. In this, as in other
respects, the appetite serves to control the amount of food in pro-
portion to the needs of the body. The purely involuntary control
of heat production consists of an involuntary reflex upon muscu-
lar metabolism and possibly in the existence of a special set of heat
centers and heat nerves. With regard to the first effect we have
the striking experiments quoted by Pfliiger,* according to which a
rabbit paralyzed by large doses of curare is no longer able to main-
tain its body temperature when the outside temperature is changed.
The rabbit behaves, in fact, like a cold-blooded animal. In the
calorimeter it shows a marked loss of heat production, and its
temperature may be made to go up and down with the outside
temperature. The same result may be obtained by section of all
the motor nerves, — that is, section of the spinal cord in the upper
cervical region. Rubner has shown by calorimetric experiments
upon animals that although the body temperature, as we know,
may remain constant when the outside temperature is changed,
the heat production is increased as the outside temperature is
lowered. This fact is well shown by the following table, compiled
by Rubner, from experiments made upon a fasting guinea-pig :f

Temperature
of air.

Temperature
of animal.

Grams of CO-> eliminated per hour
and per kilogram of animal.

0.0° C.

37.0° C.

2.905

11.1

37.2

2.151

20.8

37.4

1.766

25.7

37.0

1.540

30.3

37.7

1.317

34.9

38.2

1.273

40.0

39.5

1.454

From 0° to about 35° C. the animal's body temperature remained

*Pfliiger "Archiv f. die gesammte Physiologic, " 18, 255, 1878.
t Taken from Lusk, loc. dt.

864 NUTRITION AND HEAT REGULATION.

practically constant, but the oxidations at the lower temperature
were over twice the amount of those at the higher temperature.
At about 33° C. the metabolism of the mammal, according to Rub-
ner, is at its minimum. From 35° to 40° C. the heat regulating mech-
anism broke down, in that heat loss was prevented to such an extent
by the outside high temperature that the body temperature rose
in spite of the diminution in heat production. Cold baths, cold
winds, and various climatic conditions, such as high altitudes and
seaside conditions, also cause a marked increase in body metabolism.
Johannson * has shown that the increased oxidations that occur
under the influence of outside cold, as measured by the CO2 output,
occur only when muscular tension is increased or shivering is noticed.
We may believe, therefore, that the increased oxidations caused
by cold are due to motor reflexes upon the skeletal muscles. These
reflexes take place doubtless through the motor fibers, and lead to
an augmented muscular tone or to small contractions (shivering),
according to their intensity. This fact accords with one's personal
sensations regarding the condition of his muscles in cold weather.

The Existence of Heat Centers and Heat Nerves. — Physi-
ologists have long supposed that there may be in the body a special
set of heat nerves and heat centers, separate in their action from the
motor, secretory, and other efferent nerves that influence the me-
tabolism of the peripheral organs. It is supposed that these fibers,
if they exist, when in activity augment or inhibit the physiological
oxidations in the tissues, and that this effect has for its specific
object an increase or decrease in heat production, outside of any
functional activity of the tissues. Bernard thought at first that
he had demonstrated the existence of calorific fibers in the cervical
sympathetic, but it was afterward recognized that the fibers in
question are vasoconstrictors. Since that time very numerous
experiments have been made with this object in view, but it must
be admitted that no conclusive proof has yet been obtained of the
existence of such a system. The evidence that has been most re-
lied upon is the effect of lesions, experimental or pathological, of
definite portions of the brain or cord. The following facts are
significant: A number of observers f have found that section or
puncture of the brain at the junction of medulla and pons causes
an increase in heat production and a rise of temperature. Section
of the cord in the cervical region is, on the other hand, attended
usually by a fall in body temperature. These experiments might be
interpreted to mean that there exists in the brain anterior to the
medulla a general heat center of an inhibitory character. Under
normal conditions this center may hold the lower heat-producing

* Johannson, " Skandinavisches Archiv f. Physiologic, " 7, 123, 1897.
t See Wood, "Fever," 'Smithsonian Contributions to Knowledge."
Washington, 1880.

EXISTENCE OF HEAT CENTERS AND HEAT NERVES. 865

centers in check. When cut off by section this inhibitory influence
is removed and increase in heat production and body temperature
results. A -second important fact, brought out by Ott,* is that in-
jury to the corpus striatum causes a rise in heat production and
body temperature. This result has been confirmed by many other
investigators, making use especially of what is known as the " heat
puncture." In this experiment, made upon rabbits, a probe or
style is inserted into the brain so as to puncture the corpus stria-
tum. The result in the majority of cases is a rise of temperature
which may last for a long time, although the animal shows no par-
alysis and apparently no other effect from the operation. Accord-
ing to some observers, t the increased production of heat takes place
mainly in the liver, and is due to the oxidation of the glycogen.
According to others (Aronsohn), the increased production of heat
occurs mainly in the muscles. The fever produced by the "heat
puncture" seems to be due essentially to an irritation of the nerv-
ous system, and is an experimental demonstration of the possi-
bility of fever arising from lesions of the nerve centers. White and
others have described similar disturbances of heat production from
lesions of the optic thalamus. Heat centers have been located
also in the septum lucidum, in the cortex, the midbrain, pons, and
medulla, while Reichert places the primary heat-producing centers
(thermogenic centers), from which the hypothetical heat nerves
originate directly, in the spinal cord in the anterior horn of the gray
matter. J The great amount of experimental work done along
these lines has been inspired doubtless by the hope of discovering
a special heat-regulating nervous apparatus which if demonstrated
would enable us to explain the causation of fevers. In its most
elaborate form this hypothesis assumes the existence of primary
heat-producing (thermogenic) centers in the cord and brain from
which the calorific or heat nerves arise. These centers in turn are
controlled by regulating (thermotaxic) centers of an augmenting
and inhibitory character in the higher portions of the brain. By
reflex influences upon these latter centers the activity of the thermo-
genic centers may be increased or diminished and the production
of heat in the body controlled. While such an apparatus may
exist, it is nevertheless true that the evidence in favor of it so far
produced has failed to convince the majority of physiologists. The
existence of a special set of heat nerves, in fact, is still unproved.
Most physiologists, perhaps, believe that variations in heat pro-

* Ott, " Journal of Nervous and Mental Diseases," 1884, 1887, 1888;
also "Brain," 1889.

t Roily, " Deutsches Archiv f . klinische Medicin, " 78, 250, 1903.

t See Reichert, " University Medical Magazine, " 5, 406, 1894 ; also Kemp,
"Therapeutical Gazette," 1889, pp. 86 and 155.
55

866 NUTRITION AND HEAT REGULATION.

duction occur, as stated above, by alterations in the intensity of the
oxidations in the muscles brought about by reflex excitation through
the motor nerve fibers, and that a special set of heat fibers does not
exist. We may at present adopt the conservative view that heat
production and heat dissipation in the body are controlled not
by a special heat-regulating apparatus composed of heat centers
and heat nerves, but by the co-ordinated activity of a number of
different centers in addition to the voluntary means already
specified. The unconscious regulation of the body temperature is
effected chiefly through the following centers :

C 1. The sweat centers and sweat nerves.

TT , i- • -• J 2. The vasoconstrictor center and the vasoconstrictor
Heat dissipation 4 nerye ^ to the gkm

v 3. The respiratory center.

( 1. The motor nerve centers and the motor nerve fibers
... J to the skeletal muscles.

lon 1 2. The quantity and character of the food as deter-
mined by the appetite.

Theories of Physiological Oxidations. — Lavoisier compared
the oxidations in the body to the oxidation of organic substances
in combustions at high temperatures. He supposed that the mo-
lecular oxygen unites directly with the substances oxidized in one
case as in the other. It soon became evident, however, that this
direct analogy is not applicable. The material that is oxidized
in the body — fats, carbohydrates, proteins — is consumed with a
certain rapidity, — in the case of muscular contractions with great
rapidity, — and we know that these same materials out of the body
at a temperature of 39° C. are oxidized with extreme slowness. It
became customary, therefore, to speak of the oxidations in the body
as indirect, meaning thereby that the material is not acted upon
directly by the molecular oxygen. Within recent years it has been
shown that the oxidation in ordinary combustions — the burning
of gaseous hydrogen, for instance — is not explained by assuming
that the oxygen unites directly with the hydrogen. It is stated,
for instance, that this combustion does not take place if both gases
are entirely free from water vapor; the presence of water is necessary
for the oxidation. Chemists are not agreed as to the exact nature
of simple combustion, and it is therefore increasingly difficult to
compare these processes with the oxidations in the body. Leaving
aside the details of the process, it may still be believed that thu
metabolism of material in the body by means of which its heat
energy is produced is at bottom comparable to ordinary combus-
tions. Oxygen is absolutely necessary to the process in each case;
the same end-products are formed and the same amount of heat is
liberated in the one case as in the other. The fundamental point
that the physiologist is attempting to solve is the means by which

PHYSIOLOGICAL OXIDATIONS. 867

the body accomplishes these oxidations at such a low temperature.
The theories suggested to explain this fact have changed naturally
with the advance of chemical knowledge. After the discovery of
ozone (Schonbein, 1840) and its great power of oxidation as com-
pared with oxygen it was suggested that in some way the oxygen
in the body is ozonized and is thus able to burn the food material.
Gorup-Besanez showed that some of the oxidations that take place
in the body can be successfully accomplished outside the body
with the aid of ozone, especially in the presence of alkalies or alka-
line carbonates. Others suggested that the oxygen in the body be-
comes converted to atomic oxygen and is thus enabled to attack the
tissue materials. Hoppe-Seyler formulated a theory according to
which the living molecule is first split into smaller molecules by the
hydrolytic action of ferments. In this process, as in fermentation, to
which he compared it, hydrogen is liberated in the nascent or atomic
state, and this hydrogen acting upon the oxygen forms water with
the liberation of some atomic oxygen, which in turn oxidizes the
split products of the fermentation. Others still (Traube) laid stress
upon the possibility of the formation of hydrogen peroxid or
similar organic peroxids which are then capable of effecting the
oxidation of the body material. This latter theory, in modified
form, still prevails.*

The great amount of experimental and theoretical work upon
the nature and cause of physiological oxidations has established
pretty clearly two general beliefs which it is important to keep
in mind. It has been shown, in the first place, that the amount of
the oxidation is governed by the tissue itself and not by the quantity
of oxygen present. The view that by increasing the amount of
oxygen offered to the tissue the intensity of the oxidations can
likewise be increased was formerly held and is still met with. It
is often supposed, for example, that by breathing pure oxygen the
oxidations of the body may be augmented. On the contrary, the
facts indicate that when a sufficient supply of oxygen is provided
any further increase has no immediate effect in aiding or hastening
the oxidations. The intensity of the process is conditioned by the
tissue itself. The initial stimulus or substance that sets going the
whole reaction arises within the tissues. The second generalization
that seems to be accepted more and more of recent years is that the
oxidations of the body, those reactions that give rise to much heat,
do not affect the living tissue itself. They take place under the
influence of the living matter, or by the aid of substances (enzymes)
formed by the living matter, but the material actually burnt is not
organized living substance. As the living yeast cells break down

* See Engler and Weissberg, " Kritische Studien liber die Vorgange der
Autoxydation, " 1904.

868 NUTRITION AND HEAT REGULATION.

sugar in the liquid surrounding them, so the living tissue cells metab-
olize and oxidize the dead food material contained in the lymph
and tissue liquid in which they are bathed. The opposite point of
view was ably advocated by Pfliiger. This observer, in fact, ex-
plained the mystery of physiological oxidations by assuming that
the oxygen together with the food material is synthesized into the
highly complex and unstable living molecules. The active intra-
molecular movement within these molecules leads constantly to a
breaking down, a splitting off of simpler molecules which consti-
tute the products of physiological oxidation. The instability of
the molecule is due to its size and the activity of the intramolecular
movements, or, as Pfliiger expressed it, "The intramolecular heat
of the cell is its life." This point of view, however, has not found
acceptance of late years. It is implied or stated by most recent
authors that the food material is attacked and oxidized outside the
living molecule, in the form of fat, sugar, protein, etc. The ten-
dency for many years has been to show that these processes in the
body are chemical changes that do not differ fundamentally from
similar processes outside the body. The point of view actually
adopted by most workers is that the living matter effects its won-
derful changes in the food material with the aid of intracellular
ferments or enzymes. That such enzymes are formed, one may say
generally in the tissues of the body, has been brought out in the pre-
ceding chapters upon Digestion and Nutrition. It is necessary" only
to recall the facts that lipase, the fat-splitting enzyme, has been iso-
lated from many tissues, and that in the liver and muscles and prob-
ably other tissues there exist enzymes capable of converting glycogen
to sugar or the reverse, and of destroying the sugar completely by the
serial action of several intracellular enzymes. Finally, with regard to
the protein material it is now recognized that proteolytic enzymes
are formed within many, if not all, of the living tissues. This point
is demonstrated by the fact of autolysis, — that is, if living tissue is
taken from the body, with precautions against contamination by
bacteria, and while under perfect aseptic conditions is kept warm
and moist, it will digest itself. The proteid is split up into the
same simple hydrolytic products as are obtained by boiling it with
acids. It has been shown that this digestion is due to enzymes —
autolytic enzymes — formed within the living tissue. There is no
doubt, therefore, of the existence of intracellular enzymes, and that
these substances play a conspicuous part in the metabolism of food
material. The lipase, the diastase, and the autolytic enzymes just
referred to all belong to the group that cause hydrolytic cleavages, —
that is, they induce splitting or decomposition of the material by
a reaction with water. The supposition has naturally been made
that probably the oxidations of the body are effected also by enzymes

PHYSIOLOGICAL OXIDATIONS. 869

which in some way activate the oxygen. Enzymes of this char-
acter have been found ; they are designated in general as oxidases or
as oxidases and peroxidases, the former term referring to those
enzymes that effect oxidations in the presence of oxygen, while
the latter is applied to certain enzymes supposed to act only in the
presence of peroxids. The most conspicuous of the oxidases found
in the animal body is the one capable of oxidizing aldehydes (sal-
icylic or benzoic aldehyde)v into the corresponding acids, and hence
designated specifically as aldehydase. This enzyme has been
extracted especially from the liver, lung, and spleen. An oxidase
known as tijrosinase, first found in plant juice, has also been isolated
from animal tissues. It oxidizes tyrosin with the formation of
homogentisinic acid. So also oxidases are described capable of
oxidizing xanthin to hypoxanthin or to uric acid.* The process
of destructive metabolism of sugar in the body, glycolysis, may
be effected, it will be remembered, by the tissue juices squeezed
from the organs, or even by extracts of the tissues of muscle, liver,
etc. It may well be believed, therefore, that the oxidation of
this most important food material is accomplished by the action
of one or more enzymes. Such facts as these lend great probability
to the belief that eventually it will be shown that the oxidations in
the body are effected by the influence of oxidases or peroxidases
acting singly, or in combination, or in sequence with the hydrolytic
enzymes.

While it is perfectly obvious that more facts are needed before
positive statements are warranted regarding the chemistry of the
oxidations in the body, the view entertained regarding the general
process in the body is that the material — protein, fat, or carbohy-
drate— is first split into simpler products by the action of a hy-
drolytic enzyme, or a series of hydrolytic enzymes, formed in the
cells. These reactions are not attended by any marked formation
of heat. The split products thus produced are then acted upon by
oxidases with the formation of certain intermediate products and
eventually of carbon dioxid, water, etc., and the liberation of heat.
A specific instance of this serial action has been given in reference
to the oxidation of sugar (p. 824) : According to Stoklasa, the sugar
is first split into lactic acid, and this into carbon dioxid and alcohol ;
the alcohol then by the action of a series of oxidases is oxidized to
acetic acid, formic acid, carbon dioxid, and water. From our
present standpoint, the production of heat in the body, it is impor-
tant also to bear in mind the general view advocated by Speck and
others — namely, that the chemical changes or metabolism of the
body may be divided into two general classes: first, the heat-produc-

* For further details see Oppenheimer, "Die Fermente und ihre Wir-
kungen," second edition, 1903.

870 NUTRITION AND HEAT REGULATIOX.

ing metabolism, which results finally in the oxidation of the great
mass of the food material and which is essential for the production
of body heat, and, second, the tissue metabolism proper — that is,
the synthesis and disassimilation of the living substance itself.
This latter metabolism varies probably in the different tissues;
it is concerned with the building up and breaking down of the living
machinery and is attended by the absorption as well as the liberation
of heat, and the energy necessary for effecting these reactions is
obtained from the heat energy liberated by the oxidation processes.
In this last thought there is contained a suggestion which may
serve as an explanation of the fundamental value of the physiolog-
ical oxidations to the body. It may be supposed that these oxida-
tions furnish the energy necessary for the anabolic or synthetic
metabolism of living matter. In those organisms or cells that
lead an anaerobic existence — that is, an existence in the absence of
free oxygen — the energy necessary for the process is obtained per-
haps from hydrolytic changes alone.

SECTION IX.
THE PHYSIOLOGY OF REPRODUCTION.

With the exception of the phenomenon of consciousness, no
fact of life excites more interest and seems to offer greater diffi-
culties to an adequate explanation than the function of reproduc-
tion. The male cell (spermatozoon) and the female cell (ovum)
unite to form a new cell which thereupon begins to grow rapidly
and produces an organism that in all of its manifold peculiarities
of structure and function is essentially a replica of its parents.
The fundamental problems presented in this act of reproduction
are those of fertilization and heredity. In the former we must
ascertain why the union of the two cells is necessary or advanta-
geous, and the secret of the stimulating influence upon growth that
arises from this union. Under the term heredity we express the obvi-
ous, yet mysterious, fact that the fertilized ovum of each species de-
velops into a structure like that of its parents. Both of these im-
portant problems are essentially of a physiological character, — that
is, they deal with properties of the living material composing the
reproductive cells; but, at present, biological investigation along
these lines is largely in the morphological stage. The part of the sub-
ject that can be studied with most success is the structural changes
that are associated with fertilization and reproduction. Great,
indeed wonderful, progress has been made during the last century,
but it is needless perhaps to say that much remains unexplained,
and- that in this, as in so many other problems of nature, the greater
our knowledge the clearer becomes our vision of the difficulties and
complexities of a final scientific explanation. Outside these funda-
mental problems there are other accessoiy functions connected, for
instance, with the external genital organs which in a measure are of
more immediate practical interest. In one way or another these
functions are necessary or helpful to the final union of the repro-
ductive cells. They form a part of the reproductive life which comes
more immediately under our observation and control, and consti-
tute, therefore, a subject which has been more accessible to in-
vestigation. In the brief treatment given in the following chap-
ters more emphasis is laid upon this side, the accessory phenomena
of reproduction, than upon the deeper, more fundamental prob-

871

872 THE PHYSIOLOGY OF REPRODUCTION.

lems, in view of the fact that the accessory phenomena are the ones
which have at present the greater practical interest.

The function of reproduction is often omitted from physiolog-
ical courses, and the reason perhaps is partly that the structural
features and the development of the embryo have been assigned to
the department of anatomy, and partly because it is a function
not essential to the maintenance of the existence and reactions of
the organism. The reproductive organs might be eliminated en-
tirely and the power of the body as an organism to maintain its
individual existence not be seriously interfered with. The physio-
logical importance of the reproductive organs lies not in their
co-operation in the communal life of the various parts of the body,
but in their adaptation to produce another similar being. We
may explain, therefore, the co-ordinating mechanisms of the
body without reference to the reproductive tissues, except so far
as their supposed internal secretions affect general or specific
metabolism.

CHAPTER LIT.

PHYSIOLOGY OF THE FEMALE REPRODUCTIVE
ORGANS.

The Graafian Follicle and the Corpus Luteum. — The functional
value of the ovary is connected with the formation and rupture
of the Graafian follicles, whereby an ovum is liberated. The pri-
mordial follicles consist of an ovum surrounded by a layer of fol-
licular epithelium. Beginning at a certain time after birth and
continuing throughout the period of active sexual life, some of these
primordial follicles develop into mature Graafian follicles and mi-
grate to the surface of the ovary. The change consists in a "pro-
liferation of the follicular epithelium and the formation of a serous
liquid, the liquor folliculi, between the layers of this epithelium.
In the matured follicle there is a connective tissue covering, the
theca folliculi, formed from the stroma of the ovary and consisting
of two coats or tunics — the external and the internal. The cells
in the internal tunic develop a yellowish pigment as the follicle
grows, and are sometimes designated as lutein cells. Within the
capsule formed by the internal tunic there is a layer of follicular
cells known as the membrana granulosa and attached to one side
is a mass of the same cells, the discus proligerus — within which
the ovum is imbedded. The follicular liquid lies between. This
liquid increases in amount, and when the follicle has reached the

THE FEMALE REPRODUCTIVE ORGANS. 873

surface it forms a vesicle projecting to the exterior. This projecting
portion is nearly bloodless and thinner than the rest of the wall of
the follicle. It is designated as the stigma. When fully mature the
follicle ruptures at the stigma and the egg, together with the sur-
rounding follicular cells of the discus proligerus and a portion of the
membrana granulosa, is extruded, the egg being received into the
open end of the Fallopian tube. According to Clark,* the rupture of
the follicle is brought about by an increasing vascular congestion
of the ovary. The tension within the ovary is thereby increased,
the follicle is forced to the surface, and the circulation at the most
projecting portion is interfered with to such an extent as to cause
necrotic changes at the stigma, at which rupture finally occurs. After
the bursting of the follicle its walls collapse, and the central cavity
receives also some blood from the ruptured vessels of the theca.
Later on the vesicle becomes filled with cells containing a yellow
pigment. These cells increase rapidly and form a festooned border
of increasing thickness around the central blood clot. The vesicle
at this stage, on account of the yellow color of the new cells, is
known as a corpus luteum. The structure thus formed increases
in size for a period and then undergoes retrogressive changes and
is finally completely absorbed. The duration of the period of growth
and retrogression varies according as the egg liberated becomes
fertilized or not. If fertilization does not occur, as is the case in
the usual monthly periods, the corpus luteum reaches its maximum
size within two to three weeks and then begins to be absorbed.
•It is frequently designated under these circumstances as the false
corpus luteum (corpus luteum spurium) or corpus luteum of men-
struation. In case the egg is fertilized and the woman becomes
pregnant the life history of the corpus luteum is much prolonged.
Instead of undergoing absorption after the third week it continues
to increase in size by multiplication of the lutein cells during the
first few months of pregnancy, and does not show retrogressive
changes until the sixth month or later. The total size of the corpus
in such cases is much larger than in menstruation, and it was des-
ignated, therefore, by the older writers as the true corpus luteum
(corpus luteum verum) or corpus luteum of pregnancy. Later
observers agree that there is no essential difference in structure
between the true and the false corpus luteum, although the former
has a longer history and attains a greater size. The point of
greatest structural interest in the corpus luteum is the origin of the
yellow (lutein) cells. Histologists have been and still are divided
upon this point; some believe that they arise from the cells of the
membrana granulosa, others that they come from the connective
tissue cells in the internal capsule (theca interna) of the follicle.
* Clark, "Johns Hopkins Hospital Reports," 7, 181, 1898.

874 THE PHYSIOLOGY OF REPRODUCTION.

The majority of writers seem to favor the latter view.* Regarding
the physiological importance of the corpus opinions also differ.
Some regard it as simply a protective mechanism by means of
which the empty space in the follicle is filled up by a tissue which is
afterward easily absorbed, instead of by scar tissue. Others, how-
ever, attribute to the lutein cells secretory functions of the most
important character in connection with the subsequent develop-
ment of the egg and the activities of the uterus. Some reference
will be made to these views farther on.

Menstruation. — The attainment of sexual maturity or puberty
is marked by a number of visible changes in the body, but in the
female the characteristic change is the appearance of the men-
strual flow from the uterus. The age at which this phenomenon
occurs shows many individual variations, but the average for
temperate climates is given usually at 14 to 15 years. In the
warmer countries the age is earlier, — 8 to 10 years, — and in the cold
regions somewhat later, — 16 years. The racial characteristic in
this respect is said to be maintained, however, after generations of
residence hi countries of a different climate, as is illustrated by the
relatively early appearance of menstruation among Jews even in
the colder countries. After the phenomenon appears it occurs at
regular intervals of 28 days, more or less, and hence is known as
the monthly period, menses, menstruation, or catamenia. The
interval is not absolutely regular, and shows many individual
variations within limits which may be placed at 20 to 35 days.
Absence of the menstrual flow is designated as a condition of amen-
orrhea. Certain premonitory symptoms usually precede the
appearance of the menses, such as pains in the back or head or
a general feeling of discomfort, although in some cases these symp-
toms are absent. When these premonitory symptoms are unusually
painful or serious and the flow is difficult or irregular the condition
is designated as dysmenorrhea. The flow begins with a discharge of
mucus, which later becomes mixed with blood. The quantity of
blood lost is subject to individual variations, but it may amount to
as much as 100 to 200 gms. The flow continues for 3 or 4 days
and then subsides. Under normal conditions this phenomenon
occurs regularly throughout sexual life, — that is, during the period
in which conception is possible. If fertilization occurs the flow
ceases normally during pregnancy and the period of lactation. At
the forty-fifth to the fiftieth year the flow disappears permanently,
and this change marks what is known as the natural menopause,
climacteric, or change of life. The change is sometimes abrupt,
sometimes very gradual, being preceded by irregularities in

* For discussion and literature see Marshall, "Quarterly Journal Micro-
scopical Science," 1905, xlix., 189; and Loeb, " Journal of the American
Medical Association," 1906, xlvi., 416.

THE FEMALE REPRODUCTIVE ORGANS. 875

menstruation, and it is not infrequently associated with psychical
and physical disturbances of a serious character. If at any time
during sexual life the ovaries are completely removed by surgical
operation menstruation is brought to a close, this condition being
designated as artificial menopause.

Structural Changes in the Uterus During Menstruation. — Men-
struation is a phenomenon of the uterus. The lining mucous mem-
brane, the endometrium, in the period of four or five days preceding
the flow, becomes rapidly 'thicker and its superficial layers are con-
gested with blood, and indeed in places small collections of blood
may be noticed. Opinions differ very much as to the change under-
gone by this thickened membrane during the flow. According to
some authors, most of the membrane is thrown off and the blood
escapes from the denuded surface mixed with pieces of the mem-
brane. According to others, no material destruction of the mem-
brane occurs, the blood that escapes being due to small capillary
extravasations or perhaps mainly to a process of diapedesis. It
would seem that the amount of destruction of the endometrium
must be subject to individual variations. After the cessation of
the flow the mucous membrane is rapidly repaired by regenerative
changes in the tissues; the surface epithelium, if denuded, is re-
placed by proliferation of the cells lining the uterine glands and
the thickened, edematous condition of the membrane rapidly sub-
sides during a period of six or seven days. While the escape of
blood takes place only from the surface of the uterus, the other
reproductive organs — the ovary, the Fallopian tubes, and even the
external genital organs — share to some extent in the vascular con-
gestion exhibited by the uterus during the period preceding the
menstrual flow. The mucous membrane of the uterus may be said
to exhibit a constantly recurring menstrual cycle which falls into
four periods: (1) Period of growth in the few (5) days preceding
menstruation, characterized by a rapid increase in the stroma,
blood-vessels, epithelium, etc., of the membrane. (2) The men-
struation or period of degeneration (4 days), during which the
capillary hemorrhage takes place and the epithelium suffers de-
generative changes and is cast off more or less. (3) The period of
regeneration (7 days), during which the mucous membrane returns
to its normal size. (4) The period of rest (12 days), during which
the endometrium remains in a quiescent condition.

The Phenomenon of Heat (CEstrus) in Lower Mammals. —
The phenomenon known as heat in lower mammals resembles, in
many essential respects, menstruation in human beings, and they
may be regarded as homologous functions. Heat is a period of
sexual excitement which occurs one or more times during the year
and during which the female will take the male. The condition

876 THE PHYSIOLOGY OF REPRODUCTION.

lasts, as a rule, for several days, and in the female is accompanied
by changes which resemble those of menstruation. The external
genital organs become swollen and in many animals there, is a
discharge of mucus or mucus and blood from the uterus. His-
tologically the mucous membrane of the uterus undergoes changes
similar to those of menstruation — that is, the membrane increases
in size and becomes congested with blood — and it exhibits a phase
of degeneration during which some of the epithelial lining may be
cast off and some hemorrhage occur. As in the case of the men-
strual period, the heat period or oestrous cycle may be divided into
four subperiods (Marshall and Jolly) : the procestrum, during which
the genital organs are congested and bleeding occurs, corresponds
with menstruation; the oestrus, the period of sexual desire; the
metcestrum, the period of repair and return to normal conditions,
and the ancestrum, the period of rest. If sexual union is prevented
during this period heat passes away in a few days, but recurs again
at intervals which vary in the different mammals: 4 weeks in the
monkey, mare, etc.; 3 to 4 weeks in the cow; 2£ to 4 weeks in the
sheep; 9 to 18 days in the sow; 12 to 16 weeks in the bitch, etc.
The recurrence of the period under these circumstances suggests
at once the essential resemblance to the monthly periods of women.
According to Heape's most interesting observations upon monkeys
(Semnopithecus),* some of these animals show a regular monthly
flow lasting for 4 days, except when conception takes place. The
changes during heat must be considered as physiologically ho-
mologous to those of menstruation. The sexual excitement that
attends the condition in the lower animals is not distinctly repre-
sented in man, although it is commonly said that in the period pre-
ceding or following menstruation the sexual desire is stronger than
at other times, but in the changes undergone by the uterus and the
fact that these changes are connected, as a rule, with the liberation
of an egg from the ovary (ovulation), the two phenomena are
physiologically similar.

