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GIFT OF

TO THE

Library of the

Medical Department

of THE

University of California

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MEDICAL SCHOOL
LIB1RARY

1
A TEXT- BOO

//^•^ & T£*T1BOO<< or f^^^^JJm,

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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

i ' ! «

,ff:iiust vat**V

PHILADELPHIA AND LONDON

W. B. SAUNDERS COMPANY

1 000

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

Copyright, 1905, by W. B. Saunders & Company.

Reprinted, February, 1906.

PRESS 0«=
W. B. SAUNDERS COMPANY, PHIIAOA,

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 Aear 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

3 197

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 physiolog}' 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 the 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 may be 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 Enumera-
tion of Artificial Stimuli, 23. — The Duration of the Simple Muscle Contrac-
tion, 25. — The Curve of a Simple Muscle Contraction, 25. — The Latent Pe-
riod, 26. — The Phases of Shortening and Relaxation, 26. — Isotonic and Iso-
metric Contractions, 27. — Maximal and Submaximal Contractions, 27. —
Effect of Temperature upon the Simple Contraction, 28. — Effect of Veratrin
on the Simple Contraction, 30. — Contracture, 32. — Fatigue, the Treppe, and
Effect of Rapidly Repeated Stimulation, 33. — The Wave of Contraction and
Means of Measuring, 33 — Idiomuscular Contractions, 34. — The Energy Liber-
ated During a Muscular Contraction, 34. — The Proportional Amount of this
Energy Utilized in Work, 35. — The Curve of Work and the Absolute Power
of a Muscle, 36.— Definition of Tetanus or Compound Contraction, 39. — The
Summation of Contractions, 39. — Discontinuity of the Processes of Contraction
in Tetanus, 41. — 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, 47. — Muscle Tonus, 47. — Rigor Mortis and Rigor Caloris, 49. —
The Occurrence and Structure of Plain Muscle Tissue, 52. — Distinctive Prop-
erties of Plain Muscle, 52. — The General Properties of Cardiac Muscular Tis-
sue, 54. — The Contractility of Cilia and Their General Properties, 54.

Chapter II. — The Chemical Composition of Muscle and the Chemi-
cal Changes of Contraction and of Rigor Mortis 57

The Composition of Muscle Plasma, 57. — The Proteids of Muscle, 58. — The
Carbohydrates of Muscle, 58. — Phosphocarnic Acid, 60. — Lactic Acid in
Muscle, 60. — The Nitrogenous Extractives of Muscle, 61. — Pigments of Mus-
cle, 61. — Enzymes of Muscle, 61. — Inorganic Constituents of Muscle, 62. —
The Chemical 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 Fibre, 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. — Pfliiger's
Law of Stimulation, 84. — The Opening and the Closing Tetanus, 86. — Mode
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.

» 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, 116. — Nerve De-
generation and Regeneration, 118. — Degenerative Changes in the Central End
of the Neuron, 120.

SECTION II.
THE PHYSIOLOGY OF THE CENTRAL NERVOUS SYSTEM.

Chapter VI. — Structure and General Properties of the Nerve

Cell 122

The Neuron Doctrine, 122. — The Varieties of Neurons, 124. — Internal Struc-
ture of the Nerve Cell, 126.— General Physiology of the Nerve Cell, 128. —
Summation of Stimuli in Nerve Cells, 130. — Response of the Nerve Cell to
Varying Rates of Stimulation, 131. — The Refractory Period of the Nerve Cell,
132.

Chapter VII. — Reflex Actions 133

Definition and Historical, 133.— The Reflex Arc, 133.— The Reflex Frog, 135.—
Spinal Reflex Movements, 135. — Theory of Co-ordinated Reflexes, 137. — Spinal
Reflexes in Mammals, 138. — Dependence of Co-ordinated Reflexes upon the
Excitation of the Sensory Endings, 138. — Reflex Time, 139. — Inhibition of
Reflexes, 139. — Influence of the Condition of the Cord on its Reflex Activities,
141. — Reflexes from Other Parts of the Nervous System, 142. — Reflexes
Through Peripheral Ganglia, Axon Reflexes, 142. — The Tonic Activity of the
Spinal Cord, 144. — Effects of Removal of the Spinal Cord, 144. — Knee-jerk,
146. — Reinforcement of the Knee-jerk, 146. — Is the Knee-jerk a Reflex Act?
148. — Conditions Influencing the Extent of the Knee-jerk, 149. — The Knee-
jerk and Spinal Reflexes as Diagnostic Signs, 150. — Location of the Centers
for the Different Spinal Reflexes, 151.

Chapter VIII. — The Spinal Cord as a Path of Conduction 154

Arrangement and Classification of the Nerve Cells in the Cord, 154. — Gen-
eral Relations of the Gray and White Matter in the Cord, 156. — The Methods
of Determining the Tracts of the Cord, 156. — General Classification of the
Tracts of the Cord, 157.— The Names and Locations of the Long Tracts, 159.
— The Termination in the Cord of the Fibers of the Posterior Root, 160. —
Ascending or Afferent Paths in the Posterior Columns, 161. — Ascending or
Afferent Paths in the Lateral Columns, 164. — The Spinal Paths for the Cutane-
ous Senses (Touch, Pain, Temperature), 165. — The Homolateral or Contra-
lateral Conduction of the Cutaneous Impulses, 166. — The Descending or Ef-
ferent Paths in the Anterolateral Columns (Pyramidal System), 167. — Less
Well-known Tracts in the Cord, 169.

Chapter IX. — The General Physiology of the Cerebrum and Its

Motor Functions 171

The Histology of the Cortex, 172. — The Classification of the Systems of Fibers
in the Cerebrum (Projection, Association, and Commissural), 173. — Physio-
logical Deductions from the Histology of the Cortex, 175. — Extirpation of
the Cerebrum, 178. — Localization of Functions in the Cerebrum, Historical,
179. — The Motor Areas of the Cortex, 183. — Differences in Paralysis from
Injury to the Spinal Neuron and the Pyramidal Neuron, 185. — Voluntary
Motor Paths Other than the Pyramidal Tract, 185.— The Crossed Control of
the Muscles and Bilateral Motor Representation in the Cortex, 186. — Are the
Motor Areas Exclusively Motor? 186.

Chapter X. — The Sense Areas and the Association Areas in the

Cortex 188

The Body-sense Area, 188.— The Course of the Fillet, 190.— The Center for
Vision, 192. — Histological Evidence of the Course of the Optic Fibers, 193. —
The Decussation in the Chiasma, 195. — The Projection of the Retina on the
Occipital Cortex, 195. — The Function of the Lower Visual Centers, 197. —
The Auditory Center, 198.— Course of the Cochlear Nerve, 199.— The Physio-
logical Significance of the Lower Auditory Centers, 201. — Motor Responses
from the Auditory Cortex, 202. — The Olfactory Center, 202.— The Olfactory
Bulb and its Connections. 202.— The Cortical Center for Smell, 204.— The
Cortical Center for Taste, 204.— Aphasia, 204.— Sensory Aphasia, 206.— The
Association Areas, 207. — Subdivision of the Association Areas, 209. — The
Development of the Cortica Areas, 210. — Physiology of the Corpus Callosum,
213. — Physiology of the Corpora Striata and Optic Thalami, 214.

TABLE OF CONTENTS. 9

PAGE

Chapter XI. — The Functions of the Cerebellum, the Pons, and

the Medulla . 216

Anatomical Structure and Relations of the Cerebellum, 216. — General State-
ment of Theories Regarding the Cerebellum, 219. — Experiments upon Abla-
tion of the Cerebellum, 220. — Interpretation of the Experimental and Clinical
Results, 221. — Conclusions as to the General Functions of the Cerebellum,
223. — The Psychical Functions of the Cerebellum, 224. — Localization of
Function in the Cerebellum, 224. — The Functions of the Medulla Oblongata,
225. — The Nuclei of Origin and the Functions of the Cranial Nerves, 226.

Chapter XII. — The Sympathetic or Autonomic Nervous System . . 231

General Statements, 231. — Autonomic Nervous System, 232. — The Use of
the Nicotin Method, 233. — General Course of the Autonomic Fibers Arising
from the Cord, 233. — General Course of the Fibers Arising from the Brain,
234. — General Course of the Fibers Arising from the Sacral Cord, 236. —
Normal Mode of Stimulation of Autonomic Nerve Fibers, 236.

Chapter XIII. — The Physiology of Sleep 238

General Statements, 238. — Physiological Relations during Sleep, 238. — The
Intensity of Sleep, 239. — Changes in the Circulation during Sleep, 242. — •
Effect of Sensory Stimulation, 243. — Theories of Sleep, 244. — Hypnotic Sleep.
248.

SECTION III.

THE SPECIAL SENSES.

Chapter XIV. — Classification of the Senses and General State-
ments 249

Classification of the Senses, 249. — The Doctrine of Specific Nerve Energies,
251. — The Weber-Fechner Psychophysical Law, 253.

Chapter XV. — Cutaneous and Internal Sensations 256

General Statements, 256. — The Punctiform Distribution of the Cutaneous
Senses, 256. — Specific Nerve Energies of the Cutaneous Nerves, 258. — The
Temperature Senses, 259. — The Sense of Pressure, 260. — The Threshold Stimu-
lus and the Localizing Power, 260. — The Pain Sense, 262. — Localization or
Projection of Pain Sensations, 263. — Reflected or Misreferred Pains, 263. —
The Muscle Sense, 264. — The Quality of the Muscle Sense, 266. — Sensations
of Hunger and Thirst, 267.— The Sense of Thirst, 268.

Chapter XVI. — Sensations of Taste and Smell 270

The Nerves of Taste, 270.— The End-organ of the Taste Fibers, 272.— Classi-
fication of Taste Sensations, 272. — Distribution and Specific Energy of the
Fundamental Taste Sensations, 273.— Method of Sapid Stimulation, 275. —
The Threshold Stimulus for Taste, 275.— The Olfactory Organ, 275.— The
Mechanism of Smelling, 276.— Nature of the Olfactory Stimulus, 277. — The
Qualities of the Olfactory Sensations, 277. — Fatigue of the Olfactory Apparatus,
279.— Delicacy of the Olfactory Sense, 280.— Conflict of Olfactory Sensations,
281. — Olfactory Associations, 281.

Chapter XVII. — The Eye as an Optical Instrument. Dioptrics

of the Eye 282

Formation of an Image by a Biconvex Lens, 282. — Formation of an Image
in the Eye, 285.— The Inversion of the Image on the Retina, 287. — The Size
of the Retinal Image, 288. — Accommodation of the Eye, 289. — Limit of the
Power of Accommodation and Near Point of Distinct Vision, 292. — Far
Point of Distinct Vision, 292. — The Refractive Power of the Surfaces in the
Eye, 293.— Optical Defects of the Normal Eye, 293.— Spherical Aberration,
294. — Abnormalities in the Refraction of the Eye, Myopia, 295. — Hyperme-
tropia, 296. — Presbyopia, 297. — Astigmatism, 297. — Innervation and Control
of the Ciliary Muscle and the Muscles of the Iris, 299.— The Accommodation
Reflex and the Light Reflex, 301. — Action of Drugs upon the Iris, 303. —
The Antagonism of the Sphincter and Dilator Muscles oft the Iris, 304. — The
Ophthalmoscope, 305.

Chapter XVIII. — The Properties of the Retina. Visual Stimuli

and Visual Sensations 308

The Portion of the Retina Stimulated by Light, 308.— The Action Current
Caused by Stimulation of the Retina, 309.— The Visual Purple, Rhodopsin,
310.— Extent of the Visual Field, Perimetry, 312.— Central and Peripheral
Fields of Vision, 313. — Visual Acuitv, 315.— Relation Between Stimulus and
Sensation, Threshold Stimulus, 317.— The Light Adapted and the Dark Adapted

10 TABLE OF CONTENTS.

Eye, 318.— Luminosity or Brightness, 319. — Qualities of Visual Sensations,
320.— The Achromatic Series, 320.— The Chromatic Series, 321.— Color Satu-
ration and Color Fusion, 321. — The Fundamental Colors, 322. — The Com-
plementary Colors, 323. — After Images, Positive and Negative, 323. — Color
Contrasts, 324.— Color Blindness, 325.— Dichromatic Vision, 326.— Tests for
Color Blindness, 327. — Monochromatic Vision, 327. — Distribution of Color
Sense in the Retina, 328.— Functions of the Rods and Cones, 330.— Theories
of Color Vision, 331. — Entoptic Phenomena, 336. — Shadows of Corpuscles
and Blood-vessels, 336. — Shadows from Lens and Vitreous Humor, 337.

Chapter XIX. — Binocular Vision 338

Movements of the Eyeballs, 338. — Co-ordination of the Eye Muscles, Muscular
Insufficiency and Strabismus, 339. — The Binocular Field of Vision, 340. —
Corresponding or Identical Points, 340. — Physiological Diplopia, 342. — The
Horopter, 343. — Suppression of Visual Images, 343.— Struggle of the Visual
Fields, 344. — Judgments of Solidity, 344. — Monocular Perspective, 345. —
Binocular Perspective, 346. — Stereoscopic Vision, 347. — Explanation of Binoc-
ular Perspective, 349. — Judgments of Distance and Size, 349. — Optical De-
ceptions, 350.

Chapter XX. — The Ear as an Organ for Sound Sensations 353

The Pinna or Auricle, 354. — The Tympanic Membrane, 354.— The Ear Bones,
355. — Mode of Action of the Ear Bones, 356. — Muscles of the Middle Ear,
358. — The Eustachian Tube, 359. — Projection of the Auditory Sensations,
360. — Sensory Epithelium of the Cochlea, 360. — Nature and Action of the
Sound Waves, 361. — Classification and Properties of Musical Sounds, 362. —
Upper Harmonics or Overtones, 364. — Sympathetic Vibrations and Reso-
nance, 366. — Functions of the Cochlea, 366. — Sensations of Harmony and Dis-
cord, 369. — Limits of Hearing, 370.

Chapter XXI. — Functions of the Semicircular Canals and the

Vestibule 372

Position and Structure of the Semicircular Canals, 372. — Flourens's Experi-
ments upon the Semicircular Canals, 372. — Temporary and Permanent Effects
of the Operations, 374. — Effect of Direct Stimulation of the Canals, 374. —
Effect of Section of the Ampullary or the Acoustic Nerve, 375. — Is the Effect
of Section of the Canals Due to Stimulation? 375. — Theories of the Functions
of the Semicircular Canals, 375. — Summary of the Views upon the Function
of the Semicircular Canals, 378. — Functions of the Utriculus and Sacculus, 379.

SECTION IV.
BLOOD AND LYMPH.

Chapter XXII. — General Properties of Blood. Physiology of

the Corpuscles 381

Histological Structure of Blood, 381. — Reaction of the Blood, 382. — Specific
Gravity of the Blood, 383. — The Red Corpuscles, 384. — Condition of the
Hemoglobin in the Corpuscles, 385. — Hemolysis, 385. — Hemolysis Due to
Variations in Osmotic Pressure, 386. — Hemolysis Due to Action of Hemoly-
sins, 387. — Nature and Amount of Hemoglobin, 389. — Compounds of Hemo-
globin with Oxygen and Other Gases, 391. — The Iron in the Hemoglobin,
392. — Crystals of Hemoglobin, 393.— Absorption Spectra of Hemoglobin and
Oxyhemoglobin, 394. — Derivative Compounds of Hemoglobin, 398. — Origin
and Fate of the Red Corpuscles, 401. — Variations in the Number of Red Cor-

Euscles, 402. — Physiology of the Blood Leucocytes, 404. — Variations in Num-
er of the Leucocytes, 405. — Functions of the Leucocytes, 405. — Physiology
of the Blood Plates, 406.

Chapter XXIII. — Chemical Composition of the Blood Plasma;
Coagulation; Quantity of Blood; Regeneration After
Hemorrhage 408

Composition of the Plasma and Corpuscles. 408. — Proteids of the Blood
Plasma, 410. — Serum Albumin, 410. — Paraglobulin (Serum Globulin), 411. —
Fibrinogen, 412. — Less Well-known Proteids of the Blood, 413. — Coagula-
tion of Blood, 414.— Theories of Clotting, 415.— Why Blood Does Not Clot
Within the Vessels, 419. — Intravascular Clotting, 421. — Means of Hastening
or of Retarding Coagulation, 421. — Total Quantity of Blood in the Body,
423. — Regeneration of the Blood after Hemorrhage, 424. — Blood Transfu-
sion, 426.

Chapter XXIV. — Composition and Formation of Lymph 427

General Statements, 427. — Formation of Lymph, 428. — Lymphagogues of the
First Class, 430. — Lymphagogues of the Second Class, 431. — Summary of
the Factors Controlling the Flow of Lymph, 432.

TABLE OF CONTENTS. 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. . 434

The Circulation as Seen Under the Microscope, 434. — The Velocity of the
Blood Flow, 435. — Mean Velocity in the Arteries, Veins, and Capillaries, 438. —
Cause of the Variations in Velocity, 440. — Variations of Velocity with the
Heart Beat or Changes in the Blood-vessels, 440. — Time Necessary for a Com-
plete Circulation of the Blood, 441. — The Pressure Relations in the Vascular
System, 442. — Methods of Recording Blood-pressure, 442. — Systolic, Dias-
tolic, and Mean Arterial Pressure, 446. — Method of Measuring Systolic and
Diastolic Pressure in Animals, 447. — Data as to the Mean Pressure in Arteries,
Veins, and Capillaries, 450. — Methods of Determining Blood -pressure in the
Large Arteries of Man, 453. — Normal Pressure in Man and Its Variations, 458.

Chapter XXVI. — The Physical Factors Concerned in the Pro-
duction of Blood-pressure and Blood- velocity 460

Side Pressure and Velocity Pressure, 460. — The Factors Concerned in Pro-
ducing Normal Pressure and Velocity, 463. — General Conditions Influencing
Blood-pressure and Blood-velocity, 464. — The Hydrostatic Effect, 465. — Ac-
cessory Factors Aiding the Circulation, 466. — The Conditions of Pressure
and Velocity in the Pulmonary Circulation, 467. — Variations of Pressure in
the Pulmonary Circuit, 468.

Chapter XXVIL— The Pulse 469

General Statement, 469. — Velocity of the Pulse Wave, 470. — Form of the
Pulse Wave, Sphygmography, 472. — Explanation of the Catacrotic Waves,
474. — Anacrotic Waves, 475. — The Kinds of Pulse in Health and Disease,
475. — Venous Pulse, 475.

Chapter XXVIIL— The Heart Beat 477

General Statement, 477.— Musculature of the Auricles and Ventricles, 478. —
Contraction Wave of the Heart, 479. — The Electrical Variation, 480. — Change
of Form during Systole, 481. — The Apex Beat, 482.— Cardiogram, 482. — In-
traventricular Pressure during Systole, 484. — The Heart Sounds, 485. — Events
Occurring during a Cardiac Cycle, 488. — Time Relations of Systole and Dias-
tole, 489. — Normal Capacity of Ventricle and Work Done by the Heart, 489. —
Coronary Circulation during the Heart-beat, 491. — Suction-pump Action of
the Heart, 492. — Occlusion of the Coronary Vessels, 494. — Fibrillar Contrac-
tions of Heart Muscle, 495.

Chapter XXIX. — The Cause and the Sequence of the Heart

Beat. Properties of the Heart Muscle 496

General Statement, 496. — The Neurogenic Theory of the Heart Beat, 497. —
Myogenic Theory, 498. — Automaticity of the Heart, 500. — Action of Calcium,
Potassium, and Sodium Ions on the Heart, 501. — Connection of Inorganic
Salts with the Causation of the Beat, 503. — Maximal Contractions of the
Heart, 504. — Refractory Period of the Heart Beat, 504. — The Compensatory
Pause, 506.— Normal Sequence of the Heart Beat, 507. — Tonicity of the
Heart Muscle, 510.

Chapter XXX. — The Cardiac Nerves and Their Physiological

Action 512

Course of the Cardiac Nerves, 512. — Action of the Inhibitory Fibers, 512. —
Analysis of the Inhibitory Action, 514. — Effect of Vagus on the Auricle and
the Ventricle, 516. — Escape from Inhibition, 517. — Reflex Inhibition of the
Heart-beat, the Cardio-inhibitory Center, 517. — The Tonic Activity of the
Cardio-inhibitory Center, 518. — The Action of Drugs on the Inhibitory Ap-
paratus, 520. — The Nature of Inhibition, 520. — Course of the Accelerator
Fibers, 522. — Action of the Accelerator Fibers, 523. — Tonicity of the Accel-
erators and Reflex Acceleration, 524. — The Accelerator Center, 525.

Chapter XXXI. — The Rate of the Heart Beat and Its Variations

Under Normal Conditions 526

Variations in Rate with Sex, Size, and Age, 526. — Variations Through the
Extrinsic Cardiac Nerves, 527. — Variations with Blood-pressure, 527. — With
Muscular Exercise, 528.— With the Gases of the Blood, 529. — With Tempera-
ture of the Blood, 529.

12 TABLE OF CONTENTS.

PAGE)

Chapter XXXII. — The Vasomotor Nerves and Their Physiologi-
cal Activity 531

Historical, 531. — Methods Used to Determine Vasomotor Action, 532.— The
Plethysmograph, 533. — General Distribution and Course of the Vasocon- .
strictor Nerve Fibers, 535. — Tonic Activity of the Vasoconstrictors, 538. —
The Vasoconstrictor Center, 539. — Vasoconstrictor Reflexes, Pressor and
Depressor Fibers, 540. — Depressor Nerve of the Heart, 543. — Vasoconstrictor
Centers in the Spinal Cord, 543. — Rhythmical Activity of the Vasocon-
strictor Center, 544. — Course and Distribution of the Dilator Fibers, 545. —
General Properties of Vasodilator Fibers, 545.— Vasodilator Center and
Reflexes, 546. — Vasodilatation Due to Antidromic Impulses, 548.

Chapter XXXIII. — The Vasomotor Supply of the Different

Organs 550

Vasomotors of the Heart, 550. — Vasomotors of the Pulmonary Arteries,
551. — Circulation in the Brain and Its Regulation, 552. — Arterial Supply,
552. — Venous Supply, 553. — The Meningeal Spaces, 554. — Intracranial Pres-
sure, 556. — Effect of Changes in Arterial Pressure upon the Blood -flow Through
the Brain, 557. — The Regulation of the Brain Circulation, 559. — Vasomotor
Nerves of the Head Region, 561. — Of the Trunk and the Limbs, 562. — Of
the Abdominal Organs, 562.— Of the Genital Organs, 562.— Of the Skeletal
Muscles, 563. — The Vasomotor Nerves to the Veins, 564. — The Circulation
of the Lymph, 564.

SECTION VI.

PHYSIOLOGY OF RESPIRATION.

Chapter XXXIV. — Historical Statement. The Organs of Ex-
ternal Respiration and the Respiratory Movements. . 566

Historical, 566. — Anatomy of Organs of Respiration, 570. — Thorax as a
Closed Cavity, 571.— Normal Position of the Thorax, 571. — Inspiration by
Contraction of the Diaphragm, 572. — Inspiration by Elevation of the Ribs,
573. — The Muscles of Inspiration, 574. — Muscles of Expiration, 574. — Quiet
and Forced Respiratory Movements, Eupnea and Dyspnea, 575. — Costal and
Abdominal Types of Respiration, 576. — -Accessory Respiratory Movements,
577. — Registration of the Respiratory Movements, 577. — Volumes of Air
Respired, Vital Capacity, Tidal Air, Complemental Air, Supplemental Air,
Residual Air, Minimal Air, 579. — Size of the Bronchial Tree, 581. — Arti-
ficial Respiration, 581.

Chapter XXXV. — The Pressure Conditions in the Lungs and

Thorax and Their Influence Upon the Circulation. . . 583

The Intrapulmonic Pressure and Its Variations, 583. — Intrathoracic Pressure,
584. — Variations of, with Forced and Unusual Respirations, 585. — Origin of
the Negative Pressure in the Thorax, 586. — Pneumothorax, 587. — Respiratory
Action of the Thorax, 587. — Respiratory Waves of Blood-pressure, 588.

Chapter XXXVI. — The Chemical and Physical Changes in the

Air and the Blood Caused by Respiration 592

The Inspired and Expired Air, 592. — Physical Changes in the Expired Air,
592. — Injurious Action of Expired Air, 593. — Ventilation, 595. — The Gases
of the Blood, 596. — The Pressure of Gases, 599. — Absorption of Gases in
Liquids, 599.— The Tension of Gases in Solution, 601.— The Condition of
Nitrogen in the Blood, 602. — Condition of Oxygen in the Blood, 603. — Con-
dition of Carbon Dioxid in the Blood, 604. — The Physical Theory of Respira-
tion, 606. — Gaseous Exchanges in the Lungs, 606. — Exchange of Gases in
the Tissues, 608. — Secretory Activity of Lungs, 608.

Chapter XXXVII. — Innervation of the Respiratory Movements. 610

The Respiratory Center, 610. — Spinal Respiratory Centers, 611. — Automatic
Activity of the Respiratory Center, 612. — Reflex Stimulation of the Center,
612. — Afferent Relations of the Vagus to the Center, 614. — The Inspiratory
and Inhibitory Fibers of the Vagus, 616. — Respiratory Reflexes from the
Larynx, Pharynx, and Nose, 617. — Voluntary Control of the Respiratory
Movements, 618. — Nature of the Respiratory Center, 618. — Respiratory Cen-
ters in the Midbrain, 619. — Automatic Stimulus to the Respiratory Center,
619. — Cause of the First Respiratory Movements, 621. — Dyspnea, Hyperpnea
and Apnea, 622. — Innervation of the Bronchial Musculature, 625.

Chapter XXXVIII. — The Influence of Various Conditions Upon

the Respiration 627

Effect of Muscular Work on the Respiratory Movements, 627. — Effect of
Variations in the Composition of the Air, 627. — High and Low Barometric
Pressures, Mountain Sickness, Caisson Disease, 629. — The Respiratory Quo-
tient and Its Variations, 631. — Modified Respiratory Movements, 632.

TABLE OF CONTENTS. 13

SECTION VII.
PHYSIOLOGY OF DIGESTION AND SECRETION.

PAGE

Chapter XXXIX. — Movements of the Alimentary Canal 634

Mastication, 634. — Deglutition, 634. — Nervous Control of Deglutition, 638. —
Anatomy of the Stomach, 639.— Musculature of the Stomach, 640. — Move-
ments of the Stomach, 640. — Effect of the Nerves on the Movements of the
Stomach, 643.— Movements of the Intestines, 644. — Peristaltic and Pendular
Movements of the Intestines, 646. — Nervous Control of the Intestinal Move-
ments, 647. — Effect of Various Conditions on the Intestinal Movements, 648.—
Movements of the Large Intestines, 648. — Defecation, 650. — Vomiting, 651. —
Nervous Mechanism of Vomiting, 652.

Chapter XL. — General Consideration Upon the Composition of

the Food and the Action of Enzymes 654

Foods and Foodstuffs, 654. — Accessory Articles of Diet, 656. — Enzymes,
Historical, 657. — Reversible Reactions, 659. — Specificity of Enzymes, 661. —
Definition and Classification of Enzymes, 661. — General Properties of En-
zymes, 663. — Partial List of Enzymes, 664. — Chemical Composition of the
Enzymes, 664.

Chapter XLI. — The Salivary Glands and Their Digestive Action. 666

Anatomy of the Salivary Glands, 666. — Histological Structure, 668. — Com-
position of the Secretion, 669. — The Secretory Nerves, 670. — Trophic and
Secretory Nerve Fibers, 672. — Histological Changes during Activity, 674. —
Action of Drugs Upon the Secretory Nerves, 676. — Paralytic Secretion, 677. —
Normal Mechanism of Salivary Secretion, 678. — Electrical Changes in Glands,
679. — Digestive Action of Saliva; Ptyalin, 679. — Conditions Influencing
the Action of Ptyalin, 681. — Functions of the Saliva, 681.

Chapter XLII. — Digestion and Absorption in the Stomach 683

Structure of the Gastric Glands, 683. — Histological Changes during Secretion,
684. — Method of Obtaining the Gastric Secretion and Its Normal Composition,
685.— The Acid of Gastric Juice, 687.— Origin of the HC1, 687.— Secretory
Nerves of the Gastric Glands, 688. — Normal Mechanism of the Secretion of
the Gastric Juice, 689. — Nature and Properties of Pepsin, 691. — Artificial
Gastric Juice, 692. — Pepsin-hydrochloric Digestion, 693. — The Rennin En-
zyme, 695. — Digestive Changes in the Stomach, 696. — Absorption in the
Stomach, 699.

Chapter XLIII. — Digestion and Absorption in the Intestines. . 700

Structure of the Pancreas, 700. — Composition of the Secretion, 701. — Secre-
tory Nerve Fibers to the Pancreas, 701. — The Curve of Secretion, 702. — Nor-
mal Mechanism of Pancreatic Secretion, 703. — Secretin, 703. — Enterokinase,
704. — Digestive Action of Pancreatic Juice, 705. — Significance of Tryptic
Digestion, 707. — Action of the Diastatic Enzyme (Amylopsin), 708. — Action
of the Lipolytic Enzyme (Lipase, Steapsin), 709. — The Intestinal Secretion
(Succus Entericus), 710. — Absorption in the Small Intestine, 712. — Absorp-
tion of Carbohydrates, 713.— Absorption of Fats, 714. — Absorption of Pro-
teids, 716. — Digestion and Absorption in the Large Intestine, 717.— Bacterial
Action in the Small Intestine, 718. — Bacterial Action in the Large Intestine,
719. — Physiological Importance of Intestinal Putrefaction, 719. — Composi-
tion of the Feces, 720.

Chapter XLIV. — Physiology of the Liver and Spleen 722

Structure of the Liver, 722. — Composition of Bile, 722. — The Bile Pigments,
724. — The Bile Acids, 725. — Cholesterin, 726.— Lecithin, Fats, and Nucleo-
albumins, 727. — Secretion of the Bile, 727. — Ejection of the Bile— Function of
the Gall-bladder, 728.— Occlusion of the Bile-ducts, 730.— Physiological Im-
portance of Bile, 730. — Occurrence of Glycogen, 731. — Origin of Glycogen,
732. — Function of Glycogen, Glycogenic Theory, 734. — Glycogen in the
Muscles and Other Tissues, 736. — Conditions Affecting the Supply of Glyco-
gen, 736. — Formation of Urea in the Liver, 737. — Physiology of the Spleen, 738.

Chapter XLV. — The Kidney and Skin as Excretory Organs .... 741

Structure of the Kidney, 741. — The Secretion of Urine, 742.— Function of
the Glomerulus, 744. — Function of the Convoluted Tubule, 746. — Action of
Diuretics, 748.— The Blood-flow Through the Kidneys, 749.— The Composi-
tion of Urine, 751. — The Nitrogenous Excreta in the Urine, 752. — Origin and
Significance of Urea, 753. — Origin and Significance of the Purin Bodies (Uric
Acid, Xanthin, Hypoxanthin), 756. — Origin and Significance of the Creatinin,
758. — Hippuric Acid, 759. — The Conjugated Sulphates and the Sulphur Ex-
cretion, 759. —Secretion of the Water and Inorganic Salts, 760. — Micturition,
761. — Contractions of the Bladder, 762. — Nervous Mechanism of Micturition,
765.— Excretory Functions of the Skin, 766. — Composition of Sweat, 766. —
Secretory Fibers of Sweat Glands, 767. — Sweat Centers, 769. — Sebaceous
Secretion, 769. — Excretion of Carbon Dioxid Through the Skin, 770.

14 TABLE OF CONTENTS.

Chapter XL VI. — Secretion of the Ductless Glands — Internal

Secretion 771

Internal Secretion of Liver, 771. — Internal Secretion of the Thyroid Tissues,
772. — Extirpation of Thyroids and Parathyroids, 772. — Function of the Para-
thyroids, 773. — Theories of General Functions of Thyroid and Parathyroids,
774. — Cyon's View of Function of Thyroid, 775. — Structure and Properties
of Adrenal Bodies, 775.— General Function of Adrenals, 777. — Pituitary
Body, 777. — Internal Secretion of Testis and Ovary, 778. — Internal Secretion
of Pancreas, 780. — Internal Secretion of Kidney, 782.

SECTION VIII.

NUTRITION AND HEAT PRODUCTION AND REGULATION.

Chapter XLVII. — General Methods. History of the Proteid

Food 783

General Statement, 783. — Nitrogen Equilibrium. 783. — Carbon Equilibrium
and Body Equilibrium, 785. — Balance Experiments, 785. — Respiration
Chamber, 785. — Effect of Non-proteid Food on Nitrogen Equilibrium, 786. —
Nutritive History of the Proteid Food, 786. — Tissue Proteid and Circulating
Proteid, 787. — Amount of Proteid Necessary in Normal Nutrition, Question
of Luxus Consumption, 788. — Specific Character of Proteid Metabolism, 790. —
Nutritive Value of Albuminoids, 791.

Chapter XL VIII. — Nutritive History of Carbohydrates and Fats. 793

The Carbohydrate Supply of the Body, 793. — Fate of the Carbohydrates in the
Body, 793. — Functions of the Carbohydrate Food, 794. — Nutritive Value
of Fats, 796.— Fate of Fats in the Tissues, 797. — Origin of Body Fat, 797.—
Origin of Body Fat from Carbohydrates, 798. — Origin of Body Fat from Food
Fat, 798. — Cause of the Formation of Fat, Obesity, 799. — General Functions
of Fat, 800.

Chapter XLIX. — Nutritive Value of the Inorganic Salts and

the Accessory Articles of Diet 801

The Inorganic Salts of the Body, 801. — Effect of Ash-free and Ash-poor
Diets, 802. — Special Importance of Sodium Chlorid, Calcium and Iron
Salts, 802. — The Condiments, Flavors, and Stimulants, 804. — Physiological
Effects of Alcohol, 805.

Chapter L. — Effect of Muscular Work and Temperature on

Body Metabolism; Heat Energy of Foods; Dietetics. . 809

The Effect of Muscular Work, 809.— Effect of Sleep, 810.— Effect of Variations
in Temperature, 811. — Effect of Starvation, 812. — The Potential Energy of
Food, 814.— Dietetics, 817.

Chapter LI. — The Production of Heat in the Body; Its Measure-
ment and Regulation; Body Temperature; Calorimetry;
Physiological Oxidations 820

Historical Account of Theories of Animal Heat, 820. — Body Temperature in
Man, 821.— Calorimetry, 823.— Heat Regulation, 828.— Regulation of Heat
Loss, 823. — Regulation of Heat Production, 829. — Existence of Heat Centers
and Heat Nerves, 830. — Theories of Physiological Oxidations, 833.

SECTION IX.

PHYSIOLOGY OF REPRODUCTION.
Chapter LII. — Physiology of the Female Reproductive Organs. . . 839

General Statement, 838. — The Graafian Follicle and the Corpus Luteum, 839.
— Menstruation and Puberty, 841. — Structural Changes in the Uterus during
Menstruation, 842. — The Phenomenon of Heat in Lower Animals, 842. — The
Relation of the Ovaries to Menstruation, 843. — Physiological Significance of
Menstruation, 845. — Effect of the Menstrual Cycle on Other Functions, 845. —
Passage of the Ovum into the Uterus, 846. — Maturation of the Ovum, 847. —
Fertilization of the Ovum, 850. — Implantation of the Ovum, 851. — Nutrition
of the Ovum; Physiology of the Placenta, 852.— Changes in the Maternal
Organism during Pregnancy, 854. — Parturition, 854. — The Mammary Glands,
855. — Connection between the Uterus and the Mammary Glands, 856. —
Composition of Milk, 858.

TABLE OF CONTENTS. 15

PAGE

Chapter LIII. — Physiology of the Male Reproductive Organs. . 860

Sexual Life of Male, 860. — Properties of the Spermatozoa, 860. — Chemistry
of the Spermatozoa, 862. — The Act of Erection, 863. — Reflex Apparatus of
Erection and Ejaculation, 864.

Chapter LIV. — Heredity; Determination of Sex; Growth and

Senescence 866

Definition of Heredity, 866. — Evolution and Epigenesis, 866. — Determination
of Sex, 868. — Growth and Senescence, 871.

APPENDIX.

I. — Proteids and Their Classification 874

Definition and General Structure of Proteids, 874. — Reactions of Proteids, 875.
—Classification of Proteids, 877.— The Albumins, 878.— The Globulins, 878 —
The Albuminates, 878. — Nucleo-albumins or Phosphoproteids, 878. — Pro-
teoses and Peptones, 879. — Protamins and Histons, 879. — The Compound
Proteids, 880.— The Albuminoids, 880.

II. — Diffusion and Osmosis 881

Diffusion, Dialysis, and Osmosis, 881. — Osmotic Pressure, 881, — Electrolytes,
882,-^Gram-molecular Solutions, 883. — Calculation of Osmotic Pressure in
Solutions, 883. — Determination of Osmotic Pressure by the Freezing Point,
884.: — Application to Physiological Processes, 884. — Osmotic Pressure of
Proteids, 884. — Isotonic, Hypertonic, and Hypotonic Solutions, 885. — Diffu-
sion or Dialysis of Soluble Constituents, 885. — Diffusion of Proteids, 886.

Index 887

(?o6> ■

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 histological or 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 MUCLES 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
plasma.

There is on record an interesting observation by Kuhne * 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.)

; - V- -

■ .-.

Fig. 2. — Cross-section of two muscle
fibers of the fly: Ms, The columns of
fibrils; Sp, the sar ooplasm. — {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,
coming 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
* Kuhne, "Archiv fur pathologische Anatomie," 26, 222, 1863.

THE PHENOMENON OF CONTRACTION.

19

animals, as is indicated in the accompanying illustration. 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 its contraction — is indicated by
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
material in the protoplasm, the machinery,
so to speak, through which its shortening
is accomplished. In the striated fiber this
conclusion is supported by the fact, repre-
sented in Fig. 3, that during contraction
liquid passes from the isotropous (light) band
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 fur die gesammte Physiologie," 18, 1.

b £—

d 1

e I

fm
fl
km

Fig. 3. — To show the
appearance of the dim
(anisotropic) and light
(isotropic) bands at rest
and in contraction, as seen
by ordinary and by polar-
ized light. The figure rep-
resents a muscle fiber
(beetle) in which the lower
portion has been fixed in a
condition of contraction. —
(Engelmann.)

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 stimur-
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

Fig. 4. — n, Curve of extension of a rubber band, to show the equal extension 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. 6, 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.

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: o-x.
The abscissa gives the normal
length of muscle; at a the limit
of elasticity is passed and the
muscle lengthens by increasing
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 of 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 acting separately on the different fibers of which the muscle

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

24 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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 ob-
tained 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-Reymond induction coil. Experimental physiology

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 i, 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.

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 isolated 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.

Man 0.050 "

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 true 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 curve of the muscle is
the record of the vibrations of a tuning fork giving 50 double vibra-
tions per second ; that is, the distance from crest to crest represents
an interval of -g^ 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 probable 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 is a trifle longer, 0.05 sec.
Naturally in muscles whose duration of contraction differs from
that of the frog the time values for the shortening and the relaxation
exhibit corresponding differences. Many conditions, some of which
will be described below, alter the duration of the simple contraction,

THE PHENOMENON OF CONTRACTION. 27

and it is noteworthy that, in general, it is the phase of relaxation
which is most readily affected by these changes.

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
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

28 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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,
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

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.

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
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,

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

THE PHENOMENON OF CONTRACTION.

29

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

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.

Zb

6" io' IS' 20' 2S' S<r Ss' jr Sr *r

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.

of different animals, but the fact may be emphasized that in no
case do protoplasmic tissues withstand a very high temperature.
Functional activity is lost usually at 45° C. or below. The duration
of the contraction shows usually in frog's 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 slowly, then rapidly, 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

30 THE PHYSIOLOGY OF MUSCLE AND NERVE.

relationship between duration of contraction and temperature may
therefore be expressed by such a curve as is shown in Fig. 12, in
which the height of the ordinates represents the relative duration 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
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.)
sometimes shows also a double contraction for a single stimulus.
The very prolonged relaxation is, however, the most peculiar effect
of the veratrin. A somewhat similar effect is produced by the
* ' 'Journal de la physiol. et de la path, generate," 1899.

THE PHENOMENON OF CONTRACTION.

31

action of glycerin. We have in such substances reagents that affect
one phase of the contraction process without materially influencing

Kg-

8.1

the other. As regards the veratrin effect, it becomes less and less
marked if the muscle is made to give repeated contractions, but
reappears after a suitable period of rest. The peculiar action of

32

THE PHYSIOLOGY OF MUSCLE AND NERVE.

the veratrin is therefore antagonized seemingly by the chemical
products formed during contraction.

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.

Contracture. — The prolonged relaxation that is so character-
istic of the veratrinized muscle 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-

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.

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-

THE PHENOMENON OF CONTRACTION. 33

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
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.

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

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

34 THE PHYSIOLOGY OF MUSCLE AND NERVE.

show, however, that the process of contraction spreads over the
fibers, from the point stimulated, in the form of a wave that 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 X0.1 = 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.

Idiomuscular 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
be produced in a healthy muscle by localized mechanical stimulation, as by
drawing a blunt instrument — e. g., the handle of a scalpel — across the belly
of a muscle. The point thus stimulated stands out as a weal, 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 Heidenhain, 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-

THE PHENOMENON OF CONTRACTION. 35

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, of course, a matter of general obser-
vation. 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-milli-
meters, or 0.4 gramme ter. We can in calculations convert ex-
ternal work into heat or internal work by making use of the ascer-
tained 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 experiment would be equivalent, there-
fore, to 0.4 -*- 425, or about 0.001 of a calorie.

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. It is a matter of interest to inquire as
to the proportion of this total energy which may be converted
into useful work and the conditions under which this 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

36 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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 proportion of only 12 to 15 per cent. The last ob-
server points out that this proportion must vary greatly for dif-
ferent muscles and for muscles in different animals, while for the
same muscle it will vary with the extent and duration of the con-
tractions and other conditions. From experiments made upon dogs
in which a measured amount of work was done and in which
the energy changes were estimated from the oxygen absorbed
and carbon dioxid eliminated, Zuntzf calculates that somewhat
more than -j- of the total chemical energy liberated in the muscles
may be applied to external work, the other § taking the form of
heat. Similar experiments made by the same observer^ 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 yielded by the material oxidized in the body may
take the form of external work. When the muscular work per-
formed was effected by the muscles of the arms and upper part
of the body, as in turning 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

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

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

j Zuntz and Schumberg, "Physiologie des Marsches," Berlin, 1901.

THE PHENOMENON OF CONTRACTION. 37

more precisely by direct experiments on single muscles. A frog's

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.

SSSSi

"^IIIIII

# 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.

muscle may be isolated and the extent of its contractions and the
work done may be estimated directly. Under such conditions it

38 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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 snowing 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
proportion of work can be obtained. Third. When the load is just
sufficient to counteract the contraction of the muscle no work is
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

THE PHENOMENON OF CONTRACTION. 39

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-
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

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

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
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

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.

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
to 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
* Von Kries, "Archiv fur Physiologie," 1888, p. 537.

42 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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, Wedenski* 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
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, with 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

* Wedenski, "Du rhythme musculaire dans la contraction normale,"
"Archives de physiologie," 1891, p. 58.

THE PHENOMENON OF CONTRACTION.

43

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 movements a neuromuscular
mechanism 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
nerve into the muscle. The
contraction of voluntary muscle
has been investigated therefore
in various ways, to ascertain
whether there is any obtainable
evidence of the number of
separate contractions that are

fused together to make this normal tetanus. In the first place,
the normal movements of the muscles have been recorded graph-
ically 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
* Horsley and Schafer, "Journal of Physiology/' 7, 96, 1886.

Fig. 21. — Schema to show the innerva-
tion of the skeletal (voluntary) muscles: 1,
the intercentral (pyramidal) neuron; 2, the
spinal neuron; 3, the muscle.

44 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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
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 y1^ 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-
* Von Kries, "Archiv fur Physiologie," suppl. volume, 1886, p. 1.

THE PHENOMENON OF CONTRACTION.

45

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-

Fig. 22. — Mosso's ergograph: c is the carriage moving to and fro on runners by means
of the cord d, which passes from 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.

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 muscles 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

46

THE PHYSIOLOGY OF MUSCLE AND NERVE.

In such a record we can easily calculate the total work done by
obtaining the product of the load into the lift for each contrac-
tion and adding these products together. By this means the
capacity for work of the muscle used can be studied objectively
under varying conditions, and many suggestive results have been
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

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

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 last quoted.

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

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

THE PHENOMENON OF CONTRACTION. 47

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 contract the muscle
greatly prolong this period of complete recovery, — a fact that dem-
onstrates 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, im-
proved circulation in the muscle — produced by massage, for ex-
ample— increases the power to do work. Food also has the same
effect, and some particularly interesting experiments show that
sugar, as a soluble and easily absorbed foodstuff, quickly increases
the amount of muscular work that can be performed. (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 stimulated 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 voluntary con-
tractions, except that the contractions are not so extensive. Under
these conditions the muscle, when completely fatigued to electrical
stimulation, 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 can not be applied
to a muscle in its normal position so as to excite uniformly all the
constituent muscle fibers, although it is also quite 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
* Schumberg, "Archiv f. Physiol./' 1899, suppl. volume, p. 289.

48 THE PHYSIOLOGY OF MUSCLE AND NERVE.

involved in a muscular 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 ergo-
graph 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 interpreta-
tion, however, is not entirely certain. Recent work by Wedenski
has called attention to the fact that in the neuromuscular apparatus
the motor end-plate is a sensitive link of the chain, and that, when
the nerve is stimulated strongly with artificial stimuli at least, this
structure falls into a condition (parabiosis) in which it fails to con-
duct the nerve impulse to the muscle. It may be, therefore, that
in sustained voluntary contractions the end-plate fails first, and
thus is directly responsible for the appearance of fatigue. This
view explains readily why in such conditions the muscle is still irri-
table to direct electrical stimulation.

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 may be regarded as an impor-
tant 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
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

THE PHENOMENON OF CONTRACTION. 4£

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, as it were, 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, as it were, 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 fluid to a solid state. The rigor that appears in the muscles after
somatic death is designated usually as rigor mortis, since its occur-
rence 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
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
4

■•'/;

nu

RY

50

THHT PHYSIOLOGY OF MUSCLE AND NERVE.

OqI D^SSPft^^^"1 this case is of a more feeble character and shorter
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

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.

that the muscle undergoes. This shortening or contraction comes
on slowly, as is shown in the accompanying figure, but in extent
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 proteids 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
* "American Journal of Physiology," 9, 374, 1903.

/^■ovsuy or C'a/,£S

( -i-

v --^^ ; * » I

THE PHENOMENON OF CONTRACTION.^ 51

support from the investigations of Kuhne,* who prowti^iiMtllh^,lrt^^\,
muscle plasma is really coagulable. After first freezing and mmSIllg ' "
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° C.f According to other observers, heat rigor is due to an
ordinary heat coagulation of the proteids present in the muscle
fiber. It has been pointed out, J for instance, that in frogs' muscles
three different proteids 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° C, 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 proteids. 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 proteid
is present in smaller quantities than the other two. As long, how-

* Kuhne, "Archiv f. Physiologie," 1859, p. 788.
t Latimer, "American Journal of Physiology," 2, 29, 1899.
% Brodie and Richardson, " Philosophical Trans., Roy. Soc," London.
1899, 191, p. 127.

52 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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.

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

THE PHENOMENON OF CONTRACTION. 53

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

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 was equal to about three
seconds.

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

* Schultz, "Zur Physiologie der langsgestreiften (glatten) Muskeln,"
olume, 190
185, 1900.

" Archiv f. Physiologie," suppl. volume, 1903, p. 1. See also Stewart, "Amer-
ican Journal of Physiology," 4,

54 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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, are so directly concerned with its functions
as an organ of circulation that they may be discussed more profit-
ably 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,
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 urinif erous 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

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

THE PHENOMENON OF CONTRACTION. 55

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 met in mam-
mals show the first form of contraction. The little processes are
contracted quickly in one direction, so as to form 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 among
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 defi-
nite 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 ovi-
ducts they move or help to move the ovum toward the uterus,
and in this position, moreover, their motion is supposed to
guide the spermatozoon from the uterus toward the oviducts, — that
is, the resistance offered to the motile spermatozoon guides its
movements. 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 ade-
quately explain one will doubtless be applicable to the other.
Many interesting facts have been established regarding ciliary
movements: 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 performing 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

56 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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, "Oils 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 Kuhne 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) Proteids. (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 Proteids.f — The proteids of the muscle have been
investigated by a number of observers, but unfortunately the

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

t Von Furth, "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 Fiirth, two proteids 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
proteids (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 proteid,
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 proteid 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 proteid.
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 proteid, 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 proteids exist in the living muscle, and
that after death they undergo a partial or complete coagulation
according to the following scheme :

Mvosin. Mvogen.

I I

Myosin fibrin. Soluble mvogen fibrin.

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 the muscle fibers still retain
much proteid material, and its structural appearance, so far as
cross-striation is concerned, remains unaltered. The portion of
proteid 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. It is at present uncertain whether the myosin and
myogen represent the proteid constituents of the contractile ele-
ments of the muscle fibers or of the undifferentiated portion, the
sarcoplasm. The proteids 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 proteids 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 proteids, in addition to some nucleoproteid, are described,
one belonging to the albumin and one to the globulin class, but
the identity or relationship of these proteids 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.*

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

Q}H1203 — H20 = C«Hi0O3.

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
is consumed by the tissue during its activity, and it is assumed
that before it is thus consumed it is converted back into sugar.
The glycogen, therefore, itself represents a local deposit of carbo-
hydrate nutritive material, resembling in this respect the fat. The
sugar and the glycogen must be considered as one from the stand-

* Vincent and Lewis, "Journal of Physiology," 26, 445, 1901; also "Zeit-
schrift f. physiolog. Chemie," 34, 417, 1901-2; and Stewart and Sollman,
loc. cit.

60 THE PHYSIOLOGY OF MUSCLE AND NERVE.

point of the nutrition of the muscle. During muscular activity
the store of glycogen is used up, and if the activity is sufficiently
prolonged 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 con-
taining phosphorus was discovered by Siegfried in the muscle ex-
tracts.* This substance seems to resemble the proteids, but has a
complex and peculiar structure, as is shown by its split products
when hydolyzed by boiling with baryta water. Under these condi-
tions there are formed carbon dioxid, phosphoric acid, a carbohy-
drate body, succinic and lactic acids, and a crystallizable nitrogenous
acid body which is designated as carnic acid (C]0H15N5O3). Siegfried
assumes that this latter substance is identical with one of the pep-
tones (antipeptone) formed during digestion, and conceives, there-
fore, that his phosphocarnic acid is a complex substance built
up from a peptone and a phosphorus-containing compound. Com-
pounds of simple proteids with phosphorus-containing bodies
(nucleic acids) are designated usually as nucleins; for this com-
pound of a peptone with a phosphorus-containing complex Sieg-
fried 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 the muscle,
and as an efficient means of transportation of iron, calcium, potas-
sium, 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 some 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 interest-
ing. Its properties are such as would aid in explaining the occur-
rence 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 (C3H603). — 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 a-hydroxypropionic acid (CH3CHOHCOOH),
and differs from the lactic acid as found in sour milk in that it ro-
tates the plane of polarized light to the right. The lactic acid in

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

THE CHEMISTRY OF MUSCLE. 61

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
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 proteid material of the muscle.
The number of these substances that has 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 proteid 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 given off to the blood
and eventually excreted in the urine as creatinin (C4H7N30), which
is formed from creatin by the loss of a molecule of water. 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
(C5H4N403), xanthin (C5H4N402), hypoxanthin (C5H4N40), guanin
<C5H5N50), adenin (C5H5N5), and carnin (C7H8N403). They will
be referred to more fully in the section on nutrition. Still other
bodies of similar physiological significance have been described
from time to time. These nitrogenous extracts 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 in-
directly 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

62 THE PHYSIOLOGY OF MUSCLE AND NERVE.

the development of special enzymes. A proteolytic enzyme capable
of digesting proteids has been described by Briicke and others;
an amylolytic enzyme capable of converting the glycogen to sugar
by Nasse; a glycolytic enzyme capable of destroying the sugars
by Brunton, Cohnheim, and others; a lipase capable of splitting
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 dioxid. 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 C02 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 C02 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

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

THE CHEMISTRY OF MUSCLE. 63

changes in the muscle are equivalent to those of ordinary combus-
tion at high temperatures, the burning of wood or fats, for instance.
Moreover, the formation of the C02 in the muscle is accompanied
by the production of heat, as in combustion; and for the same
amount of C02 produced in the two cases the same amount of heat
is liberated. It has been shown, however, in the frog's muscle
freshly removed from the body, that the C02 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 C02 as long as this supply lasts. One suggestion
that is made is that the oxygen is stored as intramolecular oxygen,
— that is, the oxygen taken in by the muscle tissue while the blood
is circulating through it normally, is assimilated or combined by
the living molecules. When these molecules break down as a con-
sequence of the stimulus applied to the muscle the excess of oxygen
unites with some of the carbon to form the C02. The oxidation,
instead of being direct, as in the case of combustions, is indirect.
This and other 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.
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 Glycogen. — 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-

* Pfliiger, "Archiv f. die gesammte Physiologie," 10, 251, 1875.

64 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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. It is possible that it may
be burnt or oxidized as glycogen or sugar, with the production of
CO 2 and H20, the oxidation in some way being under the control
of the living tissue; or it may first be split into lactic acid and
other products, which then undergo oxidation. It is possible, on
the other hand, that the glycogen, after conversion to sugar, is first
combined with the living proteid material before undergoing oxi-
dation. Attention has already been called to the fact* that the
rigor of muscle comes on at a much lower temperature when the
sugar is used up, and it has been found that supplying new sugar
will restore the muscle to its normal condition in this respect, — a
fact which seems to indicate that the sugar enters into a combination
in the living tissue. In this process of the consumption of the gly-
cogen two or more enzymes are supposed to be concerned. Under
the influence of one, amylolyase, the glycogen is changed to sugar,
dextrose; while other so-called glycolytic enzymes are necessary
for its final destruction or oxidation. The fact that the glycogen
disappears as a result of the contractions does not mean necessarily
that this substance or the sugar into which it is converted is abso-
lutely necessary for the chemical changes of contraction. It is
stated that the muscle will continue to contract after all its glycogen
is used upf ; 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, perhaps
from its proteids, 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
slightly alkaline. This fact can be demonstrated by the use of
litmus paper, but perhaps more strikingly by the use of acid fuchsin.J
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 alkaline media of the body this solution remains
colorless or nearly so. If now one of the legs is tetanized the muscles

* Latimer, loc. cit.

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

% Dreser, "Centralblatt fur Physiologic," 1, 195, 1887.

THE CHEMISTRY OF MUSCLE. 65

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 actu-
ally less in the worked muscle; others have found an increase.*
The balance of evidence seems to show that there is actually 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 alkalinity
of the blood may be decreased after muscular activity. That
lactic acid is produced in the living muscle is shown by experi-
ments f 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 distinctly increased. We must believe, there-
fore, that lactic acid is a constant product of the chemical changes
of nutrition going on in the muscle, and that its production is in-
creased by the greater chemical activity during visible contraction.
This lactic acid may be partly destroyed within the muscle- itself by
oxidation, but in part it may be carried off by the blood as a lactate
to be removed probably by the action of the liver. The increased
acidity of the muscle during activity, especially when the circulation
is interrupted, is referable, in the long run, to this greater produc-
tion of lactic acid; but as the acid after its formation probably
reacts with the alkaline salts present it is usually 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 (KH2P04).

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 { ; and, so far as the processes
during contraction are concerned, the fact that lactic acid increases
.as the glycogen disappears is not a very logical proof that the former
arises from the latter. Another suggestion is that the lactic acid
arises from the phosphocarnic acid described above. This com-
pound, when split by hydrolysis, yields lactic acid; so that if
we could obtain convincing proof that such a compound exists in

* Wcrther, "Pfliiger's Archiv," 46, 63, 1890.
f Berlinerblau, "Archiv f. exp. Path. u. Pharm.," 23, 333, 1887.
t Bohm, "Pfliiger's Archiv f. d. gesammte Physiologic" 23, 44, 1880.
5

66 THE PHYSIOLOGY OF MUSCLE AND NERVE.

living muscle it would serve very well to explain the production
of lactic acid. From experiments made in general nutrition it
has been shown that in birds especially the uric acid in the urine
is replaced largely by lactic acid (ammonium lactate) when the liver
is excised. Under these conditions the quantity of lactic acid
secreted varies with the albumin destroyed in the body, and many
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 proteid material. On the other hand, a study of the
action of the enzymes present in muscle leads to the other conclu-
sion,— namely, that the lactic acid arises from a splitting of the
sugar. (Consult section on nutrition.)

The Formation of Creatin. — Creatin 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 proteid material of the muscle
plasma, which at present is explained by supposing that the con-
tained 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 C02. Hermann, in his original ex-
periments, asserts that in rigor there is, so to speak, a maximal
production of C02, — that is, all of the material in the muscle capable
of yielding C02 is broken down during rigor. The amount of C02
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 C02 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 postmortem 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

THE CHEMISTRY OF MUSCLE. 67

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-
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
demonstrated that the acid-reacting substances, sarcolactic acid
and acid potassium phosphate, are apparently responsible for this
effect. According to these experiments, the accumulation of these
acid products is responsible for the appearance of fatigue; the
muscle's own waste products, therefore, serve to limit its responsive-
ness to stimulation, and thus form a protective mechanism that
saves it from complete exhaustion. Under normal conditions these
products are quickly removed by the blood, and even in the isolated
muscle we may suppose that their depressing effect upon the irri-
tability of the muscle is rapidly removed by the neutralizing effect
of the alkaline lymph in the muscle; perhaps, also, the lactic acid
is further oxidized. This chemical theory of fatigue does not, how-
ever, explain all the phenomena, particularly the after- results.
As was stated in describing the experiments made with the ergograph,
* Ranke, " Tetanus," Leipzig, 1865.

68 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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 acid products, and we must recognize that a
part of the fatigue is due to a 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 waste products and exhaustion of
energy-yielding material, co-operate to produce the conditions
actually observed; but the former of these, the formation of acid
waste products, seems to be the protective mechanism that is
especially adapted to save the muscle from complete exhaustion.
In what way the acid products depress the irritability and con-
tractility 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
H20 and the* C02 and lactic acid which we recognize among the
products. This reaction is exothermic, — that is, some oY the chemical
or internal energy of the complex compound is liberated as heat;
some also as electrical energy, as is explained in a later chapter.
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
* Verworn, "Archiv f. Physiologie," 1900, suppl. volume, p. 152.

THE CHEMISTRY OF MUSCLE.

69

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 figurative 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
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. Ac-
cording to others (Fick), the
mechanical contraction is a
direct result of an increased
chemical affinity, while others
(Miiller) find an explanation in
supposed electrical charges
upon the doubly refractive
particles of the muscle in conse-
quence of which there are de-
veloped electrical attractions
and repulsions at the different
poles. The most specific and
comprehensible hypothesis ad-
vanced is that formulated by
Engelmann.* This author has
shown that all contractile
tissues contain doubly refrac-
tive particles, that in the
striped muscle fiber these par-
ticles are arranged in discs, —
the dim bands, — with the singly
refracting material forming the
light bands on either side. Dur-
ing contraction it has been
shown that the material of this

latter structure is absorbed 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 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

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

\

1

ifoi

S

D h

1

\Tm

r
( '

J .... ^

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° O, and " stimulated "
by the sudden increase in temperature caused
by the passage of a current through the coil.
— (After Engelmann.)

70 THE PHYSIOLOGY OF MUSCLE AND NERVE.

particles 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
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,

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.

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 (m) 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
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

THE CHEMISTRY OF MUSCLE. 71

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

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.

used to show the effect of temperature upon the extent and dura-
tion of the contractions, the effect of variations in strength of
stimulus as expressed in the amount of current used, the summation
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 this 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 especially and in plain muscle it has been shown that a
change of this sort may be conducted independently of the phe-
nomenon 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 medullated 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 histologically 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 be 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 stomach 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.

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

Motor

Secretory

Inhibito-mo-

tor
Inhibito-se-

cretory

Sensory

Reflex

Inhibito-re-
flex

f Motor.

Vasomotor.

Cardiomotor.

Visceromotor.

Pilomotor.

Salivary.
1 Gastric,
j Pancreatic.
^ Sweat.

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

/ Subdivisions corresponding to the varieties of se-
\ cretory fibers above.

Visual.

Auditory.

Olfactory.

Gustatory.

Pressure.

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. 79

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 maintains 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 mav 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: b, Binding posts for attachment
of wires from the secondary coil; s, insulating sheath of hard rubber; p, platinum points
laid upon the nerve.

indicate that there is some essential difference in structure or com-
position 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 Leyden 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.

/I

V

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. It is interesting to add
that Bethe has shown recently that this difference may be demon-
strated histologically. 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 condition of the nerve at the poles
during the passage of the galvanic current is designated as electro-
tonus, the condition at the anode being known as anelectrotonus,
on the cathodal side as catelectrotonus. The electrotonus expresses
itself as a change in the electrical condition of the nerve which gives
rise to currents known as the electrotonic currents, — a brief descrip-
tion of these currents will be given in the next chapter, — and also
by a change in irritability and conductivity. The latter changes
were first carefully investigated by Pfluger, 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 anelectrotonic decrease in irrita-
bility and conductivity. These opposite variations in the state
of the nerve are represented in the accompanying diagram. Be-
tween 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 passage

84 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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; D, 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 observa-
tions which indicate that the excitation at the anode and the
cathode during the passages 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 frequently observed that at the
moment of opening the current a tetanic contraction, persisting for
some time, is obtained instead of a single twitch. This phenomenon
is known as the opening tetanus or Ritter'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 Pfluger's tetanus. Both of these phenomena are observed
especially when the irritability of the nerve is for any reason greater
than normal, — for instance, when it has been cooled to a low tem-
perature. 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 exci-
tation 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

THE PHENOMENON OF CONDUCTION.

87

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 electrode they pass through
the motor nerve which lies under it, and if sufficiently intense will

# 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.

stimulate the nerve. The arrangement is represented in the accom-
panying schema (Fig. 33), showing the disposition of the electrodes
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

88

THE PHYSIOLOGY OP MUSCLE AND NERVE.

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
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

M. triceps (caput

longum)

M. flexor carpi ulnaris

M. flex, digitor. sub-
lim. (digiti II et III)

M. flex, digit, subl.
(digit: Ridicis et
minimi)

Jferv. ulnaris

M. flexor digit, min.

M. opponeos digit.

min.

M. abductor polUc. brer.
M. opponens pollicis

M. flex. poll. brev.

M. adductor pollic. bref.

Fig. 34. — Motor points in upper extremity.

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
distinction can be 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 PHENOMENON OF CONDUCTION.

89

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 the cathode and the closing and the opening shock when it is
the anode. The contractions resulting from these four stimuli are
designated usually as follows: The cathodal closing contraction,
CCC; the cathodal opening contraction, COC; the anodal clos-
ing contraction, ACC; and the anodal opening contraction,
A 0 C. Their relative efficiency as stimuli is given by the sequence
CCOACOAOOC O C, although this sequence is subject,
so far as the first two members are concerned, to some individual
variation. Certain pathological or traumatic lesions that cause the
degeneration of the nerves may be revealed by the use of these

cs'e/ g* e\

— ~~a> ,&■ /a, icu

vM-

—

^*

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.

methods of stimulation. The nerve trunk under such circum-
stances fails to respond to either form of stimulus, induced or gal-
vanic. The muscle, on the other hand, while it fails to respond to
induction shocks, is stimulated by the galvanic current and shows
certain qualitative changes in its reactions to this latter form of
stimulation. For instance, under these conditions the A C C is ob-
tained with less current than the C C C, a relation which is just the
reverse of the normal. 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 degen-
eration.

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

90 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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
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 MUSCLE.

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,
one tendinous end is cut off, it is found that the cut end has an
electrical potential that differs 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 current. 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-
changed living substance elsewhere.
For this reason Hermann described
the current obtained as a demarcation
current ; others have called it the cur-
rent of injury. •

0

Fig. 37. — Schema showing
the principle of construction of
the galvanometer: M, The mag-
net suspended by a thread; B,
the battery, with the wires lead-
ing off the current encircling the
magnet.

Means of Demonstrating the Demarcation Current. — The demarca-
tion current and other electrical conditions to be described require especial
apparatus for their study. To detect the existence of a current physiologists
use either a high-resistance galvanometer or a capillary electrometer. 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
passes through a wire in its vicinity. As shown in the accompanying dia-
gram, 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 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-

ELECTRICAL PHENOMENA.

93

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
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 the complete instrument in Fig. 38. A large horse-
shoe 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

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

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
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
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.

94

THE PHYSIOLOGY OF MUSCLE AND NERVE.

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
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

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 — (n) north pole, and (s)
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.

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

ELECTRICAL PHENOMENA.

95

—3

wire fused into its wall and dipping into the mercury By regulating the
pressure on the mercury the point of contact between the thread^ 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 certain distance, depending
on the strength of the current and the delicacy of the capillary. If the cur-
rent 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 physiological
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.

N on-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. This polarization expresses itself
by changes at the metal poles during the passage of
the current, changes of such a character that a cur-
rent is set up between the poles in the opposite di-
rection to the main current, thus weakening the lat-
ter. This polarization current is due to the accumulation of hydrogen gas
at the negative pole or cathode and of oxygen at the anode. What takes
place may be represented by the following diagram, in which a current is
supposed to be passing

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.

+

+

Na

— if
+
Na

+
Na

+

Na

A

CI

CI

CI

CI

—

—

s

—

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

96 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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, CI,
with their negative charges move toward the anode; there the chlorin acts
upon the water, forming HC1- and liberating oxygen. 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 physicochemical 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 amalgamated 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

The liquid part of the circuit comes into contact with the metallic part
at the junction of Zn and ZnS04. 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 (S04)
attacks the zinc instead of the water, forming ZnS04. 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
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

+

Zn

+
Zn

+
Na

+
Na

+

Na

+
Zn

+
Zn

S04

S04

CI

CI
< —

CI

S04

S04

Zn

ELECTRICAL PHENOMENA. 97

the example given, relative to that of the demarcation current is as
10 to 50 ; so that 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 con-
dition. When this condition reaches a point where it can influence
the galvanometer — that is, when it reaches b, it will diminish the
difference in potential that exists between b and c, and therefore
reduce the current

flowing from b to c. _f_

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 Fi? 42 _ Schema to indicate the method of detecting
maximum and then *ne acti°n current in a stimulated excised nerve: b and c,

. . the leading off electrodes, one on the longitudinal, one on

diminishes. More- the cut surface; the demarcation 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
_j£»., i • , negative condition, — which passes along the nerve; when

aennite VelOCltV this reaches 6 it causes a partial reversal of the demarca-
whirh is Pfl<silv tion current» Siving the negative variation or action cur-

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
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

* Bernstein, " Untersuchungen uber den Erregungsvorgang im Nerven-
und Muskelsysteme," Heidelberg, 1871.

7

98 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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,! and reflex t 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
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-

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

tGriitzner, "Pfluger's Archiv," 25, 255, 1881.

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

ELECTRICAL PHENOMENA. 99

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 b, 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 b 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
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

100 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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:
b. 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 b, since each contraction of a is accompanied by an action current which passes
through the nerve of 6 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
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

^%imf!if°%

ELECTRICAL PHENOMENA.\\ ^^ZLsyZ?

\

v M flW^'

wave of definite velocity, but at any one point th%i^BwttftJ$|i^g^) ^\^
reaches its maximum before the process of contraction^ visibter "
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 in
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 impulses), 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 experi-
ments have gone,the
nerve can not enter
into activity with-
out showing an ac-
tion current, — that
is, without showing
a moving electrical
charge. Whether
this electrical charge
constitutes the
nerve impulse or
is simply an accom-
panying phenome-
non 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 nerve is altered at each pole.
At the anode there is a condition of decreased irritability and con-
ductivity known as anelectro tonus ; at the cathode, in the begin-
ning, at least, a condition of increased irritability known as cate-
lectro tonus. In addition to these changes in the physiological prop-
erties of the nerve there is a change also in its electrical conditions
at each pole of 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 con-
dition in the nerve that makes it possible is designated as anelec-

Fig. 45. — Schema to show the direction of the elec-
trotonic currents in an excised nerve: P, The battery for
the polarizing current sent into the nerve at +, the an-
ode, and emerging at — , the cathode; g\ galvanometer
arranged with leading off electrodes to detect the anelec-
trotonic current, the direction of which is indicated by
the arrows (in the nerve it is the same as that of the po-
larizing current) ; g, galvanometer similarly arranged to de-
tect the catelectrotonic current. The anelectrotonic and
catelectrotonic currents continue as long as the polarizing
current is maintained.

*ets'

102

THE~PHTSIOLOGY OF MUSCLE AND NERVE.

f\l t^tk(Miu^\.^V^^ilar current can be led off from the nerve on the
or 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 electrical 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 un-
decided.

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-

€3

AJL=*

Fig. 46. — To show the action of the core-model: p, The polarizing current; q' 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.! 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
diagram, of a glass tube A-Bt 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

1903.

Bethe, " Allgemeine Anatomie u. Physiol, des Nervensystems," Leipzig,
t Hermann, " Handbuch der Physiologic," vol. ii, p. 174.

\y*

3 R A R N

ELECTRICAL PHENOMENA. \\ . ': 103

^/

current can be detected on the side of the anode (g') and onH^&yaJent-vto VfrtO^
the catelectrotonic current on the side of the cathode (g). The*txf&maMGJk) .
given to these currents is that as the threads of current pass into the plat
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 conductive sheath correspond-
ing 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-medullator 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 (see next chapter), it is still very uncertain whether it furnishes any
positive information concerning the processes that actually take place in the
living nerve when submitted to the action of electrical currents or other arti-
ficial 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, rela-
tively to light or electricity, exceedingly slow, — 27 meters per
second. To many minds this slow movement and the absence
of a complete circuit made the electrical theory impossible. Modern
views have taken, therefore, 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 (6) 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 turning fork wave (0.01 sec.) was 21
mms., 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 /r\fa or 30716 mms. (30.716 m.) 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
temperatures. According to Helmholtz, this variation lies between
24.6 and 38.4 m. per second for a 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 (" Miiller'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 Tfa 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 disturbance. 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.f
Moreover, all influences that alter the velocity or strength of the
nerve impulse affect the electrical disturbance in the same manner.
It is believed generally, therefore, that the electrical alteration is
an invariable accompaniment of the excitatory wave, and the dem-
onstration 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.
t Gotch 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 t, • ,

a. The stimulating electrodes; g and gr, galvanometers impulse. 11 IS not

vlriaS on e°a^helrde.°deS "^ t0 ^ ^ ^^ difficult to show by

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 afferently. We now know that in
such a case the old hypoglossal fibers degenerate completely, and
although the new ones that are eventually formed in their place may
not be outgrowths from the lingual stump they are at least not the
old efferent fibers, and hence experiments of this kind are not so

NATURE OF THE NERVE IMPULSE. 109

conclusive 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- , ,,, , . , .

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

the current of which is led into the nerve. The de- ,-i ' -r^ , • i , •

pressed irritability at both anode, +, and cathode, — , them. V UnctlOnai actlV-

^^l\TnerVGimlpnlse8taTtedataiTOmTeachine ity in 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 work, 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 Durig,f 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 Physiology," 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; so that 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. J

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 -^^-q°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 Physiologie," vol. ii, part u,
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, perhaps most, modern 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

114 THE PHYSIOLOGY OF MUSCLE AND NERVE.

very incomplete, since in the train of gunpowder the material
is entirely consumed, whereas in the nerve an indefinite series of
impulses may be transmitted and with a strength varying with
the intensity of the originating 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 conduct-
ing nerve there are any detectible waste products formed. There is
no rise in temperature, 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 electronegative 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 conductor. This view rests upon the fact that no con-
sumption of material can be demonstrated in the acting nerve fiber,
and that apparently the fiber can conduct indefinitely without show-
ing 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 assumed
that this electrical charge constitutes the nerve impulse. To ex-
plain the physics of the conduction it is supposed that the nerve
fiber has a structure essentially similar to the "core conductor"
(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-medulla ted as well as the medulla ted fibers, the
central threads are represented by the neurofibrils within the axis
cylinder and the surrounding sheath by the perifibrillar substance.
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.

NATURE OF THE NERVE IMPULSE. 115

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 stimulus. It is
evident, therefore, that in such a model, as in an ocean cable, an
electrical charge may be 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 experi-
ment among specialists. The subject is referred to here solely to
indicate the trend of modern discussion. We are far from having
an explanation of the nerve impulse resting upon such an experi-
mental basis as to command general acceptance.*

Bethe has proposed a new 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 combined energy. To account for
the electrical changes, it is assumed that, when the fibril and fibril acid
combine, electronegative ions — anions — are liberated, so that as the wave
of affinity progresses it is accompanied by an electronegative condition. f

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 hearirg
and in the other a contraction of a muscle is found in the manner

* 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 Physiologie," vol. ii, part ti, 1903; Hering,
"Zur Theorie der Nerventhatigkeit," 1899; Gotch, Schafer's "Text-book
of Physiology," vol. ii, 1900.

t Bethe, " Allgemeine Anatomie u. Physiologie des Nervensystems," p.
301, 1903.

116 THE PHYSIOLOGY OF MUSCLE AND NERVE.

of ending of the nerve, one terminating in a special part of the cortex
of the cerebrum, the other in a muscle. In this respect and 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 terminate, whether in an explosive mixture, an arc light,
or solutions of electrolytes of various kinds. We have in physi-
ology 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 reac-
tion, 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 stimu-
late 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 im-
pulses the specific energies of the various nerves — that is, the fact
that each gives only one kind of response — is referred entirely to
the characteristics 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
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).

The Nutritive Relations of the Nerve Fiber and Nerve Cell.
— In recent times in accordance with the so-called neuron doctrine
(see p. 122) every axis cylinder has been considered as a process of
a nerve cell, and therefore as a part, morphologically speaking, of

NATURE OF THE NERVE IMPULSE.

117

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 its 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. 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

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

118 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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. The older physiolo-
gists thought that if the severed 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 de-
generation is inevitable once the living continuity of the fibers has
been interrupted in any way. Any functional union that may
occur is a slow process involving an act of regeneration of the
.fibers in the peripheral stump. The time required for the degen-
eration differs somewhat for the different kinds of fibers found in
the animal body. In the dog and in other mammalia the degenera-
tion begins in a few (four) days, while in the frog it may require
from thirty to one hundred and forty days, depending upon the
season of the year. 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 seg-
ments of myelin, each containing a piece of the axis cylinder, and
these segments in turn fragment very irregularly 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

* See Howell and Huber, " Journal of Physiology," 13, 335, 1892.

&•

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

ends of the fibers remain substantially intact, it is interesting to
find that the nerve cells from which they originate undergo dis-
tinct 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 simul-
taneously with the degenerative changes, the two proceeding, as
it were, hand in hand. The regeneration 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* has emphasized this peculiar attraction, as it were, be-
tween the peripheral and the central ends, giving some reason to believe that
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
* Forsmanns, " Ziegler's Beitrage." 27, 216, 1902.
f Bethe, " Allgemeine Anat. u. Physiologie des Nervensystems," 1903.

120 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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 connec-
tion 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 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. 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 is 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, in-
stead of being due to an actual downgrowth of the axis cylinder
from the central ends.

Degenerative Changes in the Neuron on the Central Side
of the Lesion. — According to the Wallerian law of degeneration,
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 de-
generation and regeneration similar to that described for the fibers
of the peripheral stump. The degenerative changes in the fibers
in the central stump were supposed to extend back only to the first
node of Ranvier, — -to affect, therefore, only the internodal segment
actually injured. As a matter of observation, however, it is 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 remains intact as long as its cell of origin is nor-
mal. 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 stand-
ing the motor cells in the anterior horn of the cord decrease in num-
ber 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
* " Journal of Anatomy and Physiology," 3, 176, 1869.

NATURE OF THE NERVE IMPULSE. 121

has been discovered more recently and that is perhaps of more im-
portance 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 fiber is cut the corresponding cell may show distinct histo-
logical 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 be-
comes swollen and the nucleus may assume an excentric position.
These retrogressive changes continue for a certain period (about
eighteen days). After reaching their maximum of intensity the cells
usually undergo a process of restitution and regain their normal
appearance, although in some cases the degeneration is permanent.
After section of the nerve fibers, therefore, two processes of degenera-
tion may occur in the central cells : one temporary, that reaches its
maximum in two to three weeks, and from which the cell recovers
completely, as a rule, in about three months; and one permanent,
which comes on only after many months or even years and is to
be regarded as the result of prolonged inactivity.*

*Nissl, " Allgemeine Zeitschrift f. Psychiatrie," 48, 197, 1892. Also
Bethe, loc. cit.

. 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

122

PROPERTIES OF THE NERVE CELL.

123

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 is again
called into question. As was stated on p. 119, Bethe has shown apparently
that in young animals the nuclei of the neurilemmal sheath may regenerate
a new nerve fiber containing axis cylinder and myelin sheath, and this fact
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. In fact, it indi-
cates strongly the probability of an older view, according to which the axis
cylinder is formed by the fusion of a series of cells whose origin is the same
as those represented" by the nuclei of the neurilemma. Some histologists—
Ap&thy, Bethe, Nissl — have also attacked the most fundamental feature of
the neuron doctrine, — the view, namely, that each neuron represents an inde-

*"Deut. med. Wochenschrift," 1891, p. 50.

124 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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).
The neurofibrils form a continuum through which nerve impulses pass without
a break from neuron to neuron. According to this conception, the ganglion
cells play no direct part in the conduction of the impulse from one part of the
nervous" system to another; the neurofibrils alone, and the intracellular
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-
lar 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

PROPERTIES OF THE NERVE CELL.

125

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 in the network or reticulum
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 ; 6, 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 horn cells of the spinal cord, the Purkinje cells of the
cerebellum — all belong to this type. But within the nerve axis

126

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

Fig. 56. — Golgi cell (second type).
The axon, a, divides into a number of
fine branches. — (From Obersteiner, after
Andriezen.)

f>,

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
branches within the gray
matter. Assuming that in
such cells the distinction be-
tween the axon and the den-
drites is well made and that
as in the other type the
dendrites form the receiving
and the axon the discharging
apparatus, these cells would
seem to have a distributive
function. The impulse that
they receive may be trans-

Fig. 57. — Normal anterior horn cell
(Warrington), showing the Nissl granules in the
cell and dendrites : a, The axon.

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 significance
are, first, the arrangement of the neurofibrils, and, secondly, the

PROPERTIES OF THE NERVE CELL. 127

presence of a materia] 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.

128

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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 the 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 probably 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 shown 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

PROPERTIES OF THE NERVE CELL. 129

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, 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 in 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 hy
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. J 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

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

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

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

130

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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. g.,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 unheritable.* According to this result,
we should expert that a summation of the effects of rapidly
*Gotch and Burch, ''Journal of Physiology," 24, 410, 1899.

PROPERTIES OF THE NERVE CELL. 131

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. 43), 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 -^ of a second. These facts, so

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

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

132 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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. Inasmuch as it appears immediately
after the contraction, it is usually explained as being due to some
product of the chemical reaction causing the contraction, — in fact,
a state of temporary fatigue. 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 in this case also it is due to some product of the chemical reaction
that is assumed to underlie nervous activity. Using this terminol-
ogy, 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 condi-
tion 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," " Beitrage zur Anatomie u. Physiologie," Giessen, 1881, vol.
ix.

133

134 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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

REFLEX ACTIONS.

135

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-
als.

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

136 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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 purposeful and 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 purposeful
character of the movement, and, second, the almost mechanical
exactness with which a definite stimulus will give a definite re-
sponse. This definite relationship holds only for 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 im-
pulses. (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

REFLEX ACTIONS. 137

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 purposeful, 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 conclusion that all the various
motor neurons of the cord must be in physiological connection, either
direct or indirect, with all the neurons supplying the cutaneous sur-
face. 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
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 purposeful character
of the reflexes under consideration their automaton-like regularity
is an indication that their production is due to a fixed mechanical

138 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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 purposeful 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 lower 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 func-
tions 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 are
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.

REFLEX ACTIONS. 139

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 diminished
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.

140 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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
may explain why a normal frog gives reflexes that are so much
less constant and less predictable than 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, u Physiologische Studien uber d. Hemmungs-Mechanismen
f. d. Reflexthatigkeit im Gehirn d. Frosches," Berlin, 1863.

REFLEX ACTIONS. 141

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. 512). 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. The
most 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 Ttirck. 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

142 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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 neuron 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

REFLEX ACTIONS.

143

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
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 b and c gives
a pseudoreflex effect.

144 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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-

REFLEX ACTIONS. 145

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,
— that is, the vegetative or unconscious organs, — 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 sys-
tem 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

* Goltz and Ewald, " Pfliiger's Archiv fur die gesammte Physiologie,"
63, 362, 1896.
10

146 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

less than normal. Its power of preserving a constant body tem-
perature 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 less-
ened, and this fact illustrates well the great general importance
of the spinal cord and brain as reflex centers controlling the nutri-
tion and co-ordinated activities of the 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 below 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 of 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 phenomenon 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. Psychiatrie," 1875, vol. v.

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

REFLEX ACTIONS.

147

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

mm

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 hand (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 dimin-
ished the longer the interval, after which 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 hand. — {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.

148 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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 gesammte Physiologie," 27, 412, 1882.

REFLEX ACTIONS. 149

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 varying 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
variation 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.

<?