Relation of the Ovaries to Menstruation. — It appears to be
clearly demonstrated that the phenomenon of menstruation is de-
pendent upon a periodical activity in the ovaries. When the
ovaries are completely removed menstruation ceases (artificial
menopause) and the uterus undergoes atrophy. When the ovaries
are congenitally lacking or rudimentary, a condition of amenorrhea
also exists. These facts and the connection of the ovaries with
menstruation are further corroborated in a striking way by experi-
ments upon transplantation or grafting of the ovary. This experi-
ment has been performed upon lower animals (apes) as well as upon

*Heape, "Philosophical Transactions, Royal Society," 185 (B), 1894,
and 188 (B), 1897.

THE FEMALE REPRODUCTIVE ORGANS. 877

human beings. Removal of both ovaries in apes is followed by a ces-
sation of menstruation. Transplantation of an ovary under the skin
serves to maintain menstruation, but if subsequently removed this
function disappears.* In the human being Morris and Glass ob-
tained similar results, f An ovary or a piece of an ovary trans-
planted into the uterus itself or the broad ligament caused a re-
turn of the menstrual periods which had ceased after surgical re-
moval of the glands, or brought on free menstruation in conditions
of amenorrhea or dysmenorrhea.

Many views have been proposed to explain this relationship
between ovary and uterus. In most cases it has been assumed
that the menstruation in the uterus is connected with the act of
ovulation, — that is, the ripening and discharge of a Graafian follicle.
Gynecologists, it is true, have accumulated facts to show that ovu-
lation may occur independently of menstruation, but no one doubts
that, as a rule, the two acts occur together, not simultaneously but
in a definite sequence, and that the significance of menstruation is to
be found in its physiological dependence upon the fate of the ovum.
It was believed at first that the processes in the ovary influence the
uterus by a nervous reflex. This view finds its most complete
expression in the theory formulated by Pfliiger. According to this
physiologist, the congestion of the uterus which leads to menstrua-
tion and the congestion of the ovary which leads to ovulation are
both reflex vasodilator effects due to the mechanical stimulation
of the sensory nerves of the ovary by the growth in size of the fol-
licle. As this structure develops the mechanical stimulus increases
in intensity, the congestion in both organs becomes more pro-
nounced and leads finally to the bursting of the follicle and the
hemorrhage in the uterus. This very attractive theory d,oes not,
however, accord with the facts. Goltz and ReinJ have shown by
experiments upon dogs that when the nerves going to the uterus
are completely severed from their central connections the animals
can be fertilized, become pregnant, and give birth to a litter of
young. Moreover, the experiments upon transplantation referred
to above seem to show quite conclusively that a nervous connection
is not essential to the influence that the ovary exerts upon the
uterus. The present view, therefore, is that this influence is exerted
through the blood, — the other great system connecting the organs
with one another. The usual assumption is that the ovaries form an
internal secretion which is given to the blood or lymph and upon
reaching the uterine tissues serves to stimulate the mucous mem-
brane to a more active growth. This theory has been elaborated

*Halban, "Deutsche Gesellschaft f. Gynakol.." 9, 1901.

t Glass, "Medical News," 523, 1899; Morris, "Medical Record," 83, 1901.

j Rein " Archiv f. die gesammte Physiologic/' vol. xxiii.

878 THE PHYSIOLOGY OF REPRODUCTION.

most fully perhaps by Fraenkel,* who believes that this internal
secretion is furnished by the yellow cells of the corpus luteum.
This observer, from the results of operations upon women, believes
that the ovum is normally discharged two weeks before menstrua-
tion, and the resulting increased activity of the cells of the corpus
luteum is responsible for the secretion which stimulates the uterus
to the augmented growth that takes place in the premenstrual
period. In the lower animals Marshall and Jolly f have been able
to show that extracts of the ovaries, taken from an animal in or
just before heat (prooestrous or oestrous period), when injected into
an animal during the anoestrum bring on a transient condition of
heat. These authors do not believe, however, that the chemical
stimulus (hormone) formed in the ovary is developed by the cells
of the corpus luteum, since according to their observations on cats
and dogs ovulation does not occur until after heat has begun (pro-
oestrum) .

The Physiological Significance of Menstruation. — Naturally
many views have been proposed to explain the significance of men-
struation. According to the Mosaic law, it is a process of purifica-
tion; others have seen in it a mechanism to remove an excess of
nutriment in the body ; but since the period in which our knowl-
edge of the structure of the organs concerned and of the histo-
logical changes during the act became more definite, theories of the
meaning of menstruation have usually assumed that it is a prepara-
tion for the reception of the fertilized ovum. These views have
taken two divergent forms according as the act of ovulation was
believed to precede or to happen simultaneously with or subse-
quently to the act of menstruation. According to one view, the
swelling and congestion of the membrane constitute a prepara-
tion for the reception of the fertilized ovum. If the ovum fails of
fertilization, then degenerative changes ensue, and the membrane
or a portion of it is cast off in the menstrual flow, while the re-
mainder is absorbed. According to this view, menstruation is an
indication that fertilization has not taken place. J This view
falls in with the belief that ovulation normally precedes menstrua-
tion by a considerable interval. The other point of view was
advocated especially by Pfliiger in connection with his theory of the
common cause of ovulation and menstruation. He assumed that
menstruation occurs before the ovum reaches the uterus and that

* Fraenkel, " Archiv f. Gynakologie," 68 2, 1903. See also Ihm,
" Monatsschrift f. Geburtshiilfe u. Gynakol.," 21, 515, 1905, for discussion
and extensive literature.

t Marshall and Jolly, "Philosophical Transactions, Royal Society,"
London, 1905, B. cxcviii., 99.

J This view finds expression in the aphorisms: "Women menstruate
because they do not conceive," Powers, and "The menstrual crisis is the
physiological homologue of parturition," Jacobi.

THE FEMALE REPRODUCTIVE ORGANS. 879

its physiological value lies in the fact that a raw surface is thus made
upon which the ovum is grafted. Menstruation, according to him,
is an operation of nature for the grafting of the fertilized ovum
upon the maternal organism. This view finds considerable support
in the fact that in some of the lower animals (dogs) the flow of
blood (prooestrum) precedes fertilization.

The Effect of the Menstrual Cycle on Other Functions. — It
is natural to suppose that such marked changes as occur in the
ovary and uterus during the menstrual cycle should have an in-
fluence upon other parts of the body. As a matter of fact, it is
known that in general the sense of well-being varies with the phases
of the cycle. At the time of or in the period just preceding the
menstrual flow there is usually a more or less marked sense of ill-
being or despondency, and a diminution in general efficiency.
Among the various observations made by objective methods upon
the functions of the different organs during these periods the most
significant, probably, are those upon blood-pressure. According
to Mosher,* the blood-pressure falls at the time of the menstrual
periods. The curves obtained in these experiments are not entirely
regular, but at or near the menstruation the blood-pressure falls
slowly, the maximum fall being coincident with the appearance of
the flow. It would seem probable that the fall of general blood-
pressure is due directly to the vascular dilatation in the genital or-
gans and in turn is responsible for some of the secondary phenomena
observed in the organism as a whole. It is very suggestive to find
that the author quoted above obtained similar periodical falls in
blood-pressure in men, suggesting the idea that has frequently been
expressed, that in man as well as woman there is a rhythmical
activity of the genital organs, a reproductive cycle that in man
may be referred to the development and extrusion of the sperma-
tozoa in the testis, as in woman it is connected with the growth and
expulsion of the ova in the follicles of the ovary.

The Passage of the Ovum into the Uterus. — The means by
which the ovum gains entrance to the Fallopian tubes has given
rise to much speculation and some interesting experiments. It
was formerly believed (Haller) that at the time of ovulation the
fimbriated end of the Fallopian tube is brought against the ovary,
the movement being due to a congestion or a sort of erection of the
fimbrise. This movement has not been observed, and, as experi-
ments show that small objects introduced into the pelvic cavity are
taken up by the tubes, it is believed that the cilia upon the fimbriae
and in the tubes may suffice to set up a current that is sufficient
to direct the movements of the ovum. Attention has been called
to the fact that in animals with a bicornate uterus the ova may
be liberated from the ovary on one side, as shown by the presence
* Mosher, "The Johns Hopkins Hospital Bulletin," 1901.

880 THE PHYSIOLOGY OF REPRODUCTION.

of the corpora lutea, while the embryos are developed in the horn
of the other side. As further evidence for the same possibility of
migration it has been shown that the ovary may be excised on one
side and the horn of the uterus on the other and yet the animal may
become pregnant after sexual union. It would seem probable,
therefore, that the ovum is discharged into the pelvic cavity and
may be caught up by the ciliary movements at the end of the tube
on the same side, or may traverse the pelvic cavity in the narrow
spaces between the viscera and be received by the tube on the
other side. Such a view explains the possible occurrence of true
abdominal pregnancies, and suggests also the possibility that ova
may at times fail to reach the uterus at all and may undergo de-
struction and absorption in the abdominal cavity. In some of
the lower animals — the dog, for example — provision is made for
the more certain entrance of the ova into the tubes by the fact
that the latter end in connection with a membranous sac of peri-
toneum which envelopes the ovary. The sexual fertilization of the
ovum is supposed to take place shortly after its entrance into
the Fallopian tube, since spermatozoa have been found in this
region, and the fertilized ovum, before reaching the seat of its im-
plantation in the body of the uterus, has begun its development.

By the act of coitus the
spermatozoa are deposited
at the mouth of the uterus,
whence they make their way
toward the tubes, being
__d guided in their movements
very probably by the oppos-
ing force of the ciliary con-
~j~n tractions in the uterus. It
is known that the cilia of
the tubes and uterus con-
tract so as to drive inert
objects toward the vagina
and they carry the egg in

Fig. 277.— Human ovum (Lee, modified from this direction, b U t the
Nagel): n, Nucleus (germinal vesicle) containing enprrrmtn'/nfl hpino* rnnvpH
the ameboid nucleolus (germinal spot); d, deu- SpermaiOZOa, I

radiataniC«ZOnerivifellFn0s°ac|SmiC ^^ *' ^^ ^ the contractions of their

own cilia or tails, are

stimulated to advance against this ciliary current. The act of ferti-
lization of the ovum is preceded by certain preparatory changes
in the ovum itself which are described under the term maturation.
Maturation of the Ovum. — The process of maturation occurs
before or just after the spermatozoon enters the ovum. At the
time the latter is extruded from the follicle it is a single cell sur-

Fig. 278. — Schematic representation of the processes occurring during cell division.

(Boveri.)

THE FEMALE REPRODUCTIVE ORGANS. 881

rounded by a layer of follicular epithelium forming the corona ni-
diata, which is subsequently lost. The egg proper consists of
cytoplasm and a nucleus or germinal vesicle containing a nucleolus
or germinal spot. Within the cytoplasm is a definite collection of
food material or yolk which is sometimes designated as deutoplasm.
The whole structure is surrounded by a membrane known as the
zona radiata (Fig. 277) . Before or after the egg reaches the Fallopian
tube its nucleus undergoes the changes preparatory to a mitotic
division. These changes are essentially similar to those of ordi-
nary cell division as represented schematically in Fig. 278. The
nucleus at first presents the ordinary chromatin network, and in
the cytoplasm lies the minute structure known as the centrosome.
This latter divides into two daughter-centrosomes (6) which move
to opposite sides of the nucleus and become surrounded by rays,
each centrosome with its radiating system forming an astro-
sphere. The chromatin material in the nucleus meanwhile has
collected into larger threads known as chromosomes (c), and
the nuclear membrane disappears (d). The number of chromo-
somes is definite for each species of animal. The chromosomes
arrange themselves equatorially between the astrospheres and then
each divides longitudinally into two parts (/). These parts migrate
or are drawn toward their respective centrosomes (g, h, i), and this
division is followed by a separation of the cytoplasm into two parts.
Thus, two daughter-cells are formed, each containing the same
number of chromosomes as the parent-cell, but only half the amount
of chromatin material. The cell division results in a quantitative
reduction of the chromatin material. In ordinary cell division the
chromosomes again form a resting reticulum and a nuclear mem-
brane and the chromatin substance increases in quantity. In the
ovum a similar cell division takes place except that the daughter-
cells are very unequal in size ; one is very minute and is known as
the first polar body, the other as the ovum. After the formation and
extrusion of the first polar body, the ovum again undergoes division
into two unequal halves, giving rise to a second polar body. In
this division, however, the chromosomes are divided transversely,
and the ovum after the division is left with only half the number of
chromosomes characteristic of the species. In the formation and
extrusion of the two polar bodies the matured ovum has suffered
a quantitative and perhaps a qualitative reduction in chromatin ma-
terial, and is left with only half its number of chromosomes. Since
the first polar body after its separation may again divide into two
cells, the process of maturation results in the formation of four cells,
three of which are polar bodies and may be regarded as abortive
ova. The fourth, the matured ovum, retains practically all of the
original cytoplasm, but has lost a part of its chromatin material

56

882 THE PHYSIOLOGY OF REPRODUCTION.

and, according to Boveri, also its centrosome. The production
of these four cells may be represented, therefore, by a schema of
the kind shown in Fig. 279. The details of this process of forma-
tion of the polar bodies and of reduction in chromatin material
differ somewhat in different animals.* The process has not been
followed in the human ovum, but since it occurs in the eggs of all
animals with sexual reproduction, so far as they have been studied,
it is justifiable to assume that a similar change takes place in man.
From a biological standpoint the reduction of chromosomes and
the loss of the centrosome, or of the power to produce a centrosome,
throw much light upon the significance of fertilization by the male
cell. The spermatozoon before it is ripe undergoes a process of
maturation essentially similar to that described for the ovum.
Two cell divisions take place with the formation of four spermatozoa,
each of which, however, is a functional spermatozoon. In the pro-
cess of division the number of chromosomes in each cell is reduced

— Ovarian egg.

• First polar body.

Mature egg f&il • • • Abortive ova resulting *

from division of first
polar body.

Second polar body (abortive ovum).
Fig. 279. — Schema to indicate the process of maturation of the ovum. — (Boveri.)

by half. When the matured ovum and the matured spermatozoon
fuse, therefore, each brings half the normal number of chromosomes,
and the resulting fertilized ovum is a cell with its chromosomes
restored to their usual number. The chromatin material is the
essential part of the reproductive element. We have reasons to
believe, in fact, that it is the substance which has the power of
development and which conveys the hereditary structure specific
to the animal. The process which causes each element to lose a
part of this material before its union with the cell of the opposite
sex is a provision by means of which the fertilized egg, from which
the offspring develops, shall inherit the characteristics of each parent,
without increase in the typical amount of the chromosomes. The
loss of the centrosome by the matured egg is interpreted by Boveri
as follows:f This minute structure is the instrument by which the

* For details see Wilson, "The Cell in Development and Inheritance."
Second edition, 1900, New York.

f For a popular presentation see Boveri, "Das Problem der Bef ruchtung. "
Jena, 1902.

Fig. 280. — Schematic representation of the processes occurring during the fertiliza-
tion and subsequent segmentation of the ovum. — (Boveri.) The chromatin (chromo-
somes) of the ovum is represented in blue, that of the spermatozoon in red.

THE FEMALE REPRODUCTIVE ORGANS. 883

mechanical process of cell division is initiated and completed. Its
loss by the matured ovum prevents this cell from further develop-
ment, but in the act of fertilization the spermatozoon brings into
the egg a new centrosome, or causes the formation of a new centro-
some after its entrance, and thus initiates a process of cell mul-
tiplication. From this standpoint the loss of the centrosome by
the egg is a provision to necessitate sexual union, and thus insure
the benefits that presumably are associated with the fusion of two
cells originating from different individuals.

Fertilization of the Ovum. — The spermatozoon comes into
contact with the ovum probably at the beginning of the Fallopian
tubes. The meeting of the two cells is possibly not simply a matter
of accidental contact, although the number of spermatozoa dis-
charged by the male at coitus is so great that there would seem
to be little chance for the ovum to fail to meet some of them. Ex-
periments upon the reproductive elements of plants indicate, how-
ever, that the egg may contain substances which serve to attract
the spermatozoon, within a certain radius, by that force which
is described under the name of chemotaxis. However this may be,
the egg unites with a spermatozoon and under normal conditions
with only one. A number of the spermatozoa may penetrate
the zona radiata, but so soon as one has come into contact with
the cytoplasm of the egg a reaction ensues in the surface layer
which makes it impervious to other spermatozoa. The spermato-
zoon consists of three essential parts, — the head, the middle piece,
and the tail. The last named is the organ of locomotion, and
after the spermatozoon enters the egg this portion atrophies and
disappears, probably by absorption. The head of the spermato-
zoon represents the nucleus, and contains the valuable chromatin
material. On entering the egg it moves toward the nucleus of the
latter, meanwhile enlarging and taking on the character of a nu-
cleus. The egg now contains two nuclei, — one belonging to it origi-
nally, the female pronucleus; one brought into it by the sperma-
tozoon, the male pronucleus. The two come together and fuse,
— superficially at least, — forming the nucleus of the fertilized egg, or
the segmentation nucleus. The middle piece of the spermatozoon
also enters the egg, but its exact function and fate is still a matter
of some uncertainty. Boveri believes that it brings into the egg a
centrosome or material which induces the formation of a centro-
some in the ovum and is therefore of the greatest importance in
initiating the actual process of cell division which begins promptly
after the fusion of the nuclei. In the segmentation nucleus the nor-
mal number of chromosomes is restored, and it is believed that in
the subsequent divisions of the cell to form the embryo the chromo-
somes are so divided that each cell gets some maternal and some

884 THE PHYSIOLOGY OF REPRODUCTION.

paternal chromosomes, and thus shares the hereditary characteris-
tics of each parent. This -view is represented in a schematic way
by Fig. 280, taken from Boveri, the maternal and paternal chromo-
somes being indicated by different colors. According to this descrip-
tion, both egg and spermatozoon are incomplete cells before fusion.
The egg contains a nucleus and a large cell body, cytoplasm, rich in
nutritive material, but it lacks a centrosome or the conditions neces-
sary for the formation of an astrosphere, so that it cannot mul-
tiply. The spermatozoon has also chromatin for a nucleus, and
a centrosome or the material which may give rise to a centrosome,
but it lacks cytoplasm — that is, food material for growth. It
would seem that if the spermatozoon could be given a quantity
of cytoplasm it would proceed to develop an embryo without the
aid of an ovum. This experiment has, in fact, been made by
Boveri. Eggs of the sea-urchin were shaken violently so as to
break them into fragments. If now a spermatozoon entered
one of these fragments, which consisted only of cytoplasm, cell
multiplication began and proceeded to the formation of a larva.
On the other hand, it would seem to be equally evident that if a
centrosome was present in the egg or some influence could be
brought to bear upon it to make it form a centrosome it would
develop without a spermatozoon. In some animals eggs do nor-
mally develop at times without fertilization by a spermatozoon
(parthenogenesis), the eggs that have this property probably pre-
serving their centrosomes. Loeb* has shown, however, in some
most interesting experiments that certain eggs, especially those of
the sea-urchin (Strongylocentrotus purpuratus), which normally
develop by fertilization with spermatozoa, may be made to de-
velop by physicochemical means. His latest method is to treat
the egg for a minute or two with an acid (acetic, formic, etc.),
which causes the formation of a membrane. They are then placed
for a certain interval in a hypertonic sea water, made by adding
sodium chlorid to ordinary sea water. They are then transferred
to normal sea water and after an hour or so they begin to multiply
and eventually develop into normal larva?. Similar although less
complete results were obtained previously by Morgan.

Implantation of the Ovum. — After fertilization in the tube the
ovum begins to segment and multiply, and meanwhile is carried
toward the uterus, probably by the action of the cilia lining the tube.
Upon reaching the cavity of the uterus it becomes attached to the
mucous membrane, usually in the neighborhood of the fundus.
The membrane of the uterus has become much thickened mean-
while, and in this condition is known usually as the decidua. The

* Loeb, "University of California Publications," 2, pp. 83, 89, and 113,
1905. See also Wilson, "Archiv f. entwick. Mechanik," 12, 1901.

THE FEMALE REPRODUCTIVE ORGANS. 885

portion to which the egg becomes attached is the decidua serotina,
and it eventually develops into the placenta, the organ through
which the maternal nutriment is supplied to the fetus. The ovum
has made considerable progress in its development before reaching
the uterus, having formed amnion and chorion, with chorionic villi.
Some of the ectodermal cells in the chorion become specialized to
form a group of trophoblastic cells which have a digestive action,
and it is suggested that the activity of these cells enables the ovum
to become attached to the decidual membrane and to hollow out
spaces in which the chorionic papilla become inserted.* The further
development of the egg into a fetus, the formation of the decidua
graviditatis, and the placenta are anatomical features that need
not be described here. Details of these structures will be found
in works on anatomy, embryology, or obstetrics. On the phys-
iological side it has been found that removal of the ovaries, or even
destruction of the corpora lutea, shortly after pregnancy has begun
brings the process to an end, while a similar operation later in
pregnancy has no effect upon the developing fetus or the subsequent
act of parturition. It seems, therefore, that the process of implan-
tation of the ovum in the uterine mucous membrane and the devel-
opment of a placenta are dependent in some way upon the ovaries.
The apparent explanation of the connection is given in the hypothe-
sis that the corpora lutea, during their rapid development at the
beginning of pregnancy, give off an internal secretion which controls
or influences in some essential way the processes connected with
the fixing of the fertilized ovum.f

The Nutrition of the Embryo — Physiology of the Placenta.
— At the time of fertilization the ovum contains a small amount
of nutriment in its cytoplasm. The amount, however, in the mam-
malian ovum is small and suffices probably only for the initial stages
of growth. When the ovum becomes implanted in the decidual
membrane of the uterus the new material for growth must be ab-
sorbed directly from the maternal blood of the uterus. Within
a short time, however, the chorionic villi begin to burrow7 into the
uterine membrane at the point of attachment, the decidua serotina,
and the placenta gradually forms as a definite organ for the control
of fetal nutrition. The details of histological structure of this
organ must be obtained from anatomical sources. For the purposes
of understanding its general functions it is sufficient to recall that
the placenta consists essentially of vascular chorionic papilla? from
the fetus bathed in large blood-spaces in the decidual membrane of
the mother. The fetal and the maternal blood do not come into
actual contact : they are separated from each other by the w7alls of

* See Minot, "Transactions of the American Gynecological Society/' 1904.
t Marshall and Jolly and Fraenkel, loc. cit.

THE PHYSIOLOGY OF REPRODUCTION.

the fetal blood-vessels and the epithelial layers of the chorionic villi,
but an active diffusion relation is set up between them. Nutritive
material, proteid, fat, and carbohydrate, and oxygen pass from
the maternal to the fetal blood, and the waste products of fetal
metabolism — carbon dioxid, nitrogenous wastes, etc., pass from the
fetal to the maternal blood. The nutrition of the fetal tissues is
maintained, in fact, in much the same way as though it were an
actual part of the maternal organism. That material passes from
the maternal to the fetal blood is a necessary inference from the
growth of the fetus. The fact has also been demonstrated repeat-
edly by direct experiment. Madder added to the food of the mother
colors the bones of the embryo. Salts of various kinds, sugar, drugs,
etc., injected into the maternal circulation may afterward be de-
tected in the fetal blood. But we are far from having data that
would justify us in supposing that the exchange between the
two bloods is effected by the known physical processes of os-
mosis, diffusion, and filtration. The difficulties in understanding
the exchange in this case are the same as in the absorption of nour-
ishment by the tissues generally. It is perhaps generally assumed
that the chorionic villi play an active part in the process, func-
tioning, in fact, in much the same way as the intestinal villi. This
assumption implies that the epithelial cells of the villi take an active
part in the absorption of material by virtue of processes which can-
not be wholly explained, but which without doubt are due to the
chemical and physical properties of the substance of which they are
composed. This assumption does not mean that the simpler
and better understood physical properties of diffusion and osmosis
are not also important. The respiratory exchange of gases, the
diffusion of water, salts, and sugar, may be largely controlled in this
way. There are no facts at least which contradict such an assump-
tion. The passage of fats and proteids, however, would seem to
require some special activity in the chorionic tissue, which may be
connected with the presence of special enzymes. Glycogen occurs
in the placenta itself and in all the tissues of the embryo during the
period of most active growth. In the later period of embryonic
life, as the liver assumes its functions, the glycogen becomes
more localized to this organ and disappears, except for traces,
in the skin, lungs, and other tissues in which it was present at
first in considerable quantities. It would appear, therefore, that
glycogen (sugar) represents one of the important materials for the
growth of the embryo, and that in the beginning at least the tissues
generally have a glycogenetic power. The sugar brought to the
placenta in the maternal blood passes over into the fetal blood and
the excess beyond that immediately consumed is deposited in the
tissues as glycogen. The body fat of the fetus is at first slight in

THE FEMALE REPRODUCTIVE ORGANS. 887

amount, but after the sixth month begins to increase with some
rapidity. The fat-forming tissues are in full activity, therefore,
before birth, and function doubtless in the same way as in
the adult. Before birth also the various organs begin to take on
their normal activity. The kidney may form urine long before
birth, as is shown by the presence of this secretion in the bladder,
and, shortly before birth at least, it has the power of producing
hippuric acid, as may be shown by injecting benzoates into the
blood of the mother. The kidney functions of the embryo, how-
ever, are doubtless performed chiefly by the placenta and the
kidney of the mother up to the time of birth. That the liver also
begins to assume its functions early is shown by the fact that from
the fifth to the sixth month one may find bile in the gall-bladder.
In the intestine, colon, there is found also a collection of excrement,
the meconium, which shows that the motor and secretory functions
of the intestinal canal may be present in the last months of fetal
life. From the pancreas a proteolytic enzyme may be extracted at
the time of birth or before, but the amylolytic enzyme is not formed
apparently until some time later. It is stated, at least, that it is
not present at birth. In general, it is evident that for a long period
the maternal organism digests and prepares the food for the embryot
excretes the wastes, regulates the conditions of temperature, etc.,
as it does for a portion of its own substance, but as the fetus ap-
proaches term its tissues and organs begin to assume more of an
independent activity, as indeed must be the case in preparation
for the sudden change at birth. In this respect, as in all parts of
the reproductive process, we meet with regulations whose mechanism
is but dimly understood.

Changes in the Maternal Organism during Pregnancy. —
The two most distinct effects upon the mother that result from
pregnancy are the growth of the uterus and of the mammary gland.
The virgin uterus is small and firm, weighing from 30 to 40 gms.,
while at the end of pregnancy it may weigh as much as 1000 gms.
This great increase in material is due partly to the growth of new
muscular tissue and partly to an hypertrophy of the muscle already
present. In the uterus at term the muscle cells are much longer
and larger than in the organ before fertilization. The stimulus
that initiates and controls this new growth is seemingly the fertil-
ized ovum itself, but the physiological means employed are not
comprehended. We know from experiments upon lower animals
(Rein) that when all connections with the central nervous system
are severed the fetus develops normally and the uterus increases
correspondingly in size and weight. The influence of the ovum on
the uterus must be exerted, therefore, either through some local
nerve centers in the uterus, or, as seems much more probable,

XXX THE PHYSIOLOGY OF REPRODUCTION.

through some chemical stimulus which it gives to the organ. The
effect of the presence and growth of the fetus on the mammary
gland is treated in a separate paragraph below. In addition to
these two visible effects it is evident that the growth of the fetus
has an important influence on general metabolism and therefore
upon the whole maternal organism. This fact is indicated by the
marked changes often exhibited in the physical and mental con-
dition of the mother. It is shown more precisely by a study of the
nutritional changes. Numerous investigations have been made
upon this side, especially as regards the nitrogen equilibrium. Dur-
ing the latter part of pregnancy, especially, the nitrogen balance is
positive — that is, nitrogen is stored as protein — due doubtless
both to the growth of the embryo and the increase in material in
the uterus and mammary gland. The proportion of ammonia in
the urine increases during pregnancy and especially during labor
(Slemmons*).