15Q'\ p> PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

Use of the JLnee-jerk and Spinal Reflexes as Diagnostic

fQ$l [jSign^^T^jEeffct that the knee-jerk depends on the integrity of
the fpftorgrc in thelumbar 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 lumbar 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

• i % 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 m 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. 140)
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

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9riT .i9tn9 Rs/ion edt d->irl« 1« «bvoI 9dl

.oaaswtoi lo moil 9di no qi* woria
ot bna tn9vis 9-te ftgfosnm to aqumg no eoloawm k> as bie bnad-Jii

9dl dofdw ni bioa adt io ^tnsnfya* 9dt moil Vn ■ ill on.t<n9t •

J. • I J- ■ rx

8ux9ftf» :
9di no
«9nuol nio ; n to Jlood-ixsl

1

Fig. 67. — Diagrammatic representation of the lower portion of the human bulb and
spinal cord.

The cord is divided into its four regions: 1, Medulla cervicalis; 2, medulla dorsahs;
3, medulla lumbalis; 4, medulla sacralis. Within each region the spinal segments bear
Roman numbers. On the left side of the diagram the locality supplied by the sensory
(afferent) neurons is indicated by one or more words, and these latter are connected
with the bulb or the segments of the cord at the levels at which the nerves enter. The
afferent character is indicated by the arrow tip on the lines of reference.

On the right-hand side the names of muscles or groups of muscles are given, and to
them are drawn reference lines which start from the segments of the cord in which the
cell-bodies of origin have been located.

Within the cord itself, the designations for several reflex centers are inscribed in the
segment where the mechanism is localized. For example, Reflexus scapularis, Centrum
cilio-spinale, Reflexus epigastricus, Reflexus abdominalis, Reflexus cremastericus, Reflexus
patellaris, Reflexus tendo Achillis. Centrum vesicale, Centrum anale (the last two on the
left side of the diagram). (Donaldson, "Amer. Text-book of Physiology," from "Icones
Neurologicse," Strilmpell and Jakob.)

\SWers/f

Acusticus
Vestibularis

Gustus

(cum Trigemino)

Pharynx

:ophagus
Larynx, Trachea
Intestina

(Thorax, Abdomen)
[io occipitalis
li
ie

Regio humeri
Regio Nervi radialis
Regio N. mediani
Regio N. ulnaris

Muscuii faciei
Mm. pharyngis, palati
Mm. laryngis
Mm. linguae
Oesophagus

Muscuii colli et nuchae
Scaleni, Splenius
Cucullaris

Rhomboidei, Levator anguli scapulae

Supra-, infraspinatus
Deltoideus, Supinator longus

anticus, Supinator brevis

Pectoralis major (portiociavicui.)

Teres minor

Pronators, Brachial internus

Triceps

Extensores carpi et digitor. longi ) %

Pectorals major (portio costalis)
Latissimus dorsi, teres major

Flexores carpi et digitor. longi]

Extensores pollicis
Interossei lumbricales
Thenar Hpttienar

(«g!

Quadriceps femoris

Glutaei, tensor fasc. lat.

Adductores femoris

Abductores femoris

Tibialis anticus

Gastrocnemius, Soleus

Biceps Semitendi- Semimembranosus

Obturator, piriformis, quadratus femor.

Flexores pedis

Extensores digitorum

Peronei

Flexores digitorum

Interossei
Mm. perineales
Mm. vesicates
Mm. rectales

Fig. 67.

REFLEX ACTIONS.

151

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

M. sterno-cleido-

Inspiratory reflex on

Neck and back of

mastoideus.

quick pressure be-

head.

M. trapezius.

neath ribs.

Mm. scaleni et

colli.

Diaphragma.

Civ

Diaphragma.

Dilatation of the pu-

Neck.

M. supraspinatus.

pil on irritation of

Upper part of

M. infraspinatus.

the neck (C. iv-vii.)

shoulder.

M. deltoideus.

Outer side of arm.

M. biceps brachii.

M. coracobrachi-

alis.

M. supinator

longus.

M. rhomboidei.

C.v

M. deltoideus.

Scapular reflex (C.

Back of shoulder

M. biceps brachii.

v-T. i).

and arm.

M. coracobrachi-

Tendon reflexes of

Outer side of

alis.

the corresponding

upper arm and
of the forearm.

M. supinator

muscles.

longus.

M. supinator

brevis.

M. pectoralis

major (pars

clavicularis) .

M. serratus an-

terior.

Mm. rhomboidei.

M. brachialis

anticus.

M. teres minor.

C. vi

M. biceps brachii.

Tendon reflexes of the

Outer side of

M. brachialis

Mm. extensores la-

forearm.

anticus.

certi et brachii.

Back of hand and

M. pe c t o r al is

Tendon reflexes of

radial region.

major (pars

the muscles of the

clavicularis) .

wrist.

* Taken from Barker's " Nervous System."

152

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

Localization of Function in the Different Segments of the Spinal
Cord. — (Continued.)

Segments.

Muscles.

Reflexes.

Cutaneous Areas
Innervated.

C. vi (con-

M. serratus

tinued).

anterior.
M. triceps brachii.
Mm. extensores

manus et digi-

torum.
Mm. pronatores.

C. vii

M. triceps brachii
caput longum).

Blow upon the palm

Radial region of

of the hand causes

hand.

Mm. extensores

closure of the fin-

manus et digi-

gers.

torum.

Palmar reflex (C.

M. flexores

vii-T. i).

\

manus.

\

Mm. pronatores

1

manus.

J

M. pectoralis

1

major (pars
sterno-costalis) .

F

[

M. subscapularis.
M. latissimus
dorsi.

V Distribution of

/ N. medianus.

M. teres major.

1

C. viii

Mm. flexores
manus et digi-
torum.

Mm. m i n o r e s
manus.

Pupillary reflex.

)

Thoracic i . . .

Mm. extensores

pollicis.
Mm. m i n o r e s

/ f

\ Ulnar region.

/

manus.

y

Mm. eminent

\

thenar et hypo-

]

thenar.

J

T. ii-xii

Mm. dorsi.

Epigastric reflex (T.

Skin of thorax,

Mm. abdominis.

iv-vii).

back, abdomen,

Mm. erectores

Abdominal reflex

and upper glu-

spinae.

(T. vii-xi).

teal region.

Lumbar i . . .

M. iliopsoas.

Cremaster reflex

Skin of pubic re-

M. sartorius.

(L. i-iii).

gion.

Mm. abdominis.

Anterior part of
scrotum.

L. ii

M. iliopsoas.

Patellar tendon reflex

Outer side of hip.

M. sartorius.

(L. ii-iv).

Mm. flexores genus.

M. quadriceps

femoris.

L. iii

M. quadri ceps
femoris.

Anterior and inner

side of thigh.

Mm. rotatores

femoris (inward).

Mm. adductores

femoris.

REFLEX ACTIONS.

153

Localization of Function in the Different Segments of the Spinal
Cord. — {Continued.)

Segments.

Muscles.

Reflexes.

Cutaneous Areas
Innervated.

L. iv

Mm. abductores

Gluteal reflex

(L.

Inner side of thigh

femoris.

iv-v) .

and leg as far as

Mm. abductores

ankle; inner side

femoris.

of foot

M. tibialis

anterior.

Mm. f 1 e x o r e s

genus (Ferrier ?)

L. v. ...... .

Mm. rotatores

Back of hip and

femoris (out-

thigh and outer

ward).

part of foot.

Mm. flexores

genus (Ferrier ?)

Mm. flexores

pedis.

Mm. extensores

i

digitorum.

Mm. peronaei.

Sacral i-ii . . .

Mm. flexores
pedis et digi-
torum.

M. peronaei.
Mm. m i n o r e s
pedis.

Plantar reflex.

Back of thigh;
outer side of leg
and foot.

S. iii-v

M. perinsei.

Achilles tendon reflex.

Skin over sacrum,

Vesical and rectal

perineum, geni-

centers.

talia, and about

t

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 innumerable fibers 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 other-
wise 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 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 through-
out the gray matter, and according to the side on which the axon
enters into a tract they may be divided into three subgroups: (a)

154

SPINAL CORD AS A PATH OF CONDUCTION. 155

Those whose axons enter the white matter on the same side of the
cord, the tautomeric tract cells of Van Gehuchten. (6) 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
cell 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

Ventral

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.

axon divides 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

156 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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, or 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

Whife matter. — Gray matter. Enrire section.

lOO

80
60
40
SO

lOO

^Composite curves based on 4 Cases.

ffVHHinni n in r? y va w xm ix x xi xu i u ju kyi nmnffj

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 from 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-

SPINAL CORD AS A PATH OF CONDUCTION. 157

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 Muller's fluid,
staining in osmic acid and Muller'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 tracts 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."

158 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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 a short course only 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, in 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 the constituent fibers of these tracts 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 seg-
ments 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 his-
tory, and that in the most highly developed animals, man and the

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

SPINAL CORD AS A PATH OF CONDUCTION.

159

anthropoid apes, 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 deduction is borne out by facts (see p. 138).

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.

Fig. 70.— Schema of the tracts in the spinal cord (Kolliker) : g, Tract of Goll ; b, 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.

160

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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
G c- ■ 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 continues 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 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

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.

SPINAL CORD AS A PATH OF CONDUCTION. 161

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
11

162

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

endogenous fibers — that

J+tb Cervical

7-kDorscd

Zn^ Lumbar

^Lumbar

Fig. 72. — Diagrams to
show course of upward de-
generation of fibers of poste-
rior columns after section of
a number of posterior roots
of the nerves forming the
lumbosacral plexus. — (mott.)
It will be noted that in the
cervical regions the degener-
ated area is confined to the
column of Goll.

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
matter of the cord and thence the con-
duction is continued by one or more
tract cells. The conduction by this set

SPINAL CORD AS A PATH OF CONDUCTION. 163

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 tKese
columns are intact and are seriously interfered with when they are
senjToried ; but most, of the results, pathological and experimental,
indicate that when the continulty_of these Jtbers is destroyed the
sense of touch is stilTpresent in the parts supplied by the cord below
thejgsiom To summarize, therefore, we may "say thai Ihe-widence
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 fhat 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.

164

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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 from tract cells on the same
side situated in the anterior horn and the intermediate portions of
the gray matter. Many of the fibers in this tract doubtless termi-
nate 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

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

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

SPINAL CORD AS A PATH OF CONDUCTION. 165

the physiology of mese two tracts there is little experimental
and less 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. This
result together with the fact that the bundle ends in the cerebellum
gives reason for believing that the fibers mediate muscular sen-
sibility. As we shall see, much evidence of every kind 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 in 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, and Gowers* himself gives a history of some such cases
which lead him to believe that this tract constitutes a pathway for
pain impulses. Little confidence, however, can be placed in this
conclusion, since the lesions in question were not confined to the
column of Gowers, but involved neighboring regions and the gray
matter. 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 in the cerebellum. This fact would connect
them with the co-ordination of the muscles in movements of equili-
bration, and would therefore make them fibers of muscle sense.
It would seem, therefore, that all the long ascending tracts in the
posterior and lateral columns of the cord are made up of fibers of
muscle sense. 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 developed first in connection with this sense.

The Spinal Paths for the Cutaneous Senses (Touch, Pain,
and Temperature) . — From the facts stated in the last paragraph
it follows 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 sep-
arate. In the pathological condition known as syringomyelia cavi-
ties are formed in the cord affecting chiefly the central gray matter
and the contiguous portions of the white. In these cases a frequent
symptom is what is known as the dissociation of sensations; the
patient loses, in certain regions, the sensations of pain and tempera-
• Gowers, "Lancet." 1886.

166 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

ture (analgesia and thermoanesthesia), 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 tempera-
ture, 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 (posterior 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. But the number of such neurons concerned in the con-
duction as far as the medulla is not known. Regarding the path
for the touch impulses a singular amount of uncertainty prevails.
Thissense 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 im-
pulses may be conveyed up the cord by several paths: by the
long association fibers of the posterior columns and by the short
association fibers of the lateral columns. Such a view receives no
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 evi-
dence 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 jnay be that in man long
paths for the touch fibers, by way of the posterior column, have
been acquired in part.

The Homolateral or Contralateral Conduction of the
Cutaneous Impulses. — Great interest, from the medical side,
has been shown in the question of the crossed or uncrossed con-
duction of the cutaneous impulses in the cord. The matter is
naturally one of importance in diagnosis. In human beings it
was pointed out by Brown-Sequardf 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-

* Oppenheim, "Archiv f. Physiologie," 1899, suppl. volume, 1.

f Brown-Sequard, "Journal de Physiologie," 6, 124, 232, 581, 1863.

SPINAL CORD AS A PATH OF CONDUCTION. 167

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 (hgmjsQfitol) m the thoracic region, the sensi-
bility nf |.|ip pfl.r|fp .^ippliftfj hfilow t.hft _1pision is impaired upon the
same side, but not completely abolished, showing that "some
p^rnsging Vm^ taken plar^v* 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 tou^hjsjiot
complete, and muscular sensibility is affecteH only on the same
sicTeT^'On the whole, it would seem that the crossing of the__serigory
fibers in the cord is only partial, and fc mnra pv tensive in man
than m^the lower animals. This partial crossing is probably com-
pleted in the brain, especially in the great sensorvdecussation 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
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,
however, 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 reach-
ing 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 decussation or in the anterior
white commissure 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 through-
*Mott, "Brain," 1895, 1.

168

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

out the length of the cord, diminishing in area by the way as some
of their fibers terminate in each segment. This system of fibers
is supposed to represent the mechanism for effecting voluntary

movements, and according to the
general schema the voluntary motor
path from cerebrum to muscle com-
prises 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 important
exceptions, and histologically there
is proof that some of the fibers in
each pyramid (2 in Fig. 74) con-
tinue into and terminate 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 rela-
tively less important and the direct
tract in the anterior columns is
lacking 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 :

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.

Mouse 1.14 per cent.

Guinea pig 3.0 "

Rabbit 5.3

Cat 7.76

Man 11.87

* Lenhossek, "Bau des Nervensy stems," second edition, 1895.

SPINAL CORD AS A PATH OF CONDUCTION. 169

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 phylflgenetic scale, the more complete is the develop-
ment of the long pyramidal system; but even in the higher mam-
mals it is probable that the more primitive mode of motor con-
nection between brain and cord is not entirely displaced by the
evolution of the pyramidal system.

Less Well-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.*

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, s.} Fig.
75, 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 repre-
sent 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
(pp., Fig. 75) between the crossed pyramidal tract and the tract
of Gowers. 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 pons 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, it may

* Collier and Buzzard, "Brain/' 1901, 177; and Fraser, "Journal of
Physiology," 28, 366, 1902.

170

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

represent a cortico-spinal motor path in addition to that offered
by the pyramidal system.

The vestibulo-spinal fibers, v.s., 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 and perhaps in the vestibular
nucleus of Bechterew in the pons. In the cord the fibers end around
cells in the anterior horn. Since the Deiters nucleus forms a termina-
tion 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
to maintain equilibrium,
their connection in Deiters' s
nucleus with a spinal motor
path becomes very signifi-
cant as furnishing a reflex
arc through which sensory
impressions from the vestib-
ular apparatus in the ear
may automatically control
the musculature of the
body. The ventral longitu-
dinal bundle or fasciculus
sulcomarginalis (s.m., Fig.
75) lies along the border of
the anterior median fissure.
Its fibers are said to origi-
nate in the superior colliculi
of the corpora quadrigemina
and to terminate around
cells in the anterior horn,
constituting, therefore, a
second motor path between midbrain and cord. The anterior
marginal bundle, a.m., lies along the periphery of the anterior
columns, and is supposed to consist of fibers from the nucleus
fastigii of the cerebellum. Helweg's bundle is a small, triangular
area on the margin of the cord at the junction of the anterior and
lateral columns. It is conspicuous in the cervical region, and is said
to be connected with the olivary body, although little that is defi-
nite is known of its origin or termination.

a.Tris.

Fig. 75. — Diagram indicating

the location
of the" less well-known tracts of the cord: s.,
Comma tract of Schultze; p.p., the prepyram-
idal tract (Monakow's bundle) ; v.s., region in
which are found the fibers of the vestibulo-
spinal tract; h., Helweg's bundle; a.m., an-
terior marginal bundle; s.m., ventral longi-
tudinal or sulcomarginal bundle; p. and p., the
direct and crossed pyramidal tracts; /. and g.,
tracts of Flechsig and Gowers.

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

171

172 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 is not matter
or energy, and which, therefore, is not within the scope of physio-
logical explanation. In what follows, therefore, attention is called
only to the mechanical side, — the facts that have been discovered
regarding the anatomical structure and 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 minute differences the extent of which has
not been wholly determined, it is an interesting fact that the cor-
tex everywhere has a similar structure. It consists of four or five
layers more or less clearly distinguishable (see Fig. 76) :

1. The molecular layer, lying immediately beneath the pia
mater, and having a thickness of 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 some relatively large pyramidal cells, particularly in

GENERAL PHYSIOLOGY OF THE CEREBRUM.

173

the Rolandic area. Their form and con-
nections 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 (Martinotti 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. 77), 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

Tv

D

■I

Fig. 76.— To show the
structure of the cortex cere-
bri (Dejerine) : /, The molec-
ular layer; //, the layer of
vertical fusiform cells; III,
the layer of small pyramidal
cells; IV, the layer of large
pyramidal cells; V, the layer
of polymorphic cells.

174

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

Fig. 77. — Schema of the projection fibers of the cerebrum and of the peduncles of the
cerebellum ; lateral view of the internal 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 ;
«/, fibers between the auditory nucleus and the inferior quadrigeminal body; K, motor
(pyramidal) decussation in the bulb; Vt, fourth ventricle. The numerals refer to the
cranial nerves. — (Modified from Starr.)

Fig. 78. — 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. 175

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. 78). 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 arid 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.

The structure of the cortex is probably more complicated than would
appear from the above description. Numerous recent writers (Held, Apathy,
Nissl, Bethe, Hatai, et al.) have called attention to a very fine network — peri-
cellular or Golgi net — which envelops the cell body and the dendritic branches
of the neurons. Most of these observers consider that this delicate network is
of a nervous nature. It fills up the spaces between the nerve cells and makes,
therefore, a connection of exceeding complexity, and a histological feature
whose details must be worked out by improved technical methods. Nissl has
called attention to the fact that in the cortex the nerve cells, axons, dendrites,
neuroglia cells and fibers, and blood-vessels found are not sufficient to fill up the
whole space of this layer, and that there must exist an in-between substance,
which he speaks of specifically as "the gray." It seems probable, as contended
by Bethe, that this in-between substance is the network just referred to, whose
delicacy is such that it escapes detection by ordinary histological methods. If
this standpoint is correct it is evident that histology has a new field opened to
it in the study of the brain, and the structural features that may be revealed
by future study will doubtless add much to our knowledge of the mechanism
involved in brain activity.

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

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

176

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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. 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

ifr ^f

Fig. 79. — 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 Ramon y Cajal.)

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

GENERAL PHYSIOLOGY OF THE CEREBRUM.

177

animals the greater mental development is associated with a greater
complexity and richness in the connections of the neurons. As
shown in Figs. 79 and 80, 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

> I'

A »> '

A <*

V' S "

r

m

9

, » v 4 *

• * *

■»«S«Vy*-

Fig. 80. — Sections through corresponding parts of the cortex in: a, Man; &, dog;
and c, mole, to show the greater separation of the nerve cells in the higher animals. — ■
(Bethe, after Nissl.)

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
12

178 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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
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
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 experien ces 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 behavior

GENERAL PHYSIOLOGY OF THE CEREBRUM. 179

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 connections with
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,
* Goltz, "Archiv f. die gesammte Physiologie," 51, 570, 1892.

180 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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
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, particularly as it soon
became a favorite implement for the use of 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 scien-
tific men of his day of the conclusiveness of his results. At the
time that he was exploiting his doctrines in Paris, where he spent
the latter years of his life, Flourens began his celebrated experi-
mental 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. f Flou-
rens's chief experiments were made upon pigeons, and in these

* Gall (and Spurzheim), "Recherches sur la systeme nerveux en general
et sur celui du cerveau en particulier," 1810-1819.

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

GENERAL PHYSIOLOGY OF THE CEREBRUM.

181

animals he found that successive ablations of parts of the cerebrum
from before backward or from side to side was 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 acci-
dent or wounds in battle had
lost a part of the brain with-
out any apparent defect in
their mental powers. There-
fore toward the middle of the
nineteenth century the preva-
lent view in physiology was
that the cerebrum is function-
ally equivalent in all of its
parts. One fact was known
in medicine at that time which
distinctly contradicted this be-
lief , — 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 sig-
nificant to us now, was not
properly valued at the time.
The beginning of our modern
views of cerebral localization
is found in the work of Fritsch
and Hitzig* (1870), in which
they exposed and stimulated
electrically the cortex cerebri in
dogs. They found that stimu-
lation of certain definite areas,
particularly in the sigmoid

gyrus, gave distinct and constant movements in the limbs, face, etc.
(see Fig. 81). 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 defects result-

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

Fig. 81. — To show 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.

182

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

ing 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 different motor and sensory areas were definitely
circumscribed and separated one from the other, making the cere-
brum a plurality of organs, to use Gall's term. The more recent

Fig. 82. — Diagram representing the probable location of the chief motor and sensory
areas of the cerebral cortex in man: A, Lateral surface ; B, mesial surface. — (From Schafer.)

work has tended to modify these extreme views of localization and
to emphasize the fact that histologically and physiologically the
entire cerebrum is connected so intimately, part to part, that,
although the different regions mediate different functions, never-
theless 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 function has been established definitely,
but the modern view is that the cerebrum is composed of a plurality

GENERAL PHYSIOLOGY OF THE CEREBRUM.

183

of organs, not completely 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

Toes
„Ankle \
Artec

Wrist.
Tinkers

Abdomen-.

jQvest

Eyelid /Closure

Sulcus Centralis

Nose °fjal° Oberiing Vaca,} Mastication,
ofjau> cords

Fig. 83. — 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 cor-
tex 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. The location of these areas as usually given is
represented, for the human brain, by Fig. 82. It will be seen that in
general the distribution of the areas along the fissure of Rolando
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 Green-

184

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

baum,* making use of electrical stimulation, unipolar method,
have explored carefully 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 Fig. 83, 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 a paralysis of the
muscles on the other side, particu-
larly in the limbs. Pathological or
experimental lesions here, moreover,
are followed by a degeneration of the
pyramidal neurons, — a degeneration
which extends to the termination of
the neuron in the cord. With these
data we can construct a fairly com-
plete account of the mechanism of
voluntary movements. The initial
impulse arises in the large pyramidal
cells of the motor areas and proceeds
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 move-
ments; a lesion anywhere along this
tract causes paralysis, more or less
complete and on the other side
of the body in general, if the le-
sion is anterior to the decussation.
The path of the motor fibers is
represented in the schema given in
Fig. 84. Arising in the cortex, they
take the following route (see also
Fig. 77,5):

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

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

Fig. 84. — 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.

GENERAL PHYSIOLOGY OF THE CEREBRUM. 185

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
alone 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 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.

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
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 re-
move parts of the motor area by surgical operation indicate that the
voluntary control of the muscles is lost or impaired permanently.
It would seem, therefore, that in an animal as high in the scale as
the dog voluntary control of the muscles can be maintained through

186 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

tracts other than the pyramidal system, tracts, perhaps, such as
Monakow's bundle (rubrospinal tract), arising in the midbrain. In
man, however, along with the more complete development of the
pyramidal system, the efficacy of the phylogenetically older motor
systems is correspondingly reduced.

The Crossed Control of the Muscles and Bilateral Repre-
sentation 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 of the pyramidal fibers explain the 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 is involved 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 mus-
cular weakness on the same side. The paralysis in hemiplegia
affects but little, if at all, those muscles of the trunk which are accus-
tomed to act in unison, — the muscles of inspiration, for instance,
the diaphragm, 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 might 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 Melius 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-

GENERAL PHYSIOLOGY OF THE CEREBRUM. 187

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. 210 and Fig. 93).
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, mainly, 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. Moreover, the distinction be-
tween what we may call simple sensations and the more complex
psychical representations and judgments 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 dif-
ferentiated ; but many of the lower senses escape recognition in
the individual himself, since the state of consciousness accom-
panying them is of a lower order. Our muscular sensations, for in-
stance, are so indefinite as to be practically subconscious. They
are most important to us in every act of our lives, yet the unin-
formed person is unconscious of the existence of such a sensation,
and if deprived of it would recognize the defect only in the con-
sequent 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 ex-
periments of stimulation and ablation, and observations upon in-
dividuals with pathological or traumatic lesions in the brain. In
the long run, the study of neuropathological 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 recognized most clearly, and the
anatomical mechanisms involved have proved to be more accessi-
ble to investigation.

The Body-sense Area. — In his early experiments Munk in-
sisted that lesions of the cortex involving the Rolandic area are

188

SENSE AREAS AND ASSOCIATION AREAS. 189

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 show, 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. 210) 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 are largely
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 feeling. By the
stereognostic feeling 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 the sensations of
touch and temperature in combination with muscular sensibility.
On the whole, therefore, we must infer that the cortex in this
postrolandic area is concerned with the finer and more conscious

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

t Mills, American Neurological Association, 1901.

190

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

interpretations of the sensations of pressure, temperature, and
muscular conditions. The part of the cortex, if any, concerned
in the primary conscious mediation of the sense of pain 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 the cortical centers for the sensory fibers of the body

Fissure of Rolando

Internal or median 1111617

s-InternalJlrcifornv T^bres
ofhinal CorcL

Fig. 85. — Schema representing the origin and course of the fibers of the median fillet, —
the intercentral paths of the fibers of body sense.

in general lie in the parietal lobe in the region indicated above.
This evidence is connected with the path taken by the sensory
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. 85). The second sensory neurons arise in the nuclei
mentioned. Some of them pass into the cerebellum by way of the

SENSE AREAS AND ASSOCIATION AREAS. 191

inferior peduncle of the same side; but others, passing ventrally,
cross the mid-line as the internal arciform fibers, which form a
conspicuous feature in the tegmental region of sections of the
medulla at this level. This 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 decussation
the sensory fibers form a longitudinal bundle on each side known
as the median fillet, lemniscus, or laqueus, which in the pons lies
just dorsal to the pyramidal fibers.

The fillet fibers may be traced forward as far as the anterior collie-

Fig. 86. — Cross-section through midbrain (Kolliker) to show the position of the fillet (L, L):
Nr, The red nucleus ; Sn, the substantia nigra ; Pp, the crus.

ulus of the corpora quadrigemina and the thalamus (see Fig. 86),
and some are said to continue directly into the cerebrum by way of
the posterior limb of the internal capsule to end in the parietal lobe
posterior to the fissure of Rolando. Those neurons that end in the
midbrain and thalamus are continued forward by a third neuron,
which ends in the parietal lobe in the same region (see Fig. 77, 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-
tion during embryonic life and by degeneration consequent upon
long-standing disuse. As was stated in the section upon nerve de-

192 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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 estab-
lished. 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,*

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
definitely established, 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. Much of the fillet ends in the mid-
brain and 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 connections which they make, may mediate
also a 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 observations 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
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
* Hosel, "Archiv f. Psychiatrie," 24, 452, 1892.

SENSE AREAS AND ASSOCIATION AREAS. 193

animal in this condition the pupil becomes 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 oc-
cipital 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 experiments is borne out by clinical experience.
Any unilateral injury to the occipital lobes is followed by a con-
dition of hemiopia more or less complete according to the extent
of the lesion. Observation, 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
foveie centrales, 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 Histological 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 the gray matter of the external genicu-
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. 77, D). A schema representing
13

194 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

this course of the optic fibers is given in the accompanying diagram
(Fig. 87). 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

Occipital lobe.

Optic radiation.
Superior colliculus.

Lateral or external geniculate.
Optic thalamus.

Retina.

Fig. 87. — Diagram to indicate the general course of the fibers of the optic nerves and the
bilateral connection between cortex and retina.

visual fibers proper, there are other fibers in the optic tracts and
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

SENSE AREAS AND ASSOCIATION AREAS. 195

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. In accordance with this claim it is said that when a local
lesion is made experimentally in one retina the degeneration that
extends backward along the corresponding optic nerve is contin-
ued in part over into the optic nerve of the other side. The exist-
ence of this interesting commissural connection between the retinas
is, however, still a matter of much uncertainty.

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 (Fig. 82) on the
mesial surface of the brain, and this portion of the occipital lobe
should be regarded as the true cortical center for vision, the re-
* Henschen, " Brain," 1893, 170.

196

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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,t 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

LEFT RETINA

RlGHTRETINA.

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. 88) ;
so that complete foveal blind-
ness— that is, blindness of the
centers of the visual fields — can
only occur when both occipital
lobes are injured in the region
of the calcarine fissure. While
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
out that, while extensive lesions of the occipital cortex on both
sides, leave, with a few exceptions, some degree of central vision,

* Donaldson, "American Journal of Psychology," 1892, 4.

f Flechsig, "Localization der geistigen Vorgange," Leipzig, 1896.

j Schmid and Laqueur, "Virchow's Archiv," 158, 1900.

Fig. 88. — Diagram showing the probable
relations between the parts of the retina and
the visual area of the cortex. — (From Schd-
fer.) The bilateral representation of the
fovea is indicated by the course of the dotted
lines.

SENSE AREAS AND ASSOCIATION AREAS. 197

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
in the case of spinal reflexes. The existence in the midbrain of the
motor nuclei of the third nerve, and of the posterior longitudinal
* Schafer, "Brain," 11, 1, 1889, and 13, 165, 1890.

198 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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 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 proc-
esses 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 con-
nections 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 development 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-
gators vary considerably. The eighth cranial nerve springs from the
bulb by two roots: the external and the internal. The former has

SENSE AREAS AND ASSOCIATION AREAS.

199

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. 89) . It seems cer-
tain that the latter is not an auditory nerve, but is concerned
with peculiar sensations that have an important influence on mus-
cular activity, especially in complex movements. The central
course of these two roots is quite as distinct as their peripheral

Posterior nucleus.

Deiters's nucleus.

Dorsal nucleus.
Ventral nucleus.

Cochlear branch.

Vestibular branch.

Semicircular
canals.

Scarpa's ganglion.

Cochlea.

Spiral ganglion.
Fig. 89. — The medullary nuclei of the eighth nerve. — (From Poirier and Charpy.)

distribution, — a fact that bears out the supposition that they medi-
ate different functions. The central course of the cochlear branch
is indicated schematically in Figs. 89 and 90. The fibers con-
stituting 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

200

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

restiform body and known as the ventral or accessory nucleus
(V.n., Fig. 90), and one dorsally, known as the dorsal nucleus or
the tuberculum acusticum (D.n.). From these nuclei the path
is continued by secondary sensory neurons, and its further
course toward the brain is still a matter of much. uncertainty
in regard to many of the details.* The general course of the
fibers, however, is known. Those axons that arise from the
accessory nucleus pass mainly to the opposite side by slightly
different routes (Fig. 90). 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 form a dis-
tinct band long known
to the anatomist and des-
ignated as the lateral fillet or lateral lemniscus. Authors differ
as to whether the fibers of this tract arise from nerve cells in the
superior olivary and neighboring nuclei, or are the fibers from the
accessory nucleus which pass by the superior olivary body with-
out ending and then bend to run forward in a longitudinal direc-
tion. This last view is represented in the schema (Fig. 90). The
secondary sensory fibers that arise in the tuberculum 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
* For literature see Van Gehuchten, "Le Nevraxe," 4, 253, 1903.

Fig. 90. — 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 stria? (a.s.); 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.i.,
the inferior colliculus.

SENSE AREAS AND ASSOCIATION AREAS. 201

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 the 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 nu-
cleus 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 coch-
lear 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 an-
other 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. 77, E). According to Flechsig,* who has
studied the course of these fibers in the embryo by the myeliniza-
tion method, the main group passes from the internal geniculates to
the transverse gyri of the temporal lobe within the fissure of Sylvius.
The internal geniculates, in man at least, have therefore the func-
tion of a subordinate auditory center, as the external geniculates
have the function of a subordinate visual center. The internal
geniculates are connected with the inferior colliculus, and also, it
will be remembered, with each other, by commissural fibers (Gud-
den'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 Physiological Significance of the Lower Auditory Cen-
ters.— The auditory path connects directly with two or three sets
of nerve cells before terminating finally in the cortex. The lower
centers in pons, midbrain, or thalamencephalon connect probably
with motor paths through which co-ordinated reflex movements
may be effected. But whether or not any perceptible degree of con-
sciousness can be mediated through these lower centers remains
undetermined. Goltz's dog without its cerebrum could be awak-
ened from sleep by loud noises, and Schafer contends that in
monkeys the removal of both temporal lobes is "notf followed by

* Flechsig, "Localisation der geistigen %r£Qj^%\\Jz\pftgHs96fO T/) •

202 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

complete deafness. As in the case of vision, questions of this kind
will eventually find their most satisfactory answer from the study
of the results of pathological lesions in man.

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
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 following 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. 91) : After
entering the olfactory lobe the fibers terminate in certain globular
bodies, the glomeruli olfactorii (B), whose diameter varies from 0.1 to
0.3 mm. Here connections are made by contact with the dendrites
* See Barker, "The Nervous System," 1899, for references to literature.

SENSE AREAS AND ASSOCIATION AREAS.

203

of nerve cells of the olfactory lobe, the mitral and brush cells (C).
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
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,

Fig. 91. — Diagram of the central course of the olfactory fibers: /, Olfactory bulb;
//, olfactory tract; ///, cortex of the hippocampal lobe (gyrus 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 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.

* Van Gehuchten, "Le Nevraxe," 6, 191, 1904.

204 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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
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.

SENSE AREAS AND ASSOCIATION AREAS. 205

(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,
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 (£, Fig. 92.) Moreover, autopsies have
shown that in right-handed persons this center is placed or is func-
tional usually in the left cerebral 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 express 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

* Exner, "Hermann's Handbuch der Physiologie," vol. iii, part n, p. 342.
Consult for older literature.

206

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

the case of complete lesion of the center on one side, that of the
other can be taught to assume its function. Some recorded cases
seem to indicate that this substitution is possible in the young,
while in the old it is more difficult or impossible. 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 some aphasics exhibit the symptom
of loss of power to write, — a condition designated as agraphia.
The area in which the motor associations for the act of writing

are located is 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. 92).

Sensory Aphasia. —
In sensory aphasia *
(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. 92),
while loss of power to understand written or printed language, word-
blindness, is traced to lesions involving the inferior parietal con-
volution, the gyrus angularis, contiguous to the occipital visual
center (V, Fig. 92). These two conditions may occur together,
but cases are recorded in which they existed independently. It

* Consult Starr, "Aphasia," "Transactions of the Congress of American
Physicians and Surgeons," vol. i, p. 329, 1888.

H

Fig. 92. — 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. 207

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
modern 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 conceive that the varying gifts of individuals, in the
matter of the use of language, rest partly on the amount of train-
ing received 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, "Gehirnund Seele," Leipzig, 1896; also, "Archives de neurol-
ogie," vol. ii, 1900.

208 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 with 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 machinery 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. 209

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. 95), 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 fueling 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. 95, and a temporal area, 36, Fig. 95. 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.
14

210 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.

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. 93 and 94, 2 (26, £°),
5, 6, 7 (7b), 8, 15. Two areas connected with the olfactory sense
are not shown in these figures; they appear in the anterior perforate
lamina on the base of the brain and the uncinate gyrus. Later
there is developed around these primary projections areas what
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.
95 and 96. 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 2b, and 14, ub with 7. Later still
the great association areas — 34, 35, 36, Figs. 95 and 96 — acquire
their myelinated fibers. These latter centers, as indicated above, may
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:

* 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.

211

■0m

, .

+.: &

Fig. 93.— Lateral surface of the brain, showing the primordial areas, both sensory and
automatic, in dotted zones. — (Flechsig.)

■>**$

ftMfc

#

10

Fig. 94.— Same zones on the mesial surface of the brain.— (Flechsig).

212

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

M

■M ■ ■ ■ • • ;

§H j jj -^

/ Jo

* - .Wr , .....*■ ' , :• ' *?•>

F*V: ' / •

Fig. 95. — Lateral surfaces of the brain, showing the primordial and marginal zones.

— (Flechsig.)

T

36

Fig. 96. — Same areas on the mesial surface. — (Flechsig.)

SENSE AREAS AND ASSOCIATION AREAS.

213

I. Primary areas.

la. Primary projection areas (1, S, 4, 5, 6, 7, 8 (15), seven or
eight in number, and provided with projection fibers —
sensory and motor.
lb. 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.
II6, Terminal or central areas, 34, 35, 36, provided with long
association fibers.

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

Fig. 97. — Diagram to show the composition of the corpus callosum as a system of com-
missural fibers, without projection fibers. — (Cajal.)

iu suuw me uumposinun ui uie ci

missural fibers, without projection

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
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

214 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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. 97). 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,
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 muscules 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

SENSE AREAS AND ASSOCIATION AREAS. 215

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. 98.
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

216

CEREBELLUM, PONS, AND MEDULLA.

217

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 (b) 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. 98. — 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

218 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

medullary substance of the vermiform lobe (nucleus fastigii, n. glo-
bosi, and the n. embolif ormis) . The axons of many 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. Connection with the Afferent Paths of the Cord. — The ascending
fibers in the posterior columns are connected, through the nuclei of
Goll and Burdach, with the cerebellum, the fibers passing by way
of the inferior peduncles (restiform bodies). So also the fibers of
the tracts of Flechsig and Gowers terminate eventually in the cere-
bellum, as explained on p. 164. Whatever else may be their func-
tions, the fibers of these tracts undoubtedly convey impulses of
the muscle sense, and we have, therefore, the important fact that
these fibers (as a system) terminate in part in the cerebellum and
in part, by way of the median fillet, in the cerebrum.

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 (lateral or Deiters's,
median and superior) and these in turn are connected by fibers,
running probably in both directions, with the cortex of the cere-
bellum and with its subcortical nuclei. This connection is most
important physiologically, as it would seem to make the cerebellum
a center for impulses arising in these parts of the internal ear. As
we shall see, ablation of the cerebellum and destruction of the semi-
circular canals give very similar results upon animals.

3. Connections with the Cortex of the Cerebrum. — A large system of
fibers — cerebro-ponto-cerebellar system (see Fig. 77, A) — makes a
connection between the cortex cerebri and cortex cerebelli. They
emerge from the cerebellum by way of the middle peduncles, cross
the mid-line, and end in gray matter (pontal nuclei) in the pons;
thence their course is continued by new neurons, which pass for-
ward in the crus cerebri and internal capsule to make connections
with the cortex of the frontal lobe. The connection is, therefore,
a crossed one, the right cerebrum being associated with the left
cerebellar hemisphere. This system of fibers furnishes a mechan-
ism by which the cerebellar activity may be associated with and
influence the activity of the motor areas of the cerebrum.

4. Connections with the Midbrain and Cord. — The fibers of the

CEREBELLUM, PONS, AND MEDULLA. 219

superior peduncles end in the red nucleus of the midbrain on the
opposite side. Thence there may be connections forward with
the thalamus and cerebrum; but, what is more significant, con-
nections are thus made with the rubrospinal tract (Monakow's
bundle), see p. 169, which descends into the cord and connects
with the motor nerves. By this connection a relation may be es-
tablished between the cerebellum and the motor nerves of the body.
The path is doubly crossed, so that each cerebellar hemisphere is
connected with the muscles of its own side. Still another motor
path to the cord is made possible through the connections of the
vestibular nucleus. These latter, as stated on p. 170, are connected
through the vestibulospinal tract with the cells in the anterior
horn. Some authors have described a special motor tract from
cerebellum to cord, either direct or by way of the olivary bodies ; but
our knowledge of this path is too uncertain as yet to form a positive
basis for physiological conclusions.

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 rhomme," 5, 418, 1862.

220 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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. f Some of the details of the work of the latter
observer are given below.

Experimental Work Upon 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 at all, 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. Physiologie," 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 Physiologie," vol. iii, part n, p. 259, 1904.

CEREBELLUM, PONS, AND MEDULLA. 221

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 were 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

222 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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

CEREBELLUM, PONS, AND MEDULLA. 223

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

224 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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. Physiologie," 1903, 129; see also Kohnstamm,
"Archiv f. d. gesammte Physiologie," 89, 240, 1902.

CEREBELLUM, PONS, AND MEDULLA. 225

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 affect
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.
15

226 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

/.,,. nections havabepn determined by physiological experiments, but
^^OqI ^^j^^^^^Deen possible to mark out histologically the exact
^ giuupuof*Ge1ls 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 palpebral . 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

*#2EL£M

Fig. 99. — Nuclei of origin of motor and primary terminal sensory nuclei of cerebral
nerves (Held) : Schematically represented 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, the semilunar 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 ala? cinereaa, 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.

227

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. Some of
the fibers, particularly those from the lateral nucleus to the infe-
rior rectus, the internal rectus, and the inferior oblique, cross
the mid-line and emerge in the nerve of the opposite side.

The Fourth Qranial 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 cms
cerebri to reach the base of the brain. It is a motor nerve, and

Nucleus of com.

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.)

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
minor, and a large sensory root, portio major. It is, therefore, a
mixed motor and sensory nerve, supplying motor fibers to the
muscles of mastication and sensory fibers of pressure, pain, and
temperature to the face, the forepart of the scalp, the eye, nose,

228

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

portions of the ear, mouth, and tongue, and to the dura
mater (Fig. 101). In the interior of the brain the motor portion,

Fig. 101. — Diagram showing the average area of distribution of the sensory fibers of the
trigeminal nerve. — (Cushing.)

N. opht.

Accessory

motor

nucleus.

N. max. sup.

N. max. inf.

Fig. 102. — Nuclei of origin of the fifth cranial nerve. — (From Poirier and Charpy, after

Van Gehuchten.)

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

CEREBELLUM, PONS, AND MEDULLA. 229

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. intermedins 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.

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

230 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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, sphenopalatine, 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.

fSchafer's "Text-book of Physiology," 1900, vol. ii ; " Ergebnisse der
Physiologie," 1903, vol. ii, part n, p. 823 ; also " Brain," 1903, vol. xxvi.

231

232

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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 in the central nervous system
the axon of which emerges in one of the spinal
or cranial nerves and ends around the dendrites
of a sympathetic cell; and one, the axon from
the sympathetic cell which passes to the periph-
eral tissue. The first axon is spoken of as the
preganglionic fiber, the second as the post-
ganglionic fiber. Their connections are repre-
sented 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

oeuiolL

* fore.

■nwsele.

t

Fig. 103. — Schema to show the general relation between
:_ fit

the preganglionic and postganglionic
paths.

ibers of the autonomic

Fig. 104.— Illus-
trating the central ori-
gin of the autonomic
fibers.— (Langley.)

SYMPATHETIC NERVOUS SYSTEM. 233

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 ju to 4 p.. 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 connec-
tions with the sympathetic cells. So far, the course of these
fibers has been traced most successfully in the case of those sup-
plying 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.

234 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

experiments show that the white rami consist of preganglionic
fibers that arise from nerve cells in the spinal column, 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 nerves 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,

SYMPATHETIC NERVOUS SYSTEM.

235

tenth, and eleventh cranial nerves
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 portion ends have
not been definitely isolated,

Those that emerge in the third

Fig. 105. — Diagram giving a schematic
representation of the course of the autonomic
(sympathetic) fibers arising from the thoraci co-
lumbar and sacral regions of the cord. The
preganglionic fiber is represented in red, the
postganglionic 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.

236 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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 part of these fibers
ends 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-

SYMPATHETIC NERVOUS SYSTEM. 237

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.

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:

238

THE PHYSIOLOGY OF SLEEP. 239

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 dryness
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. Kohlschiitter * 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.

240

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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-

STRENGTH OF STIMULUS

800
700

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200
100

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HOURS 0,5 W L5 2.0 2.5 3.0 3.5 4.0 45 5.0 5.5 6.0 65 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 person. 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. — (Kohlschutter.)

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. Biologie," 19, 1, 1883.

THE PHYSIOLOGY OF SLEEP.

241

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Fig. 107. — Curve of intensity of sleep according to Mdnninghoff and Piesbergen. The
figures along the abscissa represent time in hours from the beginning of sleep ; those along
the ordinate the relative intensity of sleep measured in milligram-millimeters, expressing
the intensity of sound of a falling body necessary to awaken the sleeper.

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Fig. 108. — Curve of intensity of sleep in a child of three years and eight months, as deter-
mined by Czerny.

16

242 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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 Howell 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 pressuer
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, w7hile 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-
son, "Dissertation," Dorpat, 1891.

t Tarchanoff, "Archives italiennes de biologie," 21, 318, 1894.

J Brush and Fayerweather, "American Journal of Physiology," 5, 199,
1901.

§ Mosso, "Ueber den Kreislauf des Blutes im menschlichen Gehirn," 1881.

il Howell, loc. cit.

THE PHYSIOLOGY OF SLEEP.

243

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- c
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, g
quoted above, we assume that the §
blood-flow in the brain stands in a |
reciprocal relation to that in the arm, g
this curve may be taken to indicate 3
that before and after the onset of sleep 2,
the blood-flow through the brain di- g
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 sensorv stimuli of various kinds =r

J CD

affect a sleeping individual without g-

entirely awaking him is shown by the |

movements that may be caused in this §

way, and also by the nature of the J

dreams which may be provoked. It is «

very interesting to find from plethys- £

mographic observations that all kinds |-

of sensory stimulations from with- g

out and from within are liable to t

affect the circulation of the blood •

during sleep. As shown by the plethys- §

mograph, the volume of the arm dimin- r

ishes more or less in proportion to the ^

intensity of the stimulus, and the g

probable interpretation of this fact is g-

that the sensory stimulus acts reflexly S"

upon the vasomotor center in the ^

medulla and causes through it a con- g

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

244

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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 causation of sleep. Confining ourselves
to the more recent hypotheses that attempt to explain the immediate

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) insufficient 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. Psychiatrie," 29, 224, 1S72-73.

THE PHYSIOLOGY OF SLEEP. 245

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

* Pfliiger, "Archiv f. d. gesammte Physiologie," 10, 468, 1875.
t Duval, " Comptes rendus de la soc. de biol.," February, 1895; and Cajal,
"Archiv f. Anat. (u. Physiol.)/' 375, 1895.

246 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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 accompanied 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.

THE PHYSIOLOGY OF SLEEP. 247

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.

248 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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 method.* 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-
nerve through which the impulses are conveyed to the center and
the cortical center through which the reaction in consciousness
is mediated.

Classification of the Senses. — In general, we attempt to
distinguish the action of the sense organs by the differences in
their end reaction in 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,

249

250 THE SPECIAL SENSES.

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 heretofore 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 recognizable 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 con-
sciousness itself, — a subject which as yet has not been undertaken
by physiology. At present wTe accept the fact of consciousness
and the fact that there are different kinds or qualities of conscious-
ness, and our investigations are directed only toward ascertaining
the anatomical, physical, and chemical properties of the organs in-
volved 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 it 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 external

CLASSIFICATION OF THE SENSES. 251

or rather the exterior senses, or those in which the sensations 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 Muller (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 to a peculiarity of the part of the brain
in which it terminates Muller left an open question, although he
called attention to the fact that the central ending is capable of
giving its specific effect in consciousness independently of the con-

252 THE SPECIAL SENSES.

ducting 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 im-
pulses, 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

CLASSIFICATION OF THE SENSES. 253

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

254

THE SPECIAL SENSES.

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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EXCITATION X.

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.

tion; 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 -3V — 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
Ithe approximate relation between the two variables considered.
jFechner attempted to give this law a more quantitative and ex-
pensive 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

CLASSIFICATION OF THE SENSES. 255

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, in
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, fascia?, 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 sensation.
Although, as was mentioned above, the temperature sensations
under conditions — fever, vascular dilatation, etc. — may be projected
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.

The Punctiform Distribution of the Cutaneous Senses. —
A most interesting fact 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

* Blix, "Zeitschrift f. Biologie," 20, 141, 1884; Donaldson, "Mind," 39
1, 1885. See also Goldscheider, "Archiv f. Physiologie," 1885, suppl. volume.

256

CUTANEOUS AND INTERNAL SENSATIONS.

257

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-

» »

'r *

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.

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
17

258 THE SPECIAL SENSES.

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

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.

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 f 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

* Von Frey, "Konigl. Sachsischen Gesellschaft der Wissenschaften. Math.-
phys. Klasse," 1894-95-96.

t Barker, "Journal of Experimental Medicine," 1, 348, 1896.

CUTANEOUS AND INTERNAL SENSATIONS. 259

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.

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

260 THE SPECIAL SENSES.

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
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 delicate a 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

CUTANEOUS AND INTERNAL SENSATIONS. 261

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-
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 8 to 9 "

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

262 THE SPECIAL SENSES.

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.

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

CUTANEOUS AND INTERNAL SENSATIONS. 263

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
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 pressure
stimuli, the latter acting as a guide or aid in the projection. 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 misref erred to the surface of the body are desig-
nated 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
* Head, "Brain," 16, 1, 1893, and 24, 345, 1901.

264 THE SPECIAL SENSES.

for this misreference 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 misreference 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 produced
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 connection 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 re-
ferred to the symmetrical area on the other side of 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 pro-
jection is made to the area of higher sensibility most closely con-
nected 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. Sherrington! 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

* Bell, "The Nervous System of the Human Body," third edition, Lon-
don, 1844, p. 200.

f Sherrington, "Journal of Physiology," 17, 237, 1894.

CUTANEOUS AND INTERNAL SENSATIONS. 265

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
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 are traced into the
nuclei of Goll and of Burdach in the medulla and thence partly into
the cerebellum and partly into the cerebrum by way of the median
fillet. Within 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 voluntary 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

266 THE SPECIAL SENSES.

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. 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

CUTANEOUS AND INTERNAL SENSATIONS. 267

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
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

268 THE SPECIAL SENSES.

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-
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 " professional 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

CUTANEOUS AND INTERNAL SENSATIONS. 269

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
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.

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
Meckel's ganglion, while those that are contained in the glosso-

270

SENSATIONS OF TASTE AND SMELL.

271

pharyngeal reach the same ganglion through the nerve of Jacobson,
the small superficial petrosal, and the otic ganglion. A recent re-
port by Cushing,* 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. Regard-

^ptftos.swptffitxoli

^eTrosum.X'i

•"S^eus

Fig. 113- — Schema to show the course of the taste fibers from tongue to brain. —
(.Cushing.) 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.

ing 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. Cushing 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-

* Cushing, " Bulletin of the Johns Hopkins Hospital," 14, 71, 1903. Gives
also the surgical literature.

272

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
papillae, in some of the fungiform papillae, and in other 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 sensibility. 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: s, gustatory cell; r, sustentacular
cell ; m, leucocyte containing granules ; e, super-
ficial epithelial cells; n, nerve fibers.

SENSATIONS OF TASTE AND SMELL. 273

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 papillae
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 papillae thus examined, 27 gave no reaction at all, although
sensitive to pressure and temperature. In the 98 papillae 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

* Oehrwall, " Skandinavisches Archiv f. Physiologie," 2, 1, 1890.

18

?/,. 274 \~^J^ THE SPECIAL SENSES.

ers, 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 Oehrwall's 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 s 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

{CO
oX ^/ NH.
S02/

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
separate 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 SMEL^^^y. ^ 275

excite the same taste. Thus, sugar, saccharin, and BUgte^BtjEgfa v ^
(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° CL
gives the optunum 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. H20 — 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

276

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 turbinate bone. 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
'h hWr- 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.
202). 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. 115. — Cells of the olfactory region (after
v. Brunn) : a, a, Olfactory cells ; 6, b, epithelial
cells; n, n, central process prolonged as an olfac-
tory nerve fibril; I, I, nucleus; c, knob-like clear
termination of peripheral process; h, h, bunch of
olfactory hairs.

SENSATIONS OF TASTE AND SMELL. 277

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. Haycraftf 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-
delejeff, 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 Physiologie des Geruchs," Leipzig, 1895.
fHaycraft, "Brain," 1888, p. 166.

278 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 testing 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 setherei or ethereal odors, such as are given by the fruits, and
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. 279

tions 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.
It is said that certain classes of odors do not exhibit this property,
— the aromatic odors, for example, such as are caused by the cam-
phor group.

* Shields, " Journal of Experimental Medicine," 1, 1896.

280 THE SPECIAL SENSES.

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
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 ^ -^fa -^-^ of a milli-
gram in 1 liter of air or tbto" W7ro"o" °^ 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

SENSATIONS OF TASTE AND SMELL. 281

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-
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 overgratifi cation 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, where they arouse 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 physiological mechanisms for its
regulation ; and secondly we may study the properties of the retina
in relation to its reactions to light and the visual sensations them-
selves, 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
its 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 semitransparent, 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 gives the simplest explanation
of the refractive processes in the eye. To understand the formation
of an image by a biconvex lens the following physical facts must be

282

DIOPTRICS OF THE EYE.

283

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 distance.
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 theoretically by a
source of light at an infinite distance in front of the lens. Practi-
cally any luminous object not nearer than twenty feet gives parallel
rays. On the other hand, if a luminous object is placed at F the rays

Fig. 117. — Diagrams to illustrate the refraction of light by r. convex lens: a., Refrac-
tion of parallel rays; b., refraction of divergent rays; c, refraction of divergent rays from
a luminous point nearer than the principal focal distance.

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 nearer than about twenty feet, 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 points within the limits specified will have their cor-
responding conjugate foci, at which their images will be formed by

2S4

THE SPECIAL SENSES.

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
divergent 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 a.n s. 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 -h and A-c. One of these rays will be parallel, A-p, 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 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

DIOPTRICS OF THE EYE. 285

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 determine 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 b 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 -- + \ = j, in which / represents the principal focal dis-
tance and p and p1, 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

sine r
refraction.

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

286 THE SPECIAL SENSES.

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

Fig. 119.— Diagram to illustrate the surfaces as the eye is Concerned, it
in the eye at which the rays of light are chiefly . , , , , , , .

refracted. 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 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, c', lies in
the crystalline lens at n, a
distance of 7.3 mms. from
the anterior surface of the

. Fig. 120. — Diagram to illustrate the reduced

COmea. The principal focal or schematic eye with a single refracting surface

.. . \ . \. L. separating two media of different densities: c',

distance IOr thlS retracting the ideal refracting surface situated 2.1 mms.

e ,. ... . f. behind the anterior surface of real cornea: n,

Surface lies at a distance 01 the nodal point, or center of curvature of the

OO Q mmc l™l^r^ +V.« on+^ surface c', and 15.5 mms. in front of retina.

ll.?S mms. Denma tUe ante- The eyeball is supposed to be filled with a uni-

r\nv ciirfapp nf tViA onmvn rtr form substance having a refractive index of 1.33,

noi sunace or tne cornea or equal to that of the Yitieoua humor.
(22.8 — 7.3) at a distance of

15.5 mms. behind the nodal point. In the eye at rest this principal
focal distance coincides with the retina, since the refracting surfaces
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

DIOPTRICS OF THE EYE. 287

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 b. 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. m— Diagram to illustrate the construc-

t ,, , 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
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

288 THE SPECIAL SENSES.

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 +1 . .

— — = : that is

a-b a-n

Size of object Distance of object from nodal point.

Size of image " " 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
and substitute the known values for the other terms of the equation,

we have = -=■=-. or x = 0.341 mm., which is about the diame-

x 15 7 ;

ter of the fovea centralis. The retinal image of the object in

DIOPTRICS OF THE EYE. 289

this case would be, in round numbers, about nnrVini- °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 Donders.)

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
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
19

290 THE SPECIAL SENSES.

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-
flected from the observed eye : 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 re-
flecting 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

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.)

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 practi-
cally the same, but the middle image (6) becomes smaller and ap-
proaches nearer to the first (a). This result can only mean that in
the act of accommodation the anterior surface of the lens becomes
more convex. In this way its refractive power is increased and the
more divergent rays from the near object are focused on the retina.
Helmholtz 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
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

* Helmholtz, "Handbuch der phvsiologischen Optik," second edition,
1896.

DIOPTRICS OF THE EYE. 291

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

Pigment-free Ciliary Border
epithelium. process, of iris. Ciliary muscle.

Lens.

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
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 by
Helmholtz.

* See Tscherning, "Optique physiologique," Paris, 1898; and Schoen,
"Archiv f. die gesammte Physiologie," 59, 427, 1895.

292 THE SPECIAL SENSES.

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 it is said that its determination may be used to estimate the
age of the individual. Figures of this kind are given:

Age.

10

20

30

40

50

60

Near

Point.

7 cm.

or 2.76 in

10 "

" 3.94 "

14 "

" 5.61 "

22 "

" 8.66 "

40 "

" 15.75 "

100 "

" 39.37 "

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-
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

DIOPTRICS OF THE EYE. 293

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 fi (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 Surfaces in the Eye. — 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 reciprocal of their principal focal dis-
tance measured in meters; thus; a lens with a principal focal dis-
tance of yV meter is a lens of 10 diopters, 10 D., and one with a focal
distance of 10 meters is TV diopter (0.1 D.). The posterior prin-
cipal focal distance of the combination of refractive surfaces in the
eye is 22.7 mms. or ||^ meters. The reciprocal of this length of focus,
~y or 44.05 D., expresses the refractive power of the eye under the
normal conditions in which the rays are refracted into the dense
vitreous humor. As compared with a lens in air, the refractive
power of the eye would be expressed by multiplying this figure by
the index of refraction of the vitreous humor, 44.05 X 1.3665 = 58.8
D., the figure usually given to express the total refractive power.
The refractive power of the crystalline lens alone is 16 D.; that of
the cornea, 43 D. ; hence the latter surface has about two and one-
half times the refractive power of the lens. Removal of the lens,
therefore, as in cataract operations, does not lessen the refractive
power of the eye so much as when the action of the cornea is de-
stroyed, as happens in part when the head is immersed in water.

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-

294 THE SPECIAL SENSES.

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
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.

DIOPTRICS OF THE EYE. 295

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 emmetropic. 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 troubles of the eye are due
to short-sightedness or myopia, far-sightedness or hyperme-
tropia, astigmatism, old-sightedness or presbyopia, and lack of
balance in the external muscles of the eyeballs, muscular inefficiency
or heterophoria. Some description of these conditions is useful to
emphasize by contrast the mode of action of the dioptric mechanism
in the normal eye, but for a full description of the extent and com-
plexity 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
curvature of the refractive surfaces, the cornea or the lens, or to an
abnormal length of the eyeball in its anteroposterior diameter.
The last cause is the most 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 emmetropic 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

296

THE SPECIAL SENSES.

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 of a distant
object will make upon the
retina, when the eye is
not accommodated, a dif-
fusion 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 ref-
erable to a diminution in
the anteroposterior diam-
eter of the eyeball. This
condition is usually con-
genital: the eyeball from
birth is smaller than the
normal. The path of the
parallel rays in this case
is represented in the dia-
gram C, Fig. 125. When
such an eye looks at a dis-
tant object a clear image
may be obtained only by
using the ciliary muscle,
and to prevent this constant strain upon the muscle of accommo-
dation 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 constant aid of accommodation. It is obvious that in
the hypermetropic eye there is no far point of 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 be-
gins when the rays are parallel and its limits are reached with
a less degree of divergence; hence the name of far-sightedness.

Fig. 125. — Diagram showing the difference be-
tween normal (;1), 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.)

DIOPTRICS OF THE EYE. 297

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 loss of
elasticity 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 myopic
than in the emmetropic eye, since in the former the greater length
of the eyeball needs 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 auyfxa,
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 (r,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-ar). 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

298

THE SPECIAL SENSES.

a way that the meridians of greatest and least curvature are at
right angles to each other. Ordinary astigmatism 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 normally
this meridian is slightly more curved than the horizontal one. If,
on the contrary, the curvature along the horizontal meridian is
greater, the astigmatism is " against the rule." The meridians
of greatest and least curvature 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

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 of
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.

glasses so chosen as to increase the curvature along the meridian
in which the cornea has the least curvature. An eye that suffers from
a marked degree of astigmatism can not focus distinctly at the same
time lines that are at right angles to each other; hence the use of
a series of lines whose rays fall along the different meridians of the
cornea, 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

DIOPTRICS OF THE EYE.

299

^^

curvature are not at approximately right angles, or, as is more
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
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 pupillse 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

Fig. 127. — Astigmatic chart.

300

THE SPECIAL SENSES.

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
pupil lae 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 ciliary gan-
glion, whence the path
is continued by sympa-
thetic ( postganglionic )
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

Course of constrictor nerve fibers,

Course of dilator nerve fibers,

Fig. 128. — Diagrammatic representation of the
nerves governing the pupil (after Foster) : II, Optic
nerve; l.g, ciliary ganglion; r.b, its short root from
///, motor oculi nerve; sym., its sympathetic root; rl,
its long root from V, ophthalmonasal branch of oph-
thalmic division of fifth nerve; s.c, short ciliary
nerves; l.c, long ciliary nerves.

* 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.

DIOPTRICS OF THE EYE.

301

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
Oangllon..

Superior Cervical.

pnq ciiiaru nerves.

fianqlii

Dilator
jDupillae.

tyhitieter
/oupillae.

yhinal
Cord.

CihuyGaytiau Jhorf CdiapyTwvtt^ 0f Ca//T0/v^

iewical ( jsSSS^ — ^T /x HCD.^V

Fig. 129. — Schema showing the path of the preganglionic and postgaiignuiim mrers
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 spina] 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 pupillae 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

A

302 THE SPECIAL SENSES.

is rather what isjmown as an associated movement. The voluntary
ejffpijt inattgyi*^ted in the brain affects the cranial centers for both
"" rl'iuyi'les,' 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 respiratory center being accompanied by an associated
effect upon the cardio-inhibitory 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

(

DIOPTRICS OF THE EYE. V fi 303

is stimulated.* We may conclude, therefore, that thebHo^ilii^ tJpaftt
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 studenf 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 Physiologie," 47, 313, 1890.
fSee Abelsdorff and Feilchenfell, "Zeitschrift f. Psychologie und Phys-
iologie des Sinnesorgane," 34, 111, 1904.

% Schultz, "Archiv f. Physiologie," 1898, 47.

304 THE SPECIAL SENSES.

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 resuit 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.

DIOPTRICS OF THE EYE.

305

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 hard]y 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.

The Ophthalmoscope. — The light that falls into the eye is
partly absorbed by the black pig-
ment of the choroid coat and is
partly reflected back to the ex-
terior. This latter portion is re-
flected back in the direction in
which it entered. Merely holding
a light near the eye does not, there-
fore, enable 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 arrange the light to enter
the observed eye as though it pro-
ceeded from our own eye, then the
returning rays would be perceived,
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 enables the observer to
examine the interior of the eye and
thus recognize diseased conditions of
the retina ; it is also useful in detect-
ing abnormalities in the refractive

surfaces of the eye. The principle of the instrument is well repre-
sented in the original form devised by Helmholtz, as shown schemat-
ically in Fig. 131, A . I represents the observed eye and 77 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 I, and these rays on emerging
from the eye along the same line pass through the glass in part and
enter eve 77. In place of the plane unsilvered glass it is now cus-
"20

Loring's ophthalmoscope.

306

THE SPECIAL SENSES.

tomary to use a concave mirror with a small hole through the center,
the observer's eye being placed directly behind this hole. Such an
instrument is shown in Fig. 130. The instrument 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

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, II. 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, b. At a', &', c', 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.

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 / is an emmetropic eye these
points are at the principal focal distance 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 observer's

DIOPTRICS OF THE EYE. 307

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 accom-
modation. He must, in fact, in looking through the mirror gaze,
not at the eye before him, but, relaxing 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 principal focus of its refracting surfaces; consequently
the rays sent out from the illuminated retina emerge in converging
bundles and can not 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 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 ob-
server unless he exerts his own power of accommodation or inter-
poses 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 observed eye, /, 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 in the eye, whence they again diverge and light up
the retina with a diffuse illumination. The light from 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 a will be
brought to a focus at a' and from c at c'. 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 repre-
sented 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 /. The indirect method is the one usually employed in
ophthalmoscopic examinations of the retina. It gives a larger
field than the direct method, although the objects seen are of
smaller size.

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 xrrlinnr 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 -nHnFihns" mm- ano^
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. 132. — 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

308

PROPERTIES OF THE RETINA. 309

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. 132.
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.

310 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,| and the facts were afterward carefully
investigated by Kuhne.t 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. Physiologie," 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. 311

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. 133) . 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 133_ Optogram in eye of rabbit: 1, The nor-
Can be little doubt ma^ 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
plays 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,

312 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. 134. The shape
of the visual fields in the normal eye is represented in Fig. 135.
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. 313

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. 134. — Perimeter. The semicircular bar may be placed in any meridian. A
given object 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

314

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 centra] 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

Fig. 135.

-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. 193); 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. 315

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. Central vision is sometimes designated
erroneously as macular vision instead of foveal vision.

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
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
given are for ordinary room light. Out of doors, and especially in
the case of persons who live habitually an outdoor life, the physio-

* Fritsch, " Sitzungsberichte d. konig. Akad. d. Wiss.," Berlin, 1900.
t Guillery, "Zeitschrift f. Psychologie u. Physiol, d. Sinnesorgane," 12,
243, 1896.

316

THE SPECIAL SENSES.

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

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Fig. 136. — 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
0.035 mm.; that is, it has a diameter ten times as large as in the

PROPERTIES OF THE RETINA. 317

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
close 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
can 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 y%V

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

318 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 b^y 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 q- 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 as
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. The change is known as an adaptation, and in this respect
the retina differs from the sensitive photographic plate. When the
eye, for instance, is kept in the dark, the sensitiveness in the periph-
eral field increases during an hour or so, while that of the foveal field
is apparently unchanged. With such a dark-adapted eye, there-
fore, there will be a certain dim light which will be seen by the
peripheral parts of the retina, but perhaps will cause no reaction
upon the fovea. For such a degree of light, therefoi^, 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
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. 136 shows that in the dark-adapted eye

PROPERTIES OF THE RETINA. 319

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, night 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. 137. 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 " Purkirije phenomenon," — namely, the
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

* Von Kries, "Zeitschrift f. Psychologie u. Physiologie d. Sinnesorgane,"
9, 81, 1895.

320

THE SPECIAL SENSES.

all. Just as in late twilight it may be noticed that the sky remains
distinctly blue after the colors of the landscape become indis-
tinguishable. 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-
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illumination it shifts to the green (535). — (Konia.)

the spectrum, red and blue, and the colors obtained by fusion of
the spectral colors with white or with black, such, for instance, as
the olives and browns.

The Achromatic Scries. 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 dm4 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

PROPERTIES OF THE RETINA. 321

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
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 Fvsion. — By color fusion we mean the combination of two

* Gotch, "Journal of Physiology," 29, 388, 1903.
21

322 THE SPECIAL SENSES.

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 and the Complementary Colors. — By the
methods of color fusion it can be shown that three colors may be
selected from the spectrum whose combinations in different propor-
tions 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-
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-

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PROPERTIES OF THE RETINA. 323

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
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. 138). White becomes black, red a bluish green, and vice versa.
Negative after images are produced very easily by fixing the eyes

324 THE SPECIAL SENSES.

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. 138 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. 140A , 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. 1405. Each circle appears darker on its outer edge
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 yellow candle-light, will appear
* Rood, "Modern Chromatics," "International Scientific Series."

PROPERTIES OF THE RETINA.

325

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. 139. 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-
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

Fig. 1404. — Black and white disc for ex-
periment on contrast. — {Rood.)

Fig. 140S. — Showing the result when the
disc A is set into rapid rotation. — (Rood.)

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
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

* 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.

326 THE SPECIAL SENSES.

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 lmholtz theory of color vision, the
red-blind, the green-blind, and the violet-blind. The most com-
mon by far of these groups is that of so-called red blindness; 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, however, 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 describe some
of their after-images as red, the after-image of indigo-blue, for ex-
ample, but that they describe none as green. The after-image of
purple, for instance, which to the normal eye is bright green, is de-
scribed 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 individ-
ual differences. The green-blind are also, according to recent des-
criptions, 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 resembling the latter in general features, they
differ obviously in some details. Violet blindness, so called, seems

PROPERTIES OF THE RETINA. 327

to be so rare as a congenital and permanent condition that no
exact study of it has been made. 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* 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 nor 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. f A number of skeins of wool are used
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

*Siven and Wendt, "Skandinavisches Archiv f. Physiologie," 14, 196, 1903.
t For details see the works of Holmgren and of Jeffries, already quoted.
t Grunert, "Archiv fur Ophthalmologic," 56, 132, 1903.

328

THE SPECIAL SENSES.

only achromatic vision. The external world appears to them only
in 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 assumed
that this condition represents 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

°Sl 081 oU

Fig. 141. — 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).

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. 313). It will be found to vary with each individual,
so much so that it is possible that a test of this character might be

PROPERTIES OF THE RETINA.

329

used for the identification of individuals. Exceptionally it is found
that the entire retina possesses a nearly normal color sense. Usu-
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. 141. 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

*' ON 'W OH u)V

Fig. 142. — 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 or 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.

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. 142).

* Baird, "The Color Sensitivity of the Peripheral Retina," Carnegie
Publication No. 29, 1905.

330

THE SPECIAL SENSES.

Functions of the Rods and Cones. — Many facts unite in mak-
ing it probable that the rods and cones are different in function.
They differ in structure and especially in their connections. As is
shown in the diagram given in Fig. 143, the cones terminate in the
external nuclear layer in arborizations which connect with the

Fig. 143.— Schema of the structure of the human retina (Greeff) : I, Pigment layer;
II, rod and cone layer; ///, outer nuclear layer; IV, external plexiform layer; V, layer
of horizontal cells; VI, layer of bipolar cells (inner nuclear); VII, layer of amacrinal cells
(without axons); VIII, inner plexiform layer; IX, ganglion cell layer; X, nerve fiber
layer; 6, fiber of Miiller.

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

PROPERTIES OF THE RETINA. 331

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
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
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.

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:

/. The Young-Helmholtz Theory. — This theory, proposed essen-
tially by Thomas Young (1807) and afterward modified and ex-
panded by Helmholtz,t 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.

*Von Kries, "Zeitschrift f. Psychologie u. Physiol, d. Sinnesorgane,"
9, 81, 1895.

f Helmholtz, "Handbuch der physiologischen Optik," second edition,
1896, 1, 344.

332

THE SPECIAL SENSES.

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

Fig. 144. — 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.

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. 144. The figure
also indicates that it is impossible to stimulate any one of these sub-
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

PROPERTIES OF THE RETINA. 333

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
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.

77. Hering's Theory of Color Vision. — This theory also assumes
the existence in the retina of three photochemical substances, but
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. Retinal Process. Sensation.

P _. f Disassimilation = red

Keel-green <j Assimilation = green

„ ,. . . f Disassimilation = yellow

Yellow-blue { Assimilation - blue

,Tri ., , . , f Disassimilation = white

White-black . | Assimiiation = black

* For discussion of color theories see Calkins, "Archiv f. Physiologie,"
1902, suppl. volume, p. 244.

334

THE SPECIAL SENSES.

It will be observed that the theory gives an independent ob-
jective cause for the sensations of white, black, and yellow, and in
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
this theory, that only the white-black substance is present, while
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, and there

Fig. 145. — 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 b gives the conditions for the yellow-blue substance.

remains over only the disassimilatory effect on the white substance
which is exerted by all the visible rays. The effect of the various
visible rays of the spectrum on the three photochemical substances
is illustrated by the chart given in Fig. 145. Ordinates above the
abscissa representing disassimilatory effects; those below, assimi-
latory.

777. The Franklin Theory of Color Vision (Molecular Dissocia-
tion Theory). — This theory, proposed by Mrs. C. L. Franklin,* takes
into account 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

* Franklin, "Zeitschrift f. Psychologie und Phys. d. Sinnesorgane," 1892,
iv; also "Mind," 2, 473, 1893, and " Psychological Review," 1894, 1896, 1899.

PROPERTIES OF THE RETINA.

335

w

V

,'"

r

B

color blind. It assumes that the colorless sensations — white,
gra}r, black — are occasioned by the reactions of a photochemical
material which for convenience may be designated as the gray sub-
stance. This substance in the normal eye exists in both rods
and cones ; in the latter, however, in a differentiated condition ca-
pable of giving color sensations. When the molecules of this sub-
stance are completely disso-
ciated by the action of light,
gray 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 under-
gone 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 supposed to have
taken place in two stages:
first, the formation of two
groupings within the mole-
cule one of which is dissoci-
ated by the slower waves
and gives a sensation of yel-
low, and one of which is dis-
sociated by the more rapid
waves and gives the sensa-
tion of blue. This stage re-
mains 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 spec-
trum, 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

Fig. 146. — 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 in 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.

336 THE SPECIAL SENSES.

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. 146. 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 kind
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. — LTnder 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
the retinal images into consciousness. Some of these entoptic 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

* Helmholtz, "Handbuch der phvsiologischen Optik," second edition,.
I, 184.

PROPERTIES OF THE RETINA. .

337

a

-A

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
corresponding eye. If the eye is directed 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 magnified in proportion
to the distance of projection; the picture makes the impression of a
thicket of interlacing 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 shadows are thrown
upon a portion of the ret-
ina not usually affected
and for that reason per-
haps 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. 147. 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.
22

Fig. 147. — 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.

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 emmetropic 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 No. 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

338

BINOCULAR VISION. 339

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
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 move-
ment directly upward (rotation around the horizontal axis) the su-
perior rectus and inferior oblique must act together. For a similar
reason rotation directly downward requires the combined action of
the inferior rectus and superior oblique. 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 oblique, and internal rectus; movements
downward and outward — inferior rectus, superior oblique, and ex-
ternal 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 sec-
ondary 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

%<■-

\

340 \ THE SPECIAL SENSES.

Lced or co-ordinated action of the opposing muscles is neces-
The object of these movements is to bring the point looked
;iEtf 7n the fovea of each eye and thus prevent double vision, diplopia
.^ftpe following paragraphs). This object is attained when the eye-
^ Joalls 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,
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. 148). 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 two retinas are those which when
simultaneously stimulated by the same luminous object give us a

BINOCULAR VISION.

«s

331

single sensation, while non-corresponding points are those
when so stimulated give us two visual sensations. It is evidfcrif}
from our experience, that the fovese form corresponding points\p1f<
areas. When we look at any object we so move our eyes that tl
image of the point observed shall fall upon symmetrical parts of the"
fovea ; 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,

061 081 ouv

Fig. 148. — 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.

<

also, that, in a general way, portions of the retina symmetrically
placed to the right side of the fovese 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

342

THE SPECIAL SENSES.

to point correspondence has not been determined experimentally.
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
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 correspond-
ing 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 forefin-
gers 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,

Fig. 149. — 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 fovea?,— and are seen double, being projected to the plane of A, giving heter-
onymous diplopia. In // the eyes are focused on the nearer point, A, and the farther point,
B, forms images on non-corresponding points and is seen double, — homonymous diplopia,
— the images being projected to the focal plane A.

it will be noticed that when 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 dissociating 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 belongs
to the left eye, and the left-hand one to the right eye. This is easily
demonstrated by closing the eyes alternately and noting which of
the images disappears. The reason for the cross-projection of the

BINOCULAR VISION. 343

images is made apparent by the construction in Fig. 149, /, 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 bf on the left of A and that on the left eye
to b 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. 149, //, 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
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-

344 THE SPECIAL SENSES.

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,
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

BINOCULAR VISION. 345

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,
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 most 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,

* See Le Conte, ''Sight/' vol. 31 of "The International Scientific Series," 1881.

346 THE SPECIAL SENSES.

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 flat 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. They 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 very
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 by reason 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. 150. 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

BINOCULAR VISION.

347

Fig. 150. — 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.

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.
150 and 152). Any optical device that will enable us to throw the
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;

4 " — ; the one that is most frequently

i\ \ / used is the Brewster stereoscope

represented in principle in Fig.
151. Each eye views its corre-
sponding 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
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

151— Dia
principle of the
(Landois) : P and

■am to illustrate the

rewster stereoscope

the prisms, a, b,

and a, 0, the left- and right-eyed pictures,
respectively, b, /3, 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.

348

THE SPECIAL SENSES.

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

eye cuts out, in the same
way, the right-eyed image
and presents in dark outline
the left-eyed image. By
simply reversing the spec-
tacles the right-eyed image
may be thrown upon the
left eye and vice versa.
Under these conditions the
picture for most persons
may be seen in inverted
relief (pseudoscopic vision),
objects in the foreground
receding into the background. This inversion of the relief when
the projection upon the retinas is reversed is a striking indica-
tion of the potency of the normal projection as a factor in our
judgments of solid objects. It will be observed, 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. 152, 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. 324, each picture gives a double image, since it falls on

Fig. 152. — Stereoscopic picture of an octahe-
dral crystal. May be combined stereoscopically
by relaxing the accommodation by the method
of heteronymous diplopia. Hold the object at a
distance of a foot or more and gaze beyond.

BINOCULAR VISION. 349

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,
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. 149). 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. 342). 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

350 THE SPECIAL SENSES.

shown in the case of after-images (see p. 323). 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.
For objects within the limit of accommodation we depend chiefly
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,

Fig. 153. — Muller-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. 153 the lines A and B
are of the same size, but B seems to be distinctly the longer. So
in Fig. 154 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. 155.
If the book is held flat at the level of the chin and six or eight

BINOCULAR VISION.

351

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-

it.

\\

//

//
//
//
//
//
/

\

\

\

N

\

\

\

//
//

\ //

S //

\ /

S \

Fig. 154. — Zollner's lines.

/
//
//

\\

\\ /L

\\ /

W A
\\
W A

\

\

y

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

Fig. 155. — Optical illusion in projection. — (Franklin.)

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,

352 THE SPECIAL SENSES.

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. 156
gives an interesting illustration of the way in which our judg-
ment of solidity may vary with our interpretation of mathe-
matical perspective and shading when these factors are arranged

Fig. 156. — 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.

to give more than one choice. If the figure is looked at steadily
it may assume several different appearances ; two are especially
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
judgment in the matter changes from one interpretation to the
other without any apparent cause.

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. 157. — 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 tympani;
E, Eustachian tube.

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 ampulhe of the semicircular canals. We may consider
first the functions of the ear in respect to the sensations of sound.
23 353

354

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. 157 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. 158).
The walls of the funnel are slightly convex outwardly; so that

Fig. 158. — To show the structure of the
tympanic membrane, looked at from the side
of the meatus (Hensen) : 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.

355

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, when set in motion by an air wave it
shows little or no tendency to continue vibrating after the acting

Fig. 159. — 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-

356

THE SPECIAL SENSES.

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. 159 and 160. 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,
the processus gracilis or processus
Folianus, which projects forward
and is continued by a ligament, the
anterior ligament, through which
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

Fig. 160.— The bones of the
middle ear in natural connections
(Helmholtz) : M , The malleus ; Mcp,
the head; Mc, the neck; Ml, the
processus gracilis; Mm, the manu-
brium; 7c, body of the incus; lb,
short process; 77, long process; S,
the stapes.

EAR AS AN ORGAN FOR SOUND SENSATIONS.

357

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. 161. 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 as
the handle, (see Fig. 161 A). The chain of bones, therefore, acts
like a bent lever whose fulcrum is at a, the power arm being repre-

Fig. 161.— 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. 161 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. The arrows indi-
cate a movement inward of the tympanic
membrane.

sented 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 (one
and one-half times) force. 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.

358 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 Muller, 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. 359

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.

360 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. 162. They
consist of short more or less cylindrical cells (E, 6, 6', 6", Fig. 162),
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. 361

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 for 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

«s> - — : — .:=-

Fig. 162. — 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
ends of the inner hair cells are seen projecting through the openings of the reticulate
membrane. The terminal arborizations of the cochlear nerve fibers end around the
inner and outer hair cells.

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

362 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. 363

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 kymographion. The form of the wave obtained
is represented in Fig. 163. 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. 163. — 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.
164. 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 df, then a form of wave illustrated by D will be

364

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. 164. — 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. 165, 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 (6), 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.

365

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

cO

~b^-

0 ^-^

Fig. 165 — 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 wrave 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

366 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. 157). 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. cit.

EAR AS AN ORGAN FOR SOUND SENSATIONS. 367

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.
162). 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 fJ. in
the basal portion to 220 ft in the middle spiral and to 234 /j. 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-

368 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.

t Kolliker, " Handbuch d. Gewebelehre," sixth edition, vol. iii, pt. n,
p. 958, 1902.

EAR AS AN ORGAN FOR SOUND SENSATIONS.

369

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. 166, 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. 166.— 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 Physiologie," 76, 147, 1899.
24

370 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
that 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. 371

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 c7 and 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 c6 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 Tf 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 Harmonie," 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 each other (Fig. 167).
The horizontal 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 witnin the ampulla lies the
crista acustica containing the hair
cells with which the nerve fibers
communicate, and which, therefore,
are considered as the sense cells of
the organ. The hair cells are cylin-
drical 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 fi. 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.

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*

* Flourens, "Recherches experimentales sur les proprieties et les fonc-
tions du systeme nerveux," second edition, 1842.

372

Fig. 167.

-Diagrammatic hori-
zontal section through the head to il-
lustrate the planes occupied by the
semicircular canals (after Waller) : S,
Superior canal; P, posterior canal;
H, horizontal canal.

SEMICIRCULAR CANALS AND THE VESTIBULE. 373

(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.* 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
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

* 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 Physiologie," article
by Cyon, on "Espace," 1900.

374 THE SPECIAL SENSES.

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 ihco-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
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
* Experiments lasting over two years made by Dr. E. Rosencrantz.

SEMICIRCULAR CANALS AND THE VESTIBULE. 375

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 of 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:

1. The old view, first proposed by Autenrieth (1802), that the
canals or their sense cells are stimulated by sound waves and give

* Lee, "Journal of Physiology/' 15, 328, 1903.

t Gaglio, "Archives ital. de biologie," 31, 377, 1899.

J 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.

376 THE SPECIAL SENSES.

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 at.) 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. 167), 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
movements in the horizontal plane, the hair cells in one responding

SEMICIRCULAR CANALS AND THE VESTIBULE. 377

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 is 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.