Parturition. — The fetus " comes to term " usually in the tenth
menstrual period after conception — that is, about 280 days after
the last menstruation. The actual time of delivery, however,
shows considerable variation. Delivery occurs in consequence of
contractions, more or less periodical, of the musculature of the
uterus, and reflex as well as voluntary contractions of the abdom-
inal muscles. It has been shown that delivery may occur when the
nerves connecting the uterus with the central nervous system are
severed, so that the act is essentially an independent function of
the uterus, although under normal conditions the contractions of
this organ are doubtless influenced by reflex effects through its
extrinsic nerves. It has been shown that contractions of the gravid
uterus may be caused by stimulation of various sensory nerves, and
in women it is known that delivery may be precipitated prematurely
by various mental or physical disturbances. The interesting prob-
lem physiologically is to determine the normal factor or factors that
bring on uterine contractions at term. Various more or less unsatis-
factory theories have been proposed. Some authors attribute
the act to a change in the maternal organism, such as mechani-
cal distension of the uterus, a venous condition of the blood, a
degenerative change in the placenta, etc., while others suppose that
the initial stimulus comes from the fetus. In the latter case it
is suggested that the increasing metabolism of the fetus is insuffi-
ciently provided for by the placental exchange, and that therefore
certain products are formed which serve to stimulate the uterus
to contraction.

The duration of the labor pains is variable, but usually they are
longer in primiparaB, ten to twenty hours or more, than in multip-

* Slemmons, "The Johns Hopkins Hospital Reports," 12, 111, 1904.

THE FEMALE REPRODUCTIVE ORGANS. 889

ane. After the fetus is delivered the contractions of the uterus
continue until the placenta also is expelled as the "after-birth."
During these latter contractions the fetal blood in the placenta is,
for the most part, squeezed into the circulation of the new-born
child. The hemorrhage from the walls of the uterus due to the rup-
ture of the placenta may be profuse at first, but under normal con-
ditions is soon controlled by the firm contraction of the uterine walls.

The Mammary Glands. — At the time of puberty the mam-
mary glands increase in size, but this growth is confined mainly
to the connective tissue; the true glandular tissue remains rudi-
mentary and functionless. At the time of conception the gland-
ular tissue is in some way stimulated to growth. Secreting alveoli
are formed, and during the latter part of pregnancy they produce
an incomplete secretion, scanty in amount, known as colostrum.
After delivery the gland evidently is again brought under the
influence of special stimuli. It becomes rapidly enlarged and a
more abundant secretion is formed. For the first day or two
this secretion still has the characteristics of colostrum, but on
the third or fourth day the true milk is formed and thereafter is
produced abundantly, during the period of lactation, under the in-
fluence of the act of milking. If during this period a new con-
ception occurs the milk secretion is altered in composition and
finally ceases. On the other hand, if the act of nursing is aban-
doned permanently the glands after a preliminary stage of turgid-
ity undergo retrogressive changes that result in the cessation of
secretory activity. The colostrum secretion that occurs during
pregnancy and for a day or two after birth differs from milk in
its composition and histological structure. It is a thin, yellowish
liquid containing a larger percentage of albumin and globulin
and a smaller percentage of milk-sugar and fat than normal milk.
Under the microscope it shows, in addition to some fat droplets,
certain large elements, — the colostrum corpuscles.- These con-
sist of spherical cells filled with fat droplets, and are most probably
leucocytes filled with fat which they have ingested. Colostrum
corpuscles may occur in milk whenever the secretion of the gland
is interfered with, and their presence may be taken as an indi-
cation of an incomplete secretion.

The Connection Between the Uterus and the Mammary
Gland. — The physiological connection between the uterus and
the mammary gland is shown by the facts mentioned in the pre-
ceding paragraph. That the ovary also shares in this influence
either directly or through its effect on the uterus is shown by
the fact that after complete ovariotomy the mammary gland under-
goes atrophy. This undoubted influence of one organ upon the
other might be exerted either through the central nervous system

890 THE PHYSIOLOGY OF REPRODUCTION.

or by way of the circulation. There are indications that the
secretion of the mammary glands is under the control, to some
extent at least, of the central nervous system. For instance, in
women during the period of lactation cases have been recorded
in which the secretion was altered or perhaps entirely suppressed
by strong emotions, by an epileptic attack, etc. This indication
has not received satisfactory confirmation from the side of ex-
perimental physiology. Eckhard found that section of the main
nerve-trunk supplying the gland in goats, the external spermatic,
caused no difference in the quantity or quality of the secretion.
Rohrig obtained more positive results, inasmuch as he found that
some of the branches of the external spermatic supply vasomotor
fibers to the blood-vessels of the gland and influence the secretion
of milk by controlling the local blood-flow in the gland. Section
of the inferior branch of this nerve, for example, gave increased
secretion, while stimulation caused diminished secretion, as in the
case of the vasoconstrictor fibers to the kidney. These results
have not been confirmed by others — in fact, they have been sub-
jected to adverse criticism — and they cannot^ therefore, be ac-
cepted unhesitatingly.

After apparently complete separation of the gland from all its
extrinsic nerves, not only does the secretion, if it was previously
present, continue to form, although less in quantity, but in opera-
tions of this kind upon pregnant animals the glands increase in size
during pregnancy and become functional after the act of parturi-
tion.* This result confirms the older experiments of Goltz, Rein,
and others, according to which section of all the nerves going to
the uterus does not prevent the normal effect on lactation after
delivery. Regarding the question of the existence of secretory
nerves, Baschf reports that extirpation of the celiac ganglion or
section of the spermatic nerve does not prevent the secretion, but
causes the appearance of colostrum corpuscles.

Experiments, therefore, as far as they have been carried in-
dicate that the gland is under the regulating control of the cen-
tral nervous system, either through secretory or more probably
through vasomotor fibers. The bond of connection between the
mammary gland and the uterus is, however, established mainly
through the blood rather than through the nervous. system. Some
direct evidence for this point of view is furnished by the interesting
experiments of Starling and Lane-Claypon.J These authors found
that extracts made from the body of the fetus, or rather from the

* Mironow, "Archives des sciences biologiques, " St. Petersburg, 3, 353,
1894.

t Basch, "Ergebnisse der Physiologic," vol. ii., part i, 1903.

J Lane-Claypon and Starling, "Proceedings of the Royal Society," 1906,
B. Ixxvii.; see also Starling in "Lancet," 1905.

THE FEMALE REPRODUCTIVE ORGANS. 891

bodies of many fetuses, when injected repeatedly into a virgin rabbit
caused a genuine development of the mammary glands closely
simulating the growth that normally occurs during pregnancy.
Since similar extracts made from ovaries, placental and uterine
tissues had no effect, they conclude that a specific chemical sub-
stance (a hormone) is produced in the fetus itself and, after absorp-
tion into the maternal blood, it acts upon the mammary gland, stim-
ulating it to growth. Since the birth of the fetus is followed by
active secretion in the mammary glands they adopt further the
view that this substance, while promoting the growth of the gland
tissue, inhibits the catabolic processes which lead to the formation
of the secretion. With the birth of the fetus this substance is
withdrawn and secretion begins, and, on the contrary, the secretion
is suspended when a new pregnancy is well advanced.

As was said in speaking of the histology of the gland, the se-
creting alveoli are not fully formed until the first pregnancy. Dur-
ing the period of gestation the epithelial cells multiply, the alveoli
are formed, and after parturition secretion begins. As the liquid
is formed it accumulates in the enlarged galactophorous ducts, and
after the tension has reached a certain point further secretion
is apparently inhibited. If the ducts are emptied, by the infant
or otherwise, a new secretion begins. The emptying of the ducts,
in fact, seems to constitute the normal physiological stimulus to
the gland-cells, but how this act affects the secreting cells, whether
reflexly or directly, is not known.

Composition of the Milk. — The composition of milk is com-
plex and variable. The important constituents are the fats, held
in emulsion as minute oil droplets and consisting chiefly of olein
and palmitin; casein, a nucleo-albumin which clots under the in-
fluence of rennin; milk-albumin or lactalbumin, a proteid resem-
bling serum-albumin; lactoglobulin; lactose or milk-sugar; lecithin,
cholesterin, phosphocarnic acid, urea, creatin, citric acid, enzymes,
and mineral salts. It is well known also that many foreign sub-
stances— drugs, flavors, etc. — introduced with the food are secreted
in the milk. An average composition is: proteids, 1 to 2 per cent.;
fats, 3 to 4 per cent.; sugar, 6 to 7 per cent.; salts, 0.1 to 0.2 per
cent. The fact that casein and milk-sugar do not exist preformed
in the blood is an argument in favor of the view that they are formed
by the secretory metabolism of the gland cells. The special com-
position of the milk-fat and the histological appearance of the
gland cells during secretion lead to the view that the fat is also
constructed within the gland itself. Bunge has called attention
to the fact that the inorganic salts of milk differ quantitatively
from those in the blood-plasma and resemble closely the propor-
tions found in the body of the young animal, thus indicating an

892 THE PHYSIOLOGY OF REPRODUCTION.

adaptive secretion. This fact is illustrated in the following table
giving the mineral constituents in 100 parts of ash:

YOUNG PUP. DOGS' MILK. DOGS' SERUM.

K2O.. 8.5 10.7 2.4

Na20 8.2 6.1 52.1

CaO 35.8 34.4 2.1

MgO 1.6 1.5 0.5

Fe2O3 0.34 0.14 0.12

P2O5 39.8 37.5 5.9

Cl 7.3 12.4 47.6

On account of the use of cows' milk in place of human milk in
the nourishment of infants much attention has been given to
the relative composition and properties of the two secretions.
The chief difference between the two lies apparently in the casein.
The casein of human milk is smaller in amount, curdles in looser
flocks than that of cows' milk, and seems to dissolve more easily
and completely in gastric juice. The former also contains rela-
tively more lecithin and less ash, particularly the lime salts. On
the other hand, cows' milk contains less sugar and fat. In using
it, therefore, for the nutrition of infants it is customary to add
water and sugar. The composition of cows' milk is so well known
that it is easy to modify it for special cases according to the in-
dications. The rules for this procedure will be found in works
upon pediatrics.

CHAPTER LIII.
PHYSIOLOGY OF THE MALE REPRODUCTIVE ORGANS.

, The sexual life of the male is longer than that of the female.
Puberty or sexual maturity begins somewhat later, — in tem-
perate climates at about the fifteenth year; but there is no dis-
tinct limitation of the reproductive powers in old age correspond-
ing to the menopause of the female. At the time of puberty and
for a short preceding period the boy grows more rapidly in stature
and weight, and the assumption of its complete functions by the
testis exerts a general influence upon the organism as a whole.
One of the superficial changes at this period which is very evident
is the alteration in pitch of the voice. Owing to the rapid growth
of the larynx and the vocal cords the voice becomes markedly
deeper, and the change is in some cases sufficiently sudden to cause
the well-known phenomenon of the breaking of the voice. The
neuromuscular control of the vocal cords becomes for a time un-
certain. The completion of puberty can not be determined in the
boy with the same exactness as in the girl, in whom menstruation
furnishes a visible sign of sexual maturity. Much of the sexual
mechanism may be functional long before the time of puberty,
as is shown by the presence of sexual desire and the possibility
of erection; but fully developed spermatozoa are not produced
until this period, and indeed the presence of ripe and functional
spermatozoa in the testis is the only certain sign that sexual ma-
turity has been attained. Puberty consists in the maturation of
the testis in the male, and of the ovary in the female.

The Properties of the Spermatozoa. — The development and
maturation of the spermatozoa in the testis has been followed
successfully by histological means. The mother-cells of the sper-
matozoa, the spermatocytes, give rise to four daughter-cells, sper-
matids, each of which develops into a functional spermatozoon.
The process in this case is something more than mere cell division,
since in the spermatozoa eventually produced the number of
chromosomes present in the nucleus — that is, the head of the sper-
matozoon— are reduced by one-half. The process of production
of the spermatozoa is therefore quite analogous to the maturation
of the ovum during the formation of the polar bodies. The forma-
tion and maturation of the spermatozoa may be represented by

893

894 THE PHYSIOLOGY OF REPRODUCTION.

a schema similar to that used in the case of the ova, as follows
(Fig. 281): In the case of the ovum four ova are produced, but
only one is functional, and this one, the ripe egg, is characterized
by its large amount of cytoplasm, its inability to undergo further
cell division until fertilized, owing possibly to its loss of the cen-
trosome, and the reduction of its chromosomes to half the num-
ber characteristic of the body cells of the species. In the case
of the spermatozoa, the four cells produced are all functional,*
and are characterized by the practical loss of cytoplasm, reduc-
tion of chromosomes by one-half, and inability to multiply until
cell material is furnished. The two cells supplement each other,
therefore. Their union restores the normal number of chromo-
somes, part of which are now maternal and part paternal; the egg
supplies the cytoplasm and the spermatozoon nuclear material and
the definite stimulus that leads to multiplication.

The spermatozoa are produced in enormous numbers. It is
calculated that at ejaculation each cubic centimeter of the liquid

contains from sixty to seventy
Primary millions of these cells. The

ocyte- adult ripe spermatozoon is

Secondary characterized as an independ-

spermatocytes. ent Cell by its great motility,
due to the cilia-like contrac-
tions of its tail. Its power of
movement or its vitality is
Spermatozoa. retained under favorable con-
Fig. 281.— Schema to indicate the proc- ditlOnS for Very long periods,
of maturation of the spermatozoa. — J

The most striking instance of
this fact is found in the case

of bats. In these animals copulation takes place in the fall and
the uterus of the female retains the spermatozoa in activity until
the period of ovulation in the following spring. Even in the human
being it is believed that the spermatozoa may exist for many days
in the uterus and Fallopian tubes of the female. In the semen that
is ejaculated during coitus the spermatozoa are mixed with the
secretions of the accessory reproductive glands, such as the seminal
vesicles, the prostate gland, and Cowper's gland. The specific in-
fluence of each of these secretions is not entirely understood, but
experiments show that in some way they are essential to or aid
greatly in maintaining the motility of the spermatozoa. Steinachf
has found, for example, that removal of the prostate gland and

* It is an interesting fact that in some cases (bees) two kinds of spermatids
are formed by an unequal division of the spermatocyte, and the smaller
of the two is abortive, as in the case of the polar bodies of the egg.

t See Steinach, " Archiv f . d. gesammte Physiologic," 56, 1894, and Walker,
"Archiv f. Anatomic u. Physiologic," 1899, p. 313.

THE MALE REPRODUCTIVE ORGANS. 895

seminal vesicles in white rats prevents successful fertilization of the
female, although the ability and desire to copulate is not interfered
with. Direct experiments show that the secretion of the prostate
gland maintains motility much more efficiently than a solution of
physiological saline. It seems certain that the secretions of the mu-
cous membrane of the uterus and Fallopian tubes exercise a similar
favorable influence. Kolliker and others have investigated the
action of many substances upon the motility of the spermatozoa,
such as acids, alkalies, salfs of various kinds and in different con-
centrations, sugar, ethereal oils, etc. The union of spermatozoon
and ovum is believed to take place usually in the Fallopian tube,
and under normal conditions only one spermatozoon penetrates
into the egg. The remainder of the infinite number that may be
present eventually perish. The changes that take place during
the process of fertilization have already been described (p. 883).

Chemistry of the Spermatozoa. — Much chemical work has
been done upon the composition of spermatozoa, particularly in
the fishes. The results have been most interesting from a chem-
ical standpoint, and biologically they are suggestive in that the
analytical work has been done upon the heads of the spermatozoa.
These heads consist entirely of nuclear material, and contain the
substance or substances which convey the hereditary characteristics
of the father. Whatever progress may be made in the understand-
ing of the chemistry of this material is a step toward the solution of
the most difficult and mysterious side of reproduction, the power
of hereditary transmission. Miescher, in investigations upon the
spermatozoa of salmon, discovered that the heads are composed
essentially of an organic combination of phosphoric acid, since
designated as nucleic acid, united with a basic albuminous body,
protamin. This view has been confirmed and extended by later
observers, especially by Kossel and his pupils.* The head of the
spermatozoon, the male pronucleus in fertilization, may be de-
fined, in the case of the fishes at least, as "a salt of an organic
base and an organic acid, a protamin-nucleic acid compound."
The term protamin is used now to designate a group of closely
related substances obtained from the spermatozoa of different
animals. The special protamin of each species is designated ac-
cording to the zoological name of that species; thus the protamin
of salmon is salmin, of hering (Clupea harengus) clupein, and so on.
The protamins are all strong bases; their aqueous solutions give
an intense alkaline reaction, and they unite readily with various
acids to form well-defined salts.. They are albuminous bodies,
giving the biuret reaction readily even without the addition of

* For literature and details of the chemistry of spermatozoa see Burian,
in 'Ergebnisse der Physiologic," vol. iii., part i, 1904, and 1908, v., 832.

896 THE PHYSIOLOGY OF REPRODUCTION.

alkali, and they are precipitated by most of the general precipitants
of proteins, such as the neutral salts, the alkaloidal reagents, etc.
Their solutions, however, are not coagulated by heat. The molec-
ular formula for salmon is given as C30H57N17O6. When decom-
posed by the action of acids they yield simpler basic products,
the so-called hexon bases or diamino-acids, and particularly the
base arginin (C6HUN40.,.) , which is contained in the protamin of
the spermatozoa in greater abundance than in any other protein.
The protamins differ from most other protein compounds by their
relative simplicity; they contain no cystin grouping, therefore no
sulphur; no carbohydrate grouping in most of the compounds
examined; and no ty rosin complex. In the spermatozoa of some
fishes the protamins are replaced by more complex compounds
belonging to the group of histons which show properties somewhat
intermediate between those of protamins and ordinary proteins,
and in general it may be said that the head of the spermatozoon,
like the nuclei of cells in general, consists chiefly of a nucleoprotein
compound, that is, a compound of nucleic acid with a protein body
of a more or less distinct basic character.* The nucleic acid com-
ponent of the spermatozoon resembles the same substance as
obtained from the nuclei of other cells. In the spermatozoa of the
salmon this nucleic acid has the formula C40H56NUP4O26. On
decomposition by hydrolysis it yields at first some of the purin bases
(adenin, guanin), and on deeper cleavage a number of compounds,
including the pyrimidin derivatives, thymin, uracil, and cytosin.
While the chemical studies upon spermatozoa, thus briefly referred
to, have greatly extended our knowledge, it is still impossible to
say that they have given any information concerning the peculiar
functions of the spermatozoa in fertilization.

The Act of Erection. — In the sexual life of the male the act of
erection of the penis during coitus offers a most striking physical
phenomenon. During this act the penis becomes hard and erect,
owing to an engorgement with blood. The structure of the corpora
cavernosa and corpus spongiosum is adapted to this function, being
composed of relatively large spaces inclosed in trabeculae of connec-
tive and plain muscle tissue, — the so-called erectile tissue. Many
theories have been proposed to explain the mechanism of erection,
but it is generally agreed that the work of Eckhard f demonstrated
the essential facts in the process. This investigator discovered that
in the dog stimulation of the nervi erigentes causes erection. These
nerves are composed of autonomic fibers arising from the sacral por-
tion of the spinal cord (see Figs. 104 and 105). They arise from the

* Burian, loc. tit.

f Eckhard, "Beitriige zur Anatomie und Physiologie, " 3, 123, 1863, and
4, 69, 1869.

THE MALE REPRODUCTIVE ORGANS. 897

sacral spinal nerves, first to third (dog), on each side and help to
form the pelvic plexus. They contain vasodilator fibers to the penis,
as well as to the rectum and anus, and also visceromotor fibers to the
descending colon, rectum, and anus. Eckhard, Loven, and others *
have shown that when these fibers are stimulated there is a large
dilatation of the arterioles in the erectile tissue of the penis and a
greatly augmented blood-flow to the organ. If the erectile tissue
is cut or the dorsal vein is opened the blood-flow under usual con-
ditions is a slow stream, but when the nervus erigens is stimulated
the outflow is very greatly increased; according to Eckhard's
measurements, eight to fifteen times more blood flows out of the
organ. The act of erection is therefore due essentially to a vas-
cular dilatation of the small arteries whereby the cavernous spaces
become filled with blood under considerable pressure. The caver-
nous tissues are distended to the limits permitted by their tough,
fibrous wall. It seems probable that the turgidity or rigidity of
the congested organ is completed by a partial occlusion of the
venous outflow, which is effected by a compression of the efferent
vein by means of the extrinsic muscles (ischio and bulbocavernosus)
and possibly by the intrinsic musculature as well. This compres-
sion does not occlude the blood-flow completely, but serves to in-
crease greatly the venous pressure. This explanation of the act of
erection, while no doubt correct, so far as it goes, leaves undeter-
mined the means by which the dilatation of the small arteries is
produced. Vasodilator nerve fibers in general are assumed to pro-
duce a dilatation by inhibiting the peripheral tonicity of the
arterial walls. If this explanation is applied to the case under
consideration it forces us to believe that throughout life, except
for the very occasional acts of erection, the arteries in the penis
are kept in a constant condition of active tone. Moreover, on this
view we should expect that section of the vasoconstrictor fibers to
the penis, by abolishing the tone of the arteries, would also cause
erection. These constrictor fibers arise from the second to fifth
lumbar spinal nerves, and reach the organ by way of the hypo-
gastric nerve and plexus and the pudic nerve.' No such result of
their section is reported and it seems that in the matter of erec-
tion the actual mechanism of the great dilatation caused by the
nervi erigentes still contains some points that need investigation.

The Reflex Apparatus of Erection and Ejaculation.— The
dilatation of the arteries of the penis during erection is normally a
reflex act, effected through a center in the lumbar cord. This center
may be acted upon by impulses descending from the brain, as
in the case of erotic sensations, or by afferent impulses arising in

* See especially Francois-Franck, " Archives de Physiol. norm, etpathol.,"
1895, 122 and 138.
57

898 THE PHYSIOLOGY OF REPRODUCTION.

some part of the genital tract, — from the testes themselves, from
the urethra or prostate gland, and especially from the glans penis.
Mechanical stimulation of the glans leads to erection, and Eckhard
showed in dogs that section of the pudic nerve prevents this reflex
from occurring, proving, therefore, that the sensory fibers concerned
run in the pudic nerve. Stimulation of these latter fibers leads also
to erotic sensations and eventually to the completion of the sexual
orgasm. This latter act brings about the forcible ejection of the
sperm through the urethra. It is initiated by contractions of the
musculature of the vasa deferentia, ejaculatory duct, the seminal
vesicles, and the prostate gland, which force the spermatozoa, to-
gether with the secretions of the vesicles and prostate gland, into
the urethra, whence they are expelled in the culminating stage of
the orgasm by the rhythmical contractions of the ischiocavernosus
and bulbocavernosus muscles, together with the constrictor urethrae.
The immediate center for this complex reflex is assumed to lie in
the lumbar cord, since, according to the experiments of Goltz,
mechanical stimulation of the glans in dogs causes erection and
seminal emission after the lumbar cord is severed from the rest of
the central nervous system. Under ordinary conditions the act is
accompanied by strong psychical reactions which indicate that
the cortical region of the cerebrum is involved. It is interesting in
this connection to find that electrical stimulation of a definite re-
gion in the cortex* of dogs may cause erection and ejaculation.

* Pussep, quoted from Hermann's " Jahresbericht der Physiologic,"
vol. xi, 1903.

CHAPTER LIV.

HEREDITY— DETERMINATION OF SEX— GROWTH AND

SENESCENCE,

Heredity. — The development of the fertilized ovum offers two
general phenomena for consideration: First, the mere fact of mul-
tiplication by which an infinite number of cells are produced by
successive cell-divisions; second, the fact that these cells become
differentiated in structure in an orderly and determinate way so as
to form an organism of definite structure like those which gave
origin to the ovum and the spermatozoon. In other words, the
fertilized ovum possesses a property which, for want of a better
term, we may designate as a form-building power. The ovum
develops true to its species, or, indeed, more or less strictly in accord-
ance with the peculiarities of structure characteristic of its parents.
The object of a complete theory of heredity is to ascertain the me-
chanical causes — that is, the physicochemical properties — resi-
dent in the fertilized ovum which impel it to follow in each case a
definite line of development. The discussions upon this point have
centered around two fundamentally different conceptions designated
as evolution and epigenesis.

Evolution and Epigenesis. — The earlier embryologists found a
superficial explanation of this problem in the view that in the germ
cells there exists a miniature animal already preformed, and that
its development under the influence of fertilization consists in a
process of growth by means of which the minute organism is
unfolded, as it were. The process of development is a process of
evolution of a pre-existing structure. Inasmuch as countless in-
dividuals develop in successive generations, it was assumed also
that in the germ cell there are included countless miniature organ-
isms,— one incased, as it were, in the other. Some of the embry-
ologists of that period conceived that the undeveloped embryos are
contained in the ovum, — the ovists, — while others believed that
they are present in the spermatozoon, the animalculists. Other
embryologists pointed out that the fertilized egg shows no indication
of a preformed structure, and therefore concluded that development
starts from an essentially structureless cell, and consists in the
successive formation and addition of new parts which do not pre-
899

900 THE PHYSIOLOGY OF REPRODUCTION.

exist as such in the fertilized egg. This view in contradistinction
to the evolution theory was designated as epigenesis. Microscopi-
cal investigation has demonstrated beyond all doubt that the fer-
tilized ovum is a simple cell devoid of any parts or organs resem-
bling those of the adult, and the evolution theory in its crude form
has been entirely disproved. Nevertheless the controversy be-
tween the evolutionists and epigenesists still exists in modified
form. For it is evident that in the fertilized ovum there may exist
preformed mechanisms or complexes of molecules which, while in no
way resembling anatomically the subsequently developed parts of
the organism, nevertheless are the foundation stones, to use a figure
of speech, upon which the character of the adult structure depends.
Such a view in one form or another is probably held by most bi-
ologists, since it avoids the well-nigh inconceivable difficulties of-
fered by a completely epigenetic theory. If the fertilized ovum
of one animal is in the beginning substantially similar to that of
any other animal the epigenesist must ascertain what combination
of conditions during the process of development causes the egg,
in a dog, for instance, to develop always into a dog, and moreover
into a certain species of dog resembling more or less exactly the
parent organisms. The infinite difficulties encountered by such a
point of view are apparent at once. In this, as in other similar prob-
lems, experimental work is gradually accumulating facts which
throw some light upon the matter and may eventually lead us to the
right explanation. It has been made highly probable that the chro-
matin material in the nuclei of the germ cells, the chromosomes,
constitute the physical basis of hereditary transmission. In the
fertilized egg, it will be remembered, half of the chromosomes come
from the mother and half from the father, and there is good reason
for believing that the maternal chromosomes are the bearers of the
maternal characteristics, and the chromosomes derived from the
spermatozoon convey the hereditary peculiarities of the father.
Such a view, it will be noticed, implies at once preformed structures
in the chromosomes and constitutes one form of an evolutionary
hypothesis. This view is further supported by the interesting ex-
periments of Wilson.*

This author has shown that in certain molluscs (Dentalium or
Patella) if a portion of the egg is cut off, the remaining portion upon
fertilization develops into a defective animal that is not a whole
embryo, but rather a piece or fragment of an embryo. Or if the
fertilized egg after its first segmentation is separated artificially
into two independent cells each develops an embryo, but neither one
is completely formed, — each is lacking in certain structures and

* Wilson, " Science," February 24, 1905, for a popular discussion ; also
"Journal of Experimental Zoology," 1, 1 and 197, 1904, and 2, 371, 1905.

DETERMINATION OF SEX. 901

the two must be taken together to constitute an entirely normal
animal. By experiments of this kind it has been shown that cer-
tain definite portions of the egg are responsible for the formation
of particular organs in the adult. If these portions of the egg are
removed the organs in question are not developed. Facts of this
kind lead to the evolutionary view that in the fertilized ovum there
is a collection of different materials designated as formative stuffs
each of which is specific, — that is, develops into a special structure.
.Many facts connected with the regeneration of parts, — regeneration
of a lost leg in a crab, for example — may be used to support a similar
view of the existence of specific formative stuffs in the cells of the
body.* Wilson has suggested an attractive theory whiQh seems to
account for the facts known at present and forms an acceptable com-
promise between the extremes of epigenesis and evolution. Accord-
ing to him, the germ (fertilized ovum) contains two elements, one of
which undergoes a development that is essentially epigenetic, while
the other contains a preformed structure which controls and deter-
mines the course of development. The first is represented by the
cytoplasm of the egg, the second by the chro matin (chromosomes)
of the nucleus. The latter have specific structures, and under their
influence the nutritive undifferentiated material of the cytoplasm
is modified to form specific formative stuffs differing in character
in the developing ova of different animals. Mam- interesting gen-
eral theories of heredity have been proposed by Darwin, Nageli,
Weissmann, Mendel, Galton, Brooks, and others. It is impossible
to give here an outline of these theories ; the reader is referred for
such information to special treatises on the subject. f

Determination of Sex. — The conditions which lead to the
determination of the sex of the developing ovum have attracted
much investigation and speculation. In the absence of precise
data very numerous and oftentimes very peculiar theories have
been advanced.J Such views as the following have been main-
tained: that the sex is determined by the ova alone; that it is
determined by the spermatozoa alone; that one side (right ovary
or testis) contains male elements, the other female; that the sex
is a result of the interaction of the ovum and spermatozoon, the
most virile element producing its own sex, or according to another
possibility "the superior parent produces the opposite sex"; that
the sex depends on the time relation of coitus to menstruation,

* For a discussion of these facts and for various hypotheses see Morgan,
"Regeneration." New York, 1901.

fHertwig, "The Biological Problems of To-day," and Delage, "L'heredite
et les grands problemes de la biologic generale," 1903.

J For recent accounts of the various theories and discussion see Mor-
gan, "Popular Science Monthly," December, 1903; Lenhossek, "Das Problem
der geschlechtsbestimmenden Ursachen," 1903.

902 THE PHYSIOLOGY OF REPRODUCTION.

fertilization before menstruation favoring male births, after men-
struation female births; that it depends upon the nutritive con-
ditions of the ovum during development or of the maternal parent ;
that it depends upon the relative ages of the parents; that there
are preformed male and female ova and male and female sper-
matozoa, etc. What we may call the scientific study of the problem
began with the collection of statistics of births. Statistics in Europe
of 5,935,000 births indicate that 106 male children are born to
100 female, and the data from other countries show the same
fact of an excess of male children. Examination of these statistics
with reference to determining conditions led to the formulation
of the so-called Hof acker-Sadler law or laws, which may be stated
as follows: (1) When the man is older than the woman the ratio
of male births is increased (113 to 100). (2) When the parents are
of equal age the ratio of female births is increased (93.5 males to
100 females). (3) When the woman is older the ratio of female
births is still further increased (88.2 to 100). These laws have
been corroborated by some statisticians and contradicted or modi-
fied by others. Ploss attempted to show that poor nutritive con-
ditions affecting the parents, especially the mother, favor the
birth of boys. Dusing combined these results in a sort of general
compensatory law of nature, according to which a deficiency in
either sex leads, by a process of natural selection, to an increase
in the births of the opposite sex. Thus, when males are few in
number, — as the result, for instance, of wars, — females marry
later and more males are produced. When males are in excess early
marriages are the rule and this condition favors an excess of female
births. However interesting these statistics may be, it is very
evident that they do not touch the real problem of the cause of the
determination of sex.

Modern work has turned largely to observations and direct
experiments upon the lower animals, particularly the inverte-
brates, with the result that a very large number of facts have
been collected of a most interesting kind, but difficult as yet to
interpret so as to formulate a general law. The trend of modern
work tends to oppose an older view founded largely upon experi-
ments on frogs, bees, and wasps, according to which the sex is not
determined at or before fertilization, but is controlled or may be
controlled by the conditions of nourishment during development,
favorable conditions of nutriment leading to the development of
female cells from the germinal epithelium of the embryo. In
contrast with this latter view an opinion that has been frequently
advocated is that the sex of the embryo is determined in the egg
before fertilization or at the time of fertilization. This view assumes
substantially that there are male and female eggs to begin with, and

DETERMINATION OF SEX. 903

that the determination of sex resides in the maternal organism alone.
Some of the facts that support this view with more or less con-
clusiveness are as follows: (1) In certain worms (Dinophilus) eggs
of two sizes are produced; the large eggs on fertilization develop
always into females, the small ones into males. Similar facts are
recorded for other animals (Hydatina). (2) Many species of in-
vertebrates exhibit the phenomenon of parthenogenesis, — that is,
the eggs of the mother develop without fertilization. In some
cases this method forms the only means of reproduction, and the
individuals of the race are all females. But in other animals re-
production is effected either by parthenogenesis or by fertilization
according to the conditions, — change of seasons, etc. Among
these latter animals it may be shown, in some cases at least, that
the parthenogenetic eggs may give rise either to males or females, —
a fact which accords with the hypothesis of the existence of male
and female eggs in the mother. (3) In man twins may be born.
These twins may be of two kinds. First, those that are developed
from two different eggs, each of which has its own chorion and
develops its own placenta. This kind may be designated as false
twins, and in the matter of sex they may be male and female,
or both male, or both female. The matter varies as in the statis-
tics of births in general. In the other group, however, of true
twins or identical twins, the two embryos are developed from a
single ovum and are included in a single chorion. In such cases
the sexes of the twins are always the same, they are both boys
or both girls. This fact favors the view that the sex may be pre-
determined in the ovum, which may be either male or female.
However, if we grant the fundamental fact, so far as the ova are
concerned, that they are either male or female at the time of forma-
tion or are made so during the process of growth and maturation,
it is still logically possible that there may also be male and female
spermatozoa, and that in the union of the two cells the sex of the
fertilized ovum may be referable either to the ovum or spermatozoon.
It is not justifiable to assert that the paternal organism is without
influence upon the sex of the offspring. In fact, in the case of
honey bees it is observed that if the egg of the queen bee is unfer-
tilized it develops into a male, but, if fertilized, into a female, thus
indicating a determining influence upon the part of the male ele-
ment. Moreover, Wilson * has obtained some interesting results
upon insects (hemiptera) which indicate that the determination of
sex in these animals is dependent upon or correlated with a visible
difference in the chromosomes of the spermatozoon. In some cases
one-half of the spermatozoa contain an unpaired or accessory
chromosome. Those showing this structure produce females on
* Wilson, "The Journal of Experimental Zoology," 1906, iii., 1.

904 THE PHYSIOLOGY OF REPRODUCTION.

fertilization, while the others give rise to males. In other cases
all the spermatozoa exhibit the same number of chromosomes,
but one-half of them contain a large " idiochromosome, " the other
half a small one. The former give rise on fertilization to females,
the latter to males. If, on the basis of such facts, we assume the
existence of male and female eggs and male and female spermatozoa,
the question of the sex of the offspring would seem to depend upon
which of the sex-determining structures in the two cells predominates
after union. The problem still remains unsolved, although reduced
to a narrower field for observation and experiment.

Growth and Senescence. — The body increases rapidly after
birth in size and weight. It is the popular idea that the rate of
growth increases up to maturity and then declines as old age ad-
vances. As a matter of fact, careful examination of the facts shows
that the rate of growth decreases from birth to old age, although not
uniformly. At the pubertal period and at other times its downward
tendency may be arrested for a time. But, speaking generally, the
maximum rate of growth is reached some time during the intra-
uterine period, and after birth the curve falls steadily. Senescence
has begun to appear at the time we are born.* Thus, according to
the statistics of Quetelet, the average male child weighs at birth 6J
pounds. At the end of the first year it weighs 18J pounds, a gain of
12 pounds. At the end of the second year it weighs 23 pounds, a
gain of only 4J pounds, and so on, the rate of increase falling rap-
idly with advancing years. The actual statistics of growth have
been collected and tabulated with great care by a number of ob-
servers; for this country especially by Bowditch, Porter, and Beyer.f
An interesting feature of the records collected by Bowditch is the
proof that the prepubertal acceleration of growth comes earlier
in girls than in boys, so that between the ages of twelve and fifteen
the average girl is heavier and taller than the boy. Later, the boy's
growth is accelerated and his stature and weight increase beyond
that of the girl. It appears from the examinations made upon
school children by Porter and by Beyer that a high degree of
physical development is usually associated with a corresponding
pre-eminence in mental ability. The signs of old age may be de-
tected in other ways than by observations upon the rate of growth.
Changes take place in the composition of the tissues; these changes,
at first scarcely noticeable, become gradually more obvious as old
age advances. The bones become more brittle from an increase in
their inorganic salts, the cartilages become more rigid and calca-

* See Minot, 'Journal of Physiology," 12, 97.

f See Bowditch, "Report of State Board of Health of Massachusetts,"
1877, 1879, and 1891; Porter, "Transactions, Academy of Science," St.
Louis, 1893-94; Beyer, "Proceedings, United States Naval Institute," 21,
297, 1895.

GROWTH AND SENESCENCE. 905

reous, the crystalline lens gradually loses its elasticity, the muscles
lose their vigor, the hairs their pigment, the nuclei of the nerve
cells become smaller, and so on. In every- way there is increasing
evidence, as the years grow, that the metabolism of the living mat-
ter of the body becomes less and less perfect ; the power of the
protoplasm itself becomes more and more limited, and we may
suppose would eventually fail, bringing about what might be called
a natural death. As a matter of fact, death of the organism usually
results from the failure of some one of its many complex mechanisms,
while the majority of the tissues are still able to maintain their exis-
tence if supplied with proper conditions of nourishment. The phys-
iological evidences of an increasing senescence warrant the view,
however, that death is a necessary result of the properties of living
matter in all the tissues except possibly the reproductive elements.
The course of metabolism is such that it is self-limited, and even if
perfect conditions were supplied natural death would eventually
result. We do not understand the nature of these limitations, — that
is, the ultimate causes of senescence. Many examples of unusual
longevity are on record, the most authentic being probably that of
Thomas Parr. An account of his life and the results of a postmor-
tem examination by Harvey are given in volume iii of the " Philo-
sophical Transactions of the Royal Society of London." "He died
after he had outlived nine princes, in the tenth year of the tenth of
them, at the age of one hundred and fifty-two years and nine
months." The immediate cause of his death was attributed to a
change of food and air and habits of life, as he was brought from Shrop-
shire to London, "where he fed high and drunk plentifully of the best
wines."* With reference to the phenomenon of senescense as a neces-
sary attribute of living matter, Weissmann has called attention to the
fact that inasmuch as the species continues to exist after the in-
dividual dies, we must believe that the protoplasm of the repro-
ductive elements is not subject to natural death, but has a self-
perpetuating metabolism which under proper conditions makes it
immortal. Weissmann f designates the protoplasm of the germ cells
as germ-plasm, that of the rest of the body as somatoplasm, and
inasmuch as the former continues to propagate itself indefinitely
under proper conditions, while the latter has a limited existence, he
concludes that originally protoplasm possessed the property of
potential immortality. That is, barring accidents, disease, etc., it
was capable of reproducing itself indefinitely. He assumes, more-
over, that this property is exhibited at present in many of the sim-

* A picture of Parr painted by van Dyck (1635) is exhibited in the Royal
Gallery, Dresden, No. 1032.

t Weissmann, "Essays upon Heredity and Kindred Biological Prob-
lems"; also ''Germ-plasm" in the "Contemporary Science Series.'1

906 THE PHYSIOLOGY OF REPRODUCTION.

pier forms of life, such as the ameba. This latter phase of his theory
has been the subject of much interesting investigation,* but con-
clusive results have not been reached. Assuming that the poten-
tial immortality exhibited by the reproductive cells was originally a
general property of protoplasm, Weissman conceives that the phe-
nomenon of senescence and death exhibited by other cells, somato-
plasm, is a secondary property, which was acquired as a result of
variation and was preserved by natural selection because it is an
advantage in the propagation of the species. An actual immor-
tality of the entire organism, — that is, the property of indefinite
existence except as death might be caused by accidental occur-
rences of various kinds — would be a disadvantage in many ways.
The vast increase in the number of individuals might exceed the
capacity of nature to provide for; the retention of the maimed and
imperfect would make many useless mouths to feed, and perhaps
the evolution of higher and more perfect forms by the slow action
of variation and natural selection would be retarded. From this
point of view senility and natural death constitute a beneficial
adaptation, acquired because of its utility to the race, on the one
hand, and, on the other, because, after the beginning of a differen-
tiation in function among the cells, the possession of immortality
by all the cells was no longer of any value to the race, and therefore
was not brought under the preserving influence of natural selection.

* See Maupas, "Archives de zoologie experimentale et generale," 6,
165, 1888; Joukowsky, "Inaugural Dissertation," Heidelberg, 1898; Gotte,
"Ueber den Ursprung des Todes," 1883.

APPENDIX.

PROTEINS AND THEIR CLASSIFICATION.

Definition and General Structure. — Proteins or albumins are complex
organic compounds containing nitrogen which, although differing much in
their composition, are related in their properties. They are formed by
living matter, and occur in the tissues and liquids of plants and animals,
of which they form the most characteristic constituent. On ultimate analy-
sis they are all found to contain carbon, hydrogen, oxygen, and nitrogen;
most of them contain also some sulphur, and some, in addition, phosphorus
or iron. As usually obtained, they leave also some ash when incinerated,
showing that they hold in combination some inorganic salts. Percentage
analyses of the most common proteins of the body show that the above
named constituents occur in the following proportions:

Carbon 50 to 55 per cent.

Hydrogen 6.5 to 7.3 "

Nitrogen 15 to 17.6 " "

Oxygen 19 to 24 "

Sulphur 0.3 to 2.4 " "

The clearest insight into the structure of the protein molecule has been
obtained by a study of its decomposition products. When submitted to the
action of proteolytic enzymes, or putrefaction, or acid at high temperatures,
the large molecules split into a number of simpler bodies in consequence of
hydrolytic cleavage. These end-products are very numerous, and, while
they differ somewhat for the different proteins, yet a number of them are
the same or similar for all proteins. The great variety in the end-products is
an indication of the complexity of the molecule, while their similarity is proof
that the various proteins are all built, so to speak, upon a common plan, by the
union of certain groupings which may be more numerous in one protein than
in another. This fact becomes evident from a brief consideration of the prod-
ucts obtained by hydrolytic cleavage with acids. The groupings represented
by the following compounds may be supposed to exist preformed in protein
molecules, some possibly containing them all, some only a portion of the
list, while the different groups vary in their proportional amounts in the
various proteins:

1. Amino-acetic acid (glycocoll).

2. Aminopropionic acid (alanin).

3. Aminovalerianic acid.

4. Aminocaproic acid (leucin).

5. Aminosuccinic acid (aspartic acid).

6. Aminoglutaric acid (glutaminic acid).

7. Phenylaminopropionic acid (phenylalanin).

8. Oxyphenylaminopropionic acid (tyrosin).

9. Indolaminopropionic or skatol amino-acetic acid (tryptophan).

10. Guanidinaminovalerianic acid (arginin).

11. Diaminocaproic acid (lysin).

12. Histidin (rt-amino-/3-imidazolpropionic acid (Pauly).

13. Oxyaminopropionic acid (serin).

14. Aminothiopropionic acid (cystein).

15. "-pyrrollidin-carboxylic acid.

16. Oxy-a-pyrrollidin-carboxylic acid.

907

908 APPENDIX.

These split products are all amino-acids, some of them belonging to the
fatty acid (aliphatic) series of carbon compounds, some to the aromatic
(carbocyclic) series, and some to the heterocyclic (pyrrol, indol) series. In
what may be considered the simplest proteins occurring in nature — namely,
the protamins found in the spermatozoa — only from four to six of these groups
occur, while in some of the more familiar proteins, such as serum-albumin
or casein, a much larger number is found. The "-amino-acids of which these

end-products consist all contain the grouping — C — NH2, and Fischer has

COOH

shown that such bodies possess the property of combining with one another
to make complex molecules containing two, three, or more groups of amino-
acids. The combination takes place with the elimination of water formed
by the union of the OH of the carboxyl (COOH) group in one acid and the
H of the amino (NHj) group in another. Thus, two molecules of amino-acetic
acid (glycocoll) may be made to unite to form a compound, glycylglycin, as
follows:

NH2CH2COOH + NH2CH2COOH — H2O = NH2CH2CONHCH2COOH.
Glycocoll. Glycocoll. Glycylglycin.

Compounds of this kind are designated by Fischer as peptids. When formed
from the union of two amino-acids they are known as dipeptids; from three,
as tripeptids, etc. The more complicated compounds of this sort, the poly-
peptids, begin to show reactions similar to those of the proteins. Some of
them give the biuret reaction, some are acted upon and split by proteolytic
enzymes. It seems justifiable, therefore, to consider proteins as essentially
polypeptid compounds of greater or less complexity — that is, they are acid-
amids formed by the union of a number of a-amino-acid compounds. This
conception of the structure of the protein molecule explains a number of
their general characteristics — for instance: (1) The fact that they are all
decomposed and yield similar products under the influence of proteolytic
enzymes or boiling dilute acid. (2) The fact that the proteins are all so
alike in their general properties in spite of the great differences in the com-
plexity of their molecular structure. (3) The fact that they show both
basic and acid characters. (4) The fact that they all give the biuret reac-
tion* (see below).

In addition to the amino-acids some proteins — -egg-albumin, for example •
— yield a carbohydrate body upon decomposition. The carbohydrate ob-
tained is an amino-sugar compound, usually glucosamin, C6H13NO5. It is
detected by its reducing action and by the formation of an osazone. It seems
probable, therefore, that some of the proteins at least contain such a group-
ing as part of the molecular complex, but at present it is undetermined how
many possess this peculiarity of structure.

General Reactions of the Proteins. — It is evident from what has been
said in the preceding paragraph that proteins may give different reactions
according to the kinds of groupings contained in the molecule. The reac-
tions common to all proteins are few in number, the most certain perhaps
being the biuret reaction, the hydrolysis by proteolytic • enzymes or putre-
factive organisms, and the nature of the split products formed by these latter
hydrolyses or by the action of boiling dilute acids. A very large number
of reactions, however, have been described which hold for some or all of
the proteins usually found in the tissues and liquids of the body. These
reactions may be described under two heads: (1) Precipitation of the protein
when in solution; (2) color reactions.

* For further details see Cohnheim, "Chemie der Eiweisskorper, " second
edition, 1904; or Hammarsten, "Physiological Chemistry," translated by
Mandel, fourth edition, New York, 1904.

PROTEINS AND THEIR CLASSIFICATION. 909

/. Precipitants. — For one or another protein the following reagents cause
precipitation :

1. The addition of an excess of alcohol.

2. Boiling (heat coagulation).

3. The addition of mineral acids, — e. g., nitric acid.

4. The salts of the heavy metals, — e. g., acetate of lead, copper sul-

phate, etc.

5. Addition of neutral salts of the alkalies to a greater or less degree

of concentration, — e. g., sodium chlorid, ammonium sulphate.

6. Ferrocyanid of potassium after previous acidification by acetic acid.

7. Tannic acid after previous acidification by acetic acid.

8. Phosphotungstic or phosphomolybdic acid in the presence of free

mineral acids.

9 lodin in solution inv potassium iodid, after previous acidification
with a mineral acid.

10. Picric acid in solutions acidified by organic acids.

11. Trichloracetic acid.

This list might be extended still further, but it comprises the precipi-
tating reagents that are ordinarily used. Some of them, particularly Nos.
7, 8, and 9, give reactions in solutions containing excessively minute traces
of protein.

12. Precipitins. In this connection a brief reference may be made to
the interesting group of bodies known as precipitins. As stated
on p. 399, the animal organism has the power, when foreign cells
are injected into it, of forming anti-bodies by a specific biological
reaction. It has been discovered that anti-bodies, or as they
are called in this case, precipitins, may be produced in the
same way if protein solutions or solutions of animal tissue are in-
jected into the circulation. Thus, if cows' milk be injected under
the skin of a rabbit there will be produced within the rabbit's
blood a precipitin which is capable of precipitating the casein of
cows' milk, although it may have no action on the milk of other
animals. In the same way any given foreign protein, when injected
under the skin of an animal, may cause the production- of a pre-
cipitin capable of precipitating that particular protein from its
solutions. The precipitin is not absolutely specific for the protein
used to produce it, but nearly so. If a rabbit is immunized with
human blood a precipitin is produced in the animal's blood
which causes a precipitate when mixed with human blood or
with that of some of the higher monkeys, but gives no reaction
with the blood of other mammals. The reaction may be used,
therefore, in a measure to test the blood-relationship of different
animals.* It has been suggested that the reaction may also be
of practical importance in medicolegal cases, in determining whether
a given blood-stain is or is not human blood. For such a pur-
pose a human antiserum is first produced by injecting human
serum into a rabbit. The serum of the rabbit is then mixed with
an extract of the suspected blood-stain made with salt solution;
if a precipitate forms it proves that the blood stain is human blood
provided the possibility of its being monkey's blood is excluded.
Concerning the nature of the precipitins, little is known. They
combine quantitatively with the protein precipitated and they
are inactivated (hematosera) by a temperature of 70° C. Their
reactions are not sufficiently specific to be used as a means of de-
tecting or distinguishing closely related proteins.

II. The Color Reactions of Proteins.

1. The biuret reaction. The protein solution is made strongly alkaline
with caustic soda or potash and a few drops of a dilute solution of

* For many interesting experiments and the literature see Nuttall, "Blood
Immunity and Relationship." Cambridge, 1904.

910 APPENDIX.

copper sulphate are added carefully so as to avoid an excess. A
purple color is obtained. Some proteins (peptones) give a red
purple, others a blue purple. If only a blue color, without any
mixture of red, is obtained, no protein is present. At present
this reaction gives the best single test for protein. It obtains

its name from the fact that it is given by biuret HN<CONH2' a
compound that may be formed by heating urea. Two molecules
of urea give off a molecule of ammonia and form biuret.

2. The Millon reaction. The protein solution is boiled with Millon's

reagent. The solution or the precipitate, if one is formed, takes
on a reddish color, which varies in intensity with different proteins.
Millon's reagent consists of a solution of mercuric nitrate in nitric
acid containing some mercurous nitrate. This reaction is supposed
to be given by the tyrosin (oxy-aromatic) grouping in the protein
molecule, and fails, therefore, with those proteins in which tyrosin
is not present.

3. The xanthoproteic reaction. Nitric acid is added to strong acid

reaction and the solution is then boiled. After cooling ammonia
is added. The ammonia causes the development of a deep-yellow
color if protein is present. This reaction is supposed to be due
to the presence in the molecule of the groupings belonging to the
aromatic series.

4. Adamkiewicz's reaction. A mixture is made of one volume of con-

centrated sulphuric and two volumes of glacial acetic acid ; if the
protein solution is added to this mixture and warmed a reddish-
violet color is obtained. According to Hopkins and Cole, the re-
action depends upon the presence of glyoxylic acid in the acetic
acid. This reaction seems to be due to the tryptophan grouping
in the protein molecule.

5. Liebermann's reaction. Dry protein purified with alcohol and ether

gives a blue color upon boiling with strong hydrochloric acid.

6. The lead sulphid reaction. The protein solution is boiled with a

solution of a lead salt made strongly alkaline with soda or potash.
A black precipitate or black or brown coloration results, according
to the amount of protein. The color is due to the splitting off of
sulphur and formation of lead sulphid. It is given, therefore, by
the sulphur-containing groups in the protein molecule.

7. The Molisch reaction. A few drops of an alcoholic solution of a-

naphthol are added to the protein solution and then strong sul-
phuric acid. A violet color is obtained. This reaction is given
by the carbohydrate grouping in the protein molecule. The strong
acid forms furfurol from this group, which then reacts with the naph-
thol. The reaction is not given by those proteins that do not con-
tain a carbohydrate group.

Classification of the Proteins.— No classification of the proteins has
been proposed which is entirely satisfactory. Eventually a classification
will be obtained based upon the chemical structure of the various proteins,
but our knowledge at present is much too incomplete for this purpose. We
must be content with a less satisfactory system based upon empirical reac-
tions which have gradually been recognized in the course of physiological
investigations:

f Albumins.
Globulins.

Albuminates or derived albumins.
, . Nucleo-albumins (phosphoproteins).

I. Simple proteins - Proteoses and pepfones.

Histons.
I Protamins.
[ Coagulated proteins.

PROTEINS AND THEIR CLASSIFICATION. 911

(Chromoproteins (hemoglobin, hemocyanin, etc).
Glucoproteins.
Nucleoproteins.
f Keratin.
III. Albuminoids (pro- J Elastin.

tein-like bodies) j Collagen (gelatin).
[ Reticulin.

The Albumins. — In addition to the albumins found in the cellular tis-
sues, the cell albumins, the conspicuous examples of this group are serum-
albumin, milk-albumin (lactalbumin) , and egg-albumin (ovalbumin). They
are characterized as a class by the fact that they are coagulable by heat in
solutions with a neutral or acid reaction, and are soluble in water free from
salts. In accordance with the latter part of this definition they are not
precipitated by dialysis. They are precipitated from their solutions with
more difficulty by saturation with neutral salts, ammonium sulphate, than
the globulins with which they are usually associated. Empirically, as re-
gards the liquids of the body, it is stated that they require more than half
saturation with ammonium sulphate for precipitation (see section on Blood).
All three albumins referred to here may be obtained in crystallized form.
They are not precipitated by saturation with sodium chlorid or magnesium
sulphate unless the solution is made acid. They are rich in sulphur, con-
taining from 1.6 to 2.2 per cent.

The Globulins. — Proteins belonging to this group are found in the cell
tissues together with albumins. The forms that have been most studied
are serum-globulin (paraglobulin) and fibrinogen (blood, lymph, and transu-
data), milk-globulin (lactoglobulin), and egg-globulin. As contrasted with
the albumins, they are coagulable by heat, but are not soluble in water free
from salts. In consequence of this last property they are precipitated by
dialysis. This reaction is not distinctive, however, as the precipitation is
not complete. Some of the so-called globulin remains in solution after the
salts have been removed as completely as possible by dialysis. They are
also precipitated partially from their dilute solutions by the addition of
weak acids or by a stream of carbon dioxid Practically they are isolated
from accompanying albumins by precipitation with neutral salts. In neu-
tral solutions the globulins are completely precipitated by saturation with
magnesium sulphate or half saturation with ammonium sulphate. In the
blood several different forms of globulin are distinguished by the degree of
saturation with ammonium sulphate necessary for their precipitation (see
Blood). The separations made by this method are not, however, satisfac-
tory. Nor, indeed, is the separation between globulins and albumins alto-
gether satisfactory. It would seem that these proteins are so closely related
that distinctive reactions are difficult to obtain on account of the existence
of forms intermediate between the extremes that are used as types.

Albuminates or Derived Albumins. — Since the albumins and globulins
occur normally in the tissues and liquids of the body, they are frequently
designated as the native proteins. The albuminates, on the contrary, are
derived from these native proteins by the action of strong acids or alkalies.
We distinguish, therefore, acid and alkali albuminates. They are nearly
insoluble in water or in water containing small amounts of neutral salts.
They are readily soluble in dilute acid or alkaline solutions ; are not pre-
cipitated by heat, but are precipitated readily upon neutralization.

Nucleo-albumins (Phosphoproteins). — This name may be applied
to a group of native proteins which are characterized by containing phos-
phorus, such as casein of milk, vitellin from the yolk of the egg, and va-
rious similar proteins found in the cytoplasm of the cellular elements. They
are often classed with or confounded with the nucleoproteins (or nucleo-
albumins) found in the nuclei of the cells. These latter belong to the com-
pound proteins and on decomposition yield nucleic acid or its split products,
the purin bases, etc., whereas the group now under consideration gives no
such result, yielding on decomposition so-called pseudonuclein or paranuclein,
which is not a nuclein at all, but a phosphorus-containing protein body.

912 APPENDIX.

It is very desirable to select for them another name than nucleo-albumin,
since they contain no nuclein. Cohnheim suggests the name of phospho-
globulins or phosphoproteins. In addition to phosphorus these proteins
usually contain some iron, but the amount is so small that it can scarcely
be present as a constituent part of the molecule. It seems more probable
that it is an impurity. Casein contains from 0.8 to 0.9 per cent, of phos-
phorus; vitellin, 1.31 per cent, of phosphorus and only 12 per cent, of nitro-
gen. These proteins have acid properties. They are not soluble in water,
but are very readily soluble in dilute alkalies. Their solutions are not coagu-
lated by heat. Tiiey show the usual protein reactions and give the ordi-
nary end-products of hydrolytic cleavage upon digestion with proteolytic
enzymes or boiling with dilute acid. In the casein it has been shown sat-
isfactorily that no carbohydrate grouping is present in the molecule.