378 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
aroused through the semicircular canals ; they are too indistinct to
be recognized and named by an appeal to consciousness, 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 doubtless founded
in part upon these reactions and in part upon the muscle sense,
vision, and tactile sensations. 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 general co-ordination or con-
trol seems to rest normally in the nervous mechanisms of the cere-
bellum and inasmuch as the vestibular nerves make end connections
with the cerebellum, together with the fibers of muscle sense, we
may assume that the cerebellum forms the brain center in which
the semicircular canal impulses exert their influence upon muscular
contractions and muscle tone, — the cerebellum forms the nerve center
for the semicircular canals, or the semicircular canals form a periph-
eral sense organ to 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 muscu-
lature is perhaps the most acceptable view. In regard to the
means by which these nerves are normally stimulated 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 constitute the immediate
cause of their excitation. Granting that changes in position or

SEMICIRCULAR CANALS AND THE VESTIBULE. 379

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.
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

380 THE SPECIAL SENSES.

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 his back or side
and apparently loses its normal means of judging correctly its posi-
tion. In many inver tebrates 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 palaemon, 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-
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.

* 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.

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; the white corpus-
cles 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 by the mass of red corpuscles held

381

382 BLOOD AND LYMPH.

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 415. 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 titration 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 ~} that is the solution contains in each
liter i or ™ of the number of grams represented by the molecular
weight of tartaric acid (C4H606= 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

GENERAL PROPERTIES: THE CORPUSCLES. 383

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. 395) disappears at the point bf 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+ and OH — , or sub-
stances, such as sodium carbonate, which give rise to hydroxyl ions
by reaction with water. In a solution of this latter salt we may
assume that some of the molecules dissociate into the ions Na + ,
Na+ , and C03= , and that the anion, C03= , reacts with the disso-
ciated molecules of water, H+, HO — , giving HC03 — and OH — .

There will be present in the solution, therefore, the following ions, Na+ ,
OH — , and Na+ , HC03 — ; 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 — , can not 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+ to combine with
the OH — , but its own anion will combine with all of the dissociated Na-f- ;
consequently more Na3C03 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 neces-
sary to make use of the methods of physical chemistry. Those who have
employed these methodsf report that blood 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 reac-
tion. In fact, the sodium in the blood behaves substantially as if it were
present as the bicarbonate, NaHC03, — a theoretically acid salt whose dis-
sociation would be represented by the two ions Na+, HC03 — . 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 varia-
tions in the amount of alkali, Na, in combination with weak acids, such as car-
bonate or phosphate. The results represent what has been called the "titra-
tion alkalinity ' of the blood.

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.

f Fraenckel, "Archiv f. d. gesammte Physiologic," 96, 601, 1903; and
Hober, ibid., 99, 572.

384 BLOOD AND LYMPH.

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 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 and the blood plates lightest.

Red Corpuscles. — The red 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 without nuclei;
in the Camelidse they have an elliptical form. Their average diame-
ter in man is given as 7.7 // (1 [i = 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 "hemoglobin." 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.

GENERAL PROPERTIES: THE CORPUSCLES. 385

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 m 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 small amounts of lecithin and cholesterin. The stroma is a
delicate, extensible, colorless substance that gives shape to the
corpuscles; it forms a meshwork 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. The point that remains uncertain
is the condition in which the hemoglobin 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 amor-
phous 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, however, the relations of the hemoglobin within the
corpuscle may be disturbed; so that it escapes and enters into
solution in the plasma. Blood in which this has happened suffers
a change in color, becoming 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.

Hemolysis. — The act of discharging the hemoglobin from the
corpuscles so that it becomes dissolved in the plasma is designated
as hemolysis, and substances that cause this action are spoken of
as hemolytic 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 in the plasma. (2) By add-
ing ether or chloroform. (3) By adding bile or solutions of the bile
25

386 BLOOD AND LYMPH.

salts. (4) By adding amyl-alcohol. (5) By adding the serum
from the blood of certain animals. (6) By adding saponin or
sapotoxin. (7) By the addition of an excess of alkali. (8)
By various toxins found in snake venom or in the serum of other
animals or among the products of bacterial activity (natural
hemolysins) 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 isotonic
with the blood, those whose pressure is lower are designated as
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-

* For a full consideration of osmotic pressure in its relations to physio-
logical processes, see Hamburger, "Osmotischer Druck und Ionenlehre."
Wiesbaden, 1902.

GENERAL PROPERTIES*. THE CORPUSCLES. 387

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 chiorid 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
chiorid. One formula for Ringer's solution is:

Sodium chiorid 0.7 per cent.

Calcium chiorid 0.026 " "

Potassium chiorid 0.03 " "

Hemolysis Caused by the Action of Hemolysins. — 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 tl 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
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
into a guinea pig a little rabbits' blood and repeats the process several
times at intervals of a day or so it will be found that the blood of this
particular guinea pig has now a strong hemolytic action toward the
red corpuscles of rabbits. Moreover, the action is specific, — that is,
the serum is hemolytic only toward the red corpuscles of the species
whose blood was injected into it. The process of producing a specific

* Bordet, "Annales de lTnst. Pasteur," 1895.

388 BLOOD AND LYMPH.

hemolysin by injections is designated usually as immunization, on
account of its essential similarity to the means used to produce a
specific antitoxin by injecting a given toxin, — that is, of rendering
an animal immune. The specific hemolysins produced by immuniza-
tion have been studied 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 conse-
quence of the injection of the foreign blood corpuscles. This sub-
stance has been given different names, but is known most frequently
as the immune body (or amboceptor). It is not destroyed by mod-
erate heating. The immune body is enabled to act upon the cor-
puscles 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 comple-
ments, 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. The results obtained from the study of these bodies are of
extraordinary interest in connection with the subject of acquired
immunity toward various diseases, and also in the evidence they
furnish of the wonderful complexity of the reactions exhibited by
living organisms. For it is found that specific substances, lysins,
capable of destroying special kinds of cells, may be produced by the
injection of spermatozoa, epithelial cells, etc. Any foreign cell in-
troduced into the body seems to call forth the production of an
immune body capable of destroying only that particular kind of cell.
Poisons or toxins produced in this way may be designated in general
as cytotoxins, — that is, cell poisons, — and it is believed that specific
toxins are produced or may be produced for each kind of cell. Im-
munizing with spermatozoa gives rise to a spermotoxin in the blood
of the animal immunized, while injection of red corpuscles causes
the formation of a hemotoxin, or, as it is usually called in this case,
hemolysin. As the chemical nature of this reaction is beyond our
present knowledge, it is designated frequently as the biological reac-
tion of the living substance. 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, destroyed by heating, and one comparable to

* 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,
"Zeitschrift f. allgemeine Physiologie," 1,69, 1902.

GENERAL PROPERTIES: THE CORPUSCLES. 389

the immune body, but in this case designated as the interbody 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 regard 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
hemolytic 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 hemolysis 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 center 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 proteids.
Under the influence of heat, acids, alkalies, etc., it may be broken
up, with the formation of a simple proteid, globin, belonging to the
group of histons (see appendix) and a pigment, hematin. The
globin 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 proteid
body with hematin. It seems, then, that, although the hemochro-
mogen or hematin portion is the essential thing, giving to the mole-

* Schulz, "Zeitschrift f. physiologische Chemie," 24; also Lauraw, ibid.,
26.

390 BLOOD AND LYMPH.

cule of hemoglobin its valuable physiological properties as a respira-
tory pigment, yet in the blood corpuscles this substance is incorpo-
rated into the much larger and more unstable molecule of hemo-
globin, whose behavior toward oxygen is different from that of the
hematin itself, the difference lying mainly in the fact that the hemo-
globin as it exists in the corpuscles forms with oxygen a compara-
tively feeble combination that may be broken up readily, with liber-
ation of the gas.

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, C34H34N4Fe05 (Kiister). 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,
*"Die Blutkrystalle." Jena, 1871.

GENERAL PROPERTIES: THE CORPUSCLES. 391

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
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 Hufner,f
the O capacity of the Hb of ox's blood is 1.34 c.c. O to each gram of
Hb. 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 hemoglobin, or, as it is often called
by way of distinction, "reduced hemoglobin." This power of com-
bining 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
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 oxyhemo-
globin, 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

*See Simon, "A Manual of Clinical Diagnosis." Philadelphia, 1904.
f "Archiv f. Physiologie," 1894, p. 130.

392 BLOOD AND LYMPH.

gas is liable to prove fatal. The CO unites with the hemoglobin,
forming a firm compound; the tissues of the body are thereby pre-
vented from obtaining 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.

Oxyhemoglobin, 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 O and C02 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 C02
as though it held no oxygen in combination. Bohr suggests, there-
fore, that the O and the C02 must unite with different portions of the
hemoglobin — the oxygen with the pigment portion and the C02 possi-
bly with the proteid portion. Although the amount of C02 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 C02 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. Physiologie," 3, 47, 1892, and 16, 402, 1904.

GENERAL PROPERTIES: THE CORPUSCLES.

393

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. 168). 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

168. — Crystallized hemoglobin (after
b, Crystals from venous blood of man;

Fig.
Frey): a

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.

394 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. 168),
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 proteid-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 proteids and other 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. 169, 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 (S) 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 (B). 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 Physiologie," 104, 64, 1904.

GENERAL PROPERTIES: THE CORPUSCLES.

395

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. 169. — 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 "/3-band" (Fig. 170). With a solution con-
taining 0.09 per cent, of oxyhemoglobin, and examined in layers one
centimeter thick, the a-band extends over the part of the spectrum
included between the wave-lengths X 583 (yrinnnnr °f a millimeter)
and X 571, and the /?-band between X 550 and X 532 (Gamgee).
The width and distinctness of the bands vary naturally with the
concentration of the solution used (see Fig. 171), or, if the con-
centration remains the same, with the width of the stratum of liquid
through which the light passes. With a certain minimal percentage

396

BLOOD AND LYMPH.

of oxyhemoglobin (less than 0.01 per cent.) the /5-band is lost and
the a-band is very faint in layers one 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 is also absorbed. The variations in the absorp-
tion spectrum, with differences in concentration, are clearly shown
in the accompanying illustration from Rollett * (Fig. 171) ; the thick-

660

c r> e

650 6k0 630 620 610 600 sk) 580 570 560 550 5k0 53d\ 520

I.— 1....I....1....I ll.ltlll,Ji»lllmlltilll.Mlltnl|.|JtllllHMllllllLllllllllllllLl.llllllll.llllJl

mo

J

Fig. 170. — 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.

ness of the layer of liquid is supposed to be one centimeter. The
numbers on the right indicate the percentage strength of the oxyhem-
oglobin solutions. It will be noticed that the absorption which
takes 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
* Hermann's "Handbuch der Physiologie," vol. iv, 1880.

GENERAL PROPERTIES". THE CORPUSCLES.

397

show only one absorption band, known sometimes as the uf 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
oxyhemoglobin are shown in Fig. 170. The r-band is much more
diffuse than the oxyhemoglobin bands, and its limits, therefore,
especially in weak solutions, are not well defined; in solutions of
blood diluted 100 times with water, which would give a hemoglobin
solution of about 0.14
per cent., the absorp-
tion band lies in the
part of the spectrum
included between the
wave lengths X 572 and
X 542. The width and
distinctness of this band
vary also with the con-
centration of the solu-
tion. This variation is
sufficiently well shown
in the accompanying
illustration (Fig. 172),
which is a companion
figure to the one just
given for oxyhemo-
globin (Fig. 171). It
will be noticed that the
last light to be absorbed
in this case is partly in
the red end and partly
in the blue, thus ex-
plaining the purplish
color of hemoglobin so-
lutions and of venous
blood. Oxyhemoglobin
solutions can be con-
verted to hemoglobin
solutions, with a corresponding change in the spectrum bands, by
placing the former in a vacuum or, more conveniently, by adding
reducing solutions. The solutions most commonly used for this
purpose are ammonium sulphid and Stokes's reagent.* If a solu-
tion of reduced hemoglobin is shaken with air, it quickly changes to

aBC

Fig. 171. — Diagram to show the variations in the
absorption spectrum of oxyhemoglobin with varying
concentrations of the solution. — (After Rollett.) 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.

* 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.

BLOOD AND LYMPH.

emoglobin and gives two bands instead of one when exam-
through the spectroscope. Any given solution may be changed
is way from oxyhemoglobin to hemoglobin, and the reverse, a
t number of times, thus demonstrating the facility with which
moglobin takes up and surrenders oxygen.
Solutions of carbon monoxid hemoglobin also give a spec-
trum with two absorption bands closely resembling in posi-
tion and appearance those of oxyhemoglobin. They are dis-
tinguished from the
oxyhemoglobin bands
by being slightly
nearer the blue end
of the spectrum, as
may be demonstrated
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

aBC

Fig. 172. — Diagram to show the variations in the ab-
sorption spectrum of reduced hemoglobin with vary-
ing concentrations of the solution (after Rollett). 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.
171.

* For more detailed information concerning the chemistry and literature
of these compounds see Hammarsten, "Physiological Chemistry," translated
by Mandel, fourth edition, 1904; Cohnheim, "Chemie der Eiweisskorper,"
second edition, 1904.

GENERAL PROPERTIES: THE CORPUSCLES.

m

a change in color, taking on a brownish tint. This change is du i to
the formation of methemoglobin, and it is said that to some exl ent
the transition occurs very soon after the blood is exposed to the iliV
and that, therefore, determinations of the quantity of hemoglobin
by the ordinary colorimetric methods should be made promptly W
avoid a deterioration in color value. Methemoglobin may beS^
obtained rapidly by the action of various reagents on the blood,
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. 170. In alkaline solution the absorption spectrum
has three bands, two of which are nearly identical with those of
oxyhemoglobin.

Hematin (C34H34N4Fe05) is obtained when hemoglobin is de-
composed by the action of acids or alkalies in the presence or oxygen.
It may occur in the feces if the diet contains hemoglobin or hematin,
or in case of hemorrhages 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. 170.

Hemin (C34H3304N4FeCl) 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

400 BLOOD AND LYMPH.

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.

Hemochromogen (C 3 4H36N4FeO 5 ?) 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 (C34H38N406) 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 hematoidin 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
hematoidin. 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. — Both of 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.

401

^ag^J^it

cal Ucp'

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
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 oi
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 may be added also
that the blood of the splenic vein contains no hemoglobin in solu-
tion, indicating that no considerable dissolution of red corpuscles is
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, goe?
26

402 BLOOD AND LYMPH.

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 a group of nucleated, colorless
cells, erythroblasts, is 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 or normoblasts. The nuclei are subsequently lost, either by
disintegration 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, hema-
topoietic 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.*

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,f who believed that the diminished supply of oxygen
in high altitudes may be compensated by an increased amount of
hemoglobin, and subsequently ViaultJ demonstrated that living for

* Howell: "Life History of the Blood Corpuscles," etc., "Journal of
Morphology," 1890, vol. iv.

f Bert, "La pression barometrique," 1878, p. 1108.

J Viault, "Comptes rendus de l'academie des sciences," 1890 and 1891.

GENERAL PROPERTIES! THE CORPUSCLES. 403

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
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. The results published upon
these questions are so conflicting that it is difficult to make any
positive statements at present. One may, however, believe that
the increased number or concentration of red corpuscles is an adap-
tation 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 actual — that is, an absolute — increase in the total
number of red corpuscles, and therefore in the total amount of
hemoglobin. According to this explanation, one must assume fhat
the diminished amount of oxygen in the air at high altitudes or
some other condition peculiar to these altitudes acts as a stimulus
to the blood-forming tissues (red marrow) and augments the output
of corpuscles. According to another set of observers, the adap-
tation 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 hemoglobin 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. Recent
evidence seem to favor this latter explanation, particularly as
regards the nearly immediate effects of a change in altitude.
Abderhalden, for instance, has shown that, if animals of the
same species and same litter are bled to death and the total
* Kemp, "American Journal of Physiology," 10, 34, 1904.

404 BLOOD AND LYMPH.

quantity of hemoglobin is estimated, the average figures obtained
for the animals at low levels are the same as for those at the
high altitudes.*

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 can not be said that we possess any 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 used by most authors is that
adopted by Ehrlich.f According to this nomenclature, the white
corpuscles 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.

(b) 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.
(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

* For the extensive literature see Van Voornveld, "Das Blut im Hoch-
gebirge," "Pfliiger's Archiv," 92, 1, 1902; also Oliver, "A Contribution to the
Study of Blood and Blood Pressure," London, 1901.

t Ehrlich, "Die Anaemie," 1898; see also Seemann, "Ergebnisse der
Physiologic," 3, part i, 1904.

GENERAL PROPERTIES: THE CORPUSCLES. 405

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 most of the authors who have studied the ap-
pearance and variation in number of these cells under pathological
conditions, 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, my-
elocytes) 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. Another view maintained
by some authors is that the various white corpuscles in the blood
represent different stages of development. According to this view,
the small lymphocytes as received from the lymph circulation are
the young or immature form, and they develop, while in the circu-
lation, through the stages represented by the large lymphocytes
and the mononuclear leucocytes to the mature form, the poly-
morphonuclear leucocytes.

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
pathogenic bacteria. In explanation of this action it has been
suggested that they may either ingest the bacteria, and thus destroy
them directly, or they may form certain substances, defensive
proteids, that destroy the bacteria. Leucocytes that act by ingest-
ing the bacteria are spoken of as a phagocytes" {<pdysiv, to eat;
■/vtos, cell). This theory of their function is usually designated as

406 BLOOD AND LYMPH.

the "phagocytosis theory of Metchnikoff"; it is founded upon the
fact that the ameboid leucocytes are known to ingest foreign par-
ticles with which they come in contact. The theory of the protec-
tive action of leucocytes has been used largely in pathology to
explain immunity from infectious diseases, and for details of experi-
ments in support of it reference must be made to text-books of
pathology. (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
coagulation is described. (5) They help to maintain the normal
composition of the blood-plasma in proteids. 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 proteids 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 proteids. 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 fj), but they are always smaller than the
red corpuscles. Less is known of their origin, fate, and functions
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
Hayem, 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. Deetjen*

has demonstrated that 'they are capable of ameboid movements.

When removed from the blood vessels to a glass slide they usually

* " Virchow's Archiv f. path. Anat. u. Physiol.," 164, 239, 1901.

GENERAL PROPERTIES: THE CORPUSCLES. 407

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 (K2HP04), they flatten out, show a central granular portion
and a peripheral clear layer, and may make quite active ame-
boid movements. Deetjen claims also that they possess a distinct
nucleus. This latter statement is perhaps doubtful, as other ob-
servers* 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 oT 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. They are more numerous
than the leucocytes, and, according to Kemp, an average valuation
would be about yg- the number of the red corpuscles. Outside the
part that they take in the formation of thrombi and in the initia-
tion of coagulation, nothing is known of their function under
normal conditions.

* Kemp, "American Journal of Physiology," 6, 11, 1902.

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.

Proteids

Extractives, — that is, substances other
than proteids that may be ex-
tracted from the dried residue by
water, alcohol, or ether.

f Fibrinogen.

, ParaglobuHn { Eug.obul^

Serum-albumin.
Nucleo-albumin.
f Fats.
Sugar.
Urea.
Jecorin.

Glucuronic acid.
Lecithin.
Cholesterin
Lactic acid.

Salts

[ of ■

Enzymes and unknowns.

Sodium.

Potassium.

Calcium.

Magnesium.

Iron.

Chlorids
Carbonates
Sulphates
Phosphates

Internal secretions.

Enzymes { ^^ etc

I .Immune bodies (Amboceptors).
I Complements.

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

408

CHEMICAL COMPOSITION OF BLOOD-PLASMA. 409

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

Proteid 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^O 3.675 4.263 2.821

K20 0.251 0.226 0.289

Fe203 0.641 1.573

CaO 0.062 0.113

MgO 0.052 0.040 0.071

CI 2.935 4.023 1.352

P205 0.809 0.242 1.635

Inorganic :

P205 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 proteid
in the serum is greater in some cases than in others, — in the dog,
for instance, according to Abderhalden's analyses, the proteid
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 remarkabfy uniform so far as chemical analyses go. We know,
however, that the physiological properties of mammalian sera 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 defined 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 K20 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.

410 BLOOD AND LYMPH.

Proteids of the Blood-plasma. — The general properties and
reactions of proteids 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 proteids of the plasma and the part they take in
coagulation. Three proteids 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 proteids, fibrinogen and paraglobulin, belong to
the group of globulins, and hence have many properties in common.
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 proteid. It can be
obtained readily in crystalline form from the horse's blood. Its
percentage composition, according to Michel, is as follows: C, 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
liquids together with the globulins, as is the case in blood. If such
a liquid is thoroughly saturated with solid magnesium sulphate or
half saturated with ammonium sulphate, the globulins are precipi-
tated 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 proteids
not precipitated by saturation with magnesium sulphate 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 degree.
Precipitates produced in this way by heating solutions of proteids
are spoken of as coagulations — heat coagulations — and the exact
temperature at which coagulation occurs is to a certain extent
characteristic for each proteid. The temperature of coagulation of
serum-albumin is usually given at from 70° to 75° C, but it varies
greatly with the conditions, — for instance, with the reaction of the
solution or its concentration in salts. It has been asserted, in fact,
that careful heating under proper conditions gives separate coagula-
tions 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 proteids. Serum-albumin occurs in
blood-plasma and blood-serum, in lymph, and in the different
normal and pathological exudations found in the body, such as per-
* " Archiv f. exper. Pathol, u. Fharmakol.," 39, 1, 1897.

CHEMICAL COMPOSITION OF BLOOD-PLASMA. 411

icardial liquid, hydrocele fluid, etc. The amount of serum-albumin
in the blood varies in different animals, ranging among the mam-
malia 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
proteids of the food. It is known that proteid 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
proteids of an entirely different character, — namely, peptones and
proteoses, or possibly b 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 standpoint serum-albumin is often considered to be
the main source of proteid 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 proteid 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
Cu7H182N30SO38 + iH20. 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 proteid is

412 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 CO 2 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, proteids. 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 proteids 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 proteid 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

* Porges 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.

% 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. 413

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 proteid, 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; 0,22.26; while its
molecular composition, according to Schmiedeberg, is indicated by
the formula C108H162N30SO34.

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 proteids. 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 proteid 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.

The following table* gives some recent results of analyses of
blood which indicate the average amounts of the different proteids
in the blood-plasma of several animals. The figures give the weight
of the proteid in grams for 100 c.c. of plasma.

Serum-
Total Proteids. 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 Proteids of the Blood-serum or Blood-plasma. — From time to time
other proteid 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

* Lewinski, loc. cit.

414 BLOOD AND LYMPH.

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 proteid 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 proteid for which
the name albumon has been proposed. By others still this non-coagulable
proteid 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 proteids by heating. So, too, nucleoproteid 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 des-
cribed as nucleoproteid is in reality a mixture or combination of lecithin and
proteid. All the proteids when precipitated from the blood carry down with
them 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 nucleo-albumins exist 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 proteid 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-
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

COAGULATION. 415

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 be 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. It will be advantageous to postpone an
account of these methods for hastening or retarding coagulation
until the theories of coagulation have been considered.

Theories of Coagulation. — The clotting of blood is such a
prominent phenomenom that it has attracted attention at all
times, and as a result numerous theories to account for it have been
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

416 BLOOD AND LYMPH.

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 Brucke.

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 proteids 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 proteids 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-
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,f who
showed that blood received into an oxalate solution, so as to

* "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.

f "Archives de physiologie normale et pathologique, fifth series, 2, 739,
1890.

COAGULATION. 417

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 necessary to the formation 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 nucleoproteid which then combines with the
calcium present to form a calcium nucleoproteid compound which
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 nucleoproteid + 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,

* For two recent theories and literature see Morawitz, "Beitrage zur chem.
Physiol, u. Pathol./' 4, 381, 1904, and "Deutsches Archiv f. klin. Med.," 79;
Fuld, "Zentralblatt f. Physiol./' 17, 529, 1903.
27

418 BLOOD AND LYMPH.

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.

Practically all recent observers hold to the view that the
active thrombin 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 or coagulins). Others have considered that the calcium
salts constitute the efficient zymoplastic substance that converts
the prothrombin to thrombin, — a view that is contained in the first
part of Pekelharing's theory, given above. At present it would
seem necessary to adopt a combination of these views: to suppose
that in the formation of active thrombin three factors co-operate, —
namely, the calcium salts, the prothrombin, and zymoplastic sub-
stances. The calcium salts exist in solution in the plasma, the
prothrombin also according to some authors pre-exists in the plasma,
while according to others it is furnished by the cellular elements
(blood plates, leucocytes). The zymoplastic substance is a ferment
body derived from cellular elements; it has been designated by
several names, such as cytozym (Fuld), to indicate its origin from
cells, and thrombokinase (Morawitz),to indicate its activating effect
upon the prothrombin. The latter name seems preferable, and it
is important to bear in mind that such bodies may be furnished
not only by the formed elements of the blood, but also by other
tissue elements. Thus, Delezenne has shown that if the blood of
birds is withdrawn 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 evidently to be due to the fact that the
elements in the blood of these animals supposed to correspond with
the blood plates of mammalia disintegrate much 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
zymoplastic substance is furnished by the tissues. In the bird
the normal clotting of the blood to stop wounded vessels must de-
pend evidently upon this co-operation from the outside tissues. In

COAGULATION. 419

the mammal, on the other hand, the blood itself contains all the
sources necessary for prompt coagulation.

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,

«ck-s««—». /fibrin-globulin

Fibrinogen^ fibrin *

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
be made : The immediate factors necessary in coagulation are fibrin
ferment (thrombin) and fibrinogen. Calcium salts are also neces-
sary 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 some constituent (zymoplastic sub-
stance) necessary to the preparation or activation of the thrombin.
We may provisionally adopt the view that thrombin is produced
from an antecedent prothrombin by the action of the calcium
salts and zymoplastic substance, according to the schema:

Prothrombin + 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.

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

* Fuld, "Beitrage zur chem. Physiol, u. Pathol.," 2, 514.

420 BLOOD AND LYMPH.

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 amount of
active thrombin. It seems most probable that little, if any, throm-
bin 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 im-
portance. It has been shown, for instance, that, when solutions
of fibrin ferment (thrombin) are injected into the circulation,
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, an 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 with the fact that blood remains
uncoagulated for long periods if kept in contact with what 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, there-
fore, that the normal endothelial 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 antithrombin — exists in the blood and actively retards or prevents
coagulation. 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. Loebf 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

* " Travaux de Physiologie," Universite de Montpellier, 1898.
f Leo Loeb, "Virchow's Archiv," 176, 10, 1904; also " Hof meister's Bei-
trage," 5, 534, 1904.

COAGULATION. 421

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
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
intravascular 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 nucleoproteid which in turn on decomposition furnishes a
second nucleoproteid, leuconuclein, whose presence favors coagula-
tion, and a simple proteid, histon, whose action retards clotting.
Delezennef 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, causing retarded 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
* Lilienfeld, "Zeitschrift f. physiol. Chemie," 18, 473. f Loc. cit.

422 BLOOD AND LYMPH.

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. 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 altogether 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
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 the chemical properties of the proteids.

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

QUANTITY OF BLOOD. 423

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 forms,
therefore, an excellent means of testing the presence of thrombin
(Arthus).

5. By the Injection of Certain Organic Substances. — There are a
number of substances which when injected 4into 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
digestion experiments, is in reality a mixture of proteoses 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 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 used in such determi-
nations consists essentially in first bleeding the animal as thoroughly
* "Zeitschrift f. physiol. Chemie," 31, 235, 1900.

424 BLOOD AND LYMPH.

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. The results are as
follows: Man, 7.7 per cent. (TV) of the body- weight ; that is, a man
weighing 68 kgms. has about 5236 gms., or 4965 c.c, of blood in his
body; dog, 7.7 per cent.; rabbit and cat, 5 per cent.; new-born
human being, 5.26 per cent.; and birds, 10 per cent. The dis-
tribution of this blood in the tissues of the body at any time has
been estimated by Ranke,* 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 f 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.)
or Ringer's solution, are injected into the veins immediately after
a severe hemorrhage, recovery is more certain ; in fact, it is

* Taken from Vierordt's "Anatomische, physiologische, und physikalische
Daten und Tabellen," Jena, 1893.

fFredericq: "Travaux du Laboratoire" (Universite de Liege), 1, 189,

1885.

REGENERATION AFTER HEMORRHAGE.

425

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 great rapidity, the blood regaining its normal vol-

7,000,000175%)
6,000,000 (05 %)
5,000,000(55%)
4,000,000(45%)

155%)
35,000(25%)
25,000(15%)

16,000

.

c,,w

+-"*0**

~T ^^^^ \?

x _ ^ ^2^

\\ / t7

XX -7 ~'

3 \-7 _ ^ :>r

L 2

t 7

X-7 ^

iv 2 ^

t l^^N. "^ ^^

I

t

1 1 1 1 1 1 1 1 1 1 „ [

100 Erythrocyte*.

Haemoglobin.

Leucocyte*

Fig. 173. — 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,
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

IL

426

BLOOD AND LYMPH.

secc ad and third days. This latter phenomenon constitutes what
10 wn as the posthemorrhagic fall.*

lood-transfusion. — Shortly after the discovery of the circu-
ron of the blood (Harvey, 1628), the operation was introduced
transfusing blood from one individual to another or from some
«%*"# 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 intravas-
cular clotting ; secondly, 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. 387), 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 extra vascular 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 that 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.

427

g2

tr

^>

X

<f> ',

I 9

— •

428 BLOOD AND LYMPH.

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 extra vascular lymph permeating the tissue elements on
the other. The intravascular lymph may be augmented, for ex-
ample, by a flow of water from the 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 pres-
sure 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 fuller 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 proteids, the extractives (urea,
fat, lecithin, cholesterin, sugar), and inorganic salts. The salts
are found in the same proportions as in the plasma ; the proteids 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 proteids 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

COMPOSITION AND FORMATION OF LYMPH. 429

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
CaO 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 proteid in the lymph. This latter fact has been
satisfactorily explained by the experiments of Starling.f Accord-

* "Archiv f. die gesammte Physiologie," 49, 209, 1891.
t "Journal of Physiology," 16, 234, 1894.

430 BLOOD AND LYMPH.

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 comes 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.

f "Centralblatt f. Physiologie," 9, No. 2, 1895.

COMPOSITION AND FORMATION OF LYMPH. 431

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 increased. 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 movement 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

* hoc. cit. t "Zeitschrift f. Biologie," vols, xxxvi-xl, 1897 to 1900.

432 BLOOD AND LYMPH.

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 proteid, 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 which, 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 limics.
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 filtration, 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,

COMPOSITION AND FORMATION OF LYMPH. 433

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 proteids. 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.

28

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
circLilation 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 muscles of the blood-vessels. (3) The innerva-
tion of the heart and the blood-vessels, — that is, the variations in
them 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

434

VELOCITY AND PRESSURE OF BLOOD-FLOW. 435

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 can not be considered
in this connection.

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

436

CIRCULATION OF BLOOD AND LYMPH.

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
V

length =

fe cross-area

Fig. 174. — Lud wig'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.*

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-
*"Skandinavisches Archiv f. Physiol.," 3, 152, 1891.

VELOCITY AND PRESSURE OF BLOOD-FLOW.

437

merit different from those at the beginning. By means of the stromuhr
however, this experiment can be made, with this alteration, how-
ever, 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. 174,
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 izr1 =
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

1000

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. 175).
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-

>

Fig. 175. — 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,

a

pi, and forces it to an angle varyin
with the velocity. The movement
pi is transmitted through the stem, n,
which moves in a rubber membrane,
m. The angular movement 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.

438 CIRCULATION OF BLOOD AND LYMPH.

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 devise 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 mms. 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. Physiologie," 1887, 279; also Abeles, ibid., 1892,
22.

f "Archiv f. physiologische Heilkunde," 15, 255, 1856.

VELOCITY AND PRESSURE OF BLOOD-FLOW.

439

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-
An

According to this method,

Vierordt calculates 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-
over, it may be observed
that the average velocity
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

igrs

struction used to determine the size of the retinal
image when the size of the external object is known :
n, The nodal point of the eye. See text.

Fig. 177. — 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.
177.

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

440 CIRCULATION OF BLOOD AND LYMPH.

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-^-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.

VELOCITY AND PRESSURE OF BLOOD-FLOW. 441

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 it, the conductivity is in-
creased. 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 \ of the time required
for a complete circuit is spent in the lesser circulation. Attention
may also be called to the fact that the important part of the cir-
* "Journal of Physiology," 15, 1, 1894. ■

442 CIRCULATION OF BLOOD AND LYMPH.

culation, as regards the nutritive activity of the blood, is the capil-
lary 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 par-
ticle 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
Haemosta ticks," 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 Poiseuille f (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.
178, M. One leg was connected with the interior of an artery by

* For an account of the life and works of this physiologist see Dawson,
"The Johns Hopkins Hospital Bulletin," vol. xv, Nos. 159 to 161, 1904.
f Poiseuille, "Recherches sur la force du coeur aortique." Paris, 1828.
j Ludwig, "Mi'iller's Archiv f. Anatomie, Physiologie, etc.," 1847, p. 242.

VELOCITY AND PRESSURE OF BLOOD-FLOW.

443

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. 178. — 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. 178.

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.

444 CIRCULATION OF BLOOD AND LYMPH.

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 manometer may be adjusted beforehand to the
pressure that is supposed or known to exist in the artery under experiment.
By 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. 178, 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
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 itself 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
continuation 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 that of 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. 179. 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 two. The base
line represents the position of the recording pen when it is at its zero
position for the conditions of the experiment. It is necessary to multiply
the distance between the base line and the record by two because, as is seen
in Fig. 178, 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. 179) 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 in 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-

VELOCITY AND PRESSURE OF BLOOD-FLOW.

445

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. 179. — 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 blood-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. 179 should have, so far as the
heart beats are concerned, somewhat the appearance shown in Fig.
180. This latter figure gives a more accurate mental picture of
the actual conditions of pressure in the large arteries, as influenced by

446

CIRCULATION OF BLOOD AND LYMPH.

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-
mms., while the diastolic pressure is only 100 mms. In man the

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Fig. 180. — 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. 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 capillaries and in
the veins there is no pulse wave, and no difference between systolic

VELOCITY AND PRESSURE OF BLOOD-FLOW.

447

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 concerned, the mean
pressure is only a convenient expression for the average pressure
during a certain period. If we know at any moment the systolic
and the diastolic pressure in an artery we can estimate the mean
pressure with approximate accuracy by taking the arithmetical mean
of the two figures. In physiological observations, as a rule, no
attempt is made to estimate the mean pressure for any given time
with mathematical accuracy. In the ordinary tracing as given by the
mercury manometer (Fig. 179) the mean pressure for any given period
during which the variations have been symmetrical and not ex-
treme is estimated from the arithmetical mean of the highest and
lowest points reached. When desirable, the mean pressure may be

Fig. 181. — Schema to indicate the general relations of systolic, mean, and diastolic
pressures throughout the arterial system: a, Systolic; m, mean; d, diastolic; c, pressure
at beginning of the capillaries. The distance from 8 to d represents the pulse pressure at
different parts of the arterial system.

recorded by introducing a resistance (narrowing the tube) between
the artery and the manometer. The latter will then record mean
pressure and show no variations with the heart beat. A general
idea of the variations in systolic, diastolic, and mean pressure,
as also pulse pressure throughout the arterial system, may be ob-
tained from the schema given in Fig. 181.

Method of Measuring Systolic and Diastolic Pressure in
Animals. — In animals in which the manometer may be connected
directly with the artery the 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 mercury manometer
provided with maximum and minimum valves. Of the manometers
that have been devised to register accurately the quick changes in
pressure due to the heart beat, the two that are most frequently

448

CIRCULATION OF BLOOD AND LYMPH.

referred to in physiological literature are the spring manometer of
Fick* and the membrane manometer of Hurthle.f

The Fick manometer is shown in Fig. 182. 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 must 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. 183. The instrument consists essentially of a small
box or tambour of very limited capacity; the top of the tambour is covered

Fig. 182. — 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.

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. 185.
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. 179.

* Fick, "Archiv f. Physiologie," 1864, p. 583.

t "Archiv f. d. gesammte Physiologie," 49, 45, 1891.

VELOCITY AND PRESSURE OF BLOOD-FLOW

449

Fig. 183. — Diagram showing construction of Hiirthle's manometer. — (After Curtis.}
The interior of the heart of 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. 184. — 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 b alone is open.

29

450

CIRCULATION OF BLOOD AND LYMPH.

The method that depends upon the use of maximum and minimum valves
may be understood by reference to Fig. 184. 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.

Fig. 185. — 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.

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

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
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.

* See Volkmann. "Die Haemodynamik," 1850.

VELOCITY AND PRESSURE OF BLOOD-FLOW.

451

This fact is illustrated in Fig. 186, which gives a graphic represen-
tation of a number of experimental determinations (Dawson) 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,

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Fig. 186. — Curve showing the results of actual measurement of systolic, diastolic, and
mean pressure (lateral pressures) along the aorta 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
into 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.)

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

* Burton-Opitz, "American Journal of Physiology," 9, 198, 1903.

452

CIRCULATION OF BLOOD AND LYMPH.

at the rate of 1 mm. Hg for every 35 mms. of distance,
such figures as the following:

We have

Dog.
Superior vena cava

(near auricle) --

Superior vena cava

more distal =

External jugular (left) =

Right brachial =

Left facial :

—2.96 mms. Hg.

—1.38 "
0.52 mm. "
3.90 mms. "
5.12 "

Sheep.

Jugular vein 0.2 mm. Hg.

Facial vein 3.0 mms. "

Branch of brachial 9.0 " "

Crural 11.4 "

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

Fig. 187. — 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.

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
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.

* V. Kries, "Berechte d. Sachs. Gesellschaft d. Wiss. Math.-phys. Classe,"
1875, p. 148.

VELOCITY AND PRESSURE OF BLOOD-FLOW. 453

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 ^-^ 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.
187.

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. 181. 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
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. 188.

454

CIRCULATION OF BLOOD AND LYMPH.

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. 188. — Figure of the Riva-Rocci apparatus (Sahli) : 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, b, to meas-
sure the amount of pressure.

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-
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-

oc

Fig. 189. — 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.

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

* "Archives italiennes de biologie," 23, 177, 1895.

VELOCITY AND PRESSURE OF BLOOD-FLOW. 455

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. 189).

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 (b). 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. 190. — 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. 190). 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
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

* Howell and Brush, "Proceedings of the Massachusetts Medical Society,"

456

CIRCULATION OF BLOOD AND LYMPH.

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
sphygmomanometer described by Erlanger* is probably the most complete
and the most convenient for actual use. This instrument is illustrated in
Figs. 191 and 192.

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. 191 . 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

Fig. 191. — 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 ; b,
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.

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-
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

* "American Journal of Physiology," "Proceedings of the American
Phvsiological Society," 6, xxii, 1902; and "Johns Hopkins Hospital Reports,"
12, 53, 1904.

VELOCITY AND PRESSURE OF BLOOD-FLOW.

457

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

Fig. 192. — Erlanger apparatus. The collar for the arm is not shown. The parts may be
understood by reference to the schema given in Fig. 191.

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. 190. It should be added, also, that
in order to keep the lever of the tambour horizontal while the pressure in the

458 CIRCULATION OF BLOOD AND LYMPH.

system is being lowered there is 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
Potain. The same observer reports observations upon the effect
of meals, of baths, of posture, the diurnal rhythm, etc.f

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

* "La pression arterielle de l'homme." Paris, 1902.

t Erlanger and Hooker, "The Johns Hopkins Hospital Reports," vol.
xii, 1904.

VELOCITY AND PRESSURE OF BLOOD-FLOW. 459

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.

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 rams., 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. 193, 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

460

BLOOD-PRESSURE AND BLOOD- VELOCITY.

461

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
cavse 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 venae cavse 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, h'. 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-

rig. 193. — Schema to illustrate the side pressure due to resistance, and the velocity pres-
sure (Tigersledt) : 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 bv the first of these

-6

CIRCULATION OF BLOOD AND LYMPH.

factors — namely, a great resistance placed in the middle of the
bourse — may be illustrated by the model shown in Fig. 194, which
differs from that in Fig. 193 in having a stopcock in the outflow
^f be, which, when partly turned off, makes a narrow opening and a
datively great resistance. When the stopcock is open the pressure
^yMs 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 side 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. 194. — 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. 193 and 194, 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 cava?, the pressure throughout the system
would rise to a high point during systole and fall to zero during the

BLOOD-PRESSURE AND BLOOD-VELOCITY.

463

o
he
rt

■

diastole. The elasticity of the arteries, in connection with
peripheral resistance, makes an important difference. As the he
discharges into the aorta the pressure rises, but the walls of tke^
arterial system are distended by the increased pressure, and durinV.'^-. ' |
the following diastole the recoil of these distended walls maintainsv^
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. 195. 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. 195. — 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
ine pointed glass tube the peripheral resistance of the capillary area.
[f 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
ray, 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

464 CIRCULATION OF BLOOD AND LYMPH.

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. 193, as the total head of pressure (H).
An increase in rate or force of heart beat is equivalent, therefore,

BLOOD-PRESSURE AND BLOOD- VELOCITY. 465

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.
193) 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.