Proteoses and Peptones. — These names are given to the intermediate
proteins formed in the process of digestion by the proteolytic enzymes. They
may also be obtained by the hydrolytic action of acids or alkalies or by the
action of putrefactive organisms. If further hydrolyzed they split into some
of the amino-acids already referred to as constituting the end-products of
protein hydrolysis. Since they are obtained most readily in peptic and
tryptic digestion, they have been supposed to be especially important in
the absorption of the protein foods. They consist of smaller and more sol-
uble molecules than those of the proteins from which they are derived. Many
different kinds of preteoses have been described, but it is difficult to assign
absolutely distinctive characteristics to these compounds, since they form
a series of products intermediate between the original protein and the stage
of peptones. The so-called peptones are characterized by their solubil-
ity and the facts that they are not coagulated by heat and are not precip-
itated by complete saturation with ammonium sulphate. They give the
biuret (red) reaction as well as the xanthoproteic and Millon's reaction, but
are not precipitated by the mineral acids, trichloracetic acid, picric acid,
acetic acid and potassium ferrocyanid, etc. They are precipitated by phos-
photungstic or phosphomolybdic acid. The proteoses in general are dis-
tinguished by the following reactions: They are not coagulated by heat:
they are precipitated from their solutions by the addition of acetic acid and
potassium ferrocyanid ; they are precipitated by nitric acid and this precip-
itate dissolves on warming and reappears on cooling; they are precipitated
by saturation with ammonium sulphate and by all the so-called alkaloidal
reagents, — namely, phosphotungstic acid, trichloracetic acid, picric acid,
tannic acid, etc. The proteoses form a group the members of which are
variously named. It is customary to speak of the primary proteoses (pro-,
toproteose and heteroproteose) as distinguished from the secondary pro-
teoses (deuteroproteoses A, B, C). The former resemble more the native
proteins, while the latter approach the peptones. The distinction between
the primary and secondary proteoses is made chiefly upon the ease of pre-
cipitation. For example, the primary proteoses are precipitated by a lower
degree of saturation with ammonium sulphate and by nitric acid alone,
whereas the secondary proteoses require previous saturation with a salt
(sodium chlorid) before nitric acid will precipitate them, and they are precip-
itated by saturation with ammonium sulphate with much more difficulty,
some of them only after making the reaction acid.

Protamins and Histons. — The protamins have been obtained (Miescher-
Kossel) from the heads of the spermatozoa in fishes, in which they exist in
combination with nucleic acid. They differ considerably in the spermatozoa
of different animals, and are therefore designated according to the zoological
name of the fish from which they arise, as salmin, sturin, clupein, scom-
brin, etc. They show a biuret reaction, but in most cases fail to give Millon's
reaction. On hydrolysis they give split products which consist chiefly of
the so-called diamino-bodies (arginin, histidin, lysin) rather than the mon-
amino-acids. Some of the latter may occur, however, such as alanin, serin,
aminovalerianic or «-pyrrollidin-carboxylic acid. The protamins all give
an alkaline reaction, form salts with acids, and are precipitated easily. Their
molecular structure is relatively simple. Salmin is given the formula C30H57-

PROTEINS AND THEIR CLASSIFICATION. 913

N17O6. The molecule contains no sulphur and is characterized also by its
large percentage of nitrogen. Protamin must be regarded as the simplest
form of protein occurring normally in the animal body, a protein in which
many of the groupings, such as cystin, tyrosin, carbohydrates, found in the
usual protein molecule are entirely lacking and in which the basic groupings
(arginin) predominate. The histons form a series of compounds intermediate
in many ways between the protamins and the usual proteins. The reaction
usually considered as characteristic of the class is that they are precipitated
by ammonia. They are precipitated also by the alkaloidal reagents — e. g.,
phosphotungstic acid— in neutral solutions. Ordinary proteins give a pre-
cipitate with these reagents only in acid solutions, while the protamins give
one even in alkaline solutions. Protamins, histons, and the usual proteins
form a series, therefore, in which the basic reaction is less and less marked.
The best known of the histons is the globin obtained from hemoglobin ; an-
other form has been obtained from the nucleohiston in the white corpuscles,
from the spermatozoa of mackerel (scombron), codfish (gadushiston), sea-
urchin (arbacin), and frog (lotahiston). They do not occur free in the liquids
or tissues of the body, but in combination, as in the case of hemoglobin.
They give the biuret reaction, a faint Millon reaction, and also respond to the
tests for sulphur. The products obtained by their hydrolytic cleavage are
much more numerous than in the case of the protamins — a fact which would
indicate that their molecular structure is correspondingly more complex.

The Compound Proteins. — The chromoproteins may be defined as
consisting of a simple protein in combination with a pigment grouping, such
as occurs in the case of hemoglobin. A. number of such compounds are
known — hemoglobin, hemocyanin, hemerythrin, chlorocruorin — all char-
acterized physiologically by the fact that they serve to transport oxygen
from the air or water to the tissues. On boiling, heating with alkalies or
acids, etc., they readily decompose into their constituent parts (see Blood).
Glucoproteins are compounds of a carbohydrate group with a simple protein.
Numerous bodies have been put in this class ; some of them contain phos-
phorus (phosphoglucoproteins). Those free from phosphorus fall into two
divisions : one, the mucins, which on decomposition yield the carbohydrate
group in the form of an amino-sugar (glucosamin), and one, the chondropro-
teins, found in the connective tissues and in the pathological substance known
as amyloid, which yield their carbohydrate group in the form of chondroitin-
sulphuric acid (C18H.,7NSO17). True mucin is obtained from the secretion
of the salivary glands and the mucous glands of the various mucous mem-
branes. The nucleoproteins constitute the most interesting of the group
of compound proteins. They are recognized as forming an important con-
stituent of the cell nuclei. They may be defined as consisting of a compound
of simple protein with a nucleic acid. In the nuclei (head) of spermatozoa
the compound, in some cases at least (fishes), contains a nucleic acid and a
protamin. In other cases the protein constituent is more complex. On
digestion with pepsin-hydrochloric acid the more complex nucleoproteins
split, with the formation, first, of a protein substance and a simpler nucleo-
protein, richer in phosphorus and designated as a nuclein. On further de-
composition this latter yields a nucleic acid. Nucleic acid is, therefore, the
characteristic constituent, and a number of different forms have been de-
scribed, all rich in phosphorus, such as thymonucleic acid, salmonnucleic acid,
guanylic acid, etc. On hydrolytic decomposition they yield some of the
purin bases — xanthin, guanin, adenin, etc.; some pyrimidin derivatives —
uracil, thymin, cytosin; a carbohydrate group — pentose, levulinic acid; and
phosphoric acid. These final decomposition products are characteristic of
the true nucleoproteins as distinguished from the phosphorus-containing
simple proteins, the nucleo-albumins or phosphoproteins, such as casein.
The percentage of phosphorus in the nucleoproteins varies, according to the
complexity of the molecule, between 0.5 and 1.6 per cent.

The Albuminoids. — This general name is reserved for a group of nitrog-
enous bodies found chiefly in the supporting connective tissues of the body,
such as the keratin of the epidermis, hairs, etc.; the elastin of the elastic
58

914 ' APPENDIX.

connective tissues ; the collagen (ossein) of the white, fibrous connective
tissues and bones, from which gelatin is made ; and the reticulin of the retic-
ular connective tissues of the lymphatic tissues. They resemble the pro-
teins closely in general composition, reactions, and end-products of hydro-
lytic cleavage, but differ from them evidently in some structural feature,
since it has been found by nutritive experiments that they cannot be used
by the body to replace its protein tissues (see p. 819). Collagen (gelatin)
has the following percentage composition (Chittenden) : C, 49.38; H, 6.8;
N, 17.97; S,0.7; O, 25.13.

DIFFUSION AND OSMOSIS.

In recent years the physical conceptions of the nature of the processes
of diffusion and osmosis have changed considerably. As these newer concep-
tions have entered largely into current medical literature, it seems advis-
able to give a brief description of them for the use of those students of phys-
iology who may be unacquainted with the modern nomenclature. The
very limited space that can be devoted to the subject forbids anything more
than a condensed elementary presentation. For fuller information refer-
ence must be made to special treatises.*

Diffusion, Dialysis, and Osmosis. — When two gases are brought into
contact a homogeneous mixture of the two is soon obtained. This inter-
penetration of the gases is spoken of as diffusion, and it is due to the con-
tinual movements of the gaseous molecules to and fro within the limits of
the confining space. So also when two miscible liquids or solutions are
brought into contact a diffusion occurs for the same reason, the movements
of the molecules finally effecting a homogeneous mixture. If the two liquids
happen to be separated by a membrane diffusion will still occur, provided
the membrane is permeable to the liquid molecules, and in time the liquids
on the two sides will be mixtures having a uniform composition. Not only
water molecules, but the molecules of many substances in solution, such
as sugar, may pass to and fro through membranes, so that two liquids sepa-
rated from each other by an intervening membrane and originally unlike
in composition may finally, by the act of diffusion, come to have the same
composition. Diffusion of this kind through a membrane is frequently
spoken of as dialysis or osmosis. In the body we deal with aqueous solu-
tions of various substances that are separated from each other by living
membranes, such as the walls of the blood capillaries or of the alimentary-
canal, and the laws of diffusion through membranes are of immediate im-
portance in explaining the passage of water and dissolved substances through
these living septa. In aqueous solutions such as we have in the body we must
take into account the movements of the molecules of the solvent, water,
as well as of the substances dissolved. These latter may have different de-
grees of diffusibility as compared with one another or with the water mole-
cules, and it frequently happens that a membrane that is permeable to
water molecules is less permeable or even impermeable to the molecules of
the substances in solution. For this reason the diffusion stream of water
and of the dissolved substances may be differentiated, as it were, to a greater
or less extent. In recent years it has become customary to limit the term
osmosis to the stream of water molecules passing through a membrane,
while the term dialysis, or diffusion, is applied to the passage of the mole-
cules of the substances in solution. The osmotic stream of water under vary-
ing conditions is especially important, and in connection with this process
it is necessary to define the term osmotic pressure as applied to solutions.

Osmotic Pressure. — If we imagine two masses of water separated by
a permeable membrane, we can readily understand that as many water mole-

* Consult Cohen, "Physical Chemistry for Physicians and Biologists,"
translated by Fischer, 1903. H. C. Jones, "The Theory of Electrolytic Dis-
sociation," 1900 ; " Diffusion Osmosis, and Filtration," by E. W. Reid, in
Schiifer's "Text-book of Physiology," 1898.

DIFFUSION AND OSMOSIS. 915

cules will pass through from one side as from the other; the two streams,
in fact, will neutralize each other, and the volumes of the two masses of
water will remain unchanged. The movement of the water molecules in
this case is not actually observed, but it is assumed to take place on the
theory that the liquid molecules are continually in motion and that the
membrane, being permeable, offers no obstacle to their movements. If,
now, on one side of the membrane we place a solution of some crystalloid
substance, such as common salt, and on the other side pure water, then it
will be found that' an excess of water will pass from the water side to the
side containing the solution. In the older terminology it was said that the
salt attracted this water, but in the newer theories the same fact is expressed
by saying that the salt in solution exerts a certain osmotic pressure, in conse-
quence of which more water flows from the water side to the side of the
solution than in the reverse direction. As a matter of experiment it is found
that the osmotic pressure varies with the amount of the substance in solu-
tion. If in experiments of this kind a semipermeable membrane is chosen
— that is, a membrane that is permeable to the water molecules, but not to
the molecules of the substance in solution — the stream of water to the side
of the crystalloid will continue until the hydrostatic pressure on this side
reaches a certain point, and the hydrostatic pressure thus caused may be
taken as a measure of the osmotic pressure exerted by the substance in solu-
tion. Under these conditions it can be shown that the osmotic pressure
is proportional to the concentration of the solution, or, in other words, to
the number of molecules (and ions) of the crystalloid in solution. As a
matter of fact, most of the membranes that we have to deal with in the
body are only approximately semipermeable — that is, while they are readily
permeable to water molecules, they are also permeable, although with more
or less difficulty, to the substances in solution. In such cases we get an
osmotic stream of water to the side of the dissolved crystalloid, but at the
same time the molecules of the latter pass to some extent through the mem-
brane, by diffusion, to the other side. In course of time, therefore, the
dissolved crystalloid will be equally distributed on the two sides of the mem-
brane, the osmotic pressure on both sides will become equal, and osmosis
of the water will cease to be apparent, since it is equal in the two directions.
All substances hi true solution are capable of exerting osmotic pressure,
and the important discovery has been made that the osmotic pressure, meas-
ured in terms of atmospheres or the pressure of a column of water or mer-
cury, is equal to the gas pressure that would be exerted by a number of
molecules of gas equal to that of the crystalloid in solution, if confined within
the same space and kept at the same temperature.* A perfectly satisfactory
explanation of the nature of osmotic pressure has not been furnished. We
must be content to use the term to express the fact described. It is a matter
of great importance to measure the osmotic pressures of various solutions.
As was stated above, this measurement can be made for any solution pro-
vided a really semipermeable membrane is constructed. As a matter of
fact, however, the use of such membranes has not been general. In actual
experiments other methods have been employed, and a brief statement
of a theoretical and a practical method of arriving at the value of osmotic
pressures may be of service in further illustrating the meaning of the term.
Before stating these methods it becomes necessary to define two terms —
namely, electrolytes and gram-molecular solutions — that are much used
in this connection.

Electrolytes. — The molecules of many substances when brought into

* The interesting researches of Morse and Frazer (" The American Chemi-
cal Journal," 34, 1, 1905), who have succeeded in making semipermeable
membranes in such a form as may be used for determining directly the os-
motic pressures of concentrated (normal) solutions, have shown that this
law is not accurately stated. The actual pressure is that which would be
exerted if the particles in solution were gasified at the same temperature and
kept to the volume of the pure solvent used (water), instead of the volume
of the entire solution.

916 APPENDIX.

a state of solution are believed to be dissociated into two or more parts,
known as ions. The completeness of the dissociation varies with the sub-
stance used, and for any one substance with the degree of dilution. Roughly
speaking, the greater the dilution, the more nearly complete is the dissocia-
tion. The ions liberated by this act of dissociation carry an electrical charge
and when an electrical current is led into the solution it is conducted in a
definite direction by the movements or migration of the charged ions. The
molecules of perfectly pure water undergo almost no dissociation, and water,
therefore, does not appreciably conduct the electrical current. If some
NaCl is dissolved in water, a certain number of its molecules become dis-
sociated into a Na ion charged positively with electricity and a ( '1 ion charged
negatively, and the solution becomes a conductor of the electrical current.
Substances that exhibit this property of dissociation into electrically-charged
ions are known as electrolytes, to distinguish them from other soluble sub-
stances, such as sugar, that do not dissociate in solution and, therefore, do not
conduct the electrical current. Speaking generally, it may be said that all
salts, bases, and acids belong to the group of electrolytes. The conception of
electrolytes is very important for the reason that the act of dissociation ob-
viously increases the number of particles moving in the solution and thereby
increases the osmotic pressure, since it has been found experimentally that, so
far as osmotic pressures are concerned, an ion plays the same part as a mole-
cule. It follows, therefore, that the osmotic pressure of any given electrolyte
in solution is increased in proportion to the degree to which it is dissociated.
As the liquids of the body contain electrolytes in solution it becomes neces-
sary, in estimating their osmotic pressure, to take this fact into consideration.

Gram-molecular Solutions. — The concentration of a given substance
in solution may be stated by the usual method of percentages, but from the
standpoint of osmotic pressure a more convenient method is the use of the
unit known as a gram-molecular solution. A gram-molecule of any sub-
stance is a quantity in grams of the substance equal to its molecular weight,
while a gram-molecular solution is one containing a gram-molecule of the
substance to a liter of the solution. Thus, a gram-molecular solution of
sodium chlorid is one containing 58.5 gms. (Na, 23; Cl, 35.5) of the salt to
a liter, while a gram-molecular solution of cane-sugar contains 342 gins.
(C^HggOn) to a liter. Similarly a gram-molecule of H is 2 gms. by weight
of this gas, and if this weight of H were compressed to the volume of a liter
it would be comparable to a gram-molecular solution. Since the weight
of a molecule of H is to the weight of a molecule of cane-sugar as 2 is to
342, it follows that a liter containing 2 gms. of H has the same number of
molecules of H in it as a liter of solution containing 342 gms. of sugar has
of sugar molecules. On the assumption that a molecule in solution exerts
an osmotic pressure that is exactly equal to the gas-pressure exerted by a
gas molecule moving in the same space and at the same temperature, we
are justified in saying that the osmotic pressure of a gram-molecular solu-
tion of cane-sugar, or of any other substance that is not an electrolyte, is
equal to the gas-pressure of 2 gms. of H when compressed to the volume
of 1 liter. This fact gives a means of calculating the osmotic pressure of
solutions in certain cases according to the following method:

Calculation of the Osmotic Pressure of Solutions. — To illustrate this
method we may take a simple problem such as the determination of the
osmotic pressure of a 1 per cent, solution of cane-sugar. One gm. of H at
atmospheric pressure occupies a volume of 11.16 liters; 2 gms. of H, there-
fore, under the same conditions will occupy a volume of 22.32 liters. A
gram-molecule of H — that is, 2 gms. of H — when brought to the volume
of 1 liter will exert a gas-pressure equal to that of 22.32 liters compressed
to 1 liter — that is, a pressure of 22.32 atmospheres. A gram-molecular solu-
tion of cane-sugar, since it contains the same number of molecules in a liter,
must therefore exert an osmotic pressure equal to 22.32 atmospheres. A
1 per cent, solution of cane-sugar contains, however, only 10 gms. of sugar
to a liter; hence the osmotic pressure of the sugar in such a solution will
be ~ of 22.32 atmospheres, or 0.65 of an atmosphere, which in terms of

DIFFUSION AND OSMOSIS. 917

a column of mercury gives 760 X 0.65 = 494 mms. This figure expresses
the osmotic pressure of a 1 per cent, solution of cane-sugar when dialyzed
against pure water through a membrane impermeable to the sugar molecules.
In such an experiment water would pass to the sugar side until the hydro-
static pressure on this side was increased by an amount equal to the pres-
sure of a column of mercury 494 mms. high. Certain additional calculations
that it is necessary to make for the temperature of the solution need not be
specified in this connection. If, however, we wish to apply this method
to the calculation of the osmotic pressure of a given solution of an electro-
lyte, it is necessary first to ascertain the degree of dissociation of the electro-
lyte into its ions, since, as was said above, dissociation increases the num-
ber of parts in solution and to the same extent increases osmotic pressure.
In the body the liquids that concern us contain a variety of substances in
solution, electrolytes as well as non -electrolytes. In order, therefore, to
calculate the osmotic pressure of such complex solutions it is necessary to
ascertain the amount of each substance present, and, in the case of electro-
lytes, the degree of dissociation. Under experimental conditions such a
calculation is practically impossible, and recourse must be had to other
methods. One of the simplest and most easily applied of these methods
is the determination of the freezing point of the solution.

Determination of Osmotic Pressure by Means of the Freezing Point.
— This method depends upon the fact that the freezing point of water is low-
ered by substances in solution, and it has been discovered that the amount
of lowering is proportional to the number of parts (molecules and ions)
present in the solution. Since the osmotic pressure is also proportional to
the number of parts in solution, it is convenient to take the lowering of the
freezing point of a solution as an index or measure of its osmotic pressure.
In practice a simple apparatus (Beckmann's apparatus) is used, consisting
essentially of a very delicate and adjustable differential thermometer. By
means of this instrument the freezing point of pure water is first ascertained
upon the empirical scale of the thermometer. The freezing point of the
solution under examination is then determined, and the number of degrees
or fractions of a degree by which its freezing point is lower than that of pure
water is noted. The lowering of the freezing point in degrees centigrade
is expressed usually by the symbol A- For example, mammalian blood-
serum gives A = 0.56° C. A 0.95 per cent, solution of NaCl gives the same
A ,* hence the two solutions exert the same osmotic pressure, or, to put it in
another way, a 0.95 per cent, solution of NaCl is isotonic or isosmotic with
mammalian serum. The A of any given solution may be expressed in terms
of a gram-molecular solution by dividing it by the constant 1.87, since a
gram-molecular solution of a non-electrolyte is known to lower the freezing
point 1.87° C. Thus, if blood-serum gives A = 0.56° C., its concentration in

terms of a gram-molecular solution will be -r^,, or 0.3. In other words,

. lo/

blood-serum has 0.3 of the osmotic pressure exerted by a gram-molecular
solution of a non-electrolyte, — that is, 22.32 X 0.3, or 6.696 atmospheres.

Remarks upon the Application of the Foregoing Facts in Physiol-
ogy.— In the body water and substances in solution are continually pass-
ing through membranes, — for example, in the production of lymph, in the
absorption of water and digested foodstuffs from the alimentary canal, in
the nutritive exchanges between the tissue elements and the blood or lymph,
in the production of the various secretions, and so on. In these cases it is a
matter of the greatest difficulty to give a satisfactory explanation of the
forces controlling the flow to and fro of the water and dissolved substances,
but there can be little doubt that in all of them the physical forces of fil-
tration, diffusion, and osmosis take an important part. Whatever can be
learned, therefore, concerning these processes must in the end have an im-
portant bearing upon the explanation of the nutritive exchanges between
the blood and tissues. Some additional facts may be mentioned to indicate
the applications that are made of these processes in explaining physiological
phenomena.

Osmotic Pressure of Proteins. — The osmotic pressure exerted by crys-

918 APPENDIX.

talloids, such as the ordinary soluble salts, is, as we have seen, very con-
siderable, but the ready diffusibility of most of these salts through animal
membranes limits very materially their influence upon the flow of water in
the body. Thus, if we should inject a strong solution of common salt directly
into the blood-vessels, the first effect would be the setting up of an osmotic
stream from the tissues to the blood and the production of a condition of
hydremic plethora within the blood-vessels. The salt, however, would soon
diffuse out into the tissues, and to the degree that this occurred its effect in.
diluting the blood would tend to diminish because the part of the salt that
got into the extravascular lymph spaces would now exert an osmotic press-
ure in the opposite direction, drawing water from the blood. This fact,
together with the further fact that an excess of salts in the body is soon re-
moved by the excretory organs, gives to such substances a smaller influence
in directing the water stream than would at first be supposed when the inten-
sity of -their osmotic action is considered. In addition to the crystalloids the
liquids of our bodies contain also a certain amount of protein, the blood,
especially, containing over 6 per cent, of this substance. It has been gen-
erally assumed that proteins in solution exert little or no osmotic pressure,
but Starling * and others have claimed, on the contrary, that they exert a
distinct, although small, osmotic pressure, and it is possible that this fact
is of special importance in absorption, because the proteins do not diffuse
or diffuse with great difficulty, and their effect remains, therefore, so to
speak, as a permanent factor. According to Starling, the osmotic pressure
exerted by the proteins of serum is equal to about 30 mms. of mercury. That
the osmotic pressure of the serum proteins is so small is not surprising if we
remember the very high molecular weight of this substance. In serum the
proteins are present in a concentration of about 7 per cent., but owing to
their large molecular weight comparatively few protein molecules are present
in a solution of this concentration ; and, assuming that the dissolved protein
follows the laws discovered for crystalloids, its osmotic pressure would depend
upon the number of molecules in solution. By means of this weak but con-
stant osmotic pressure of the indiffusible protein it is possible to explain
theoretically the fact that an isotonic or even a hypertonic solution of diffusi-
ble crystalloid may be completely absorbed by the blood from the peritoneal
cavity. Reid f has published experiments wrhich indicate that pure proteins
exert no osmotic pressure ; that as they occur in the body liquids they are
combined or mixed with certain substances to which the feeble osmotic pres-
sure formerly attributed to the proteins really belongs. Since these unknown
substances are themselves indiffusible, the arguments just used still hold for
the conditions in the body. It seems probable, however, that in the method
used by Reid to purify the proteins the nature of these substances was
altered, the state of aggregation of the molecules, for example, and that, there-
fore, his negative results do not apply to the proteins as they exist in the
blood.

Isotonic, Hypertonic, and Hypotonic Solutions. — In physiology the
osmotic pressures exerted by various solutions are compared usually with
that of the blood-serum. In this sense an isotonic or isosmotic solution is
one having an osmotic pressure equal to that of serum, a hypertonic or hy-
perosmotic solution is one whose osmotic pressure exceeds that of serum,
and a hypotonic or hyposmotic solution is one whose osmotic pressure is
less than that of serum.

Diffusion, or Dialysis, of Soluble Constituents. — If two liquids of
unequal concentration in a given constituent are separated by a membrane
entirely permeable to the dissolved molecules of the substance, a greater
number of these molecules will pass over from the more concentrated to the
less concentrated side, and in time the composition will be the same on the
two sides of the membrane. Diffusion of soluble constituents continually
takes place, therefore, from the points of greater concentration to those of
less, and this may happen quite independently of the direction of the osmotic

* "Journal of Physiology," 24, 317, 1899.
t Reid, "Journal of Physiology," 1905.

DIFFUSION AND OSMOSIS. 919

stream of water. If, for instance, a 0.9 per cent, solution of sodium chlorid
is injected into the peritoneal cavity, it will enter into diffusion relations
witli the blood in the blood-vessels; its concentration in sodium chlorid
being greater than that of the blood, the excess will tend to pass into the
blood, while sodium carbonate, urea, sugar, and other soluble crystalloidal
substances will pass from the blood into the salt solution in the peritoneal
cavity. Through the action of this process of diffusion we can understand
how certain constituents of the blood may pass to the tissues of various glands
in amounts greater than can be explained if we supposed that the lymph
of these tissues is derived solely by filtration from the blood-plasma. An-
other important conception in this connection is the possibility that the
capillary walls may be permeable in different degrees to the various soluble
constituents of the blood, and furthermore the possibility that the permea-
bility of the capillary walls may vary in different organs. With regard to
the first possibility it has been shown that the blood capillaries are more
permeable to the urea molecules than to sugar or NaCl. With the aid of
these facts it is possible to explain in large measure the transportation of
material from the blood to the tissues, and vice versa. For example, to follow
a line of reasoning used by Roth, we may suppose that the functional activity
of the tissue elements is attended by a consumption of material which in
turn is made good by the dissolved molecules in the tissue lymph. The
concentration of the latter is thereby lowered, and in consequence a diffu-
sion stream of these substances is set up with the more concentrated blood.
In this way, by diffusion, a constant supply of dissolved material is kept
in motion from the blood to the tissue elements. On the other hand, the
functional activity of the tissue elements is accompanied by a breaking down
of the complex protein molecule, with the formation of simpler, more stable
molecules of crystalloid character, such as the sulphates, phosphates, and
urea or some precursor of urea. As these bodies pass into the tissue lymph
they tend to increase its concentration, and thus by the greater osmotic
pressure developed they serve to attract wrater from the blood to the lymph,
forming one efficient factor in the production of lymph. On the other hand,
as these substances "accumulate in the lymph to a concentration greater than
that possessed by the same substances in the blood, they will diffuse toward
the blood. By this means the waste products of activity are drawn off to
the blood, from which, in turn, they are removed by the action of the excretory
organs.

Diffusion of Proteins. — This simple explanation on purely physical
grounds of the flow of material between the blood and the tissues can only
be applied, however, at present to the diffusible crystalloids, such as the
salts, urea, and sugar. The proteins of the blood, which are supposed to
be so important for the nutrition of the tissues, are practically indiffusible,
so far as we know. It is difficult to explain their passage from the blood
through the capillary walls into the lymph. Provisionally it may be assumed
that this passage is due to filtration. The blood-plasma in the capillaries is
under a slightly higher pressure than the lymph of the tissues, and this higher
pressure tends to squeeze the blood constituents, including the protein, through
the capillary walls. This explanation, however, cannot be said to be satis-
factory ; and in this respect the purely physical theory of lymph formation
waits upon a clearer knowledge of the nature of the nutritive proteins and
their relations to the capillary wall (see Lymph, p. 440).

NDEX.