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
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
30

466 CIRCULATION OF BLOOD AND LYMPH.

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.

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
* Hill and Barnard, "Journal of Physiology," 21, 321, 1897.

BLOOD-PRESSURE AND BLOOD-VELOCITY. 467

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 conti actions 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
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. 441), 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.

* For a discussion of the special physiology of the pulmonary circulation
and for references to literature see Tigerstedt, "Ergebnisse der Physiologie,"
vol. ii, part n, p. 528, 1903.

468 CIRCULATION OF BLOOD AND LYMPH.

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 sys-
temic pressure, as taken in the carotid, varying from 144 to 222 mms.,
that in the pulmonary artery changes 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 pres-
sure 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 there-
fore the amount of flow and the pressure in the pulmonary artery,
depends mainly on the amount of blood received through the
venae cavse by the right auricle. If one of the venae cavee 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 this means, there-
fore, the variations in blood-flow in the systemic circulation in-
directly 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 completely, 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
variations in intrathoracic pressure upon the pulmonary circulation
are described in connection 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

469

470 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
becomes imperceptible.*

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
prepagation 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
a given point in each artery may be recorded by some convenient

* 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. 471

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. 196.

Fig. 196. — 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.

472

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 7= 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 m. fco 4.5 m. We can imagine, therefore, that before

Fig. 197. — 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.

473

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.

The pulse wave obtained from the radial artery is represented
in Fig. 199. It will be seen from this figure that the artery dilates
rapidly and then falls more slowly. The ascending portion of the
wave is spoken of as the anacrotic limb, the descending as the
catacrotic limb. Under usual conditions the anacrotic limb is
smooth, — that is, shows no secondary waves, — while the catacrotic

Fig. 198.— 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.

Fig. 199. — Sphygmogram from the radial artery, Dudgeon sphygmograph : D, The dicrotic
wave; P, the predicrotic wave.

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 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

474 CIRCULATION OF BLOOD AND LYMPH.

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 emphasized and may be detected by the finger. A pulse
of this kind is known as a dicrotic pulse.

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 which immediately
'precedes the dicrotic wave. The general belief, therefore, is that the
dicrotic wave results from the closure of the semilunar 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 smaller waves, such as the predicrotic, and the postdicrotic,
have been explained (Landois)* simply as elasticity waves, — that
is, as elastic vibrations of the arterial walls. According to other
authors, f an important — perhaps the chief factor — in the produc-
tion of the secondary waves is the reflection that occurs from the
periphery. Where each arterial stem breaks up into its smallest
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

* Landois, " Die Lehre von Arterienpuls," 1872.
t See von Frey, loc. cit.

THE PULSE. 475

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.
200. 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,* 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.

Fig. 200. — Anacrotic pulse from a case of aortic stenosis (Mackenzie): b, The anacrotic

wave.

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
or low, and a similar inference may be drawn from the character
of the sphygmogram; but since the introduction of the sphygmo-
manometer (p. 453) it seems evident that this instrument 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

* Von Kries, " Studien zur Pulslehre " 1892.

476 CIRCULATION OF BLOOD AND LYMPH.

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 applies to an entirely different phenomenon,
— namely, to a pulse seen especially in the external jugular vein.
When this vein is prominent or is made prominent by some com-
pression a pulse may be seen and recorded which is synchronous
with the heart beat. It is not a wave that has come through the
capillary circulation in the head, since if the vein be completely
blocked by the finger the wave disappears on the upper side. It is
due to the heart beat; and is usually attributed to the auricular
contraction. At each contraction of the auricle the venous flow
is partially blocked; at each relaxation the flow is suddenly aug-
mented. Under pathological conditions a marked venous pulse
of a different origin maybe seen in the jugular or may be felt over the
liver (liver pulse). This wave is usually described in connection
with an insufficiency of the auriculo- ventricular valves. Under such
a condition it is evident that the contraction of the ventricles will
be accompanied by a regurgitation toward the auricles and the
production of a positive wave in the venae cavse and their branches.*

* For a discussion of the venous pulse consult works on clinical methods, —
e. g., Sahli, " Lehrbuch der klinischen Untersuchungs-Methoden," 1902.

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 not by the auricles proper, but by a con-
traction of the mouths of the large veins — vense cavse or pulmonary
veins, where they open into the auricle. The tissue in these veins
corresponds physiologically to a definite chamber, the venous

Fig. 201. — 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 right 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. 201). It will be noted that the auricular systole is

477

478

CIRCULATION OF BLOOD AND LYMPH.

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

Fig. 202. — 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. I. The superficial muscle layer
originating in the right and left auriculo-ventric-
ular rings and posterior half of tendon of conus.
//. The superficial layer originating in the anterior
half of the tendon of the conus (fills in the gap of
Fig. I). 77/. The scroll fibers in several layers
forming the deeper strata of the heart's muscu-
lature.

THE HEART BEAT. 479

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
superficial 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 end in the papillary muscles
and through their tendons in the auriculo-ventricular ring of the
other ventricle. Those that begin on the outer surface in one ven-
tricle end on the inner surface in the other. This arrangement is rep-
resented in Fig. 202, I and 77. 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 left to right. Beneath these superficial fibers
lie thicker bands, the fibers of which have a more transverse course.
According to MacCallum,* these 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. 202, 777. 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.! 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 at the mouths of the great veins opening into
the auricles, and thence passes to the auricles first and subsequently
to the ventricles. The continuity of the muscular tissue enables us
to understand how this contraction passes quickly from cell to cell
in the direction of the muscular fibers. In the mammalian heart

* 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. Anatomie," 1904, p. 1; and Braeunig, "Archiv
f. Physiologie," 1904, suppl. volume, p. 1.

480 CIRCULATION OF BLOOD AND LYMPH.

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 con-
cerned. 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).* 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.

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
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
results can be studied in detail. The variation is diphasic. If one

* See Tigerstedt, " Die Physiologie des Kreislaufes," 1893, p. 80, for litera-
ture.

THE HEART BEAT. 481

electrode is placed toward the base of the heart and the other at the
apex, then, according to most observers, the base first becomes nega-
tive as regards the apex and later the apex negative as regards the
base. This result agrees with the view stated above of the di-
rection taken by the wave of contraction in the ventricular muscle.
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 in all diameters or only certain diameters?
The question is one that can not 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

* See Haycraft and Edes, "Journal of Physiology," 12, 426.
31

>$-

/

».-,. *k

482

CIRCULATION OF BLOOD AND LYMPH.

ventrifclfe. Owing to the whorl made by the superficial fibers at
this rgoiiit as they turn to pass into the interior (see Fig. 202, I),
the ^syatole causes a rotation of the apex, which is thereby
forced /more firmly against the chest wall. This rotation and
(Te&fiJn of the apex during systole may be seen upon the exposed
{f neajyof the lower mammals and has been described also for man
incases in which the heart is covered only by the skin, owing to

formation 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. 203.
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.

ft* i

the air of the tambour which are transmitted through tubing t >'•* :
recording tambour and recorded on a kymographion. A simpi
and effective cardiograph may be made by pressing a fu:
against the skin over the apex and connecting the stem of ifok*

Fig. 203. — 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. 204. — 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. 204, 7, and a curve more difficult to interpret in
Fig. 204, 8. It should be borne in mind that the cardiograph curve

484 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. 205. — Synchronous record of the intraventricular pressure (V), and the aortic
pressure (A) : S, The time record, — each vibration = T&5 sec. ; 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.
449) seems to have met the requirements more satisfactorily than
any other of the numerous instruments described. A typical curve
obtained by means of the Hiirthle manometer is given in Fig. 205, V.
(Consult also the classical curve obtained b}^ Chauveau and Marey
from the heart of the horse [Fig. 201].) 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. 205) is determined

THE HEART BEAT. 485

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. 205, V).

(a) Period of tension (0 to 1), during which the auriculo- 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.

(b) 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.

(b) 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. 201.

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,f
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

* Hiirthle, "Archiv f. d. gesammte Physiologie," 49, 84, 1891.
t Journal of Physiology/' 11, 486, 1890.

486 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.

487

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. 206. — To show the time relation of the heart sounds to the ventricular beat
(Marey) : V.D., Tracing of the ventricular pressure in the right ventricle of the horse. Be-
low 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. 206. 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. 207. 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-b). Over the

* Einthoven and Geluk, " Archiv f. d. gesammte Physiologie, " 57, 617,
1894.

488

CIRCULATION OF BLOOD AND LYMPH.

base of the heart (second intercostal space) the first sound is heard
(b to c-d) just at the time when the semilunar valves are opened
(bf), — that is, at the beginning of the period of emptying according
to the classification given on p. 485. 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. 207. — 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; S, 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
Geluk.)

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 auric ulo- 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.

momentarily blocking or retarding the flow from the large veins,
whence the normal venous pulse in the jugular veins. The ven-
tricular 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- ventric-
ular valves are tightly closed, the first sound is heard, and 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 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 dur-
ing 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 systole 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.] 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 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 ob-
servers 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

rails of the ventricles yield readily to pressure, and it is difficult

>r impossible to imitate exactly the conditions of pressure that

>revail during life. Nor is it certain whether normally the ventricles

impty themselves completely during systole. The older observers

490 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 4^ of the body weight. For
a man weighing, say, 72 kilograms (158 lbs.) 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 (sis) of the body weight; for a rate of 120 beats per minute
it was equal to 0.0014 (totf)- 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 f
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.

Left 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 y9g5 = 1.28 grammeters,
or for 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 Physiologie des Kreislaufes," p. 152, 1893.

THE HEART BEAT. 491

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

Hoorweg 47

Zuntz 60

Tigerstedt 50-100

Plumier 70

Loewy and v. Schrotter .... 55

for weight of 72 kgms.

it a (i ti a

it tt tt 65 It

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.

492 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. 208, 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, and this
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. 208. — Simultaneous record of the blood-pressure (A) and the blood-velocity (B)
in the coronary arteries (Chauveau and Rebatel) : 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. 493

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 Hurthle instrument
(p. 449), 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-
ologie," vol. iii, part n, 1904.

494 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.

t "Journal of Physiology," 13, 513, 1892.

THE HEART BEAT. 495

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 ventricle 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-

Ificient to stop the contractions or cause fibrillation both ventricles
stop together. It is not possible to stop one alone. 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.

496

PROPERTIES OF THE HEART MUSCLE. 497

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 auriculo-
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 for
its co-ordination. The many muscular fibers of the ventricle
contract normally in a definite manner and sequence; so that the
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
e 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 Physiologie," vol. i, part n, 1902; and Cyon,
" L'innervation du cceur " Richet's " Dictionnaire du Physiologie," vol. iv,
1900. y

32

498 CIRCULATION OF BLOOD AND LYMPH.

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. Recently
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 impossible for us to apply the results of this ex-
periment 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. 504), can be tetanized, and
gives submaximal contractions.! 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 supports the
neurogenic 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,

PROPERTIES OF THE HEART MUSCLE. 499

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. 479).

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. Such an experiment makes it
most probable that the contraction is propagated 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-
periments, initiated by Gaskell and since extended by numerous

500 CIRCULATION OF BLOOD AND LYMPH.

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 to act as a motor center. Histology does
not warrant such an assumption, and we must believe that these
results demonstrate an inherent property of rhythmicity 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 stimulus. 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. According to this last
view, each contraction results in the formation of certain products
which stimulate the muscle to a new contraction (Langendorff).
Regarding this view there is nothing of the nature of direct ex-
perimental 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 which is of funda-
mental significance. While the older physiologists paid attention

PROPERTIES OF THE HEART MUSCLE. 501

mainly to the 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
completely ionized. Attention has been directed mainly to the
influence of the metallic ions, the cations, of which three are es-
pecially 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 (NaCl, 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 per cent.

KC1 = 0.03 " "

CaCl = 0.025 " "

The addition of a trace of alkali, HNaC03, 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, *l>^enca\i^Y¥palf^r%^:i^*v
iology," 2, 47, 1898, and 6, 181, 1901. jf W^'lJ „' U<XliiOr^.

502 CIRCULATION OF BLOOD AND LYMPH.

<&al DeparVP*^

^*- of uVij'fgftrrfnan can be" carried in simple physical solution in the
liquid. 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.; NaHC03, 0.01 to 0.03 per cent.; and glucose, 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 glucose, 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 can not 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 specific role. We may say that the presence of these salts
in normal proportions is an absolute necessity for heart activity.
A striking experiment showing the importance of the calcium ion
is that of irrigating 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
sodium chlorid exists in blood-plasma to the extent of 0.5 to 0.6

PROPERTIES OF THE HEART MUSCLE. XJ\^// 503

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
with an interaction of an alternating kind between these ions and
the living contractile substance of the heart.

Connection of the Inorganic Salts with the Causation of the
Beat. — 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 pro-
duced 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 living substance constitutes the inner stimulus,

504 CIRCULATION OF BLOOD AND LYMPH.

and from this standpoint the heart is kept beating by the alternating
influence of the calcium and sodium and potassium ions.

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. 209. 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.

PROPERTIES OF THE HEART MUSCLE. 505

defined this refractory period as falling within the first part of the
systole, and stated that its duration varies with the actual strength

Fig. 209. — 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 proceeded before the stimulus is applied.

506 CIRCULATION OF BLOOD AND LYMPH.

of the stimulus. Later experiments by other investigators make
it probable that the refractory period lasts during the entire systole.*
According to this point of view, therefore, the heart muscle during
its whole 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 can not be thrown into 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 throw some light also on the rhythmical character of the
beat. Assuming that the inner stimulus is a constantly acting
stimulus, its effect must necessarily be to produce rhythmical
contractions if the heart muscle at each contraction falls into a
condition of non-excitability from which it recovers only gradually.
On the other hand; if the production of the inner stimulus is rhyth-
mical, as is suggested in the preceding paragraph, the relatively slow
development of irritability after a contraction must influence the
actual rhythm of the heart beat. The occurrence of the refractory
period and the subsequent gradual return of irritability are con-
nected 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 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 b}^ the discovery
(p. 498) 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 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 stimu-

* See paper by Woodworth, loc. cit.

t Cushny and Matthews, "Journal of Physiology," 21, 227, 1897.

PROPERTIES OF THE HEART MUSCLE. 507

lated 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 se-
quence 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 rather first the mouths of the great veins,
then auricle and ventricle. This sequence from venous to arterial
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

* Gaskell, "Journal of Physiology," 4, 61, 1883; also vol. ii, p. 180, of
Schafer's "Text-book of Physiology," 1900.

508 CIRCULATION OF BLOOD AND LYMPH.

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
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. 479). 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
* See " Lehrbuch der Physiologie des Kreislaufes," 1893.

PROPERTIES OF THE HEART MUSCLE. 509

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. 210). The
lesion producing this condition has not yet been determined.*

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

Fig. 210. — 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 entirely quiescent so long as normal blood
flows through it. It would seem from these facts that in the mam-
malian 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 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-

* See Erlanger, " Centralblatt f. Physiologie," 19, 1, 1905.

510 CIRCULATION OF BLOOD AND LYMPH.

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
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 leacT
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

* See Howell, "American Journal of Physiology," 2, 47, 1898.

PROPERTIES OF THE HEART MUSCLE. 511

tone waves, an alternate slow shortening and slow relaxation quite
independent of the rhythmical beats. The tissue of the auricle and
especially of the sinus venosus exhibits this property to a much
more marked extent (see Fig. 211). 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. 211 — To show tone waves in heart muscle. The record shows contractions of a,
strip of the 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 doubt-
less 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. 212 and 213.

512

THE CARDIAC NERVES.

513

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
directly in several instances upon
living men.* These inhibitory fi-
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,

Fig. 212. — 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

tractions of the ventricle, me vagus

auricle ; the lower (II) the con-
The
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.

* 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.
33

514 CIRCULATION OF BLOOD AND LYMPH.

especially in the terrapin, the inhibitory fibers are found exclusively
or mainly in the right vagus, and several observers have asserted
that in the mammals also the right vagus, as tested by direct
stimulation, shows a stronger inhibitory action than the left vagus.
Analysis of the Action of the Inhibitory Fibers. — The prom-
inent effect of the action of the inhibitory fibers is the slowing

Fig. 213. — To show the inhibition of the heart from stimulation of the vagus. Record
B is the blood-pressure tracing. The vagus was stimulated twice. The marks x, x, indi-
cate 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 removal of the stimulus.
The upper curve (K) is a plethysmographic (oncometer) tracing of the volume of the kid-
ney. 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
* See Bayliss and Starling, "Journal of Physiology," 13, 410, 1892.

THE CARDIAC NERVES.

515

one may, by using weak stimuli, obtain only a weakening of the
auricular beats without any interference with the rate (Fig. 214),
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 auriculo- 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
may 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 Physiologie des Kreislaufes," 1893, p. 247.

Fig. 214. — 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.

516 CIRCULATION OF BLOOD AND LYMPH.

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. 212). When a block is produced in the
mammalian heart between auricle and ventricle — by clamping the
uniting muscular bundle, for instance — stimulation of the vagus
stops the auricle only (Erlanger), but this result may be due to
the fact that the clamp has interrupted the inhibitory fibers on
their way to the ventricle, or to some other reason connected with
the peculiar properties of the auriculo- ventricular muscle bundle.
As far as the mammalian heart is concerned, one must believe
logically that the vagus affects the ventricle directly, as Tiger-
stedt has well said, from the mere fact that, when the con-
nection between auricle and ventricle is severed or paralyzed
the ventricle continues to beat at its own rhythm without any
obvious pause. It is evident 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 experimented with the subject that the action of the vagus
is exerted mainly upon the auricles.

* Engelmann, "Archiv f. Physiologie," 1900, p. 313, and 1902, suppL
volume, p. 1.

THE CARDIAC NERVES. 517

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 animals — cats, for example — the strongest stimulation of the
nerve serves 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.| 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."t 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 sensory fibers from the thoracic and abdominal

* See Hough, "Journal of Physiology," 18, 161, 1895.

t "Journal of Physiology," 6, 246.

j Goltz, " Virchow's Archiv f. pathol. Anatomie, etc.," 26, 11, 1863.

518 CIRCULATION OF BLOOD AND LYMPH.

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 or sudden emptying of
the bladder. In man similar results are noticed very frequently.
Acute dyspepsia, inflammation of the peritoneum, painful stimu-
lation of sensory surfaces, — the testes, for instance, or the middle
ear, — may cause a marked slowing of the heart, — a condition des-
ignated as bradycardia. What takes place in all such cases is that
the sensory 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 this 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-inhibitory 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-

THE CARDIAC NERVES.

519

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. 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 severed sepa-

■^iM^y***

WsmmJ

Fig. 215. — To show the effect of section of the two vagi 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.)

rately 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. That

520 CIRCULATION OF BLOOD AND LYMPH.

is, it is not due to automatic processes generated within the nerve
cells by their own metabolism or by changes in their liquid environ-
ment, 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 course, that certain sensory paths may be in specially
close functional relationship to the center. One may suppose,
from the anatomical relations and from physiological experiments,
that the sensory 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, u Text-book of Pharmacology and Therapeutics."
Philadelphia, 1903.

THE CARDIAC NERVES. 521

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 (6) were connected with a
galvanometer. Under such conditions a strong demarcation cur-
rent was obtained flowing through the galvanometer from b 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. f

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 Gaskell ?s 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 Physiologie," 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.

522 CIRCULATION OF BLOOD AND LYMPH.

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 sutured to the peripheral end of the cut vagus, it will,
after time for regeneration has been allowed, cause when stimulated
the usual stoppage 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
terminate differently in these fibers. Nothing more specific can be
said.

The Course of the Accelerator Fibers. — The heart receives
efferent or motor nerve fibers from the sympathetic system in
addition to those reaching it by way of the vagus nerve. Atten-
tion was first called to these sympathetic fibers by Legallois (1812),
but our recent knowledge dates from the experiments made by
von Bezold (1862) which were afterward completed by the Cyon
brothers, — M. and E. Cyon,f 1866. These fibers when stimulated
cause an increased rate of beat and are therefore 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 Fig. 216, which represents 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 byway of the an-
nulus of Vieussens (7) to the inferior cervical ganglion. A num-
ber 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. The pregan-
glionic portion of some of the accelerator fibers ends around the

* Erlanger, "American Journal of Physiology," 13, 372, 1905.

f For the history and literature of the accelerator nerves see Cvon, article
"Cceur," p. 103, in Richet's " Dictionnaire de Physiologic," 1900; or Tiger-
stedt, " Lehrbuch der Physiologie des Kreislaufes," 260, 1893.

THE CARDIAC NERVES.

523

ganglion cells in the first thoracic ganglion, while others apparently
make their first termination in the inferior cervical ganglion. The
accelerator 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 cer-
vical sympathetic above the
inferior cervical ganglion.

At various times investiga-
tors have asserted that accel-
erator fibers are contained also
in the vagus nerve. Thus, it
has been shown that, after the
paralysis of the inhibitory fibers
in the heart by atropin, stimula-
tion of the vagus causes an accel-
eration of the heart. Little at-
tention has been paid to the
physiology of these fibers, since it
seenis evident that the great
outflow of accelerators is made
via the sympathetic system.

The Action of the Ac-
celerator Fibers. — In ex-
perimental work the accel-
erators are usually stimu-
lated in one or more of the
branches represented sche-
matically as 5, 3, 2, in Fig.
216, or in the annulus. ' 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 acceleration 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. 217). In some cases, perhaps in most 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

Fig. 216. — 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-sympathetic trunk
going to cardiac plexus (some of these — 3, 5, —
carry accelerator fibers; 9, the inferior laryngeal
nerve.

524 CIRCULATION OF BLOOD AND LTMPH.

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 seem to
incline to the view that the accelerator nerves, so called, contain in
reality two sets of fibers, one, the accelerators proper, whose func-
tion is simply to accelerate the rate, and one, the augmentors, that
cause a more forcible beat. Under normal conditions we may sup-
pose that these fibers act either separately or in combination.

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.

Fig. 217. — To show the acceleration of the rate of heart beat upon stimulation of the
accelerator nerve, and the long latent period (Beaunis) : PF, The pulse beat registered by
a mercury manometer connected with the femoral artery. The duration of the stimulus
is indicated by the broad marking on line E. The line A shows the beginning of accelera-
tion, and indicates the long latent period.

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
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,.

* 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.

THE CARDIAC NERVES. 525

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
which seem to indicate that increase in heart rate from reflex action
is usually due to 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. It is perhaps dangerous to draw
positive conclusions from such experiments in regard to the work-
ings of these delicate and independent mechanisms under normal
conditions, but since our only positive knowledge must rest upon
experiments we may accept this result provisionally at least. We
may assume, therefore, that the accelerator and the inhibitory
fibers are working constantly on the heart, and its rate is the re-
sultant 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 mainly to a reflex effect upon the car-
dio-inhibitory center. When this center is stimulated to greater
activity, a slower rate results; when it is inhibited, a faster rate.
The tonic activity of the accelerator from this standpoint acts as a
more or less constant opposing force to the inhibitory influence,
so that this latter works against a constant resistance which may be
likened figuratively to that exerted by a spring.

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.

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 fqr 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

526

THE RATE OF THE HEART BEAT. 527

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. 524) 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.

528 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 sensory nerves of the heart itself are stimulated or
sensory fibers distributed to the root 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, J 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.
t Johannson, "Skandinavisches Archiv f. Physiologie," 5, 20, 1895.
j "Centralblatt f. Physiologie," S, 75, 1894.

THE RATE OF THE HEART BEAT.

529

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 C02 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. 218). 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. 219. 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.
34

Fig. 218.— 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.

530

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
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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
have 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,
Johns Hopkins University," 4,
Papers/' p. 97, 1895.

Studies from the Biological Laboratory,
275, 1890; also " Collected Physiological

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."

531

532 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. 462).
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. 533

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 plethysmography
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. 220) . 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 Francois-Franck-
Marey's "Travaux du Laboratoire, " 1876, p. 1.

534

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. 221. 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. 220. — 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;
s, 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. 220, 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. 535

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 hydrosphygmo graph.

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. 221. — 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 of 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. 231) 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

536

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
prevertebral 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. 222. — 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 spiral 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. 233). 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. 537

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. 222). In the general region

Fig. 223. — 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 vasoconstrictor fibers) ; 5, plethysmography tracing of the volume of the kidney
(oncometer) j stimulation of the splanchnic causes a diminution in volume of the kidney
owing to the constriction of its arterioles.

Knder consideration (lower cervical to upper lumbar) each ramus
ommunicans between a spinal nerve and a sympathetic ganglion
onsists, therefore, of two parts, one (white ramus) of preganglionic
ibers passing from the spinal nerve to the ganglion, the other
(gray ramus) of postganglionic fibers coming from the ganglion to

538 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.

539

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.
224. The exact location of the
group of cells that plays the im-
portant role of a vasoconstrictor
eenter has not been determined
histologically. Its 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. 224. — Schema to show the path
of the vasoconstrictor fibers from the vaso-
constrictor center to the blood-vessel and
the mechanism for the reflex stimulation
of these fibers: v. c, The vasoconstrictor
center; 1, the medullary neuron on the

vasoconstrictor path ; 2, the spinal neuron
(preganglionic 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.

540 <\V £*BCULATTON OF BLOOD AND LYMPH.

^*—» — te-4*»*"Tfescription, 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 sensory 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-

\r

THE VASOMOTOR NERVES.

5*

cially perhaps of the cutaneous nerves. And there i
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

artrtV

«&

^^^MMt****

Fig. 225. — Plethysmography 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
to 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.

542 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. 225) ; and we may find an explanation of the value of the reflex
in the supposition that the rise of arterial pressure thus produced

Fig. 226. — Effect of stimulating the central end of the depressor nerve of the heart. — ■
(Dawson.) The time record marks seconds. On 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 normal level. This complete recovery is not shown in the por-
tion of the record reproduced.

forces more blood through the brain (p. 560). 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. 543

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. 226). 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.* Anatomical studies show
that in the heart the fibers arise in part at least in the walls
of the ventricle, and physiological experiments indicate that
the nerve plays an important regulatory role.f When, for in-
stance, blood-pressure rises above normal limits it may be sup-
posed that the endings of this nerve in the heart are stimu-
lated 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. { In this
position the effect of supranormal aortic pressures may more
readily effect a stimulation of their endings and cause a fall of
pressure. 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.

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

* 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, u Archiv f . die gesammte Physiologie, " 93, 24,.
1902.

544 CIRCULATION OF BLOOD AND LYMPH.

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 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. 227. — Rhythmical vasomotor waves of blood-pressure (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. 227), 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-
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.

THE VASOMOTOR NERVES. 545

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 in 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 only
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

* See " Recherches experimentales sur le systeme nerveux vasomoteur, "
Dastre and Morat, 1884.
35

546 CIRCULATION OF BLOOD AND LYMPH.

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.f

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
to believe that they are all 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

* Bowditch and Warren, ''Journal of Physiology," 7, 439, 1886.

t Howell, Budgett, and Leonard, " Journal of Physiology, " 16, 298, 1894.

THE VASOMOTOR NERVES. 547

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 possibility of definite reflex stimulation
of the vasodilator fibers. As stated above, reflex dilatation of the
blood-vessels may be produced by stimulating various sensory nerve
trunks. 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 sensory fibers, — the
pressor and the depressor. The action of the former predominates
usually, but in deep anesthesia, and particularly 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 explana-
tion 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 vaso-
dilator 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. So that some of the many depressor effects
occurring in the body must be due to reflex stimulation of the dila-
tors and others to reflex inhibition of the constrictors. It would be
convenient to retain the name depressor for the sensory fibers caus-
ing the latter effect, and to designate those of the former class by a
different name, such as reflex vasodilator fibers.* Only experi-
mental 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 vaso-
dilator fibers are known to exist. Thus, the 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

548 CIRCULATION OF BLOOD AND LYMPH.

during contraction. Gaskell and others have given reasons for
believing that the vessels in the muscles are supplied with vaso-
dilator nerve fibers, and Kleen* has shown that mechanical stimula-
tion of the muscles — kneading, massage, etc. — causes a fall of arte-
rial 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:

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,
nerve libers. } n Vasodilator fibers— distributed especially to

the erectile tissue, glands, bucco-facial region,
and muscles; not connected with a general
center and not in tonic activity.

I. 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

,fQr^^flflgo™g < 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
the different organs in proportion to their needs. When the blood-
vessels of a given organ are constricted the flow through that organ

* Kleen, " Skandinavisches Archiv f . Physiologie," 247, 1887.

f Bayliss, " Journal of Physiology, " 26, 173, 1900, and 28, 276, 1902.

Efferent vasomotor

vasomotor reflexes.

THE VASOMOTOR NERVES. 549

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 through the reflex activity of the nervous system
exerted partly upon the vasomotor fibers and partly upon the regu-
latory nerves of the heart.

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
diastole will naturally vary with the extent of relaxation of the
cardiac muscle. Since stimulation of either of the 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.

f Porter, " Boston Medical and Surgical Journal, " January 9, 1896.
j Maas, "Archiv f. die gesammte Physiologie, " 74, 281, 1899.

550

VASOMOTOR SUPPLY OE THE ORGANS. 551

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 investigations that the existence of
vasomotor 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. 467, 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 greater 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 cava?, 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 conclude 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.
f Bradford and Dean, " Journal of Physiology,' ' 16, 34, 1894.

552 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 (Francois-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. Plunder f
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.
t Plumier, "Journal de physiologie et de pathologie generate, " 6, 665,
1904; see also "Archives internationales de physiologie," 1, 189, 1904.

VASOMOTOR SUPPLY OF THE ORGANS.

553

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

^1

T)ura??2ater.

^J/racknoitl^ ->j

(Jul 'arachnoids' Z^.
Sftcvce. '~

Cerehrum.

Fig. 228. — 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, but, 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.

554

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 the bone, the pia mater
invests closely the surface of the brain, while between lies the
arachnoid (Fig. 228). 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 rilled
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. 229).
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 cisternse, which
are in communication one
with another by means of the
less conspicuous canals (see
Fig. 230) . 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,

jSHull.

Brain-.
Dura/ftater

JLiouid-

Column*.
DuraJTlater.
Cerebre Spinal lu/tud..
jjfrinal Cord.

Fig. 229. — Diagram to show the connec-
tion of the subarachnoidal space in the brain
and the cord.

VASOMOTOR SUPPLY OF THE ORGANS.

555

pear-shaped protrusion of the arachnoidal membrane into the inte-
rior of a sinus, as represented schematically in Fig. 231. 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 proteids and other
organic substances, which may vary under pathological conditions.
It is much thinner and more watery than the lymph, resembling
rather the aqueous humor of the eye. The amount of this fluid

Fig. 230. — Diagram to show the location
of the cistemae and canals of the subarach-
noidal space. — (Poirier and Charpy.)

Fig. 231. — Schema to show the relations of the Pacchionian bodies to the sinuses:
a, a, 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

556 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. 232. A system with an artery, capillary area,

VASOMOTOR SUPPLY OF THE ORGANS.

557

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
pressure is least.

the internal

^

^\

%

f*

\

%

f

i/

-4

1

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 simply 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

* 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.

Fig. 232. — 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 fijled 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.

558 CIRCULATION OF BLOOD AND LYMPH.

of blood flowing 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. 229) 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. 233. — Simultaneous record of pulse in the circle of Willis (c) and in the torcu-
lar Herophili (t). 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. 233. 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. 559

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,— Hiirthle, Francois-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.

X Hiirthle, " Archiv f. die gesammte Physiologic/ ' 44, 574, 1889 ; Francois-
Franck, "Archives de physiol. normale et pathologique," 1890; Cava-
zanni, "Archives italiennes de biologie," 19, 214, 1893.

560 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 Francois-Franck has
shown that the sympathetic in the neck contains afferent fibers
which give such reflexes * As an argument in favor of the presence
of vasomotor fibers it may also be mentioned that a number of
observers — Gulland, Huber, Hunter f have demonstrated that the
vessels of the brain are provided with perivascular nerve plexuses.
It must be admitted, however, that this histological fact is not con-
clusive unless it is supplemented by experimental evidence. Judged
from this latter standpoint, we have no satisfactory proof at present
of the existence of cerebral vasomotors, and, accepting this negative
evidence, 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.
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

* Francois-Franck, "Journal de phys. et de path, gen.," 1, 724, 1889.
f See Hunter, " Journal of Physiologie, " 26, 465, 1902.

VASOMOTOR SUPPLY OF THE ORGANS. 561

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 at least the constrictor
fibers for the head take a somewhat different course. It was
shown by Schiff, long ago, that in the rabbit the ear receives vaso-
motor 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 vaso-
dilator fibers for the head are supplied in part by way of the cervical
sympathetic, following the same general path as the constrictors,
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-
tation in the membrane of the nose, soft palate, tonsils, uvula, roof
of mouth, upper lips, gums, and pharynx. 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,
>arotid and orbital glands. Dastre and Morat describe the vaso-
lilators in the cervical sympathetic as reaching the fifth cranial
nerve by communicating branches from the superior cervical
;anglion 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.
36

562 CIRCULATION OF BLOOD AND LYMPH.

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 such fibers are found in the sympathetic
system following the same general course as the constrictors has
not been shown conclusively. The most definite work at present
(Bayliss) indicates that the vasomotor effect is directly caused in
some unknown way by sensory fibers arising in the posterior roots
of the nerves forming the brachial and the sciatic plexus. The
unsatisfactory explanations offered for this result have been re-
ferred to (p. 548).

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 (Francois-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 vasocon-
strictor 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
eleventh, twelfth, and thirteenth thoracic nerves, and those for the
liver (Frangois-Franck and Hallion) come from about the same
region. The vasomotor supplies of the spleen and the bladder have
not as yet been investigated successfully.

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

VASOMOTOR SUPPLY OF THE ORGANS. 563

best known of the sacral autonomic system. They enter the ner-
vus 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
dilator fibers and thus allows the effects of the constrictors to mani-
fest themselves. Since, however, Bayliss has shown or claimed (p.
548) that the dilator effect in the limbs is due to the antidromic
action of sensory 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 uncertain
whether this result is brought about solely by an increased activity
of the heart or by the combined effect of vasodilatation and in-
crease in heart- work. Kaufmann J 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

* For the bibliography of the vasomotor supply to the various organs see,
Langley, " Ergebnisse der Physiologie, " vol ii, part II, p. 820, 1903.

fGaskell, " Journal of Physiology," 1, 262, 1878-79.

X Kaufmann, " Archives de physiologie normale et pathologique, " 1892,
pp. 279 and 495.

564 CIRCULATION OF BLOOD AND LYMPH.

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.

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, however, 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* but this supply may be exceptional, as the portal
system itself is unique. The portal vein, indeed, plays the role
physiologically of an artery in regard to the liver. Roy and
Sherrington f give some evidence for the existence of venomotor
nerves to the large veins of the neck, and Thompson, as also Ban-
croft^ reports experiments in which it was found that stimulation
of the sciatic nerve caused a visible constriction of the superficial
veins of the 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
circulation.

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

* Mall, " Archiv f . Physiologie, " 1892, p. 409.

f Roy and Sherrington, "Journal of Physiology," 11, 85, 1890.

% Bancroft, "American Journal of Physiology," 1, 477, 1898.

VASOMOTOR SUPPLY OF THE ORGANS. 565

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 pendular 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-
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-

566

HISTORICAL. 567

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

568 PHYSIOLOGY OF RESPIRATION.

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,

HISTORICAL. 569

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 certain parts of physiology to-day
we can recognize a similar state of affairs and from the history
of respiration we may assume that periods of this character are
necessary transitions to a fuller and more satisfactory knowledge.
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 combustion 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 C02
and H20, 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 physiological 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-

570 PHYSIOLOGY OF RESPIRATION.

bination with the hemoglobin. The nature of the combination of
the carbon dioxid in the blood is not yet entirely understood, while
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 structure of the trachea and
bronchi is 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

EXTERNAL RESPIRATION AND RESPIRATORY MOVEMENTS. 571

glands. All these organs, therefore, lie outside the lungs. A
schematic view of these relations is represented in Fig. 234.

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. 234, 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, then at once
the lungs shrink in size, 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

Fig. 234. — Schema to indicate the re-
lations of the parietal and visceral layers of
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.

572 PHYSIOLOGY OF RESPIRATION.

constitutes an active expiration, which will drive some air out of the
lungs. It is evident, however, that after an active inspiration the
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 vertebra?, 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 tend to antagonize the inspira-
tory action of the diaphragm, and other muscles are apparently

EXTERNAL RESPIRATION AND RESPIRATORY MOVEMENTS. 573

Fig. 235.-

Sixth dorsal vertebra and
rib. — (Reichert.)

brought into play to prevent this result. As stated below, the
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. 235).
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
Moreover, as the rib moves upward there

Fig. 236.— 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 (st.), the antero-
posterior or dorsoventral di-
ameter of the chest is in-
creased) . Any movement from
the position a' would cause an
expiration.

direction (see Fig. 236).

574 . PHYSIOLOGY OF RESPIRATION.

- fm^s I

is^ifi obvious enlargement of the chest in the lateral diameter.

result may be referred to two causes : In the first place, the

of the rotation of the ribs, — that is, the line joining the head

id the tubercle of the rib is inclined downward so that the plane

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 that 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 noted. In
other cases, however, it is necessary to make use of the method
first suggested by Newell Martin, — namely, to determine whether
the contraction of the muscle in respiration occurs simultaneously
with that of the diaphragm or alternately with it. In the former
case it is inspiratory, in the latter expiratory. The following mus-
cles may be classed as inspiratory : Levatores costarum. They arise
from the transverse process 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.

EXTERNAL RESPIRATION AND RESPIRATORY MOVEMENTS. $75

O '

in size of the thorax — may also be produced in two ways: Fhtet,^
by forcing the diaphragm farther into the thoracic cavity. This '
result is obtained, not by any direct action of the diaphragm, b\t
by contracting the muscular walls of the abdomen, the external am
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 process is used 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 t he 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. So far as the author knows,
such experiments have not been made.

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.

576 PHYSIOLOGY OF RESPIRATION.

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.

EXTERNAL RESPIRATION AND RESPIRATORY MOVEMENTS. 577

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-
noicl 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. 237.
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.
37

578

PHYSIOLOGY OF RESPIRATION.

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. 237. — Figure of Marey's pneumograph. — (Verdin.) The instrument consists of
a tambour (t), 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. 238. — 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

EXTERNAL RESPIRATION AND RESPIRATORY MOVEMENTS. 579

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. 238. 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 spirometer, — a form of gasometer
adapted to this purpose. The con-
struction of this apparatus is repre-
sented in Fig. 239. It consists of a
graduated cylinder (A) and a receiver
(B) 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

Eig. 239. — Wintrich's modifi-
cation of Hutchinson's spirometer.
— (Reichert.)

580 PHYSIOLOGY OF RESPIRATION.

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 and 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.

EXTERNAL RESPIRATION AND RESPIRATORY MOVEMENTS. 581

The Size of the Bronchial Tree and 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. 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 its total
capacity may be reckoned at 140 c.c* At each inspiration,
therefore, 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 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 amount
of hydrogen 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 respirations 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 naturally can not 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-
pressing the lower part of the chest while the subject is in a supine
position. Schaefer, who has recently compared these different
* See Loewy, " Archiv f. die gesammte Physiologie, " 58, 416.

582 PHYSIOLOGY OF RESPIRATION.

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. 240) 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 upbn

Xi

i

WW . -,_-.X-^ — -?-7^

Fig. 240. — 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. lxxxvii,
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. 241.

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

583

. — 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.

584 PHYSIOLOGY OF RESPIRATION.

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. Donders 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 Donders 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. 241) . 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

PRESSURE CONDITIONS IN LUNGS AND THORAX. 585

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 Donders 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 inspiration
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 of 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 (755.36)
and at the end of expiration — 3.02 mms. Hg (756.98), — 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. 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 Physiologie, " 29, 265, 1882.

t Aron, quoted from Emerson, "Johns Hopkins Hospital Reports," 11,
194, 1903.

586 PHYSIOLOGY OF RESPIRATION.

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 to 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 Physiologie, " 30, 276, 1883.

PRESSURE CONDITIONS IN LUNGS AND THORAX. 587

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.

Pneumothorax. — 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
lungs 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 cavae 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.

588 PHYSIOLOGY OF RESPIRATION..

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. 242). 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.
243). 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

PRESSURE CONDITIONS IN LUNGS AND THORAX. 589

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. 242. — 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.

590

PHYSIOLOGY OF RESPIRATION.

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. 243. — 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 rise. 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 Physiologie, " vol. ii, part n, 560, 1903.