ABDOMINAL respiration. 593

type of respiration, 597
Absolute power of muscle, 38
Absorption coefficient, 621

in large intestine, 738

in small intestine, 733

in stomach, 718

of carbohydrates, 734

of fats, 735

of proteins, 737

spectra of hemoglobin, 406
Acapnia, 646, 651
Accelerator center for heart, 545

nerves, effect of, on heart rate, 547
of heart, 541
reflex stimulation of, 543
Accessory thyroids, 794
Accommodation in eye, limits of, 296
mechanism of, 293

reflex, 306
Acetone bodies, 827
Achromatic series of visual sensa-
tions, 329
Achroodextrin, 701
Acid albumin in gastric digestion, 714

aceto-acetic, 827

amino-acetic, 727, 907

aminocaproic, 727, 907

aminoglutaric, 907

amino-oxypropionic, 907

aminopropionic, 907

aminosuccinic, 727, 907

aminothiolactic, 907

aminovalerianic, 727, 907

cholic, 746

conjugated sulphuric, 782

diaminocaproic, 907

glutaminic, 727, 907

glycocholic, 746

glycuronic, 825

guanidinaminovalerianic, 907

hippuric, 781

lactic, 60

oxalic, 825

oxybutyric, 827

oxyphenylaminopropionic, 907

phenylaminopropionic, 907

phosphocarnic, 60

pyrrolidin-carboxylic, 907

saccharic, 825

taurocholic, 746

Acromegaly, 802
Action current, diphasic, 98
in heart, 497
in muscle, 96
in nerve, 96
in retina, 317
monophasic, 98
relation of, to contraction wave,

100

to nerve impulse, 100
Adamkiewicz's reaction for proteins,

910

Addison's disease, 799
Adenase, 685, 779
Adenin, 61, 778

Adrenal bodies, functions of, 801
Adrenalin, 800
Aerial perspective, 354
Aerotonometer, 622
Afferent fibers in cranial nerves, 79

position of, in posterior roots, 77
nerve fibers, 75
After-images in eye, 331
Air, effect of variations in, on res-
pirations, 648
Alanin, 727, 907
Alexins, 400
Albumin, properties of, 911 (see

also Protein)

Albuminates, properties of, 911
Albuminoids, nutritive value of, 818

properties of, 913
Albumon, 426
Alcohol as food, 838

effect of, on gastric absorption, 719
physiological action of, 836
Alimentary canal, movements of, 655
glycosuria, 735
principles of food, 675
Altitude, effect of, on red corpuscles,

414

Amboceptors, 400
Ametropia, 299
Amino-acetic acid, 727, 907
Amino-acids as part of protein mole-
cule, 727, 907

Aminocaproic acid, 727, 907
Aminoglutaric acid, 907
Amino-oxypropionic acid, 907
Aminopropionic acid, 727, 907
Aminosuccinic acid. 727, 907
921

922

INDEX.

Aminothiolactic acid, 907
Aminovalerianic acid, 727, 907
Aminopurins, 778
Ammonia compounds in urine, 773

salts, relation of, to urea, 775
Ammonium carbamate as precursor
of urea, 775

carbonate as precursor of urea, 775
Amylolytic enzyme, 683
Amylopsin, 729
Anacrotic pulse, 489
Anaglyph, 357
Anelectrotonic currents, 101
Anelectrotonus, 83
Anisotropous substance in muscle, 19
Anode as stimulus to muscle, 82
to nerve, 82

physical, 89

physiological, 89
Anoxemia, 649
Anterior commissure, 177, 204

roots of spinal nerves, 77
Antidromic impulses in vasodilator

nerve fibers, 78, 568
Antilytic secretion, 698
Antiparalytic secretion, 698
Antipeptone, 726
Antithrombin, 433
Antrum pylori of stomach, 660
Anus praBternaturalis, 738
Apex beat of heart, 500
Aphasia, motor, 206

sensory, 208
Apnea, 643
Arginase, 776
Arginin, 728, 776, 896, 912
Argyll-Robertson pupil, 307
Arterial pressure (see Circulation)
Artificial muscle of Engelmann, 69

respiration, 602, 612

stimuli of nerve fibers, 80
Ascending paths in spinal cord, 162
Aspartic acid, 727, 907
Asphyxia, 644

effect of, on heart-rate, 549
Aspiratory action of thorax, 608
Association areas in brain, 209, 211

system of fibers in cerebrum, 177
Astereognosis, 191
Astigmatism, 302
Atropin, action of, on heart, 539
on iris, 308

on salivary secretion, 697
on sweat secretion, 791
Auditory center in cortex, 200

nerve, course of, in brain, 201
effect of section of, 385

sensations (see Ear)

stria?, 203
Auricle (see Heart)

Auriculoventricular muscle bundle,
496

Auriculoventricular muscle bundle,

effect of compressing, 527
Auscultation, 504
Autolysis, 868
Autolytic enzymes, 685
Automaticity of heart beat, 514
Autonomic fibers from brain, 237

from sacral cord, 239

from spinal cord, 236
nerve fibers, normal stimulation of,

239
nervous system, general relations

of, 234
Axial stream in arteries, 448

in veins, 448
Axon reflexes, 144

BACTERIAL action in intestines, 739

Balance experiments in nutrition,
810

Balloon ascensions, effect of, 651

Barometric pressures, effect of, 650

Bartholin, duct of, 687

Basilar membrane, function of, 377

Bathmotropic nerve fibers to heart.
535

Bechterew's nucleus, 201, 220

Bell-Magendie law, 77

Bilateral representation in motor
areas, 187

Biological reaction, 399

Bile, composition of, 744
curve of secretion of, 750
effect of occluding bile ducts, 751
ejection of, into duodenum, 749
functions of, summary, 751
quantity of, 744
secretion of, 748

Bile-acids, composition of, 746

Bile-pigments, 400, 412, 745

Bile-salts, importance of, in fat diges-
tion, 736

Bilirubin, 745

Biliverdin, 745

Binocular perspective, 356, 358
vision, 347

horopter in, 353
struggle of visual fields in, 353
value of, in judgments of dis-
tance, 359
in judgments of size, 359

Births, ratio of male and female, 902

Biuret reaction for proteins, 909

Bladder, urinary, movements of, 784
gall, movements of, 750

Blind spot in eye, 317

Blood, blood-plates of, physiology

of, 418

circulation of (see Circulation)
coagulation of, 426
condition of carbon dioxid in, 625
of nitrogen in, 623

INDEX.

923

Blood, curve of dissociation of oxy-
hemoglobin, 624

defibrinated, 393

gases of, 617

general properties of, 392

hemoglobin in, 396
amount, 401
nature, 401

hemolysis of red corpuscles, 397

histological structure of, 392

leucocytes of, 416

nucleoprotein in, 426

osmotic pressure of, 397

proteins of, 420, 422

reaction of, 393

reasons for not clotting in vessels,
432

red corpuscles of, 395
fate of, 412
origin of, 412

regeneration of, after hemorrhage,
437

specific gravity of, 394

total quantity of, 436

transfusion of, 439
Blood-plasma, composition of, 420
Blood-plates, part taken by, in coagu-
lation, 432

properties of, 418
Blood-pressure, 455

diastolic, 459

effect of menstruation upon, 879

in brain, 577

in capillaries, 465

in man, 466, 471

mean, 459

relation of, to heart rate, 547

respiratory waves of, 609

systolic, 459

Traube-Hering waves of, 564

venous, 479
Blood-serum, 393, 421
Body equilibrium in nutrition, 810

sense area, 191

temperature in man, 853
Bowman's theory of urinary secre-
tion, 764
Brain, association areas of, 209

auditory center in, 200

center for taste, 206
for olfaction, 204

centers affected in aphasia, 206

development of cortical areas, 212

effect of variations in arterial
pressure upon, 577

intracranial pressure in, 576

histological differentiation of cor-
tex of, 215

localization of function in, 181

motor areas of, 184

regulation of circulation in, 579

sensory areas of, 190

Brain, vascular supply of, 572
Brightness in visual sensations, 327
Bronchi, capacity of, 602

constrictor and dilator fibers of, 646
Buffy coat of blood, 427
Burdach, column of, 163

CAFFEIN, 778, 836

Caisson disease, 650

Calcarine fissure, relation of, to vision,

198

Calcium salts, effect of, on heart, 520
importance of, in clotting of

blood, 429

in curdling of milk, 716
nutritive value of, 833
secretion of milk, 442
Calorie, definition of, 855
Calorimeters, varieties of, 855
Calorimetric equivalent, 857

measurements, 860
Calorimetry, indirect, 859

principles of, 855
Cannula, washout, 457
Capillary blood-pressure, 465

electrometer, construction of, 94
Carbohemoglobin, 404
Carbohydrates, absorption of, 734
as glycogen formers, 753
as source of body fat, 829
fermentation of, in intestine, 739
general functions of, 825
metabolism of, in body, 826
of muscle, 59

regulation of supply of, 821
supply of, in body, 821
Carbon dioxid, action on respiratory

center, 642

condition of, in blood, 625
effect of, in inspired air, 642, 650
excretion of, through skin, 792
in balance experiments, 810
in saliva, 690

production of, in muscle, 62
tension of, in alveolar air, 628
in arterial blood, 629
in tissues, 629
in venous blood, 628
equilibrium, 810
monoxid hemoglobin, 403
Cardiac cycle, 506

glands of stomach, 703
muscle, properties of, 54, 523
nerves (see Heart)
Cardiogram, 500
Cardio-inhibitory center, 536
Carnin, 61

Casein, 716, 891, 911
Catalase, 680, 685
Catalysis, 680

Catelectrotonic currents, 101
Catelectrotonus, 83

924

INDEX.

Cathode as stimulus, 82

physical and physiological, 89
Centers in cerebrum (see Cerebrum)
Central field of vision, 321
Centrosome, 881

Cerebellum, ending of spinal tracts I
in, 165, 221

experimental work upon, 223

general functions of, 226
Cerebellum, localization of function
in, 227

paths connecting with other parts
of brain, 220

psychical functions of, 227

structure of, 218
Cerebrospinal liquid, 574
Cerebrum, association areas of, 209

center for hearing, 200
for olfaction, 204
for vision, 194

centers affected in aphasia, 207

commissural system of fibers in, 177

development of cortical areas in,
212

general physiology of, 173

histology of cortex, 174

histological differentiation of cor-
tex, 215

localization of function in, 181

motor areas of, 184

projection system of fibers in, 175

results of ablation of, 179

sensory areas of, 190

system of fibers in, 175

vasomotor supply of, 579
Cerumen, 792
Chemotaxis, 120
Cheyne-Stokes respiration, 654
Cholesterin, 742, 747, 792
Cholic acid, 746
Cholin, 748

Chorda tympani nerve, 274, 688, 691
Chromatic aberration in eye, 298

visual sensations, 328
Chromatolysis, 121
Chromophile substance in nerve cells,

128

Chromoproteins, 913
Chromosomes, 881, 900
Chronotropic nerve fibers to heart,

535

Chyle fat, 736
Chymosin, 715

Ciliary muscle, action of, in accom-
modation, 295
nerves to, 304
Ciliated epithelium, 54
Circulating proteins, 812
Circulation, accessory factors in, 480

as seen under microscope, 448

curve showing pressures in, 460,464,
465

Circulation, data concerning pressures

in (man), 471
mean pressures in, 463
diastole and systole of heart, 494
effect of adrenal extracts upon,

799
of heart beat and size of arteries

upon, 453

explanation of side-pressure in, 473
of velocity changes in, 452
of velocity-pressure in, 474
factors of normal pressure and

velocity in, 476
form of pulse wave, 486
general curve of velocities in, 452
general statement of pressure rela-
tions, 455

hydrostatic effects upon, 478
importance of elasticity of arteries,

475

in brain, 572
in kidneys, 769

means of determining blood-pres-
sure in, 455, 466
velocities in, 451
pressures in coronary system, 509

in pulmonary system, 480
pulse pressures in, 459
respiratory waves of pressure in,

609

regulation of blood supply, 568
systole and diastole of heart, 494
systolic, diastolic, and mean pres-
sures in, 459

and mean velocities in, 451
time required for complete, 454
Traube-Hering waves of pressure

in, 564

velocity in capillaries, 451
in coronary system, 509
in man, 451

in pulmonary system, 480
of pulse wave, 484
Clarke's column, 157
Clotting (see Coagulation)
Coagulation, blood, 426
intravascular, 433
means of hastening and retarding,

434

theories of, 427
Cocain, action of, on iris, 308
Cochlea, functions of, 376

sensory epithelium of, 370
Cold spots on skin, 260
Color blindness, 333
contrasts, 332
fusion, 330
saturation, 329
sense of retina, 336
vision, theories of, 340
Combustion equivalents of foods, 846
Comma tract of Schultze, 171

INDEX.

925

Commissural system of fibers (cere-
brum), 177

Common sensations, 253
Compensatory pause in heart-beat,525
Complemental air, 601
Complementary colors, 331
Compound muscular contractions, 39
Condiments, 677, 835
Conduction as physiological property,

72

direction of, in nerve fibers, 107
Conjugate foci, 287
Conjugated sulphates, 781
Contraction, 17, 32, 33 (see also

Musde)

Contralateral conduction in cord, 168
Convoluted tubules of kidney, 762,

767

Core-model of nerve, 102
Coronary arteries, effect of occlusion

of, 512

vasomotor supply of, 570
Corpora quadrigemina, relation of, to

visual apparatus, 196, 199
striata, functions of, 216
Corpus callosum, structure and func-
tion, 216
luteum, 873
trapezoideum, 202
Corresponding points of retina, 350
Cortex of cerebrum, general physi-
ology of, 177
histology of, 174, 215
Corti, rods of, 371
Costal respiration, 597
Cowper's glands, 894
Cranial nerves, afferent fibers in, 79
efferent fibers of, 79
nuclei of origin of, 229
Cranioscopy, 181
Creatin, 61, 66, 780
Creatinin, 61, 780
Cresol-sulphuric acid, 740, 782
Cretinism, 795

Curve, contraction, of artificial mus-
cle, 70

of arterial pulse, 487, 490
of plain muscle, 53
of skeletal muscle, 25
dissociation of oxy hemoglobin, 624
extensibility and elasticity of mus-
cle, 19

gastric secretion, 710
intensity of sleep, 243
pancreatic secretion, 723
pressures in vascular system, 460,

464, 465

relations of heart sounds, 505, 506
respiratory movements, 599
secretion of bile, 750
systolic, diastolic, and mean blood-
pressures, 459

Curve, velocity of blood-flow, 452
venous pulse, 491, 492
visual acuity of retina, 324
work of muscle, 36

Cycloplegia, 308

Cystin, 747, 907

Cystinuria, 747

DEAD space of lungs, 602
Death rigor, chemical changes dur-
ing, 66
in muscle, 49
Death, theories of, 905
Defecation, 671

Degeneration in nerve fibers, 118, 120
Deglutition, 655

nervous control of, 659
Deiters's cells in cochlea, 370
Deiters's nucleus, 201. 220
Demarcation current, muscle and

nerve, 91

Demilunes of salivary glands, 689
Depressor nerve fibers, 560

of heart, 563

Derived albumins, properties of, 911
Descending paths, spinal cord, 168,

171

Deutero-albumoses, 714, 912
Deuteranopia, 334
Diabetes, 822

mellitus, 823

pancreatic, 822

phloridzin, 823
Dialysis, definition of, 918
Diaphragm, action of, 593
Diaphragmatic respiration, 593
Diastase, 683

discovery of, 678
Diastole, duration of, in heart, 503,

507
Diastolic arterial pressure, 459

method of determining in

animals, 461
method of determining, in

man, 468

Dicrotic pulse wave, 488
Diet, accessory articles of, 677, 835

average daily, 849

effect of reduction of salts in, 833
Dietetics, general principles of, 848
Diffusion circles on retina, 293
Diffusion, definition of, 914
Digestion in large intestine, 738

in small intestine, 721

in stomach, 717
Diopter, definition of, 297
Dioptrics of eye, 286
Diplopia, 349, 351
Direct field of vision, eye, 321
Discord, physiological explanation of,

379
Dissociation of oxy hemoglobin, 624

926

INDEX.

Diuretics, action of, 769

Dromograph, 450

Dromotropic nerve fibers to heart,

535
Duct of Bartholin, 687

of Rivinus, 687

of Stenson, 687

of Wharton, 687

of Wirsung, 721
Dyspnea, 596, 643

EAR, effect of section of auditory
. nerves, 385
of stimulation of semicircular

canals, 384

Eustachian tube of, 369
Flourens's experiments on semi-
circular canals, 383
functions in analyzing sound waves,

376

of cochlea, 376
of ear-bones, 365
of sacculus, 389
of utriculus, 389
intrinsic muscles of, 368
limits of hearing, 380
position of bones in, 365
projection of auditory sensations,

370

semicircular canals of, 382
sensations of discord, 379

of harmony, 379

sensory epithelium in cochlea, 370
structure of, 371, 377

bones of, 365

theories of functions of semicircu-
lar canals of, 385
tympanic membrane of, 364
Eck fistula, 775
Efferent nerve fibers, 75

occurrence in anterior roots, 77
in cranial nerves, 79
Ejaculation of spermatic liquid, 897
Elasticity and extensibility of muscle,

19
Electrical currents during heart beat,

497

Electrocardiograms, 498
Electrodes, non-polarizable, 95

stimulating, 81
Electrolytes, effect of, on osmotic

pressure, 916
Electrotonic currents, 101
Electrotonus, 83
Eleventh cranial nerve, nucleus of,

233

Embryo, nutrition of, 885
Endogenous fibers of spinal cord, 163
Energy of muscular contraction, 34
Enterokinase/725, 732
Entoptic phenomena, 344
Enzymes, adenase, 685, 779

Enzymes, amylopsin, 729

arginase, 776

chemistry of, 685

classification of, 682

definition of, 682

enterpkinase, 725, 732

erepsin, 728, 732

general properties of, 684

glycolytic, 685, 806, 824

guanase, 685, 779

historical account of, 678

intracellular, 868

inverting, 732

lipase, 730

of muscle, 61

oxidases, 683, 866

pepsin, 711

peroxidases, 867

ptyalin, 700

rennin, 715

reversible reactions of, 680

specificity of, 682

thrombin, 428, 431

trypsin, 726

Epicritic sensations, 260
Epigenesis, 899
Epinephrin, 800
Erection, physiology of, 896
Erepsin, 728, 732
Ergograph, 45
Erythroblasts, 413
Erythrocytes (see Red corpuscles')
Erythrodextrin, 701
Eserin, action of, on iris, 308
Esophoria, 349
Ethereal sulphates, 781
Eupnea, 596
Eustachian tube, 369
Evolution, hypothesis of, in heredity>

899

Excretin, 742

Exogenous fibers in spinal cord, 163
Exophoria, 349
Expiration (see also Respiration')

definition of, 592

expiratory center, 639

muscles of, 595
Expired air, composition of, 613

injurious effects of, 614
Extensibility of muscle, 19
External geniculates, 196, 199
Eye, abnormalities in refraction of,
299

accommodation in, 293

action of drugs upon, 308

acuity of vision in, 323

after-images in, 331

as optical instrument, 286

binocular field of vision, 350
perspective, 356

chromatic aberration in, 298

color blindness of, 333

INDEX.

927

Eye, color contrasts in, 332

vision in, 328
complementary colors, 331
corresponding points in, 350
dark adapted, 318, 326
diffusion circles in, 293
diplopia in, 349, 351
direct field of vision in, 321
entoptic phenomena in, 344
far point of distinct vision, 297
function of cones, 337

of rods, 337

fundamental color sensations, 330
horopter, 353

indirect field of vision in, 321
inversion of image in, 291
light adapted, 318, 326

reflex in, 306
movements of, 347
muscular insufficiency, 349
nature of visual stimuli, 318
near point of distinct vision, 296
nodal point of, 290
ophthalmoscopic examination of,

311
optical defects of, 298

delusions, 360

physics of formation of image in, 289
qualities of visual sensations, 328
reduced schematic (Listing), 290
refractive power of, 297
size of retinal images, 292
spherical aberration in, 299
stereoscopic vision, 356
struggle of visual fields, 353
suppression of visual images, 353
theories of color vision, 340
threshold stimulus of, 325
visual field of, 320

judgments, 354

purple of, 318
Eye-muscles, action of, 347

FACIAL nerve, dilator fibers in, 565

nucleus of, 232

Far point of distinct vision, 297
Fat, absorption of, 735
as glycogen former, 755
digestion of, 730

in stomach, 720
excessive formation of, in obesity,

829

in bile, 748

metabolism of, in body, 826
nutritive value of, 826
of chyle, 736
origin of, from carbohydrates, 829

in body, 829

Fatigue, in nerve fibers, 110
muscular, 47
of olfactory organs, 283
theories of, 66

Feces, composition of, 741
Fermentation in intestine, 739

of carbohydrates in small intestine.

735

Ferments, historical account of, 678
Fertilization of ovum, 883
Fibrillary contractions of heart, 513
Fibrin factors, 429

ferment, preparation of, 428

globulin, 431

relations to blood-clot, 426
Fibrinogen, 424

preparation of, 428
Fictitious meal (Pawlow), 709
Fifth cranial nerve, 230
Fillet, lateral, 202

median, 192
Fistula, Eck's, 775

gall-bladder, 743

stomach, 706

Thiry-Vella, 731
Flavors, 677

dietary importance of, 835
Flechsig's myelinization method, 158

tract of, 165

Fluorid solution, effect on clotting, 435
Food, composition of, 675

definition of, 675

potential energy of, 845
Foodstuffs, definition of, 675
Fourth cranial nerve, nucleus of, 230
Fovea, center for, in occipital cortex,
198

of retina, size of, 322
Franklin theory of color vision, 343
Freezing point, method of determin-
ing, 917

Fundic glands of stomach, 703
Fundus of stomach, 660

GALL-BLADDER, functions of, 749

nerves of, 750
Galvanometer, construction of, 92

d'Arsonval, 93
Gases, laws governing absorption

of, 620
of blood, 617
pressure of, 620
tension of, in solution, 622
Gas-pump, 618
Gastric glands, 703

histological changes in, during

secretion, 704
secretory nerves of, 708
secretion, acid of, 707
composition of, 705
curve of, 710
means of obtaining, 705
normal mechanism of, 709
Gelatin, nutritive value of, 818
Genital organs, vasomotor supply of,
583

928

INDEX.

Germ plasm, definition of, 905

Globin, 401, 913

Globulicidal action of blood-serum,

398

Globulins, general properties of, 911
Glomerulus of kidney, functions of,

765

Glossopharyngeal nerve, dilator fibers
in, 565

nucleus of, 232
Glucoproteins, 913
Glucosamin, 908
Glutaminic acid, 727, 907
Glutolin, 423
Glycocholic acid, 746
Glycocoll, 727, 746, 908
Glycogen, amount of, in liver, 753

discovery of, 752

glycogenic theory, 756

importance of, in embryo, 886

in muscle, 59, 757

loss of, during muscular contrac-
tions, 64

metabolism of, in body, 824

origin of, 753

supply of, in body, 821
Glycolysis of sugars in body, 824
Glycosuria, 822

alimentary, 735
Glycylglycin, 908
Gmelin's reaction for bile pigments,

745
Golgi's nerve cells, second type, 127

pericellular nerve net, 128
Goll, column of, 163
Gowers's tract, 165
Graafian follicle, structure of, 872
Gram-molecular solution, 916
Growth, 904
Guanase, 685, 779
Guanin, 61, 778
Gudden's commissure, 197, 203

HARMONY, physiological cause of, 379
Hearing (see Ear)

cortical center of, 200

limits of, 380

Heart, accelerator center for, 545
nerves of, 541

action current of, 497

action of inhibitory nerves, 531

analysis of inhibition, 533

apex beat of, 500

automaticity of, 514

capacity of ventricles of, 507

cardiac nerves of, course, 531

cardiogram, 500

cardio-inhibitory center of, 536

causation of beat, 514

change in form of ventricle in sys-
tole, 499

compensatory pause of, 525

Heart, contraction wave in, 496
coronary circulation in, 509
course of cardiac nerves, 531
depressor nerve of, 561
diastole and systole of, 494

time relations of, 507
effect of drugs on, 539
of calcium upon, 520
of occlusion of coronaries upon,

512

of potassium upon, 520
of sodium upon, 520
electrical changes in, 497
escape from inhibition, 536
events of a cardiac cycle, 506
fibrillary contractions, 513
historical account of beat of, 515
inhibition of auricle, 535

of ventricle, 535
intraventricular pressure during

systole, 502
intrinsic nerves of, 516
maximal contractions of, 523
musculature of, 495
myogenic theory of beat of, 517
negative pressure in, 510
neurogenic theory of beat of, 516
rate of beat as affected by age, 546
by blood-pressure, 547
by extrinsic nerves, 547
by muscular exercise, 548
by sex, 546
by size, 546
by temperature, 549
reflex acceleration of beat, 543
refractory period of, 523
sequence of beat of, 525
sounds of, 503
suction-pump action of, 510
systole and diastole of, 494

time relations of, 507
systolic plateau of beat, 503
theories of inhibition of, 539
tonic inhibition of, 537
tonicity of muscle of, 529
vasomotors of, 570
ventricle of, in systole, 500
work done by, 507
Heart-block, 527
Heart-muscle, general properties of,

54, 523
Heat centers, 864

equivalent of foodstuffs, 846

loss of, physiological regulation of,

860

nerves, 864 t

production, physiological regula-
tion of, 863
puncture, 865
regulation, general statement of,

860
rigor of muscle, 51

INDEX.

929

Heat, sexual, in lower animals, 875
Helmholtz theory of color vision, 340
Helweg's bundle, spinal cord, 172
Hematin, 402, 411
Hematoidin, 412
Hematopoietic tissue, 413
Hematoporphyrin, 412
Hemeralopia (night-blindness), 339
Hemin, 411
Hemipeptone, 726
Hemiplegia, 186
Hemochromogen, 401, 412
Hemodromograph, 450
Hemoglobin, absorption spectra of,
406

compounds of, with carbon dioxid,

404

with carbon monoxid, 403
with nitric oxid, 403
with oxygen, 403

condition of, in corpuscles, 396

crystals of, 405

curve of dissociation of oxyhemo-
globin, 624

derivative compounds of, 410

iron in, 404

nature and amount of, 401
Hemolysins, natural and acquired,

398

Hemolysis, 397
Hemorrhage, effect of, 437
Heredity, definition and history, 899
Hering theory of color vision, 341
Heterophoria, 349
Hexon bases, 896
Hippuric acid, 781
Histidin, 728, 907
Histohematins, 412
Histons, 896, 912

effect of, on coagulation of blood,

434

Hofaeker-Sadler law, 902
Homoiothermous animals, 853
Homolateral conduction in cord, 168
Hormones, 711
Horopter, 353
Hunger, sense of, 270
Hydrocele liquid, 423
Hydrochloric acid, function of, in pep-
tic digestion, 713
in gastric juice, 707
Hydrolysis, 683

Hydrostatic factor in circulation, 478
Hyperglycemia, 822
Hypermetropia, 300
Hyperpnea, 643
Hypertonic solutions, 918
Hypnotic sleep, 251
Hypoglossal nerve, nucleus of, 233
Hypophysis cerebri, 801
Hypotonic solutions, 918
Hypoxanthin, 61, 777, 779

59

IDENTICAL points of retina, 350
Identity theory of nerve impulse, 116
Immune body, 400
Incongruence of retinas, 351
Indican, 782

Indirect calorimetry, 859
field of vision, eye, 321
Indol group in protein molecule, 728
Indoxyl sulphuric acid, 740, 782
Induction coil, 23
Inert layer in circulation, 448
Infundibular body, 801
Inhibition, escape from, in heart, 536
of heart, 531
of knee-jerk, 148
of reflexes, 140

of respiratory movements, 637
reflex of heart, 536
theories of, 539
Inotropic nerves to heart, 535
Inspiration (see also Respiration)
definition of, 592
increased heart-rate during, 612
means of producing, 593
muscles of, 595

Inspired air, composition of, 613
Intermediary products of muscle

metabolism, 64

metabolism of carbohydrates, 824
of fats, 826

of nucleo-proteins, 816
of proteins, 811
Internal secretion, adrenals, 798

definition and historical account,

793

kidney, 806
liver, 794
ovary, 802
pancreas, 804
sensations, 254
testis, 802
thyroid tissues, 794
Intestinal movements, effect of va-
rious conditions upon, 669
secretion, 731

Intestines, bacterial action in, 739
large, movements of, 670
nervous control of movements of,

669

reaction of contents of, 739
small, movements of, 666
Intracellular enzymes, 868
Intracranial pressure, 576
Intraocular pressure, 310
Intrapulmonic pressure, 604
Intrathoracic pressure, 605
origin of, 607

variations of, with forced breath-
ing, 606

Intraventricular pressure, 502
Introductory contractions of muscle,
33

930

INDEX.

Invertase, 685, 717, 732

in stomach, 717
Involuntary muscle, 52
lodothyrin, 795
Iris, action of drugs upon, 308

antagonistic action of muscles

upon, 305

muscles and nerves of, 304,
Iron in hemoglobin, 404

salts, source and nutritive impor-
tance of, 833
Irritability, definition of, 22

of muscle, 22

of nerve fibers, 80
Isodynamic equivalent of foodstuffs,

848

Isometric muscular contractions, 27
Isotonic muscular contractions, 27

solutions, definition of, 885
Isotropous substance in muscle, 19

JACOBSON, nerve of, 687
Judgments, visual, of distance and

size, 359
of perspective or solidity, 354

KIDNEY, action of diuretics on, 748

blood-flow through, 769

composition of secretion of (urine),
772

function of convoluted tubules, 767
of glomerulus, 765

internal secretion of, 806

secretion of urine in, 763

structure of, 762
Kjeldahl's method for determination

of nitrogen, 773, 809
Knee-jerk, conditions influencing, 150

definition of, 147

explanation of, 149

reinforcement of, 147

use of, as diagnostic sign, 151

LABOR, physiology of, 888
Lactic acid in muscle, 60

increase of, during contraction,

64

Laked blood, 397
Langerhans, islands of, 806
Large intestine, digestion and absorp-
tion of food in, 738
movements of, 670
Larynx, reflex effects from, on respi-
rations, 638

Latent period of muscular contrac-
tion, 26
Lecithin, 748
Lemniscus, lateral, 202

median, 192
Leucin, 727, 907

Leucocytes, effect of hemorrhage
upon, 438

Leucocytes, functions of, 416

in formation of thrombin, 429

structure and classification, -4 Hi

variations in number of, 417
Leuconuclein, effect upon blood coag-
ulation, 434
Liebermann's . reaction for proteins,

910
Liebig's classification of foodstuffs,

840

Light-reflex in eye, 306
Lipase, 683

in pancreatic secretion, 730

in stomach, 717, 720

reversible reaction of, 681
Listing's law, 349

schematic eye, 290
Liver, bile-pigments of, 745
acids of, 746

defensive action of, in coagulation,
432

formation of urea in, 758

glycogen of, 752

glycogenic action of, 756

internal secretion of, 794

pulse, 491

quantity of bile, 744

secretion of bile, 748
Localization of function in cerebellum,

227

in cerebrum, 181
Localizing power of skin, 264
Locke's solution, 521
Locomotor ataxia, 164
Lud wig's theory of urinary secretion,

763

Luminosity of visual sensations, 327
Lungs, gaseous exchanges in, 627

vasomotors of, 571
Luxus consumption, 813
Lymph, action of lymphagogues, 443

circulation of, 585

formation of, 441

summary of factors concerned in

formation of, 445
Lymphocytes, 416
Lysin, 728, 907, 912

MALTASE, 685, 700, 730, 732

Maltose, 701, 730

Mammary glands, effect of uterus

upon, 889

structure and functions, 889
Manometer, Fick's spring, 461
Hurthle's, 462

maximum and minimum, 462
use of, for determining blood-pres-
sure, 455
Mast cells, 417
Mastication, 655
Mathematical perspective, 355
Mean blood-pressure, 460

INDEX.

931

Medulla oblongata, 228

respiratory center in, 631
Medullary striae, 203
Meningeal spaces, 574
Menstruation, 874

effect of, on other functions, 879
physiological significance of, 878
Mercury manometer, use of, for blood-
pressures, 455
Metabolism, definition of, 808

intermediary, of carbohydrates, 824
of fats, S26
of nucleoproteins, 816
of proteins, 811
Methemoglobin, 410
Methylpurins, 778
Micturition, physiology of, 783
Milk, composition of, 891
Millon's reaction for proteins, 910
Minimal air, 601
Miosis, definition of, 308
Molisch reaction for proteins, 910
Monakow's bundle, 171, 187
Motor aphasia, 206
areas of brain, 184
paths in spinal cord, 168
points in man, 88
Mountain sickness, 650
Movements of alimentary canal, defe-
cation, 671
deglutition, 655
large intestine, 670
mastication, 655
small intestine, 656
stomach, 661
vomiting, 672
Mucin in saliva, 690
Muscarin, action of, on heart, 539
on iris, 308
on sweat glands, 791
Muscle, absolute power of, 36
action current of, 96
artificial stimulation of, 23
carbohydrates of, 59
cardiac, properties of, 54, 523
chemical changes of, in contrac-
tion, 62

composition of, 57
compound contractions of, 39
contraction of, 26
contraction wave of, 33
contracture of, 33
curve of work of, 36
death rigor, 49
demarcation current of, 91
direct irritability of, 22
disappearance of glycogen in, 63
effect of temperature upon, 28

of veratrin upon, 30
energy liberated in, 34
Engelmann's artificial, 69
enzymes of, 61

Muscle, ergographic records from, 45

extensibility and elasticity of, 19

fatigue of, 33, 47, 66

glycogen of, 757

heat rigor of, 49

inorganic salts of, 62

introductory contractions of, 33

isotonic and isometric contrac-
tions of, 27

lactic acid of, 60

latent period of contraction of, 26

maximal and submaximal contrac-
tions of, 27

nitrogenous extractives of, 61

number of stimuli necessary for
tetanus, 42

pigments of, 61

plain, 52

plasma, 18, 57

proteins of, 57

sarcoplasm, 18

simple contraction of, 24

stroma, 59

structure of fiber, 18
by polarized light, 19

summation of contractions of, 39

theories of nature of contraction,
68

tone of, during contraction, 41

tonicity of, 48

vasomotor supply of, 583

voluntary contractions of, 43

white and red fibers of, 30
Muscle-sense, cortical area for, 191

distribution and characteristics of,
268

importance of, in visual judg-
ments, 355

paths for, in spinal cord, 164, 166

quality of, 269

Muscular insufficiency in movements
of eyeballs, 349

work, effect of, on heart rate, 548
on physiological oxidations,

840

on protein metabolism, 841
on respiratory movements, 648
Musical sounds, classification and

properties of, 372
Mydriasis, definition of, 308
Myelin sheath of nerve fibers, func-
tion of, 73
Myelinization method of Flechsig,

158, 212
Myogen, 58

fibrin, 58

Myogenic theory of heart beat, 517
Myohematin, 412
Myopia, 300
Myosin, 58

fibrin, 58
Myxedema, 795

932

INDEX.

NARCOSIS, effect of, upon nerve im-
pulse, 109

Near point of distance vision, 296
Negative pressure in thorax, 605, 607

in ventricle, 510
variation in muscle and nerve, 96,

98

Nerve, abducens, nucleus of, 232
auditory, 201

chorda tympani, 274, 688, 691
facial, nucleus of, 232
fourth cranial, nucleus of, 230
glossopharyngeal, nucleus of, 232
hypoglossal, nucleus of, 233
motor and sensory roots of, 77
olfactory, 204
optic, 195
recurrent sensibility of anterior

roots, 77

spinal accessory, nucleus of, 233
third cranial, nucleus of, 229
trigeminal, nucleus of, 230
twelfth cranial, nucleus of, 233
vagus, nucleus of, 233
Nerve-cell, chromatolysis of, 121

classification of, in spinal cord,

155

degenerative changes in, 121
general physiology of, 129
internal structure of, 127
metabolism in, 130
neuron doctrine, 123
reaction of, 129
refractory period of, 133
summation of stimuli in, 130
varieties of, 125

Nerve-fibers, action current of, 96
afferent and efferent, 75
anodal and cathodal stimulation

of, 82

antidromic impulses in, 78
artificial stimuli of, 80
autoregeneration of, 120
classification of, 75
core model of, 102
degeneration and regeneration

of, 118

demarcation current of, 91
direction of conduction, 107
du Bois-Reymond's law of stim-
ulation, 82
electrical stimulation of, in man,

89

electrotonic currents of, 101
electrotonus of, 83
impulse in, historical, 104
independent irritability of, 80
metabolism in, during activity,

112

myelin sheath of, 73
nutritive relations to nerve cells,
117

Nerve-fibers, opening and closing tet-
anus of, 86

Pfliiger's law of stimulation of, 84
stimulation of, in man, 86
structure of, 73
unipolar method of stimulating,

87

Nerve-impulse, historical, 104
metabolism during, 111
modification of, by various in-
fluences, 109

qualitative changes in, 76, 116
relation of, to action current, 100,

107

theories of, 113
velocity of, 105
Nervi erigentes, 239, 565, 583
Neurogenic theory of heart beat, 516
Neuron doctrine, 123
Neurons, varieties of, 125
Nicotin, action of, on salivary secre-
tion, 697

on sweat secretion, 790
use of, in tracing autonomic fibers,

236

Night-blindness, hemeralopia, 339
Ninth cranial nerve, nucleus of, 232
Nissl's granules, 128
Nitric oxid hemoglobin, 404
Nitrogen, condition of, in blood, 623
determination of, 809
equilibrium, 808

effect of non-protein food on, 811
excretion in urine, 773
Nitrogenous extractives of muscle, 61
Nodal point of eye, 290
Non-polarizable electrodes, 95
Normoblasts, 414
Nuclease, 779
Nucleo-albumin, general properties

of, 911
in bile, 748
Nucleon, 60
Nucleoproteins, 913
in blood, 426
intermediary metabolism of, 816

OBESITY, physiological cause of, 829
Ohm's law of composition of sound

waves, 375
Olf action, end-organ for, 279

mechanism of, 280
Olfactometer, 284
Olfactory associations, 285

bulb, histological structure of, 204

center in cortex, 204

nerve, course of fibers of, in brain,
204

organs, fatigue of, 283

sensations, classification of, 281
conflict of, 285
qualities of, 281

INDEX.

933

Olfactory sensations, threshold stim-
ulus, 283
sense cells, 280
stimuli, nature of, 281
Oncometer, 770
Ophthalmoscope, 311
Ophthalmometer, 314
Opotherapy, 793
Opsonins, 418
Optic chiasma, decussation in, 197

structure of, 195 „

nerve, course of fibers of, in brain,

195

radiation, 196
thalamus, functions of, 216

in vision, 199
tracts, structure of, 197
Optical deceptions, 360
Optograms on retina, 319
Osmosis, definition of, 914
Osmotic pressure, definition of, 914
determination of, 916
of blood, 397

Oval field of Flechsig, 171
Ovaries, internal secretion of, 803

relation of, to menstruation, 877
Overtones, production of, 374
Ovulation, 873
Ovum, fertilization of, 883

implantation of, in uterus, 884
maturation of, 880
passage of, into uterus, 879
Oxalate solutions, effect of, on coagu-
lation, 435
Oxidases, 683, 866
Oxidations, theories of, 866
Oxygen, action of, on respiratory

center, 641, 649
compound of, with hemoglobin,

403

condition of, in blood, 624
effects of, on muscular irritability,

63

varying pressures of, on respira-
tion, 649

tension of, in alveolar air, 628
in tissues, 629
in venous blood, 628
Oxyhemoglobin, 403
Oxypurins, 778

PACCHIONIAN bodies of brain, 575
Pain sense, distribution and char-
acteristics of, 266
localization of, 267
path for, in cord, 167
Pancreas, action of lipase in, 730
anatomy of, 721
curve of secretion of, 723
digestive action of secretion. 725

on carbohydrates, 729
internal secretion of, 804

Pancreas, normal mechanism of secre-
tion, 724

secretory nerves of, 722
Paraglobulin, 423
Paralysis (motor), 186
Paralytic secretion (saliva), 698
Parapeptone, 714
Parathyroid, structure and function

of, 794, 795

Parthenogenesis, 884, 903
Parturition, physiology of, 888
Pendular movements (intestine), 666

sound waves, 373
Pepsin, 711

discovery of, 678

properties of, 711
Pepsin-hydrochloric acid digestion,

713

Peptids, 729, 908
Peptone, 714, 912

absorption of, in stomach,. 720

effect on clotting of blood, 435

hemi- and anti-, 726
Peptozym, 436
Pericardial liquid, 423
Perimeter, 320
Peripheral field of vision, 321

resistance in circulation, 477
Peristalsis, 666
Peroxidases, 869
Perspiration (see Sweat)
Pettenkofer's reaction, 746
Pfluger law of stimulation, 84

tetanus, 86
Phagocytes, 418
Phenolsulphuric acid, 781
Phenylalanin, 727, 907
Phloridzin diabetes, 823
Phosphocarnic acid, 60
Phrenology, 181
Physiological diplopia, 351

oxidations, theories of, 866
Lavoisier's work, 588, 852

point (vision), 323

saline, 398

Physostigmin, action of, on iris, 308
Pilocarpin, action of, on heart, 539
on iris, 308

on salivary glands, 697
on sweat glands, 791
Pituitary body, structure and func-
tions of, 801
Piqure, 822

Placenta, functions of, 885
Plain muscle, 52

Plasma of blood, composition of, 420
Plethysmography, 553
Pneumogastric nerve (see Vagus)
Pneumograph, 599
Pneumothorax, 608
Poikilothermous animals, 853
Polar bodies of ovum, 881

934

INDEX.

Polypeptid, 729, 908

Positive electrical variation in heart,

540
Posterior columns, descending tracts

of, 171
tracts of, 162

root, termination in cord, 161

cells of, origin of, 78
Postganglionic nerve fibers, 235
Potassium phosphate in muscle, 65

salts, action of, on heart, 520
Potential energy of food, 845
Precipitins, 909
Predicrotic pulse wave, 488
Preganglionic nerve fibers, 235
Pregnancy, changes in, 887
Prepyramidal tracts, 171
Presbyopia, 296, 301
Pressor nerve fibers, 560
Pressure of gases in solution, 622

sense,. distribution of, 263
deep, 260

localizing power, etc., 264
Primary proteoses, 714
Principal axis of lens, 287

focal distance, 287
Projection system of fibers (brain),

175

Propeptone, 714
Prostate gland, 894, 898
Protalbumoses, 714
Protamins, 895, 912
Protanopia, 334

Proteins, absorption of, in intestine,
737

as glycogen-formers, 754

classification of, 910

definition and structure of, 907

diffusion of, 919

excretion of nitrogen of, 773

general reactions of, 908

in blood-plasma, 422

necessary amount of, in diet, 813

normal metabolism in body, 811

of muscle, 57

osmotic pressure of, 918

putrefaction of, in large intestine,
740

specific dynamic action of, 818
Proteolytic enzymes, 683
Proteoses, general properties of, 714,

912

Protopathic sensations, 260
Prothrombin, 430
Proximate principles of food, 675
Psychophysical law, 256
Ptyalin, 690

action of, in stomach, 663

digestive action of, 700

effect of various conditions upon,

701
Puberty, 874, 893

Pulmonary arteries, vasomotors of.

571 '

circulation, peculiarities of, 480
variations of pressure in, 481
Pulse, anacrotic waves of, 489
catacrotic waves of, 488
form of wave, 487
general statement, 483
varieties of, in health and disease,

490

velocity of, propagation of, 484
venous, 491
Pulse-pressure, 459
Purin bases, 61, 777
Purkinje, images of, 294

phenomenon, 328
Putrefaction in intestines, 740
Pyloric glands of stomach, 703

secretion of, 713
Pyramidal tract in brain, 185

in spinal cord, 169

Pyrrol compounds in protein mole-
cule, 727
Pyrrolidin-carboxylic acid, 727, 907

REACTION time, 106

of degeneration, 89
Reactions for proteins, 908

biological, 399

Gmelm's, 745

of blood, 393

of contents of small intestine,
739

of urine, 772

Pettenkofer's, 746
Recurrent sensibility of anterior roots,

Red blood-corpuscles, chemical com-
position of, 421

condition of hemoglobin in, 396
effect of hemorrhage upon, 413
hemolysis of, 397
influence of spleen upon, 413
number and size of, 395
origin and fate of, 412
variations in number of, 414

Reduced hemoglobin, 403
schematic eye, 290

Reflex actions, axon reflexes, 144
classification of, 137
definition and historical, 134
from parts of brain, 143
influence of condition of cord on,

142

of sensory endings upon, 139
inhibition of, 140

of heart, 536
knee-jerk, 147

of erection and ejaculation, 897
of respiratory center, 633, 638
of vasomotor nerves, 560
preparation of reflex frog, 136

INDEX.

935

Reflex actions, reflex arc, 134

respiratory, from nose, larynx,

and pharynx, 638
special and deep reflexes of cord,

151

spinal reflexes, 136
theory of, 138

through peripheral ganglia, 143
through vasodilator nerves, 566
time of, 140

Tiirck's method of studying, 142
Refractive power of eye, 297 „.
Refractory period of heart beat, 523

of nerve cell, 133
Regeneration in nerve fibers, 118

of parts of body, 901
Reinforcement of knee-kick, 147
Rennin, 715

of kidney, 807

Reproduction, changes during preg-
nancy, 887

in uterus in menstruation, 875
chemistry of spermatozoa, 895
determination of sex, 901
erection, 896
fertilization of ovum, 883
functions of placenta, 885
general statements, 871
growth and senescence, 904
heredity, 899

implantation of ovum, 884
mammary glands, 889
menstruation, 874
nutrition of embryo, 885
ovulation, 872
parturition, 888
properties of spermatozoa, 893
relation of ovaries to menstrua-
tion, 876
structure and functions of corpus

luteum, 872

of Graafian follicles, 872
Residual air, 601

Resonance, importance of, in func-
tions of ear, 376

Respiration, abdominal type, 597
acapnia, 646, 651
accessory centers of, in brain, 640

respiratory movements, 598
anatomy of thorax, 591
apnea, 643
artificial, 602, 612
aspiratory action of, on blood-flow,

608

asphyxia, 644
automatic action of respiratory

center, 633

bronchoconstrictor and broncho-
dilator fibers, 646
calorimeter, 859
capacity of the bronchi, 602
chamber, 810

Respiration, chemical composition of
inspired and expired air, 613

Cheyne-Stokes type of, 654

complemental air, 601

condition of carbon dioxid in blood,
625

costal, 597

definition of inspiration and ex-
piration, 592

dissociation of oxy hemoglobin, 624

dyspnea, 596, 643

effect of anemia upon, 654

of changes in barometric pressure

upon, 650

in composition of air, 648
of muscular work upon, 648

exchange of gases in, 613

forced, 596

gaseous exchange in lungs, 627

gases of blood, 617

history of, 587

hyperpnea, 643

increased heart-rate during inspira-
tion, 612

injurious effect of expired air, 614

intrapulmonic pressure, 604

intrathoracic pressure, 605

mechanism of inspiration, 593

methods of recording, 598

minimal air, 601

modified respiratory movements,
653

mountain sickness, 650

muscles of expiration, 595
of inspiration, 595

negative pressure in thorax, 606

normal stimulus of, 640
ventilation of alveoli, 602

of swallowing, 657

origin of negative pressure in
thorax, 607

physical theory of, 627

physiological anatomy of organs
of, 591

pneumothorax, 608

reflex stimulation of respiratory
center, 633

relation of vagus nerve to, 635

residual air, 601

respiratory center, 631
quotient, 652
waves of blood-pressure, 609

secretion of gases in lungs, 630

spinal respiratory centers, 632

supplemental air, 601

tension of gases in alveolar air, 628
in arterial blood, 629
in tissues, 629
in venous blood, 628

tidal air, 601

value of nitrogen in, 623

ventilation, principles of, 614

936

INDEX.

Respiration, vital capacity, 600

volumes of air respired, 600

voluntary control of, 639
Respiratory center, 631, 639
automatic activity of, 633
normal stimulus of, 640
reflex stimulation of, 633

quotient, 652

waves of blood-pressure, 609
Retina, action current of, 317

acuity of vision in, 323

after-images from, 331

color blindness of, 333
contrasts in, 332
vision in, 328

corresponding points of, 350

distribution of color sense in, 336

entopic phenomena, 344

function of rods and cones of, 337

fundamental and complementary
colors, 330

light adapted and dark adapted,
326

portion of, stimulated by light, 316

projection of, on occipital lobes, 197

qualities of visual sensations from,
328

size of fovea in, 323

theories of color vision in, 340

threshold stimulus of, 325

visual purple of, 318
Retinoscope, 313

Reversible chemical reactions, 680
Rheoscopic frog preparation, 99
Rhodopsin, 318

Ribs, action of, in inspiration, 594
Rigor of muscle, 49, 51, 62, 66
Ringer's solution, 520
Ritter's tetanus, 86
Rivinus, ducts of, 687
Rods and cones of eye, functions of,

337

Romberg's symptom, 224
Rubrospinal tract, 171, 187

SACCULUS, functions of, 389
Saliva, chorda, 692
composition of, 690
digestion action of, 700
general functions of, 702
secretory nerves for, 691
sympathetic, 692
Salivary glands, action of drugs upon,

697

anatomical relations, 687
histological changes during ac-
tivity, 694
structure of, 687
normal stimulation of, 698
secretory centers for, 699

nerve fibers of, 691
theory of secretory nerves, 693

Salts, absorption of, in stomach, 719

excretion of, 782, 833

general nutritive importance of, 832
Sarcolactic acid, 60
Sebaceous glands, secretion of, 791
Secondary axes of a lens, 288

degeneration, nerve fibers, 117, 158

proteoses, 714, 912
Secretin, gastric, 711

pancreatic, 724
Secretion, 687

internal, 793

paralytic (saliva), 698

of bile, 748

of gastric juice, 708

of intestinal juice, 731

of pancreatic juice, 722

of saliva, 691

of sebaceous glands, 791

of sweat, 788

of urine, 772

Secretogogues of gastric glands, 710
Secretory nerves of salivary glands,

691

Semicircular canals, direct stimula-
tion of, 384

Flourens's experiments upon, 383
structure of, 382
temporary and permanent effects

of operations on, 384
theories of functions of, 385
Seminal vesicles, function of, 894
Senescence, 904
Senses, classification of, 252

cutaneous and internal, 259
Sensory aphasia, 208

areas of cortex, 190

paths in spinal cord, 162, 165
Sequence of heart beat, 525
Serin, 907
Serum, action of foreign, 398

-albumin, 422

-globulin, 423

Seventh cranial nerve, nucleus of, 232
Sex, determination of, 901
Side-pressure in blood-vessels, 473
Sixth cranial nerve, nucleus of, 232
Skatoxylsulphuric acid, 740, 782
Skeletal muscular tissue, physiology

of, 18

Skiascope, 313
Skin, excretory functions of, 788

sweat glands of, 788
Sleep, changes in circulation during,
245

curves of intensity of, 243

effect of sensory stimulation dur-
ing, 246

hypnotic, 251

metabolism during, 842

physiological phenomena of, 241

theories of, 247

INDEX.

937

Small intestine, absorption in, 733

Smegma prseputii, 792

Smell, center for, in brain, 204

end-organ of, 279
Smelling, mechanism of, 280
Sodium chlorid, nutritive value of,

833

salts, effect of, on heart-beat, 520
Somatoplasm, definition of, 905
Sound, sensations of (see Ear}
waves, nature and action of, 372
overtones of, 374 «

simple and compound, 373
Specific energy of taste sensations,

277

gravity of blood, 394
nerve energies, doctrine of, 116, 254

of cutaneous nerves, 262
Spectra, absorption, blood, 406
Spectroscope, 407
Spermatozoa, chemistry of, 895
maturation of, 893
properties of, 893
Spermin, 803

Spherical aberration in eye, 299
Sphygmography, 486
Sphygmomanometers for determin-
ing blood-pressure in man, 467
Spinal cord, as path of conduction, 155
classification of tracts in, 158
effect of removing, 145, 672
general relations of gray and

white matter in, 157
groups of cells in, 155
Helweg's bundle in, 172
homolateral and contralateral

conduction in, 168
less well-known tracts of, 170
Monakow's bundle in, 171, 187
paths in, for cutaneous impulses,

167

pyramidal tracts of, 168
reflex activities of, 134
tonic activity of, 145
tracts of, in lateral column, 165
in posterior column, 162
in white matter, 158
vestibulo-spinal tract, 171, 220
reflex movements, 136
reflexes in mammals, 139
respiratory center, 632
Spirometer, 600
Spleen, physiology of, 759
Stannius, first ligature of, 528
Stapedius muscle, function of, 368
Starvation, effect of, on body-metab-
olism, 843

Steapsin (see Lipase)
Stenson's duct, 687
Stereognostic sense, 191
Stereoscopic vision, 356
Stethoscope, 503

Stimulants, 677

nutritive importance of, 836
Stimuli, artificial, of muscle, 23

of nerve, 80

Stokes- Adams syndrome, 527
Stokes 's reducing agent, 409
Stomach, absorption in, 718

anatomy of, 660

automaticity of, 665

digestion in, 717

glands of, 703

histological changes in, during
activity, 704

means of obtaining secretion of, 705

mechanism of gastric secretion, 709

movements of, 661

musculature of, 661

properties of pepsin of, 711

secretory nerves of, 708
Strabismus, 350
Stromuhr, 449
Subliminal stimulus, 325
Submaxillary ganglion, 668
Succus entericus, 731
Sugars (see Carbohydrates)
Sugar puncture, 822
Sulphur, forms in which excreted, 781
Summation of muscular contractions,
39

of stimuli in nerve centers, 131
Superior olivary body, relation of, to

auditory paths, 202
Supplemental air, 601
Swallowing, 655

respiration, 657

Sweat, amount and composition of,
788

nerve centers for, 791

secretory fibers of, 789
Sweat-nerves, action of, in heat regu-
lation, 861

Sympathetic nervous system, general
relations, 234

resonance, 376
Syntonin, 714

Systole, duration of, in heart, 507
Systolic arterial pressure, 459

determination of, in animals,

461
in man, 467

plateau of ventricular contraction,
503

TABES dorsalis, 164
Taste buds, 276

center for, in brain, 206
nerves of, 274

sensations, classification of, 276
specific energy of, 277
threshold stimulus, 279
sense of, 274
stimuli, mode of action, 278

938

INDEX.

Taurin, 747
Taurocholic acid, 747
Tectorial membrane, 378
Temperature (see Heat)

effect of, on body metabolism, 842
on gases in solution, 621
on heart rate, 550
on muscular contraction, 28

of human body, 854

sense, distribution and character-
istics, 260, 263
path for, in spinal cord, 167
punctiform distribution of, 260
Tension of gases in solution, 622
Tensor tympani muscle, function of,

368

Tenth cranial nerve, nucleus of, 233
Testis, internal secretion of, 802
Tetanus, number of stimuli necessary
for, 42

of artificial muscle, 71

of muscle, 39

opening and closing, 86
Theobromin, 778, 836
Third cranial nerve, nucleus of, 229
Thirst, sense of, 272
Thorax, as closed cavity, 592

aspiratory action of, 608

normal position of, 592

origin of negative pressure in, 607
Thrombin, 428, 430
Thrombokinase, 430
Thrombogen, 430
Thymus, 798
Thyroid, extirpation of, 795

function of, 797

internal secretion of, 794
• theory of (Cyon), 797
Tidal air, 601

Tigroid substance in nerve cells, 128
Tissue protein, 812
Tissues, exchanges of gases in, 629
Tone (musical) of muscular contrac-
tion, 41
Tonicity of heart muscle, 529

of muscle, 48

of nerve centers, 145
Touch sense, path of, in cord, 167
Tracts in spinal cord, 158

of Burdach, 160, 163

of Flechsig, 160, 165

of Goll, 160, 163

of Cowers, 160, 165

of Helweg (olivo-spinal), 172

of Monakow (rubro-spinal). 171,
187

in cerebellum, 220
Traube-Hering waves, 564
Treppe of muscular contractions, 33
Trigeminal nerve, area of distribu-
tion of, 231
' nucleus of, 230

Tritanopia, 334

Trophic nerve fibers, salivary glands,

693

Trypsin, 683, 726
Tryptophan, 728

Turck's method for reflex time, 142
Twelfth cranial nerve, nucleus of,

233

Tympanic membrane, 364
Tyrosin, 727, 907

UNIPOLAR method of stimulation, 87
Urea, formation of, in liver, 758

origin and significance of, 774, 815
Ureters, contractions of, 783
Urethra, sphincter of, 785
Uric acid, 61

in spleen, 761
significance of, 777, 816
Uricolytic enzyme, 779
Urinary bladder, movements of, 784
nerves of, 787

pigments, 772
Urination, physiological mechanism

of, 783
Urine, composition of, 772

nitrogenous excreta of, 773

origin of acidity of, 768, 772

reaction of, 772

secretion of, 763

secretion pressure of, 767
Uterus, changes of, during menstrua-
tion, 875

effect of, on mammary glands, 889
Utriculus, function of, 389

VAGUS nerve, action of, on gastric

secretion, 708

on heart, 531 (see also In-
hibition)
on pancreas, 722

as motor nerve to stomach, 664

nucleus of, 233

relations of, to respiratory cen-
ter, 635

Vasomotor fibers, centers for, in cord,
564

in brain, 580

to pulmonary arteries, 571
nerves, action of, in heat regula-
tion, 862

antidromic impulses in, 568

course and distribution, 555, 568

general properties of dilators, 565

history of discovery of, 551

methods used to demonstrate
552

of heart, 570

position of constrictor center, 558

reflex actions of, 560

rhythmical action of constrictor
center, 564

INDEX.