PRESSURE CONDITIONS IN LUNGS AND THORAX. 591

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 ai . 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

592

CHANGES IN AIR AND BLOOD IN RESPIRATION. 593

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.
38

594 PHYSIOLOGY OF RESPIRATION.

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 such a substance. Individuals kept
in a confined space for a number of hours give no symptoms of 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

CHANGES IN AIR AND BLOOD IN RESPIRATION. 595

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 = — , in which d represents in cubic meters the delivery of fresh
air per hour; e, the amount of C02 expired per hour in liters; and r
the ratio of permissible vitiation of the air by C02. Assuming this
latter factor, in accordance with the above statement, to be equal to
0.2, 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 cubic meters of air per hour for each
person. The rapidity of renewal of air will depend naturally upon

596 PHYSIOLOGY OF RESPIRATION.

the cubic space allotted to each individual. The smaller this space,
the more ample must be the ventilation. 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 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. 244. 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
Bt which is to contain the blood, is connected with F, as shown in the figure,

* Taken from Bergey, " The Principles of Hygiene, " 1904.

CHANGES IN AIR AND BLOOD IN RESPIRATION.

597

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. 244. — Gas pump for extracting the gases of blood (Grehant) : M and Ff
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

598 PHYSIOLOGY OF RESPIRATION.

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 C02 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 C02. 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 following formula:

yi = 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 time 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 Pfluger the following
figures were obtained reckoned in volumes per cent. : O, 22.6; C02,
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 C02 measured at 0° C. and 760 mms.
Hg. An analysis of human blood (Setschenow) gave closely similar
figures; O, 21.6 per cent.; C02J 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. co2. N.

Arterial blood 20 38 1.7

Venous blood 12 45 1.7

Difference .~8 ~7 ~~0~

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.

CHANGES IN AIR AND BLOOD IN RESPIRATION. 599

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 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 mechani-
cal theory of gases 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 -g-X760= 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 percen-
tages 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

600 PHYSIOLOGY OF RESPIRATION.

shown, in accordance with this mechanical conception, that the
amount of a given gas dissolved by a given liquid varies, the temper-
ature remaining the same, directly with the pressure, — that is,
it increases and decreases proportionally with the rise and fall of
the gas pressure. This is the law of Henry-Dai ton. 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 a 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 : 0,0.0262; N, 0.0130; C02, 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 C02 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.

CHANGES IN AIR AND BLOOD IN RESPIRATION. 601

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 the gas the partial pressure
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.
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, C02, 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. 245. It is known as an aero-
tonometer (Pfluger). 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
A by dropping the bulb. Blood is allowed

602

PHYSIOLOGY OF RESPIRATION.

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 of Henry and Dal ton. If an
animal is permitted to breathe an atmosphere of oxygen and
hydrogen the nitrogen disappears from the blood, and the nitrogen
contents of the arterial and venous bloods exhibit no constant
difference in quantity. It seems certain, therefore, that the nitro-
gen plays no direct role in the physiological processes. It is ab-
sorbed by the blood in proportion to its partial pressure in the

Fig. 245. — Diagram to show the
principle of the aerotonometer : A, The
tube containing a known mixture of
gases, O, COj, N; C, the outside jacket
for maintaining a constant body tem-
perature. When stopcock b 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.

CHANGES IN AIR AND BLOOD IN RESPIRATION.

603

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-

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*4

t

//;

t

*)

i

;r

9*

7,

'.

i,

'.

4

1

n

*t

[

tt

/;

86f.

7*
id-

Fig. 246. — 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. t 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

* Hufner, "Archiv f. Physiologie, " suppl. volume, 1901, p. 213.
t Loewy, " Archiv f . Physiologie, " 1904, p. 245.

604 PHYSIOLOGY OF RESPIRATION.

of dissociation in the body. The results obtained by Loewy are
indicated in the curve of dissociation shown in Fig. 246, 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 Henry-Dalton law 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 mms.) the chemically
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 chemi-
cal combination is from a quantitative standpoint much more
important 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
hemoglobin 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, 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 C02 does not vary proportion-
ally to the pressure of C02 in the surrounding medium in accordance
with the law of Henry and Dalton. Examination of the blood by
means of the gas pump shows that C02 is contained in both the
corpuscles and the plasma or serum. The results of various analyses
would indicate that about J of the total amount is held in the cor-
puscles and about f in the liquid of the blood, and, since the cor-
puscles make up about % of the bulk of the blood, this fact would
indicate that the C02 is distributed uniformly throughout the mass
of the blood. The condition of the C02 in the blood may be con-
sidered under three heads: (1) The part in solution; (2) the part in

CHANGES IN AIR AND BLOOD IN RESPIRATION. 605

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. 600, 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 present
in the plasma is held partly in loose 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 C02 is given off; to obtain the
remainder, the so-called fixed C02, it is necessary to add some
weak acid. If the full blood is used in such an experiment all of the
C02 may be obtained, — a fact which indicates that the red corpuscles
(hemoglobin) play the part, in this respect, of a weak acid. The
form in which the C02 is held in the plasma is not entirely
understood. It is supposed that it is combined with the alkali
of the blood as sodium carbonate (Na2C03) or sodium bicar-
bonate (HNaC03). When the carbon dioxid pressure in the sur-
rounding medium is lowered, some of the bicarbonate dissociates,
giving off CO 2 ; and the reverse takes place when the pressure of the
carbon dioxid is raised. Essentially, therefore, the process of taking
up and giving off C02 from the plasma may be represented by the
reaction: Na2C03 + C02+H20^± 2(HNaC03). In the blood, how-
ever, the conditions are more complex than in a simple aqueous solu-
tion of carbonate of soda. The proteid present has also an affinity for
the alkali and thus acts like a weak acid in aiding the dissociation
of the bicarbonate. One may say that the alkali of the blood is
distributed between the C02 and the proteid in accordance with
the law of mass action, and that the proteid thus plays an important
part as well as the alkali in controlling the conditions under which
the CO 2 is held. The phosphoric acid in the blood, so far as it is
present, plays naturally a similar role in combining with the alkali
and thus influencing the dissociation of the compound of the C02
with the alkali. If the proteids (and phosphates) were not present
the combination between the alkali and C02 would be so strong that
the compound would fail to fulfill its respiratory functions, — that is,
ijt would not dissociate readily when the pressure of the C02 in the
surrounding medium is lowered.

The portion of the C02 that is held in the corpuscles is contained
in part in combination with the alkali present, under the same con-
ditions as those described for the plasma. But, according to
Bohr,* the hemoglobin is capable of combining directly with the
C02, and, indeed, independently of the amount of oxygen that it
may hold in combination. He suggests that the C02 combines with
* Bohr, " Skandinavisches Arehiv f. Physiologie, " 16, 402, 1904.

606 PHYSIOLOGY OF RESPIRATION.

the proteid portion (globin) of the molecule, whereas the oxygen, as
is well known, unites with the pigment portion, the hematin. The
condition of the C02 in the blood is therefore not so simple as that
of the oxygen ; but so far as the mechanism affecting the exchange
of CO 2 in the tissues and in the lungs is concerned it must be
regarded as dependent upon a reaction between the gas and the
alkali of the blood, influenced, as above stated, by the presence of
the proteid. There is apparently no specially developed organic
substance which acts as a carrier of C02 in the same way that
hemoglobin behaves toward oxygen.

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
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. A normal
expiration contains 500 c.c; hence the alveolar air constitutes only
360 c.c. or y! of the entire amount. If the expired air contains 4.38
per cent, of C02, then the alveolar air must contain 4.38 -*- -g-f ov 6

CHANGES IN AIR AND BLOOD IN RESPIRATION. 607

per cent, of carbon dioxid. By the same mode of calculation the
oxygen in the alveoli, assuming that the expired air contains 16
per cent, and the nitrogen suffers no change, should be equal to 14
per cent, of an atmosphere or 106 nuns, of Hg (760 X 0.14). Actual
observations made by these authors upon human beings in which
the expired air was analyzed indicate that the composition of the
alveolar air may vary between the following limits: Oxygen be-
tween 11 and 17 per cent, of an atmosphere (83.6 to 129.2 mms.
Hg) ; carbon dioxid between 3.7 and 5.5 per cent, of an atmosphere
(27.9 to 41.8 mms. Hg).

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
(40.2 mms. Hg), and the C02 under a tension of 6 per cent. (45.6
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 83.6 to 129.2 mms. 27.9 to 41.8 mms.

Membrane j 1

f •

Venous blood . . . 40.2 mms. 45.6 mms.

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 (Pfluger). 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,

* Loewy and von Schrotter, " Zeitschrift fur experimentelle Pathologie
und Therapie," 1, 197, 1905.

608 PHYSIOLOGY OF RESPIRATION.

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. (tifWfif)-

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 (28.1 to 41.8 mms. Hg). 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
C02 is present under a tension (Strassburg) of 7 to 9 per cent. (53.2
to 68.4 mms.). The high tension of the C02 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 substance is combined in some way
in a chemical compound too firm to dissociate. The physical con-
ditions are therefore such as would cause a stream of C02 from
tissue to blood and a stream of oxygen in the reverse direction.

Oxygen. Carbon Dioxid.

Arterial blood 75 mms. 28.1 to 41.8 mms.

Wall of capillary J- —

Tissues 0 mm. 53.2 to 68.4 mms.

It is to be remembered that in this exchange the blood and
the lymph act as intermediaries. The C02 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

* " Skandinavisches Archiv f. Physiologie," 16, 402, 1904.

t See Haldane and Smith, " Journal of Physiology," 20, 497, 1896.

CHANGES IN AIR AND BLOOD IN RESPIRATION. 609

claim that the tension of the oxygen in the arterial blood is higher than the
pressure of oxygen in the alveolar air, and Bohr has stated that the pressure
of C02 in the air in the trachea is higher than that in the venous blood. If
these facts were fully demonstrated they would show that the physical theory
outlined above is insufficient, and would indicate that the membranes con-
cerned 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 impossible, 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 ob-
servers who have worked in the same field, and it seems probable that they
may be due to experimental errors. A well-known set of experiments that
strengthen this conclusion has been reported by Wolffberg and by Nussbaum *
and has since been repeated upon man. In these experiments one bron-
chus 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 C02, while the tension of
the C02 in specimens of the venous blood taken from the right heart was
practically identical. If there is an active secretion of C02 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.

* " Archiv f. die gesammte Physiologie," 4, 465, 1871, and 7, 296, 1873.

39

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 (noeud 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 Physiologie, " 7, 583, 1873; and "Cen-
tralblatt f. d. med. Wissenschaften," No. 34, 1885.

610

M

INNERVATION OF THE RESPIRATORY MOVEMENTS. Gil

O ;

2 or 3 mms. posterior to the calamus. No especial group of cells^
can be found in this region sufficiently separated anatomically lb°_
make it probable that they constitute the center in question. ThV % /,
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 Gadf 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 casej 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-Sequard, 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.

j See Kehrer, " Monatshefte f. prakt. Dermatol.," 28, 450, 1892.

612 PHYSIOLOGY OF RESPIRATION.

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
eord 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-,
ma tic, 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 fifth,
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.

INNERVATION OF THE RESPIRATORY MOVEMENTS.

613

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
medulla. As stated above, the
effect of these sensory nerves
upon the activity of the respiratory center is varied ; the rate may

Fig. 247.— To show the augmenta-
tion of the respiratory movements caused
by stimulation of the sciatic nerve. Ex-
periment upon a rabbit.

rt«»*--S'Hi

S1v>n.C«nl>*l Em! Vagus- Weak,

Fig. 248. — To show the inhibition of the resoiratory 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

614 PHYSIOLOGY OF RESPIRATION.

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. 247 and 248).
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. 249).
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 obtained
only after section of both nerves. This result is not a temporary
one due 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

INNERVATION OF THE RESPIRATORY MOVEMENTS. 615

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. 249. — 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. 248), or, second,
the rate of the inspiratory movements ma}^ 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. 250),

Fig. 250. — 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

616 PHYSIOLOGY OF RESPIRATION.

stimuli, and has led to much difference of opinion among investi-
gators.* The two main effects described above and obtained
with stimuli not too strong are usually interpreted to mean that the
vagus contains two kinds of sensory fibers which are distributed to
the lungs and act normally on the respiratory 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 inspiratory 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 dif-
ference 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 . Physiologie, "
1892, p. 340; also "New York Medical Journal, " January 18, 1890. Le-
wandowsky, " Archiv f. Physiologie," 1896, pp. 195 and 483.

INNERVATION OF THE RESPIRATORY MOVEMENTS. 617

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, CI, NH3, S02, 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-

Iposeful end in the expulsion of the stimulating object. In this case
* "Archiv f. die gesammte Physiologie, " 42, 273.
■

618 PHYSIOLOGY OF RESPIRATION.

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.

INNERVATION OF THE RESPIRATORY MOVEMENTS. 619

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 a schema 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.
t "Archiv f . Physiologie, " 1896, 489.

620 PHYSIOLOGY OF RESPIRATION.

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,
the center acts more feebly or may fail to act altogether, giving the
condition known as apnea. These facts may be accepted as com-
pletely 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 through-
out life? The three possible views have been defended : (1) That
the normal stimulus is a lack of sufficient oxygen (Rosenthal).
When sufficient O is supplied the center ceases to act, becomes
apneic. (2) That the normal stimulus is the presence of an excess
of C02 (Traube). When this excretion is quickly removed the cen-
ter 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 C02 fast enough and does not supply sufficient oxygen. It is
difficult, indeed impossible, to arrive at any certain conclusion upon
this point. 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 C02 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. Physiologie," 1897, 379. See also Friedlander
and Herter, "Zeit. f. physiol. Chemie," 2, 99, and 3, 19.

INNERVATION OF THE RESPIRATORY MOVEMENTS. 621

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, oxygen " " " " = 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 is 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. C02 " " " " 9.060 "

Air of 18.06 per cent. O, 2.97 per

cent. C02 " " " " 11,326 "

Air of 18.42 per cent. O, 11.5 per

cent. C02 " " " " 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 respirator}^ 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 facts seem to favor rather the view that it is the
constant presence of the C02 which directly or indirectly occasions
the normal discharges from the respiratory center. It is, of course,
possible that other constituents of the blood may play an important
part in providing accessory conditions of rhythmical activity, as
in the case of the heart beat.

The Cause of the First Respiratory Movement. — The mam-
malian fetus under normal conditions makes no respiratory move-

* Bert, "La pression barometrique, " 1878, 691.
f Haldane, " Journal of Physiology, " 18, 442, 1895.

622 PHYSIOLOGY OF RESPIRATION.

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 following interruption of the placental circulation.
During the intra-uterine period it is evident that the fetal blood is
aerated by exchange with the maternal blood sufficiently well not
to act as a stimulus to the fetal respiratory center. The fetus is,
physiologically 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 respiratory 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
the pain nerves, or by an increased venosity of the blood, — that is,
by an increase in the C02 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

* Cohnstein and Zuntz, " Arch. f. die gesammte Physiol," 42, 342, 1888.

INNERVATION OF THE RESPIRATORY MOVEMENTS. 623

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,
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-

Fig. 251. — 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.)

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
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. 251). One may produce a similar condition upon

624 PHYSIOLOGY OF RESPIRATION.

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 apncea 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-
thal's 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
assumed that this latter condition is due to an overoxygenation of
the blood, but since the vigorous respirations lower the contents of
the blood in C02 it is possible, as insisted upon by Traube, that this
factor may be the more important. At present there are no facts
which will enable us to decide definitively between these views;
but, since, in the preceding paragraphs, some evidence has been
given to show that the normal stimulus to the center is due to the

* 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 Physiologie, " 42, 245, 1888; and
Langendorff, "Archiv f. Physiologie," 1888, p. 286.

INNERVATION OF THE RESPIRATORY MOVEMENTS. 625

presence of C02, 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. Experimentally 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 affect. This observation is further supported by recent
experiments by Mosso* upon men, in which he shows that apnea
can not be produced by inflation with carbon dioxid. This author
designates the condition of diminished C02 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.

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. t 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 —
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 C02 lead to a bronchoconstriction and this reflex, as stated on

* 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.
40

626 PHYSIOLOGY OF RESPIRATION.

p. 617, 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 C02
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 Physiologie, " 42, 189,

1888.

627

628 PHYSIOLOGY OF RESPIRATION.

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.

INFLUENCE OF VARIOUS CONDITIONS ON RESPIRATION. 629

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 C02.

Increased Percentages of Carbon Dioxid. — It was pointed out
clearly by the researches of Friedlander and Herter* that death
from increased percentages of C02 is accompanied by symptoms
quite different from those due to lack of oxygen. As the C02 is
increased a noticeable hyperpnea may be observed (Zuntz) at a
concentration of about 3 per cent. When the concentration of C02
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.

630 PHYSIOLOGY OF RESPIRATION.

etc. At certain altitudes, from 3000 to 4000 meters, disagreeable
symptoms are experienced by many 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 nuns., so that
there is an oxygen pressure of 92 nuns., — 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 it, 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 Kronecker, " Die Bergkrankheit," Berlin, 1903. Mosso and Marro,
" Archives italiennes de biologie, " 39, 387, also vols. 40 and 41. Cohnheim,
article on " Alpinismus, " " Ergebnisse der Physiologie, " vol. ii, part i, 1903.

INFLUENCE OF VARIOUS CONDITIONS ON RESPIRATION. 631

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 C02, — 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: ~=^ =1. All the
oxygen used in the combustion might be considered as uniting with
the C to form C02, 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

C6H1206 + 602 = 6C02 + 6H20. R. Q. = f = 1.

The number of molecules of C02 formed in the oxidation is equal
to the number of molecules of 02 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(C16H3102)3 = C^H^CV
2(CS1H9806) + 14502 = 102CO2 + 98H20.

R. Q- = m = 0.7.

632 PHYSIOLOGY OF RESPIRATION.

In the same way it may be estimated that the R. Q. for the oxidation
of proteids 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 C02 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. 252.— Record showing typical Cheyne-Stokes respiration (from a case of aortic and
mitral insufficiency with arteriosclerosis). The time 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 C02 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

INFLUENCE OF VARIOUS CONDITIONS ON RESPIRATION. 633

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, etc. 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. 252). The cause of this rhythm has not been
discovered. It is not certain whether the apnea between the
groups of respiration is a true apnea or an inhibitory apnea or an
apnea of some other kind resulting from some different kind of
action upon the respiratory center. A similar rhythm is often
observed in the beats of an isolated heart of the cold-blooded
animals under conditions which imply an insufficient supply of
oxygen. More or less rhythmical variations in the strength of the
breathing movements have been described also in normal sleep,
hibernation, chloral narcosis, etc., but nothing so definite and
characteristic as in these very interesting Cheyne-Stokes cases.

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
pterygoids 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,

634

MOVEMENTS OF THE ALIMENTARY CANAL. 635

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 . Physiologie, " 1883, suppl. volume,
p. 328; also "Journal of Experimental Medicine, " 2, 453, 1897. For later
work, 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 Physiologie," 99, 513,
1903.

636 PHYSIOLOGY OF DIGESTION AND SECRETION.

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 levator 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 uvulae 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.

MOVEMENTS OF THE ALIMENTARY CANAL. 637

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

638 PHYSIOLOGY OF DIGESTION AND SECRETION.

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.

MOVEMENTS OF THE ALIMENTARY CANAL.

639

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

num.,

J-Pyiorus-

Pyloric part of stomach
or antrum. jbyiori.

Position, of
traitsuersebcmcL

Intermediate or
jorebylorie regioru

Fig. 253. — 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 (/. 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, " Archiv f . Anatomie, "1903, p. 345.

t Some recent writers confine this term antrum pylori to that portion
of the pyloric region bordering upon the pyloric orifice.

640 PHYSIOLOGY OF DIGESTION AND SECRETION.

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 recentlyf 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.
t Hofmeister und Schutz, " Archiv f . exper. Pathologie und Pharmakol-
ogie, " 1886, vol. xx.

MOVEMENTS OF THE ALIMENTARY CANAL. 641

ods. The first noteworthy contributions to this subject were
those made in this country 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 of contraction serve
to press the stomach contents against the pylorus. According to
Cannon, they occur in the cat at intervals of 10 sec. and each
wave requires about 20 sec. to reach the pylorus. According to
Beaumont's observations, the contraction waves follow at longer
intervals in man (2 to 3 min.). 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 contents into the duodenum with
considerable force. The mechanism controlling the relaxation
of this sphincter is obscure. It does not occur with the ap-
proach of each contraction wave, but at irregular intervals.
Cannon connects it with the consistency of the food. Solid
objects forced against the pylorus prevent relaxation and retard
the passage of the chyme into the intestine. Wheh liquid food
alone is taken into the stomach numerous observations made by
means of intestinal fistulas show that the material is forced into
the duodenum within a few minutes. According to this description,

* 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 Physiologie, " 10, 85, 1898.

% Hofmeister and Schiitz, loc. cit.

§ Moritz, " Zeitschrift f . Biologie, " 32, 359, 1895.
41

642 PHYSIOLOGY OF DIGESTION AND SECRETION.

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 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 be-
comes 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
especially 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
rtoma-of^rS^d&tiSnS walls of the stomach, while the
S0Jiffehreenttr S^-(Sr&^ gThe succeeding portions were arranged
food was given m three portions and regularly in the interior in a COn-
colored differently: first, black; sec- . „ , . . ,
ond, white (indicated by vertical centric fashion, as shown in the
marking) ; third, red (indicated by n ^ , »

transverse marking). figure. Such an arrangement of

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
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. Cannonf 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

* Grutzner, " Archiv f. die gesammte Physiologie, " 106, 463, 1905.
t Cannon, "American Journal of Physiology, " 12, 387, 1904.

MOVEMENTS OF THE ALIMENTARY CANAL. 643

carbohydrate food begins to pass out from the stomach soon after
ingestion, and requires only about one half as much time as the pro-
teids 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. There is an indication, therefore, that the relaxation of the
sphincter may be controlled in some way by chemical stimuli
originating in the digested food.

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 it seems probable that its orderly
movements may be merely regulated through these extrinsic fibers,
and that it is essentially an automatic 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 the older observers * that gastric digestion may proceed normally
both as regards secretion and movements after section of the
extrinsic nerves. The point has not yet perhaps been demonstrated
conclusively, but provisionally we may regard the stomach, con-
sidered 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 Auer-
bach), is a question that can not be answered 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

* See Heidenhain in Hermann's " Handbuch der Physiologie, " vol. v,
p. 118.

644 PHYSIOLOGY OF DIGESTION AND SECRETION.

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 caus-
ing more or less well marked contractions 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 musculature is supplied by motor
fibers from these nerves. The fibers coming through the splanch-
nics, on the contrary, are mainly inhibitory. 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 physio-
logical varieties. Through their activity, without doubt, the move-
ments of the stomach may be influenced, favorably or unfavorably,
by conditions directly or indirectly affecting the central nervous
system. Wertheimer* has shown experimentally that stimulation
of the central end of the sciatic or the vagus nerve may cause reflex
inhibition of the tonus of the stomach, and Doyonf has confirmed
this result in cases in which the movements and tonicity of the stom-
ach were first increased by the action 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.

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

* "Archives de physiologic normale et pathologique, " 1892, p. 379.
f Ibid., 1895, p. 374.

MOVEMENTS OF THE ALIMENTARY CANAL. 645

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 sometimes in isolated pieces of intestine or in the exposed
intestine of living animals when stimulated artificially, and Griitz-
ner* 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 con-
ditions. The peristaltic wave normally passes downward, and that
this direction of movement is dependent upon some definite ar-
rangement in the intestinal walls is shown by the experiments of
Mallf 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 examined 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.

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

*" Deutsche medicinische Wochenschrift, " No. 48, 1894.
t" Johns Hopkins Hospital Reports," 1, 93, 1896.
% "Journal of Physiology," 24, 99, 1899.

if f'^-Wl PHYSIOLOGY OF DIGESTION AND SECRETION.

Kit

la

r i^tereceded by a wave of relaxation or inhibition. The force of the
$ fiSjifbraction as measured by Cash * in the dog's intestine is very small,
eight of five to eight grams was sufficient to check the onward
^m/vement of the substance in the intestine and to set up violent,
^Joolicky contractions which caused the animal evident uneasiness.
/ f§>s^e may suPPose that under normal conditions each injection of
//chyme from the stomach into the duodenum is followed by a
peristalsis that, beginning at the duodenum, passes slowly down-
ward over a part or all of the small intestine. According to most
observers, the movement is blocked at the ileocecal valve, and the
peristaltic movements of the large intestine form an independent
group.

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.

Pendular Movements. — In addition to the peristaltic wave a
second kind of movement may be observed in the exposed intestines
of a living animal. This movement is characterized by a gentle
swinging to and fro of the different loops, whence its name of pendu-
lar movement. Mallf has shown that the main feature of this
movement is a rhythmical contraction of the circular muscles.
He prefers to speak of the movements as rhythmical instead of
pendular contractions, and points out that, owing to the arrange-
ment of the blood-vessels in the coats of the intestine, the rhythmical
contractions should act as a pump to expel the blood from the
submucous venous plexus into the radicles of the superior mesenteric
vein, and thus materially aid in keeping up the circulation through
the intestine and in maintaining a good pressure in the portal vein,

*" Proceedings of the Roval Society," London, 41, 1887.
t" Johns Hopkins Hospital Reports," 1, 37, 1896.

MOVEMENTS OF THE ALIMENTARY CANAL.

in much the same way as happens in the case of the spleen. Bay i£ 3
and Starling corroborate this view, except that they find that b\t
the circular and longitudinal layers of muscle are concerned in
movement. The rhythmical contractions, according to theVe'
observers, are entirely muscular in origin, since they persist afteV 7^
the application of nicotin or cocain. Vfi

Cannon* has studied the movements of the small intestines most
successfully by means of the Roentgen rays. He finds, in the cat,
that the most characteristic phenomenon is that due to the rhyth-
mical or pendular movements. By means of these contractions
masses or strings of the food 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. 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 absorptive 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 pieces are caught, as it were,
by an advancing peristaltic wave, moved forward a certain dis-
tance, 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. Some-
what similar movements have been described by Bunch f from
observations on the isolated intestine. The curious observation is
reported J 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. 703).

The Nervous Control of the Intestinal Movements. — As
stated, there is some evidence to show that the rhythmical con-
tractions 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 de-
pendent for either movement upon its connections with the central
nervous system. Like the stomach, it is an automatic organ whose
activity is regulated through its extrinsic nerves.

* Cannon, "American Journal of Physiology," 6, 251, 1902.

t Bunch, " Journal of Physiology," 22, 357, 1897.

I Boldireff, "Archives des sciences biologiques, " 11, 1, 1905.

648 PHYSIOLOGY OF DIGESTION AND SECRETION.

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
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 C02, 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

* " Archiv f . Physiologie, " 1889, suppl. volume.

MOVEMENTS OF THE ALIMENTARY CANAL. 649

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 filled 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
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 f 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

* Cannon, loc. cit.

t 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.

650 PHYSIOLOGY OF DIGESTION AND SECRETION.

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
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

MOVEMENTS OF THE ALIMENTARY CANAL. 651

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
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
*"Archiv f. die gesammte Physiologie, " 8, 160, 1874; 63, 362, 1896.

6o2 PHYSIOLOGY OF DIGESTION AND SECRETION.

during the act. ( )n 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
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
*"Archiv f. Physiologie, " 1889, p. 552.

MOVEMENTS OF THE ALIMENTARY CANAL. 653

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:

Water.

Inorganic salts.
Proteids.

Foodstuffs ( Albuminoids, a group of bodies resembling proteids, 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.
Proteids, 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

654

COMPOSITION OF FOOD AND ACTION OF ENZYMES.

655

molecules into simpler compounds. The chemical changes of metab-
olism or nutrition are, on the whole, exothermic, — that is, they are
attended by the production of heat. Some of the chemical or in-
ternal energy that held the complex molecules together assumes the
form of heat, or perhaps muscular work, after these molecules are
broken down to simpler, more stable structures, such as water, carbon
dioxid, and urea. Proteids, fats, and carbohydrates form materials
that the tissue cells are adjusted to act upon after they have under-
gone 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 can not act upon
them. Such substances can not be considered as foods in the scien-
tific sense. When, therefore, we desire to know the food value of any
animal or vegetable product, we analyze it to determine its com-
position as regards water, salts, proteids, 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.

Water.

Proteid.

Fat.

Carbohydrate.

In 100 Parts.

Digestible.

Cellulose.

Ash.

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

EffffS

1.1

3-4

Cows' milk

Human milk

Wheat flour

Wheat bread

Rye flour

Rye bread

Rice

0.7
0.2
0.5
1.1
1.4
1.5
1.0

Corn

1.5

Macaroni

Peas, beans, lentils
Potatoes

0.5
2-3
1.0

Carrots

0.9

Cabbages

Mushrooms

Fruit

1.3

1.2
0.5

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 proteid or of
proteid and fat. With regard to the last two foodstuffs, meats differ

* See Konig, " Die menschlichen Nahrungs und Genussmittel " ; and
At water and Bryant, " The Chemical Composition of American Food Mate-
rials, " Bulletin 28, United States Department of Agriculture, 1899.

656

PHYSIOLOGY OF DIGESTION AND SECRETION.

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.

Proteid.

Fat.

73.03

20.96

5.41

72.31

18.88

7.41

75.99

17.11

5.77

72.57

20.05

6.81

62.58

22.32

8.68

10.00

3.00

80.50

71.6

18.8

8.2

Carbohydrate.

Ash.

Beef, moderately fat . .

Veal, fat

Mutton, moderately fat,

Pork, lean ,

Ham, salted

Pork (bacon), very fat*
Mackerel *

0.46
0.07

1.14

1.33

1.33

1.10

6.42

6.5

1.4

The vegetable foods are distinguished, as a rule, by their large
percentage in carbohydrates and the relatively small amounts of
proteids and fats, as seen, for example, in the composition of rice,
corn, wheat, and potatoes. Nevertheless, it will be noticed that the
proportion of proteid 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 proteids. The composition of peas
and other leguminous foods is remarkable for the large percentage
of proteid, 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 proteids 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.

COMPOSITION OF FOOD AND ACTION OF ENZYMES. 657

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 (Payen 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
42

658 PHYSIOLOGY OF DIGESTION AND SECRETION.

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.
A very large literature is developing, and the subject is therefore
correspondingly difficult to present in brief compass. 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

* 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 Henri, " Lois generates de Taction des diastases, " 1903.

COMPOSITION OF FOOD AND ACTION OF ENZYMES. 659

undergoes no change, and it is said, therefore, 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 according to the reaction
H202 = H20 + O, but the decomposition is greatly hastened by
the presence of a catalyzer. Thus, Bredig has shown that plati-
num 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 extracts of various
tissues also catalyze the hydrogen peroxid readily, and this effect
has been attributed to the action of an enzyme (catalase). 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 understanding
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 pro-
teid, 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 + C2H5OH = CH3COOC2H5 + H20.

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

660 PHYSIOLOGY OF DIGESTION AND SECRETION.

takes place in opposite directions, figuratively speaking, — a fact
which may be indicated by a symbol of this kind:

CH3COOH + C2H5OH ^± CH3COOC2H5 + H20.

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 :

C3H7COOC2H5 + H20 ^± 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.

COMPOSITION OF FOOD AND ACTION OF ENZYMES. 661

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-
teids 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
proteids, 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: A ferment is a

substance, produced by living cells, which acts by catalysis. The

* Fischer, " Zeitschrift f . physiolog. Chemie," 26, 71, 1898.

662 PHYSIOLOGY OF DIGESTION AND SECRETION.

ferment itself remains unchanged in this process, and it acts specifi-
cally,— that is, each ferment exerts its activity only upon substances
whose molecules have a certain definite structural and stereochemical
arrangement.

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 proteid-splitting enzymes. Examples: pepsin

of gastric juice, trypsin of pancreatic juice. They cause a hydro-
lytic cleavage of the proteid 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, (b) 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-

teids. 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. 833).

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 :

COMPOSITION OF FOOD AND ACTION OF ENZYMES. 663

C^H^On + H20 = C6H,206 + C6H1206.

Maltose. Dextrose. Dextrose.

And the hydrolysis of the neutral fats by lipase may be expressed
so:

C.H.CCmH.A), + 3H20 = C,H5(OH)8 + SJPuPmOX

Tristearin. 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
proteid 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
substance and its enzyme the action of the latter is not complete, —
that is, all of the substance does not disappear. An explanation 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 proc-
esses 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 co-
agulating 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 zymogen. The zymogen may
be stored in the cell in the form of granules which are converted into

664

PHYSIOLOGY OF DIGESTION AND SECRETION.

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.

f

i

-Sail
^■2 J

Enzyme.

Ptyalin (sali-
vary diastase.

A m y lop s i n
(pancreatic
diastase) .

Liver diastase.

Invert ase.
Maltase.

Lactase.
Glycolytic?

Lipase (steap-
sin).

'S
'55

2

Pepsin.
Trypsin.

Erepsin.

Group of auto-
. lytic enzymes.

Guanase.
Adenase.

Oxidases.
Catalase.

Where Chiefly
Found.

Salivary secretion.

Pancreatic secre-
tion.

Liver.

Small intestine.

Small intestine, sal-
ivary and pan-
creatic secre-
tion, liver.

Small intestine.

Muscles?

Pancreatic secre-
tion, fat tissues,
blood, etc.

Gastric juice.
Pancreatic juice.

Small intestine.
Tissues generally.

Thymus, adrenals,

pancreas.
Spleen, pancreas,

liver,

Lungs, liver.
Many tissues.

Action.

Converts starch to sugar

(maltose) .
Converts starch to sugar

(maltose) .

Converts glycogen to dex-
trose (maltose).

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 proteids to pep-
tones and proteoses.

Splits proteids into sim-
pler crystalline prod-
ucts.

Splits peptones into sim-
pler products.

Split proteids into nitrog-
enous bases and amido-
bodies.

Converts guanin to xan-

thin.
Converts adenin to hypo-

xanthin.

Cause oxidation of organic

substances.
Decomposes hydrogen

peroxid.

Chemical Composition of the Enzymes. — It was formerly
believed that the enzymes belong to the group of proteids. They
are formed from living matter, and the solutions as usually prepared
give proteid reactions. Increased study , however, has made this belief
uncertain. The enzymes cling to the proteids when precipitated,
and it seems possible that the proteid reactions of their solutions may

COMPOSITION OF FOOD AND ACTION OF ENZYMES. 665

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
proteid 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 attention"
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 autonomics (or cerebral fibers) and
the sympathetic autonomics. 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. 255). The sympathetic
autonomics 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

666

THE SALIVARY GLANDS.

667

glands arises from the brain in the facial nerve and passes out in the
chorda tympani branch (Fig. 256). This latter nerve, after emerging
from the tympanic cavity through the Glaserian fissure, joins the

Tdroui ,
Ganglion.

Fig. 255. — 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,

^Branches to. __
Sub- ■MtaxilLa.ry- am
Su.6Un.yua.L

branches
Sublinyual^&jTongiLe

Gatwliotu

Fig. 256.

-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

668 PHYSIOLOGY OF DIGESTION AND SECRETION.

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 autonomics 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 in 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 . Physiologie, " 1902, suppl. volume, 166.
f See Huber, " Journal of Experimental Medicine," 1, 281, 1896.

THE SALIVARY GLANDS. ■ 669

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 proteid 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 C02 might be obtained
from the saliva, of which 42.5 per cent, was in the form of carbon-
ates. The amount of C02 in solution and combined is an indication
of the active chemical changes in the gland.

Of the organic constituents of the saliva the proteid exists in
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 proteids, glyco-
proteids (see appendix), consisting of a proteid 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 and specific
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

670 PHYSIOLOGY OF DIGESTION AND SECRETION.

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 clogs, 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 fur die gesammte Physiologie, " 17, 1, 1878; also
in Hermann's "Handbuch der Physiologie/' 1883, vol. v, part i.

THE SALIVARY GLANDS. 671

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
alone in any part of their course gives an abundant, thin, and watery
saliva, poor in solid constituents. Stimulation of the sympathetic
fibers alone (provided the cerebral fibers have not been stim-
ulated 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

672 PHYSIOLOGY OF DIGESTION AND SECRETION.

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 ab.ove 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

THE SALIVARY GLANDS. 673

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.

An interesting fact with reference to the secretion of the parotid in dogs
has been noted by Langley, and is of special interest, since, although it may
be reconciled with the theory of trophic and secretory fibers, it is at the same
time suggestive of an incompleteness in this theory. As has been said, stimu-
lation of the sympathetic in the dog causes usually no secretion from the pa-
rotid. Langleyf finds, however, that, if the tympanic nerve is stimulated just
previously, stimulation of the sympathetic causes an abundant, but brief,
now from the parotid. One may explain this in terms of the theory by as-
suming that the sympathetic does contain a few secretory fibers proper, but
that ordinarily their action is too feeble to start the flow of water. Pre-
vious stimulation of the tympanic nerve, however, leaves the gland cells
in a more irritable condition, so that the few secretory fibers proper in the
sympathetic branches are now effective in producing a flow of water.

The way in which the trophic fibers act has been briefly indicated.
They may be supposed to set up metabolic changes in the protoplasm
of the cells, leading to the formatton of certain definite products, 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, to consist
in a disassociation or breaking down of the complex living material,
with the formation of the simpler and more stable organic con-
stituents of the secretion. 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 ana-
bolic 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. Heidenhain's own view rests upon the fact that no more water
leaves the blood capillaries than afterwards appears in the secretion;
that is, no matter how long the secretion continues, the gland does
not become edematous nor does the velocity of the lymph-stream in
the lymphatics of the gland increase. This being the case, we must
suppose that the stream of water is regulated by the secretion, that
is, by the activity of the gland-cells. If we suppose that some con-

* "Journal of Physiology," 1. 96, 1878. f Ibid., 10, 291, 1889.

43

674 PHYSIOLOGY OF DIGESTION AND SECRETION.

stituent of these cells has an attraction for water, or, to use the
modern expression, exerts a high osmotic pressure, then, while the
gland is in the resting state, water will diffuse first from the base-
ment membrane, this in turn supplies its loss from the surrounding
lymph, and the lymph obtains the same amount of water from the
blood. As the amount of water in the cell increases a point is reached
at which an equilibrium is established, and the osmotic stream from
blood to cells comes to a standstill. The water in the cells does not
escape into the lumen of the tubule or of the secretion capillaries,
because the periphery of the cell is modified to form a layer offering
considerable resistance to filtration. The action of the secretory
fibers proper consists in so altering the structure of this limiting layer
of the cells that it offers less resistance to filtration; consequently
the water under tension in the cells escapes into the lumen, and the
osmotic pressure of its substance again starts a stream of water
from capillaries to cells, which continues as long as the nerve-stimu-
lation is effective.

Histological Changes during Activity. — The cells of both the
albuminous and mucous glands undergo distinct histological changes
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
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. 257, 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. 257, B),
so that each cell now shows an outer, clear border and an inner,
granular one. If the stimulation is continued the granules become
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. 257, C, D). Evidently the granular material is used
* "Journal of Physiology," 2, 260, 1879.

THE SALIVARY GLANDS.

675

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

D

Fig. 257. — 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 pilocarpin; C, after
stronger secretion, pilocarpin and stimulation of sympathetic; D, after long-continued
stimulation of sympathetic. — (After Langley.)

the formation of new protoplasmic 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 suppose that the clear substance
during the resting periods undergoes metabolic 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.

676

PHYSIOLOGY OF DIGESTION AND SECRETION.

Fig. 258. — Mucous gland: submaxillary of dog; rest-
ing stage.

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. 258), 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 be-
come distinctly smaller.
After prolonged secretion
the changes become more
marked (Fig. 259) and,
according to Heidenhain,
some of the mucous cells
may break down comr
pletely. According to
most of the later observ-
ers, 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
♦"Journal of Physiology," 10, 433, 1889.

Fig. 259. — Mucous gland: submaxillary of
dog after eight hours' stimulation of the chorda
tympani.

THE SALIVARY GLANDS. 677

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,* prevents the action of the secretory
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 gang lion 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
* " Proceedings of the Royal Society, " London, 46, 423, 1889.

678 PHYSIOLOGY OF DIGESTION AND SECRETION.

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
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 lately 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 number
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.

♦Gerhardt, "Archiv f. die gesammte Physiologie, " 97, 317, 1903.

THE SALIVARY GLANDS. 679

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-
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. f

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

* See Pawlow, " The Work of the Digestive Glands, " translation by
Thompson, London, 1902; also " Ergebnisse der Physiologie, " vol iii, part i,
1904, and "Archives internationales de physiologie," 1, 119, 1904.

f See Biedermann, " Electro-physiology, " translation by Welby, London,
1896.

680 PHYSIOLOGY OF DIGESTION AND SECRETION.

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
C12H22On, and some form of dextrin, a non-crystallizable poly-
saccharid. When the digestion is effected in a vessel some dextrose
(C6H1206) 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
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

THE SALIVARY GLANDS. 681

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. 642) shows, on the contrary, that
some of the food in an ordinary meal may remain in the fundic
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.

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 hydra ted 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

682 PHYSIOLOGY OF DIGESTION AND SECRETION.

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 XLIL

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. 260). 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.

* See Haane, "Archiv f. Anatomie," 1905, 1.

f Griitzner, " Archiv f. die gesammte Physiologie, " 106, 463, 1905.

683

684

PHYSIOLOGY OF DIGESTION AND SECRETION.

-J

Ifisf ological Changes in the Gastric Glands during Secretion.