939

Vasomotor nerves to abdominal or-
gans, 582

to dilator center and reflexes, 566

to genital organs, 583

to head, 581

to kidneys, 770

to skeletal muscles, 583

to trunk and limbs, 582

to veins, 584

tonic activity of, 558
Veins, vasomotor supply <5f, 584
Velocity of blood-flow (see Circu-
lation)

pressure in blood-vessels, 474 *
Venous pulse, 491

in brain sinuses, 578
Venous blood-pressure, 479
Ventilation, principles of, 614
Ventricle (see Heart)
Veratrin, effect of, on muscle, 30
Vernix caseosa, 792
Vestibular nerve, 201
Vestibulo-spinal tract of spinal cord,

171, 220

Vision (see Eye and Retina)
Visual acuity, 323
center in cortex, 194

Visual field, binocular, 350

monocular, 322
fields, conflict of, in binocular

vision, 353
purple, 318
Vital capacity, 600
Voluntary muscular contractions, 43
Vomiting, 672

WALLERIAN degeneration, 117, 158

Warm spots of skin, 260

Water, absorption of, in stomach, 718

excretion of, 782
Weber-Fechner law, 256
Wharton's duct, 687
Wirsung, duct of, 721
Work done by contracting muscle, 37

XANTHIN, 61, 777

oxidase, 779, 817
Xanthoproteic reaction for proteins,

910

ZYMOGEN, 684
granules, 696

Zymoplastic substances in coagula-
tion of blood, 430, 432

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Prevalent Diseases of the Eye. By SAMUEL THEOBALD, M. D.,
Clinical Professor of Ophthalmology and Otology, Johns Hopkins
University. Octavo of 5 50 pages, with 2 19 text-cuts and several colored
plates. Cloth, $4.50 net ; Half Morocco, $6.00 net.

JUST READY— FOR THE PRACTITIONER

With few exceptions all the works on diseases of the eye, although written
ostensibly for the general practitioner, are in reality adapted only to the specialist ;
but Dr. Theobald in his book has described very clearly and in detail those condi-
tions, the diagnosis and treatment of which come within the province of the general
practitioner. The therapeutic suggestions are concise, unequivocal, and specific.
It is the one work on the Eye vvritien particularly for the general practitioner. .

Charles A. Oliver, M.D..

Clinical Professor of Ophthalmology, Woman s Medical College of Pennsylvania.

" I feel I can conscientiously recommend it, not only to the general physician and mec! cal
student, for whom it is primarily written, but also to the experienced ophthalmologist. Most
surely Dr. Theobald has accomplished his purpose."

CHEMISTRY AXD EYE, EAR, NOSE, AND THROAT. 5

Wells' Chemical Pathology

Chemical Pathology. Being a Discussion of General Pathology
from the Standpoint of the Chemical Processes Involved. By H.
GIDEON WELLS, PH.D., M.D., Assistant Professor of Pathology in the
University of Chicago. Octavo of 549 pages. Cloth, $3.25 net; Half
Morocco, $4.75 net.

JUST ISSUED

Dr. Wells here concisely presents the latest work systematically considering the
subject of general pathology from the standpoint of the chemical processes
involved. It is written for the physician, for those engaged in research in pathol-
ogy and physiologic chemistry, and for the medical student. In the introductory
chapter are discussed the chemistry and physics of the animal cell, giving the
essential facts of ionization, diffusion, osmotic pressure, etc., and the relation of
these facts to cellular activities. Special chapters are devoted to Diabetes and to
Uric-acid Metabolism and Gout.

Wm. H. Welch, M. D., Professor of Pathology r, Johns Hopkins University.

" The work fills a real need in the English literature of a very important subject, and I shall
be glad to recommend it to my students."

American Text-Book qf
Eye, Ear, Nose, and Throat

American Text-Book of Diseases of the Eye, Ear, Nose, and
Throat. Edited by G. E. DE SCHWEINITZ, M.D., Professor of Ophthal-
mology in the University of Pennsylvania ; and B. ALEXANDER RANDALL,
M. D., Clinical Professor of Diseases of the Ear in the University of
Pennsylvania. Imperial octavo, 1251 pages, with 766 illustrations, 5,3
of them in colors. Cloth, $7.00 net; Sheep or Half Morocco, $8.50 n*.t.

This work is essentially a text-book on the one hand, and, on the other, a
volume of reference to which the practitioner may turn and find a series of articles
written by representative authorities on the subjects portrayed by them. There-
fore, the practical side of the question has been brought into prominence. Par-
ticular emphasis has been laid on the most approved methods of treatment.

American Journal of the Medical Sciences

" The different articles are complete, forceful, and, if one may be permitted to use the term,
'snappy.' in decided contrast to some of the labored but not more learned descriptions which
have appeared in the larger systems of ophthalmology."

SAUNDERS' BOOKS ON

Brtihl, Politzer, arid Smith's
Otology

Atlas and Epitome of Otology. By GUSTAV BRUHL, M. D., of
Berlin, with the collaboration of PROFESSOR DR. A. POLITZER, of
Vienna. Edited, with additions, by S. MACCUEN SMITH, M.D., Pro-
fessor of Otology in the Jefferson Medical College, Philadelphia.
With 244 colored figures on 39 lithographic plates, 99 text illustra-
tions, and 292 pages of text. Cloth, $3.00 net. In Saunders' Hand-
Atlas Series.

INCLUDING ANATOMY AND PHYSIOLOGY

The work is both didactic and clinical in its teaching. A special feature is
the very complete exposition of the minute anatomy of the ear, a working knowl-
edge of which is so essential to an intelligent conception of the science of otology.
The association of Professor Politzer and the use of so many valuable specimens
from his notably rich collection especially enhance the value of the treatise. The
work contains everything of importance in the elementary study of otology.

Clarence J. Blake. M. D.,

Professor of Otology in Harvard University Medical School, Boston.

" The most complete work of its kind as yet published, and one commending itself to both
the student and the teacher in the character and scope of its illustrations."

Haab arid deSchweinitz's
Operative Ophthalmology

Atlas and Epitome of Operative Ophthalmology. By DR O.

HAAB, of Zurich. Edited, with additions, by G. E. DE SCHWEINITZ,
M. D., Professor of Ophthalmology in the University of Pennsylvania.
With 30 colored lithographic plates, 154 text-cuts, and 375 pages of
text. In Saunders1 Hand- Atlas Series. Cloth, $3.50 net.

RECENTLY ISSUED

Dr. Haab's Atlas of Operative Ophthalmology will be found as beautiful and
as practical as his two former atlases. The work represents the author' s thirty
years' experience in eye work. The various operative interventions are described
with all the precision and clearness that such an experience brings. Recognizing
the fact that mere verbal descriptions are frequently insufficient to give a clear
idea of operative procedures, Dr. Haab has taken particular care to illustrate
plainly the different parts of the operations.

Johns Hopkins Hospital Bulletin

" The descriptions of the various operations are so clear and full that the volume can well
hold place with more pretentious text-books."

DISEASES OF THE EYE.

Haab and DeSchweinitz's
External Diseases qf the Eye

Atlas and Epitome of External Diseases of the Eye. By DR. O.

HAAB, of Zurich. Edited, with additions, by G. E. DESCHWEINITZ,
M. D., Professor of Ophthalmology, University of Pennsylvania. With
98 colored illustrations on 48 lithographic plates and 232 pages o.
text. Cloth, 33.00 net. In Sanndcrs Hand-Atlas Series.

SECOND REVISED EDITION— RECENTLY ISSUED

Conditions attending diseases of the external eye, which are often so complicated,
have probably never been more clearly and comprehensively expounded than in
the forelying work, in which the pictorial most happily supplements the verbal
description. The price of the book is remarkably low.

The Medical Record, New York

"The work is excellently suited to the student of ophthalmology and to the practiMn-;
physician. It cannot fail to attain a well-deserved popularity."

Haab and DeSchweinitzV
Ophthalmoscopy

Atlas and Epitome of Ophthalmoscopy and Ophthalmoscopic
Diagnosis. By DR. O. HAAB, of Zurich. From the Third Revised
and Enlarged German Edition. Edited, with additions, by G. E.
DESCHWEINITZ, M. D., Professor of Ophthalmology, University of
Pennsylvania. With 152 colored lithographic illustrations and 85
pages of text. Cloth, $3.00 net. In Saunders1 Hand- Atlas Series.

The great value of Prof. Haab's Atlas of Ophthalmoscopy and Ophthalrr.o-
scopic Diagnosis has been fully established and entirely justified an English
translation. Not only is the student made acquainted with carefully prepared
ophthalmoscopic drawings done into well-executed lithographs of the most im-
portant fundus changes, but, in many instances, plates of the microscopic lesions
are added. The whole furnishes a manual of the greatest possible service.

The Lancet, London

"We recommend it as a work that should be in the ophthalmic wards or in the library of
every hospital into which ophthalmic cases are received."

SA UA7DERS ' BOO A'S O.V

Barnhill and Wales* Otolog'y

A Text-Book of Modern Otology. By JOHN F. BARNHILL, M. D.,
Professor of Otology, Laryngology, and Rhinology, and EARNEST DE \Y.
WALES, M. D., Associate Professor of Otology, Laryngology, and
Rhinology, State College of Physicians and Surgeons, Indianapolis.
Octavo of 600 pages, with 300 original illustrations.

JUST READY

The authors, in writing this work, kept ever in mind the needs of the physician
engaged in general practice. It represents the results of personal experience as
practitioners and teachers, influenced by the instruction given by such authorities
as Sheppard, Uundas Grant, Percy Jakins, Jansen. and Alt. Much space is de-
voted to prophylaxis, diagnosis, and treatment, both medical and surgical. Great
pains have been taken with the illustrations, in order to have them as practical and
as helpful as possible, and at the same time highly artistic. A large number rep-
resent the best work of Mr. H. F. Aiken.

Grunwald and Grayson on Larynx

Atlas and Epitome of Diseases of the Larynx. By DR. L.

GRUXWALD, of Munich. Edited, with additions, by CHARLES P. GRAY-
SON, M. D., Clinical Professor of Laryngology and Rhinology, Univer-
sity of Pennsylvania. With 107 colored figures on 44 plates, 25 text-
cuts, and 103 pages of text. Cloth, $2.50 net In Saundcrs* Hand-Atlas
Scries.

British Medical Journal

"Excels everything we have hitherto seen in the way of colored illustrations of diseases of the
larynx. . . . Not only valuable for the teaching of laryngology, it will prove of the greatest
help to those who are perfecting themselves by private study."

Saxe's Urinalysis

Examination of the Urine. By G. A. DE SANTOS SAXE, M. D.,
Pathologist to Columbus Hospital, New York City. I2mo of 391
pages, fully illustrated. Flexible leather, $1.50 net.

RECENTLY ISSUED

This work is intended as an aid in diagnosis, by interpreting the clinical
significance of the chemic and microscopic urinary findings.

Francis Carter Wood, M. D.

Adjunct Professor of Clinical Pathology, Columbia University,

"It seems to me to be one of the best of the smaller works on this subject ; it is indeed, better
than a good many of the larger ones."

NOSE, THROAT, AND EAR.

Cradle's
Nose, Pharynx, and Ear

Diseases of the Nose, Pharynx, and Ear. By HENRY GRADLE,
M. D., Professor of Ophthalmology and Otology, Northwestern Uni-
versity Medical School, Chicago. Handsome octavo of 547 pages,
illustrated, including two full-page plates in colors. Cloth, $3.50 net.

INCLUDING TOPOGRAPHIC ANATOMY

This volume presents diseases of the Nose, Pharynx, and Ear as the author
has seen them during an experience of nearly twenty-five years. In it are
answered in detail those questions regarding the course and outcome of diseases
which cause the less experienced observer the most anxiety in an individual case.
Topographic anatomy has been accorded liberal space.

Pennsylvania Medical Journal

"This is the most practical volume on the nose, pharynx, and ear that has appeared
recently. ... It is exactly what the less experienced observer needs, as it avoids the confusion
incident to a categorical statement of everybody's opinion."

Kyle's
Diseases of Nose and Throat

Diseases of the Nose and Throat. By D. BRADEN KYLE, M. D.,
Professor of Laryngology in the Jefferson Medical College, Phila-
delphia; Consulting Laryngologist, Rhinologist, and Otologist, St.
Agnes' Hospital. Octavo, 669 pages; over 184 illustrations, and 26
lithographic plates in colors. Cloth, $4.00 net.

JUST ISSUED— THE NEW (4th) EDITION

Your large editions of this excellent work fully testify to its practical
value. In this edition the author has revised the text thoroughly, bringing
it absolutely down to date. With the practical purpose of the book in mind, ex-
tended consideration has been given to treatment, each disease being considered in
full, and definite courses being laid down to meet special conditions and symptoms.

Dudley S. Reynolds, M. D.,

Formerly Professor of Ophthalmology and Otology, Hospital College of Medicine, Lonhril'e.
" It is an important addition to the text-books now in use, and is better adapted to tnc uses
of the student than any other work with which I am familiar. I shall be pleased to commend
Dr. Kyle's work as the best text-book."

io SJUXDEftS1 BOOKS ON

Greene and Brooks'
Genito-Urinary Diseases

A Text=Book of Genito-Urinary Diseases. By ROBERT H. GREENE,
M. D., Professor of Genito-Urinary Surgery at Fordham University;
and HARLOW BROOKS, M. D., Assistant Professor of Pathology, Univer-
sity and Bellevue Hospital Medical School. Octavo of 550 pages,
profusely illustrated.

JUST READY

This new work covers completely the subject of genito-urinary diseases, pre-
senting both the medical and surgical sides. It has been designed as a work of
quick reference, and has therefore been written in a clear, condensed style, so
that the information can be readily grasped and retained. Kidney disease are
very elaborately detailed, and especially well presented is surgery of the kidney.
The text is profusely illustrated with original line-drawings.

Gleason on Nose, Throat,
and Ear

A Manual of Diseases of the Nose, Throat, arid Ear. By E.

BALDWIN GLEASON, M. D., LL. D., Clinical Professor of Otology,

Medico-Chirurgical College, Philadelphia. I2mo of 556 pages, \ ro-
fusely illustrated. Flexible leather, 32.50 net.

JUST ISSUED

Anatomy, physiology, and pathology of the upper respiratory tract and ear
have been carefully presented, the author rightly believing such knowledge essen-
tial to the efficacious treatment of diseases of these organs. Methods of treat-
ment have been simplified as much as possible, so that in most instances only
those methods, drugs, and operations have been advised which have proved
essential. A valuable feature consists of the collection of formulas.

American Text=Book of Genito-Urinary Diseases, Syphilis, and
Diseases of the Skin. Edited by L. BOLTON BANGS, M. D., late
Professor of Genito-Urinary Surgery, University and Bellevue Hospital
Medical College, New York ; and W. A. HARDAYVAY, M. D.. Professor
of Diseases of the Skin, Missouri Medical Colege. Octavo, 1229
pages, 300 engravings, 20 colored plates. Cloth, $7.00 net.

DISEASES OF THE SKIN. n

Mracek and Stelwagon's
Diseases of the Skin

Atlas and Epitome of Diseases of the Skin. By PROF. DR. FRANZ
MRACEK, of Vienna. Edited, with additions, by HENRY W. STELWAGON,
M. D., Professor of Dermatology in the Jefferson Medical College,
Philadelphia. With 77 colored plates, 50 half-tone illustrations and
280 pages of text. In Saunders1 Hand-Atlas Series. Clo., $4.00 net.

RECENTLY ISSUED-NEW (2nd) EDITiON

This volume, the outcome of years of scientific and artistic work, contains,
together with colored plates of unusual beauty, numerous illustrations in black,
and a text comprehending the entire vield of dermatology. The illustrations are
all original and prepared from actual cases in Mracek' s clinic, and the execution
of the plates is superior to that of any, even the most expensive, dermatologic
atlas hitherto published.

American Journal of the Medical Sciences

" The advantages which we see in this book and which recommend it to our minds are :
First, its handiness; secondly, the plates, which are excellent as regards drawing, color, and the
diagnostic points which they bring out."

Mracek and Bangs'
Syphilis and Venereal

Atlas and Epitome of Syphilis and the Venereal Diseases.

By PROF. DR. FRANZ MRACEK, of Vienna. Edited, with additions, by
L. BOLTON BANGS, M. D., late Prof, of Genito-Urinary Surgery, Univer-
sity and Bellevue Hospital Medical College, New York. With 71
colored plates and 122 pages of text. Cloth, $3.50 net. In Saunders'
Hand-Atlas Series.

CONTAINING 71 COLORED PLATES

'According to the unanimous opinion of numerous authorities, to whom the
original illustrations of this book were presented, they surpass in beauty anything
of the kind that has been produced in this field, not only in Germany, but
throughout the literature of the world.

Robert L. Dickinson, M. D.,

Art Editor of " The American Text-Book of Obstetrics."

" The book that appeals instantly to me for the strikingly successful, valuable, and graphic
character of its illustrations is the 'Atlas of Syphilis and the Venereal Diseases.' I know of
nothing in this country that can compare with it."

12 SAUNDERS* BOOKS ON

Holland's Medical
Chemistry and Toxicology

A Text-Book of Medical Chemistry and Toxicology. By JAMES
W. HOLLAND, M. D., Professor of Medical Chemistry and Toxicology,
and Dean, Jefferson Medical College, Philadelphia. Octavo of 592
pages, fully illustrated. Cloth, $3.00 net.

RECENTLY ISSUED

Dr. Holland's work is an entirely new one, and is based on his thirty-five
years' practical experience in teaching chemistry and medicine. Recognizing
that to understand physiologic chemistry, students must first be informed upon
points not referred to in most medical text-books, the author has included in his
work the latest views of equilibrium of equations, mass action, cryoscopy, os-
motic pressure, dissociation of salts into ions, effects of ionization upon electric
conductivity, and the relationship between purin bodies, uric acid, and urea.
More space is given to toxicology than in any other text-book on chemistry.

American Medicine

" Its statements are clear and terse ; its illustrations well chosen; its development logical,
systematic, and comparatively easy to follow. . . . We heartily commend the work."

Grtinwald and Newcomb's
Mouth, Pharynx, and Nose

Atlas and Epitome of Diseases of the Mouth, Pharynx, and
Nose. By DR. L. GRUNWALD, of Munich. From the Second Revised
and Enlarged German Edition. Edited, with additions, by JAMES E.
NEWCOMB, M. D., Instructor in Laryngology, Cornell University Medical
School. With 1 02 illustrations on 42 colored lithographic plates, 41
text-cuts, and 219 pages of text. Cloth, $3.00 net. In Saunders*
Hand- Atlas Series.

INCLUDING ANATOMY AND PHYSIOLOGY

In designing this atlas the needs of both student and practitioner were kept
constantly in mind, and as far as possible typical cases of the various diseases
were selected. The illustrations are described in the text in exactly the same way
as a practised examiner would demonstrate the objective findings to his class.
The illustrations themselves are numerous and exceedingly well executed,
editor has incorporated his own valuable experience, and has also included exten-
sive notes on the use of the active principle of the suprarenal bodies.

American Medicine

" Its conciseness without sacrifice of clearness and thoroughness, as well as the excellence
of text and illustrations, are commendable."

EYE, EAR, NOSE, AND THROAT. 13

Jackson on the Eye

A Manual of the Diagnosis and Treatment of Diseases of the Eye.

By EDWARD JACKSON, A M., M.D., Professor of Ophthalmology, Uni-
versity of Colorado. I2mo volume of 615 pages, with 184 beautiful
illustrations. Cloth, $2.50 net.

JUST ISSUEp-NEW (2d) EDITION

The Medical Record, New York

" It is truly an admirable work. . . . Written in a clear, concise manner, it bears evidence
of the author's comprehensive grasp of the subject. The term ' multum in parvo ' is an appro-
priate one to apply to this work."

Grant on the
Face, Mouth, and Jaws

A Text=Book of the Surgical Principles and Surgical Diseases of
the Face, Mouth, and Jaws. For Dental Students. By H. HORACF
GRANT, A. M., M. D., Professor of Surgery and of Clinical Surgery,
Hospital College of Medicine, Louisville. Octavo of 231 pages, with
68 illustrations. Cloth, $2.50 net.

Annals of Surgery

" The book is well illustrated, the text is clear, and on the whole it serves well for the
purpose for which it is intended."

Friedrich and Curtis'
Nose, Larynx, and Ear

Rhinology, Laryngology, and Otology, and Their Significance in
General Medicine. By DR. E. P. FRIEDRICH, of Leipzig. Edited by
H. HOLBROOK CURTIS, M. D., Consulting Surgeon to the New York
Nose and Throat Hospital. Octavo volume of 350 pages. Cloth,
$2.50 net.

Boston Medical and Surgical Journal

" This task he hns performed admirably, and has given both to the general practitioner and
to the specialist a book tor collateral reference which is modern, clear, and complete."

14 SAUNDERS' BOOKS ON

Ogden on the Urine

Clinical Examination of Urine and Urinary Diagnosis. A Clinical
Guide f>r the Use of Practitioners and Students of Medicine and Sur-
gery. By J. BERGEN OGDEN, M. D., Late Instructor in C.cmistry,
Harvard University Medical School ; Formerly Assistant in Clinical
Pathology, Boston City Hospital. Octavo, 418 pages, 54 illustrations,
iuid a number of colored plates. Cloth, $3.00 net.

SECOND REVISED EDITION— RECENTLY ISSUED

In this edition the work has been brought absolutely down to the present day.
Important changes have been made in connection with the determination of Urea,
Uric Acid, and Total Nitrogen ; and the subjects of Cryoscopy and Beta-Oxybutyric
Acid have been given a place. Special attention has been paid to diagnosis by
the character of the urine, the diagnosis of diseases of the kidneys and urinary
passages ; an enumeration of the prominent clinical symptoms of each disease ;
and the peculiarities of the urine in certain general diseases.

The Lancet, London

" We consider this manual to have been well compiled ; and the author's own experience,
so clearly stated, renders the volume a useful one both for study and reference."

Vecki's Sexual Impotence

The Pathology and Treatment of Sexual Impotence. By VICTOR
G. VECKI, M. D. From the Second Revised and Enlarged German
Edition. I2mo volume of 329 pages. Cloth, $2.00 net.

THIRD EDITION, REVISED AND ENLARGED

The subject of impotence has but seldom been treated in this country in the
truly scientific spirit that its pre-eminent importance deserves, and this volume will
come to many as a revelation of the possibilities of therapeutics in this important
field. The reading part of the English-speaking medical profession has passed
judgment on this monograph. The whole subject of sexual impotence and its
treatment is discussed by the author in an exhaustive and thoroughly scientific
manner. In this edition the book has been thoroughly revised, and new matter
has been added, especially to the portion dealing with treatment.

Johns Hopkins Hospital Bulletin

" A scientific treatise upon an important and much neglected subject. . . . The treatment
of impotence in general and of sexual neurasthenia is discriminating and judicious."

CHEMISTRY, SKIN, AND VENEREAL DISEASES. j c,

American Pocket Dictionary mh ""E**^

THE AMERICAN POCKET MEDICAL DICTIONARY. Edited J)y W. A.
NEWMAN BORLAND, M. D., Assistant Obstetrician to the Hospital
of the University of Pennsylvania. Containing the pronunciation
and definition of the principal words used in medicine and kindred
sciences. Flexible leather, with gold edges, $1.00 net ; with thumb
index, #1.25 net.
James W. Holland, M.D.,

Professor of Medical Chemistry and Toxicology, and Dean, Jefferson Medical College,
Philadelphia,

" I am struck at once with admiration at the compact size and attractive exterior. 1
can recommend it to our students without reserve."

Stelwagon's Essentials of Skin

ESSENTIALS OF DISEASES OF THE SKIN. By HENRY W. STEL-
WAGON, M. D., PH.D., Professor of Dermatology in the Jeffer-
son Medical College, Philadelphia. Post-octavo of 276 pages,
with 72 text-illustrations and 8 plates. Cloth, $1.00 net. In
Saunders' Question- Compend Series.
The Medical News

" In line with our present knowledge of diseases of the skin. . . . Continues to mam-
tain the high standard of excellence for which these question compends have been noted."

Wolffs Medical Chemistry SbtRecEedn«yIi»uedised

ESSENTIALS OF MEDICAL CHEMISTRY, ORGANIC AND INORGANIC.
Containing also Questions on Medical Physics, Chemical Physiol-
ogy, Analytical Processes, Urinalysis, and Toxicology. By LAW-
RENCE WOLFF, M. D., Late Demonstrator .of Chemistry, Jefferson
Medical College. Revised by SMITH ELY JELLIFFE, M. D., PH.D.,
Professor of Pharmacognosy, College of Pharmacy of the City of
New York. Post-octavo of 222 pages. Cloth, $1.00 net. ///
Sounders* Question- Compend Series.

Martin's Minor Surgery, Bandaging, and the Venereal

Diseases Second Edition, Revised

ESSENTIALS OF MINOR SURGERY, BANDAGING, AND VENEREAL
DISEASES. By EDWARD MARTIN, A. M., M. D., Professor of Clin-
ical Surgery, University of Pennsylvania, etc. Post-octavo, 166
pages, with 78 illustrations. Cloth, $1.00 net. In Sounders'
Question- Compend Series.

Senn's Genito-Urinary Tuberculosis

TUBERCULOSIS OF THE GENITO-URINARY ORGANS, MALE AND
FEMALE. By N. SENN, M. D., Ph. D., LL. D., Professor of Surgery
in Rush Medical College. Octavo of 317 pages, illustrated.
Cloth, $^.oo net.

16 URINE, EYE, EAR, NOSE, AND THROAT.

Wolfs Examination of Urine

A- LABORATORY HANDBOOK OF PHYSIOLOGIC CHEMISTRY AND
URINE-EXAMINATION. By CHARLES G. L. WOLF, M. D., Instructor in
Physiologic Chemistry, Cornell University Medical College, New
York. I2mo volume of 204 pages, fully illustrated. Cloth, $1.2-5 net-
British Medical Journal

" The methods of examining the urine are very fully described, and there are at the
end of the book some extensive tables drawn up to assist in urinary diagnosis."

Jackson's Essentials of Eye Third Revised Edition

ESSENTIALS OF REFRACTION AND OF DISEASES OF THE EYE. By
EDWARD JACKSON, A. M., M. D., Emeritus Professor of Diseases of
the Eye, Philadelphia Polyclinic. Post-octavo of 261 pages, 82 illus-
trations. Cloth, $1.00 net. /// Saunders1 Question- Compend Series.
Johns Hopkins Hospital Bulletin

" The entire ground is covered, and the points that most need careful elucidation
are made clear and easy."

Gleason's Nose and Throat Third Edition, Revised

ESSENTIALS OF DISEASES OF THE NOSE AND THROAT. By E. B.
GLEASON, S. B., M. D., Clinical Professor of Otology, Medico-
Chirurgical College, Philadelphia, etc. Post-octavo, 241 pages, 1 12
illustrations. Cloth, $1.00 net. In Saunders' Question Compends.
The Lancet, London

" The careful description which is given of the various procedures would be sufficient
to enable most people of average intelligence and of slight anatomical knowledge to
make a very good attempt at laryngoscopy."

Gleason's Diseases of the Ear Third Edition, Revised

ESSENTIALS OF DISEASES OF THE EAR. By E. B. GLEASON, S. B.,
M. D., Clinical Professor of Otology, Medico-Chirurgical College,
Phila., etc. Post-octavo volume of 214 pages, with 114 illustra-
tions. Cloth, $ I. oo net. In Saunders1 Question-Compend Series.
Bristol Medico-Chirurgical Journal

" We know of no other small work on ear diseases to compare with this, either in
freshness of style or completeness of information."

Wilcox on Genito-Urinary and Venereal Diseases ReiseSued

ESSENTIALS OF GENITO-URINARY AND VENEREAL DISEASES. By

STARLING S. WILCOX, M. D., Professor of Genito-Urinary Diseases

and Syphilology, Starling Medical College, Columbus, Ohio. I2mo

of 313 pages, illustrated. Cloth, $1.00 nc:. Saunders^ Compeuds.

Stevenson's Photoscopy j™t Ready

PHOTOSCOPY. (Skiascopy or Retinoscopy) By MARK D. STEV-
ENSON, M. D., Ophthalmic Surgeon to the Akron City Hospital.
I2mo of 126 pages, illustrated. Cloth, $1.25 net.

Dr. Stevenson's work fully and clearly explains the use of this objective test and eluci-
dates the reasons of the various phenomena observed. The illustrations have been drawn
with special attention to their practical usefulness.

UNIVERSITY OF CALIFORNIA
MEDICAL SCHOOL LIBRARY

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