— TnB tells of the gastric glands, especially the so-called chief cells,
show^Astinct changes as the result of prolonged activity. Upon
presei'/ed specimens, taken from dogs fed at intervals of twenty-four
hoiaS^ Heidenhain found that in the fasting condition the chief cells
trge and clear, that during the first six hours of digestion the
cells as well as the border cells increased in size, but that in a
econd period, extending from the sixth to the fifteenth hour, the
chief cells became gradually smaller, while the border cells remained

Fig. 260.— Glands of the fundus (dog) : A and A1, during hunger, resting condition £
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. 260).

Langley * has succeeded in following the changes in a more satis-
factory way by observations made directly upon the living gland.
He finds that the chief cells in the fasting stage are charged with
granules, and that during digestion the granules are dissolved, dis-
* " Journal of Physiology, " 3, 269, 1880.

685
©

appearing first from the base of the cell, which then becomes filed
with a non-granular material. Observations similar to those ma^^
upon other glands demonstrate that these granules represent in
probability a preliminary material from which the gastric enzym
are made during the act of secretion. The granules, therefore,
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 which 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

Eressure would crush them, and yet they were voided uninjured. So also
e 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
for examination. A silver cannula is placed in the fistula, and
at any time the plug closing the cannula may be removed and

* 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.

686

PHYSIOLOGY OF DIGESTION AND SECRETION.

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 pump, but in
such cases it is necessarily more or less diluted or mixed with food
and can not 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. 261 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 proteid, 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
becoming putrid and with very little change, if any, in its digestive

Fig. 261. — To show Pawlow's operation for
making an isolated fundic sac from the stomach:
v, Cavity of the stomach ; s, 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. 687

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 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 digestion it may reach (Horn-
borg) 0.4 to 0.5 per cent., and these figures express probably its
strength as secreted. The acidity of the dog's gastric 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.

688 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 time 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,
toge her 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 = Na2HP04 + 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. 689

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-
filtterung). 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 stimulation 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 that given by 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 reflex stimulations arising in the stomach
itself. The mucous membrane of the stomach contains sensory
fibers which, when stimulated, act reflexly upon the secretory fibers
and set up a secretion. It seems that some foods contain substances
capable of giving this effect, while others do not. 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

* Hornborg, " Skandinavisches Archiv f. Physiologic," 15, 209, 1904!
44

690

PHYSIOLOGY OF DIGESTION AND SECRETION.

gastric 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 product of their digestion in turn becomes ca-
pable of stimulating the secretory paths by a reflex from the stomach.
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 chemical nature
of these last-named
stimuli is undeter-
mined.

The researches of
Pawlow and his co-
workers seem also to
indicate that the
quantity and prop-
erties of the secre-
tion vary with the
character of the food.
The quantity of the
secretion varies, also,
other conditions be-
ing 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 secre-
tions varying not
only as regards quan-
tity, but also in their
acidity and digestive
action. The secre-
tion 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.

id

is o

"8 t-i

a » <d

Co

Milk, Meat, Bread,
600 c.c. 100 gms. 100 gms.

f

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

\

s

i

\

i

\

i

\

^

/

10

V

8

\

6

\

4

V

2

k

i

.

i

f

\

0

Hours

/ ZS4£6Y8? W1T1I

Quantity of secretion.

Acidity.

Digestive power.

Fig. 262. — 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
Khigine.)

DIGESTION AND ABSORPTION IN THE STOMACH. 691

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. 262. 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 and 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
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 "Brucke'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 proteid or proteid-containing

692 PHYSIOLOGY OF DIGESTION AND SECRETION.

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
proteid nature which contains sulphur and also some chlorin, but no
phosphorus. It does not belong, therefore, to the group of nucleo-
proteids.

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
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. Glaessnerf
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. Whether the pyloric glands take any
chemical part in gastric digestion must remain undecided. From
the description of the events in the stomach (p. 641) it would seem
that the food material which is churned and stirred by the contrac-
tions 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 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 which may be used in
place of the normal secretion for many purposes. In laboratory
experiments it is customary to employ a glycerin extract of the
gastric mucous membrane, and to add a small portion of this extract
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 proteids 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

* Pekelharing, "Zeitschrift f. physiol. Chemie," 35, 8, 1902.

t Glaessner, " Beitrage zur chem. Physiol, u. Pathol.," 1, 24, 1901.

DIGESTION AND ABSORPTION IN THE STOMACH. 693

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 phos-
phoric acid it is given as 2 per cent.

The Pepsin-Hydrochloric Acid Digestion of Proteids. — It has
long been known that solid proteids, when exposed to the action of a
normal or an artificial gastric juice, swell up and eventually pass into
solution. The soluble proteid thus formed was known not to be
coagulated by heat and was remarkable also for being more diffusible
than other forms of soluble proteids. This end-product of digestion
was formerly conceived as a soluble proteid with properties fitting
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 proteid 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 propeptone. The present concep-
tion of the process we owe chiefly to Kiihne. This author believed
that the proteid passes through three general stages before reaching
the final condition of peptone. This view is indicated briefly by the
following schema :

Native proteid.

Acid albumin (syntonin) .

Primary proteoses (protalbumoses).

Secondary proteoses (deutero-albumoses).

Peptone.

The first step is the conversion of the proteid 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.*

* The products intermediate between the original proteid and the pep-
tone are described in general as albumoses or as proteoses, according as one
takes the term proteid or albumin as the generic name for the original sub-
stance. The term proteid is generally used in English ; hence, the intermedi-
ate products are more appropriately designated as proteoses.

694 PHYSIOLOGY OF DIGESTION AND SECRETION.

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 proteids 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 Kuhne's sense, is that compound
or group of compounds formed in peptic digestion which, while still
showing proteid reactions (biuret reaction), is not coagulated by
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 proteid 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 proteid 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 whose
molecular weights are perhaps only 250 to 400 or less.

It was formerly believed that pepsin was not able to split the complex
proteid 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 proteid molecule may be as complete as after the action
of trypsin, or after hydrolysis by acids (see Proteids 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
amido-acids and nitrogenous bases which constitute the final end-products
of the breaking up of the proteid 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 proteid 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
* See Hofmeister, " Ergebnisse der Physiologic," vol. i, part i, 796, 1902.

DIGESTION AND ABSORPTION IN THE STOMACH. 695

five minutes in water at 95° C. After some time the tube is cut into
lengths of 10 to 15 rams, 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
milk has been known from remote times, and has been utilized in the
manufacture of cheeze 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 action 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 it 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 setting 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.

696 PHYSIOLOGY OF DIGESTION AND SECRETION.

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 proteid constituent of milk,
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 proteids.*

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 proteolytic 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. 387). If rennin be injected subcutaneously 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

* For references to the very abundant literature consult Oppenheimer,
loc. cit.

f See Pawlow and Parastschuk, " Zeitschrift f . physiol. Chemie, " 42, 415.

DIGESTION AND ABSORPTION IN THE STOMACH. 697

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 food-
stuffs by the dissolving action of the gastric juice upon proteids,
they are liquefied by the heat of the body, and they are disseminated
through the chyme in a coarse emulsion by 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 impor-
tant in the digestion of the milk-fat by infants. Regarding the
proteids, the practical point of interest is 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 proteids, primary
or secondary proteoses, peptones, or even the final split products
of proteolytic action. The true value of peptic digestion is not
so much in its own action as in its combined action with the
trypsin of the pancreatic juice. The digestion of the proteids of
the food is effected by both enzymes, and normally we are justified
in considering them together as forming a peptic-try ptic digestion.
The preliminary digestion in the stomach is important as regards the
proteid 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 accelerated. Indeed,
in some cases this preliminary action of the pepsin-hydrochloric acid
may be absolutely necessary. Native proteids, such as serum-
albumin, are not acted upon by trypsin, but if submitted first to
pepsin-hydrochloric acid they are quickly digested by this enzyme.
Third, for some as yet unknown reason proteids submitted to peptic
digestion are split by the trypsin in a way different from its action

698 PHYSIOLOGY OF DIGESTION AND SECRETION.

on proteids 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
from starch, or that may have been eaten as such; the proteoses and
peptones formed in the peptic digestion of proteids 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.f 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 jiot-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 bf 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 in dilute solutions. Not until its

*Ludwig and Ogata, "Archiv f. Physiologie, " 1883, p. 89; Carvallo
and Pachon, "Archives de physiologie norm, et path.," 1894, p. 106.

t Compare von Mering, " Verhandl. des Congresses f. innere Med.,"
12, 471, 1893; Edkins, " Journal of Physiology," 13, 445, 1892; Brandl,
" Zeitschrift f. Biologie," 29, 277, 1892.

DIGESTION AND ABSORPTION IN THE STOMACH. 699

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 prfl.nt.infl.lly not absorbed ^ t^ st.nmfl.nh, 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.

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, laclpse,
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. The processes of saponification and
emulsification are supposed to be preliminary steps to absorption,
and, as these processes take place after the fats have reached the
small intestine, there seems to be no doubt that in the stomach fats
as usually ingested escape absorption.

* Zimz, "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, Kuhne, 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

700

DIGESTION AND ABSORPTION IN THE INTESTINES. 701

of the secretion are formed they are frequently designated as zymogen
granules. The pancreas contains also certain peculiar groups of
cells, the islands (or bodies) of Langerhans. These cells have noth-
ing to do with the digestive activity of the pancreas. Their 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, with 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 1J 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 proteid 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 — gave negative results in the hands of most
observers so far as the pancreatic secretion was concerned. Pawlowf
and his coworkers, however, 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.

t 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, 19^4^\^SaJ^t*r^-Archives
des sciences biologiques, " 7, 1, 1899.

LIERaRY

702

PHYSIOLOGY OF DIGESTION AND SECRETION.

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
of the secretion. These observations are usually taken as proof of the

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Fig. 263. — 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.

existence of secretory nerve fibers to the pancreas; but, as will be
explained below, it is not yet clear how far these fibers are con-
cerned in arousing the flow of secretion during digestion.

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
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

DIGESTION AND ABSORPTION IN THE INTESTINES. 703

is reached, may depend upon the difference in rate at which these
foods are ejected from the stomach. Cannon (p. 642) has shown that
the carbohydrate foods leave the stomach sooner than the proteids 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
proteid 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. 263. 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. Inasmuch as
the pancreatic gland possesses secretory fibers it was assumed 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 stated, however,
that the same effect takes place after section of the vagus and
splanchnic nerves (Popielski),and Bayliss and StarlingJ have called

* Glaessner, loc.cit.

t Boldireff, "Archives des sciences biologiques, " 11, 1, 1905.

j Bayliss and Starling, " Journal of Physiology, " 28, 325, 1902.

704 PHYSIOLOGY OF DIGESTION AND SECRETION.

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. Whether the
acid in addition causes reflex stimulation of the secretory nerves is
not certain, although this statement is made. It is not clear, also, by
what means the secretion of pancreatic juice is maintained through
the six or seven hours or more of gastro-intestinal digestion. The
increased flow during the first hours is connected with the increas-
ing discharge of food from stomach to intestine, but whether the
effect upon the pancreas is traceable entirely to a continual forma-
tion of secretin, or partly to secretin and partly to nerve stimulation,
are matters not yet settled.

Enterokinase. — It was discovered in Pawlow's laboratory
(Chepowalnikow) that the pancreatic juice obtained from a fistula
may have little or no digestive action on proteids, 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, tripsinogen 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 tripsinogen. 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.

DIGESTION AND ABSORPTION IN THE INTESTINES. 705

The Digestive Action of Pancreatic Juice. — The digestive
action of the secretion depends upon the three enzymes trypsin,
diastase (amylopsin), and lipase. The specific effects of each
may be considered separately.

Action of Trypsin. — The activated trypsinogen causes hydrolytic
cleavage of the proteid molecule in a manner analogous to that
described for pepsin. Its action differs from that of pepsin, however,
in several respects. It attacks the proteid in neutral as well as in
slightly acid or markedly alkaline solutions. Its effect upon the
proteid is more rapid and powerful than that of pepsin and the
proteid molecule is broken up more completely. As was said in
describing the action of pepsin, it and the trypsin really act
together, — 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 proteid 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 proteid
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. Kuhne supposed that the proteid molecule contains
two groups, the hemi and the anti. Under the influence of the trypsin
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 proteid 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 proteid the end-products are closely similar to those
obtained by boiling proteid with acids. The hydrolysis caused
by the acids and by the trypsin seems to be nearly identical. The
45

706 PHYSIOLOGY OF DIGESTION AND SECRETION.

numerous products obtained by this complete hydrolysis consist
chiefly of amino-acids, — that is, organic acids containing one or more
amido-groups (NH2) in direct union with carbon. Some of these
bodies are monamino-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, such as the pyrrol and the indol
group. 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 organic chemistry:

I. MONAMINO-BODIES.
FATTY ACID SERIES.

Glycocoll or amido-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-amidopropionic acid: CH3CHNH2COOH.

Amidovalerianic acid: ^3^CHCHNH2COOH.

Leucin or amidocaproic acid: Qg3^CHCH2CHNH2COOH. As stated

above, this compound was one of the first end-products of proteid
hydrolysis that was recognized. It may be obtained readily in
crystalline form.

CHNH2COOH
Aspartic or amidosuccinic acid :

CH2COOH.
Glutaminicacid: CH2/g™H2COOH

BENZENE OR AROMATIC SERIES.

Tyrosin (para-oxyphenylamidopropionic acid) : C6H4OH . CH2 . CHNH2-
COOH. This substance was also among the first recognized prod-
ucts of proteid 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 proteid molecule.

Phenylalanin (phenylamidopropionic acid) : C6H5CH2CHNH2COOH. This
benzene derivative is, according to Abderhalden, split off from the
proteid with difficulty by the action of trypsin, although readily
produced by acid hydrolysis.

PYRROL AND INDOL SERIES.

CH— CH2

! I

a-Pyrrolidin carbonic acid : CH2 CHCOOH. This substance, discovered

\/
NH

* Abderhalden, " Zeitschrift f. physiol. Chemie," 44, 17, 1905. Consult
for general description of the digestion of proteids.

DIGESTION AND ABSORPTION IN THE INTESTINES. 707

first by Fischer among the products of acid hydrolysis of proteids,
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

S\

Tryptophan (skatolamido-acetic acid) : C6H4 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
structure was determined by Hopkins and Cole (1901). According
to Ellinger,* tryptophan is an indol compound of the formula
C . CHCOOHCH2NH2. When fed to dogs it causes the appear-

C6H40CH

NH

ance of kynurenic acid (C10H7NO3) in the urine.

It is interesting as shpwing the existence of an indol grouping
in the proteid molecule.

v II. The Diamino-bodies (Hexon Bases).

Lysin (a-e-diamidocaproic acid): CeHMN202 or CH2NH2(CH2)3CHNH2-

COOH.
Arginin (guanidin a-amidovalerianic acid) : C6HHN402 or NHCNH2NH-

CH2(CH2)2CHNH2COOH.
Histidin: C6H9N302.
These three substances occur among the products of pancreatic digestion.

They may be separated from the monamino-bodies by the fact that

they are precipitated in acid solutions by phosphotungstic acid

while the monamino-acids are not.

The Significance of Tryptic Digestion. — It was formerly
supposed that the object of peptic and tryptic digestion is to
convert the insoluble and non-dialyzable proteids into the simpler,
more soluble, and more diffusible peptones and proteoses. In this
way absorption of proteid 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 proteid molecule is split into
a number of simpler, crystalline substances, the various amino-
bodies. At present different views exist as to the extent of this latter
process. Some believe that the proteid 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 synthet-
ically 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 lat-
ter enzyme is exerted especially upon the albumoses and peptones,
* Ellinger, " Zeitschrift f. physiol. Chemie," 43, 325, 1904.

708 PHYSIOLOGY OF DIGESTION AND SECRETION.

breaking them down into the amido-acids, so that apparently what-
ever peptone or albumose may escape the final action of the trypsin
before absorption is likely to be acted upon by the erepsin before
reaching the blood.* Another interesting view is that suggested
by Abderhalden. f According to this author, the hydrolysis of the
proteid by pepsin and trypsin (and perhaps by erepsin) is not
complete. Many amido-bodies, such as tyrosin, leucin, arginin, etc.,
are split off from the proteid 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 poly peptid. 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 mona-
mido- and diamido-bodies. A schema of peptic-tryptic digestion
from this standpoint may be given as follows :

Native proteid.

Peptone.

Polypeptid. Tyrosin, leucin, glutaminic acid, aspartic acid,
a-pyrrolidin carbonic 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 proteid of the
food lies in the possibility that thereby the body is able to construct
its own peculiar type of proteid. Many different kinds of proteids
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 proteids are broken down more or less completely during
digestion the tissue cells may reconstruct from the pieces a form of
proteid adaptable to their needs. At present our knowledge of what
takes place during the absorption of proteid is very incomplete, and
a satisfactory theory of proteid nutrition is scarcely possible until
this portion of the subject is cleared up.

Action of the Diastatic Enzyme (Amylopsin) of the Pan-
creatic Secretion. — This enzyme is found in the secretion of the

* Vernon ("Journal of Physiology," 30, 330, 1904) believes that the
pancreatic secretion contains two proteolytic enzymes, — trypsin proper,
which converts the proteids to peptones, and pancreatic erepsin, which breaks
up the peptones into the simpler end-products, the amido-bodies.

t Abderhalden, loc. cit.

DIGESTION AND ABSORPTION IN THE INTESTINES. 709

pancreas or it may be extracted from the gland. Its action upon
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 digestion 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(C15H31COO)3 + 3H20 = 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.

710 PHYSIOLOGY OF DIGESTION AND SECRETION.

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. 660) 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 Lieberkuhn,
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.

t Consult Herzog, " Zeitschrift f. physiol. Chemie, V 37, 383, 1903.

DIGESTION AND ABSORPTION IN THE INTESTINES. 711

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. 704) , 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. 705), 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:

C12H22Ou + H20 = C6H1206 + C6Hi206

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, may play

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.

712 PHYSIOLOGY OF DIGESTION AND SECRETION.

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 proteid 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.

DIGESTION AND ABSORPTION IN THE INTESTINES. 713

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 a Thiry-
Vella 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. J

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.
t Wallace and Cushny, " Archiv f . die gesammte Physiologie, " 77, 202,
1899.

JCohnheim, "Zeitschrift f. Biologie," 37, 443, 1899.

714 PHYSIOLOGY OF DIGESTION AND SECRETION.

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. Pharmakol.," 25, 240, 1889,
and 26, 355, 1890.

t Macfadyen, Nencki, and Sieber, loc, cit.

DIGESTION AND ABSORPTION IN THE INTESTINES. 715

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 oh 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. Physiologie, " 1892, 497, and 1894, 297.

716 PHYSIOLOGY OF DIGESTION AND SECRETION.

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 Proteids. — Most of the experimental work on
record shows that the digested proteids are absorbed by the blood-
vessels of the villi, although after excessive feeding of proteid 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 proteid, as is indicated by the urea excreted during the
period. 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 proteid, it is found that there is no
increase in the quantity of the lymph or in its proteid contents.
The form in which proteid is absorbed remains, however, a mystery.
Under normal conditions the proteid food is digested by the success-
ive 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 amido-bodies, leucin, tyrosin, arginin, etc., and the intermediate
compounds, the polypeptids or peptoids (see p. 708), and be absorbed
in the form of these split products. Examination of the blood does
not show, however, the presence of any of these bodies, and in spite
of the fact that the process of absorption is long continued and the
total amount of absorbed products in any given specimen of blood
may therefore be very small, it is perplexing not to be able to ob-
tain indubitable proof of the existence in the blood of some of the
products of digestion. Several possibilities have been suggested.
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 proteids of the blood, the serum-albumin or globulin; it is possi-
ble 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 proteids of the body,
or it is possible that the absorbed proteid exists in the blood in
some special form not as yet recognized. The whole question is
evidently one that can not 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 proteid
may be absorbed apparently without previous digestion. This fact
has been demonstrated for isolated loops of the small intestine and
* See Mendel, " American Journal of Physiology, " 2, 137, 1899.

DIGESTION AND ABSORPTION IN THE INTESTINES. 717

also for parts of the large intestine. It is, moreover, borne out by
the medical practice of giving enemata into the rectum when the
conditions are such that the patient can not be fed in the normal
way. That absorption and utilization of the proteid take place
under such conditions is shown not only by the improved nutritive
condition of the individual, but also by the increased output of
nitrogen in the urine. This phenomenon occurs in parts of the
intestinal canal in which normally no proteolytic enzymes occur, so
that the whole process must be referred to an activity of the cells
composing the walls of the intestine. There seems at present little
grounds for a satisfactory explanation of the absorption of proteids,
with or without digestion, by a direct application of the known
laws of osmosis, diffusion, and imbibition. Examination of the
contents of the small intestine at its junction with the large shows
that under normal conditions most of the proteid has been ab-
sorbed before reaching this point. The process is continued in the
large intestine, modified somewhat by bacterial action, and the
amount that finally escapes absorption and appears in the feces
varies, in perfectly normal individuals, with the character of the
proteid eaten. According to Munk,* the easily digestible animal
foods — such as milk, eggs, and meat — are absorbed to the extent of
97 to 99 per cent., while with vegetable foods the utilization is less
complete; from 17 to 30 per cent, of the proteid may be lost in the
feces if the vegetable food is in such form as not to be attacked readily
by the digestive secretions.

Digestion and Absorption in the Large Intestine. — Observa-
tions upon the secretions of the large intestine have been made upon
human beings in cases of anus praeternaturalis, in which the lower
portion of the intestine was practically isolated, and also upon
lower animals, in which an artificial anus was established at the
end of the small intestine. These observations all indicate that
the secretion of the large intestine, while it contains much mucus
and shows an alkaline reaction, is not characterized by the presence
of distinctive enzymes. When the contents of the small intestine
pass the valve they still contain a certain amount of unabsorbed
food material. As was stated in the chapter on the movements of the
intestine, this material remains a long time in the large intestine, and
since it contains the digestive enzymes received in the duodenum the
digestive and absorptive processes no doubt continue as in the small
intestine. This general fact is well illustrated in experiments made
upon dogs most of whose small intestine (70 to 83 per cent.) had been
removed.f These animals could digest and absorb well, and formed

* See Munk, " Ergebnisse der Physiologie, " vol. i, part I, 1902, article,
" Resorption," for literature and discussion.

t Erlanger and Hewlett, "American Journal of Physiology," 6, 1, 1902.

718 PHYSIOLOGY OF DIGESTION AND SECRETION.

normal feces, provided care was taken with the diet. An excess of
fat or indigestible material caused diarrhea and serious loss of food
material in the feces. An interesting feature in the large intestine
is the marked absorption of water. In the small intestine no doubt
water is absorbed in large quantities, but its loss is evidently made
good by osmosis or secretion of water into the intestine, since the
contents at the ileocecal valve are quite as fluid as at the pylorus.
In the large intestine the absorption of water is not compensated by
a secretion; the material becomes more and more solid as it ap-
proaches the rectum, and is thus formed into the feces. The alkaline
reaction of the contents of the large intestine makes a favorable
environment for the growth of bacteria, particularly the putrefactive
bacteria that attack proteid material. Putrefaction is a normal
occurrence in the large intestine, and much interest has been shown
in its extent and its possible physiological significance.

Bacterial Action in the Small Intestine. — Bacteria are con-
stantly present in both the large and the small intestine. Under
normal conditions, however, it would seem that in the small intestine
only those bacteria capable of fermenting carbohydrate food show any
distinct activity. Putrefactive fermentation of proteid material
is limited or absent in this part of the intestine as long as the products
of proteid digestion are promptly absorbed. Conditions that prevent
or retard this absorption favor the occurrence of proteid putrefaction.
Opinions among investigators differ as to the means by which the
proteid contents are protected from the action of the bacteria. It
has been shown that the presence of carbohydrate material has a
restraining effect upon proteid putrefaction. The simplest explana-
tion of this relation is that the fermentation of the carbohydrates
gives rise to a number of organic acids, — lactic, acetic, etc., — and
these acids inhibit the action of the proteid bacteria. To make this
explanation satisfactory, however, it is necessary to show that the
contents of the small intestine possess an acid reaction. Concerning
this point, however, opinions also differ. The secretions of the small
intestine are all alkaline and we should expect their contents to have
this reaction. Examination shows that the contents of the small
intestine are acid or not according to the indicator used. With
phenolphthalein they may give an acid reaction, while with litmus,
lakmoid, etc., no such reaction is obtained.* Such a result as this
indicates that no strong organic acids, such as acetic and lactic,
are present, the phenolphthalein being affected possibly by the C02.
As Munk has stated, however, it seems that the contents of the small
intestine throughout the duodenum and jejunum are at least never

* Consult Macfadyen, Nencki, and Sieber, loc. cit.; Moore and Bergin,
"American Journal of Physiology," 3, 316, 1900; Munk, " Centralblatt f.
Physiologie," 16, 33 and 146, 1902.

DIGESTION AND ABSORPTION IN THE INTESTINES. 719

alkaline, and when carbohydrates are used the reaction may not only
be acid to phenolphthalein, but also to the stronger indicators. On
the whole, therefore, it would seem probable that the small amount
or total lack of proteid putrefaction in the small intestine is due in
part to the rapid absorption of the digested proteid 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 proteids. When the former
have conditions favorable for growth, their increase in some way
affects injuriously the proteid bacteria.*

Bacterial Action in the Large Intestine. — In the large intestine
proteid putrefaction is a constant and normal occurrence. The
reaction here is stated to be alkaline, and whatever proteid may have
escaped digestion and absorption is in turn acted upon by the bacteria
and undergoes so-called putrefactive fermentation. The splitting
up of the proteid 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 amido-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, C6H5OS02OH, 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 C9H8NOS02OH,
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 proteid 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 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.

720 PHYSIOLOGY OF DIGESTION AND SECRETION.

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,| who finds that animals in
the Arctic regions in many cases have no bacteria in their intestines.
Schottelius J 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. Physiologie," 16, 249, 1904.
j " Archiv f. Hygiene," 42, 48, 1902.

DIGESTION AND ABSORPTION IN THE INTESTINES. 721

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 C78H156S02has 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, C02, 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. Biologie," 35, 335, 1897; and Tsuboi, ibid.,
p. 68.

46

V

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 proteid, 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

722

ubrXf

PHYSIOLOGY OF THE LIVER AND SPLEEW^/,,/. 723

this way to the exterior, and it is an interesting physiological
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 Hammarstenf 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

^fhin}... 0.0220 0.1286

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. Physiologie," 1894, No. 8.

724 PHYSIOLOGY OF DIGESTION AND SECRETION.

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 biliverdin. Biliverdin is supposed to stand to bilirubin
in the relation of an oxidation product. Bilirubin is given the formula
C16H18N203, and biliverdin C16H18N204, 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.

PHYSIOLOGY OF THE LIVER AND SPLEEN. 725

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 C26H43N06,
and taurocholic acid the formula C26H45NS07. 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^NO, + H20 = C^H^O, + CH?(NH2)COOH.

Glycocholic acid. Cholic acid. Glycocoll (amido-acetic-acid).

C„H„NS07 + H20 = C24H40O5 + C2H4NH2S02OH

Taurocholic acid. Cholic acid. Taurin (amido-ethyl-

sul phonic 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

726 PHYSIOLOGY OF DIGESTION AND SECRETION.

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
proteid 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 proteid 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, C6H12N2S204, is known
to occur as one of the end-products in the acid hydrolysis of proteids, 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 proteid
molecule is found. Cystin may be oxidized to cysteinic acid (COOHC2H3NH2-
S02OH) and from this taurin (C2H4NH2S02OH) may be obtained. It is prob-
able, therefore, that the taurin is formed normally from cystin in the body
and that the latter represents one of the split products of proteid. f Some
of the sulphur of the cystin appears also in the urine in oxidized form as sul-
phate. 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
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.

Cholesterin. — Cholesterin is a non-nitrogenous substance of the
formula C27H460. 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
body. According to Naunyn, however, the cholesterin is not secreted

* Friedmann, " Hofmeister's Beitrage," 3, 1, 1902.

t See Simon, " Johns Hopkins Hospital Bulletin, " 15, 365, 1904.

PHYSIOLOGY OF THE LIVER AND SPLEEN. 727

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, C^H^NPOg
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

728 PHYSIOLOGY OF DIGESTION AND SECRETION.

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. f" Archives des sciences biologiques, " 7,87, 1899.

PHYSIOLOGY OF THE LIVER AND SPLEEN.

729

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 proteids and fats or some of the
products of their digestion. The gall-bladder has a muscular coat

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Fig. 264. — 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.} 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 physiologie, " 1894, p. 19.

730 PHYSIOLOGY OF DIGESTION AND SECRETION.

the experiments made by this author together with later experiments
reported by Freese, 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. Sensory fibers capable of causing a reflex con-
striction or dilatation of the bladder are found in both the vagus and
splanchnic nerves. Stimulation of the central end of the cut splanch-
nic 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 in-
testine. 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. — It is an in-
teresting fact that, when the flow of bile is completely prevented by
ligation of the bile-duct, the stagnant liquid is not reabsorbed by the
blood directly, but by the lymphatics of the liver. The bile pig-
ments and bile acids in such cases may be detected in the lymph as it
flows from the thoracic duct. In this way they get into the blood,
producing a jaundiced condition. The way in which the bile gets
from the bile-ducts into the hepatic lymphatics is not definitely
known, but possibly it is due to a rupture, caused by the increased
pressure, at some point in the course of the delicate bile capillaries.

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 proteids
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
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

PHYSIOLOGY OF THE LIVER AND SPLEEN. 731

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 proteid 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.*

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

*The extensive literature of glycogen is. collected and reviewed by Cre-
mer in the u Ergebnisse der Physiologie, " vol. i, part i, 1902; and by Pfluger,
" Archiv f. die gesammte Physiologie," 96, 1, 1903.

732 PHYSIOLOGY OF DIGESTION AND SECRETION.

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,
that 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-

PHYSIOLOGY OF THE LIVER AND SPLEEN. 733

sented in substance by the formula C6H1206 — H20 = C6H10O5.
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 Proteid on Glycogen Formation. — In his first studies
upon glycogen Bernard asserted that it may be formed from proteid
material. Since that time there have been much discussion and
experimentation upon this point. The usual view is that proteid
must be counted among the true glycogen-formers in the sense that
some of the material of the proteid molecule is directly converted to
glycogen. The proteid in digestion undergoes, it will be remembered,
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 with some of the carbon being changed
to urea, while the non-nitrogenous residue is converted to sugar.
Among the split products of proteid that have been especially
investigated in this relation the results with leucin and glucosamin
have been chiefly negative.! Experimentally observers find for
the warm-blooded animals at least that feeding with proteids,
even in the case of those proteids, such as casein, that con-
tain no carbohydrate grouping, causes an increased production of
glycogen. % The conclusion to be drawn from these experiments
is strengthened by clinical experience upon human beings suf-
fering from diabetes. In severe forms of this disease all the car-
bohydrate material of the food appears in the urine. If under
these conditions the individual is given an exclusively proteid diet
sugar still continues to appear in the urine, and it would seem that
this sugar can only arise from the proteid food. In the similar

* Voit, " Zeitschrift f. Biologie, " 28, 285, 1891.

t Halsey, " American Journal of Physiology, " 10, 229, 1904.

% See Stookey, " American Journal of Physiology, " 9, 138, 1903.

734 PHYSIOLOGY OF DIGESTION AND SECRETION.

condition of severe glycosuria that may be produced by the use of
phloridzin it has been shown that the animal continues to excrete
sugar even when fed on proteid 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 proteid
molecule. On this supposition 58.4 per cent, of the proteid may be
converted to sugar. So also the fact that during prolonged starva-
tion, lasting for forty or even ninety days, the blood retains a practi-
cally constant composition in sugar indicates that this material is
being formed from either the proteid or fat supply of the body.
Other considerations exclude the fat, and we are, therefore, led to
the belief that the proteid can give rise to sugar in the body. If
this change is part of the normal metabolism of the body it would
make proteid a glycogen-former, since the sugar formed from the
proteid may, of course, be converted to glycogen. Whether or not
all proteids yield glycogen or sugar in the body is not entirely de-
termined. Some authors have thought that only those proteids
that contain a carbohydrate residue have this property; but, as
stated above, casein and other proteids 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 proteid 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
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

PHYSIOLOGY OF THE LIVER AND SPLEEN. 735

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 time 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.*
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 proteid 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
* Tebb, " Journal of Physiology, " 22, 423, 1897-98.

736 PHYSIOLOGY OF DIGESTION AND SECRETION. '

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. Apparently muscular
tissue, as well as liver tissue, has a glycogenetic function — that is,
it is capable 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
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. In a starving animal glycogen finally disappears,
* "Zeitschrift f. Biologie, " 27, 237, 1890.

PHYSIOLOGY OF THE LIVER AND SPLEEN. 737

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 glycogen. The further history of glycogen is considered in
the section on nutrition.

Formation of Urea in the Liver. — The nitrogen contained in
the proteid material of our food is finally eliminated, after the metab-
olism of the proteid is completed, mainly in the form of urea. It
has been definitively 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 functions of the liver cell.
Schroder* performed a number of experiments 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 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 equa-
tion (NH4)2C03 — 2H20 = CON2H4. Schondorff f in some later work
showed that if the blood of a fasting dog is irrigated through the hind
legs of a well-nourished animal, no increase in urea in the blood can

* "Archiv f. experimentelle Pathologie und Pharmakologie, " 15, 364,
1882, and 19, 373, 1885.

t " Pfliiger's Archiv f. die gesammte Physiologie, " 54, 420, 1893.
47

738 PHYSIOLOGY OF DIGESTION AND SECRETION.

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 can not
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 ex-
cretion 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* 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
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 trabecular. In addition

*Laudenbach, " Centralblatt fur Physiologie, " 9, 1, 1895.

t Paton, Gulland, and Fowler, " Journal of Physiology, " 28, 83, 1902.

PHYSIOLOGY OF THE LIVER AND SPLEEN. 739

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 trabecular,
— 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,* 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
theory can not 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 has been shown by Horbaczewsky that the
spleen contains a substance from which uric acid or xanthin may
readily be formed ; but further investigation has shown that the same
substance is found in lymphoid tissue generally. If, therefore, uric
acid is produced in the spleen, it probably originates in the large

* "Journal of Physiology," 3, 203, 1881.
t "Journal of Physiology," 20, 1, 1896.

740 PHYSIOLOGY OF DIGESTION AND SECRETION.

amount of lymphoid tissue contained in it, and is not a product char-
acteristic of the splenic tissue proper. In this connection it may be
stated that Jones* has demonstrated the existence in the spleen of an
enzyme, adenase, which converts adenin, C5H3N4NH2, into hypoxan-
thin, C5H3N4OH. The lymphoid tissue of the spleen must also
possess the property of producing lymphocytes, since, according to
the general view, these corpuscles are formed in lymphoid tissue
generally wherever the so-called "germ-centers" occur. (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 enterokinase.
* Jones and Winternitz, " Zeitschrift, f. physiol. Chemie," 44, 1, 1905.

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 loop 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-

Fig. 265. — 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; e,
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; E,
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. 265, A). It consists

741

742 PHYSIOLOGY OF DIGESTION AND SECRETION.

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
mirdbile, 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 nitration 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. 265, 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-

KIDNEY AND SKIN AS EXCRETORY ORGANS. 743

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, but which
implies that the epithelial cells participate in the process and do
not act 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 between 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 the controversies between 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 inhibition, so far as they are known, do not suffice for a satis-

744 PHYSIOLOGY OF DIGESTION AND SECRETION.

factory explanation of the facts. As in similar cases, our knowl-
edge of the physical structure and chemical properties of the wall
of living cells is still very deficient, and it seems necessary to desig-
nate the activities of this wall 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 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 glomeruli 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
the chance for removal of C02, — 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

KIDNEY AND SKIN AS EXCRETORY ORGANS. 745

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-
damped, 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 nuns, 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-
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

746 PHYSIOLOGY OF DIGESTION AND SECRETION.

the filtration 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 filtration theory. Exact figures, however, regard-
ing the capillary pressure in the kidney can not be obtained; so
that the experiment, on the whole, gives us no satisfactory in-
formation regarding the theory of secretion. Dreser has used a
different argument to prove that the production of the water in-
volves the performance of work on the part of the epithelial cells.
He points out that in some conditions — e. g., after drinking beer —
the urine may be very dilute, as shown by the fact that its freezing
point may be only 0.18° C. or 0.16° C. below that of pure water, —
that is, A = —0.18° C. or —0.16° C. (see appendix). Since blood-
serum has A = — 0.56° C, the difference in concentration between
the blood and the urine in such a case of extreme dilution shows an
osmotic pressure in favor of the blood equivalent to A = — 0.4° C.
Measured in mechanical units, this would indicate an initial osmotic
pressure of 49.08 meters of water tending to drive the water from
the uriniferous tubules into the blood, whereas the filtration pres-
sure driving the water in the other direction could not at a max-
imum exceed 2.72 meters of water. If this argument is valid, the
elimination of the water takes place against a strong opposing os-
motic pressure, and the energy necessary for its secretion can be
referred only to the activity of the epithelial cells.

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-

KIDNEY AND SKIN AS EXCRETORY ORGANS. 747

what indirect; a single example may suffice. Cushny states* 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 (CI and S04) 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
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, Gurwitschf) 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 are 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. Later experiments by
Adami and by Beddard % have thrown doubt upon this otherwise
crucial experiment. Adami claims that ligature of the renal arte-
ries does not shut off completely the glomerular circulation, while
Beddard, although he corroborates Nussbaum in the point that
complete occlusion of the renal arteries suspends entirely the secre-

* "Journal of Physiology," 27, 429, 1902.

t See Gurwitsch, " Archiv f. die gesammte Physiologie, " 91, 71, 1902.-

t Beddard, " Journal of Physiology, " 28, 20, 1902.

748 PHYSIOLOGY OF DIGESTION AND SECRETION.

tion of urine, finds that under these conditions injection of urea into
the circulation is not followed by a secretion. (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 in-
jected into the dorsal lymph sac of a frog, and an hour or so later
the kidneys are examined, it will be found that the convoluted tu-
bules 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, although one
may adopt the less probable view that the cells produce the acid
phosphates by a selective absorption of alkaline salts. 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

KIDNEY AND SKIN AS EXCRETORY ORGANS. 749

the kidney, those who adopt the Bowman-Heidenhain theory as-
sume usually that these substances exert also a direct stimulating
action on the secretory cells.

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
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
* " Skandinavisches Archiv f. Physiologie, " 4, 241, 1892.

750 PHYSIOLOGY OF DIGESTION AND SECRETION.

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
the small arteries of the kidney, a shrinkage in volume of the whole
organ as measured by the oncometer (see Fig. 223), 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 is as 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-

KIDNEY AND SKIN AS EXCRETORY ORGANS. 751

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
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.

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 (NaH2P04); but, according to
Folin,* 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
C02), 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
* " American Journal of Physiology, " 9, 265, 1903.

752 PHYSIOLOGY OF DIGESTION AND SECRETION.

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 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 proteids — 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 proteids).
The water is eliminated in the urine, the sweat, saliva, etc., and the
expired air. The C02 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 proteid material,
is found in minute part in the sweat, to a larger extent in the feces,
but in by far the main amount in the urine. In all problems con-
cerning proteid 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
proteid 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-
teid broken down, since nitrogen forms, on the average, 16 per
cent, of the weight of the proteid 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-
teid. 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.

KIDNEY AND SKIN AS EXCRETORY ORGANS. 753

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 of the physiological oxidation of the proteids of
the body, and also of the albuminoids when they appear in the food.
If we know how much urea is secreted in a given period, we know
approximately how much proteid has been broken down in the
body in the same time. In round numbers, 1 gm. of proteid 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 proteid is eliminated in other forms — uric acid, creatinin, etc. —
even an exact determination of all the urea is not sufficient to de-
termine with accuracy the total amount of proteid broken down.
This fact is arrived at more perfectly, as stated above, by a deter-
mination 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 kid-
neys by the blood for elimination. 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 ammonium 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
proteid 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 investigations have thrown a great deal of light on the whole
process, and they give hope that before long the entire history of
48

754 PHYSIOLOGY OF DIGESTION AND SECRETION.

the derivation of urea from proteids and albuminoids will be known.
The results of this work may be stated briefly as follows:

1 . Urea arises from proteids by a process of hydrolysis and oxida-
tion, with the formation eventually of ammonia compounds, which
are then conveyed to the liver and there changed to urea. Drechsel
has suggested that ammonium carbamate forms one at least of the
ammonia compounds that are converted to urea, and gives the fol-
lowing evidence for this view. In the first place, Drechsel found
carbamic acid in the blood of dogs, and Drechsel and Abel have
shown that it occurs normally in the urine of horses as calcium car-
bamate. Abel has shown, also, that it may be found in the urine
of dogs or infants after the use of lime-water. Drechsel has shown,
further, that ammonium carbamate may be converted into urea.
If one compares the formulas of ammonium carbamate and urea,
it is seen that the former may pass over into the latter by the loss
of a molecule of water, as —

Ammonium Urea,

carbamate.

Drechsel supposes, however, that this dehydration is effected in an
indirect manner; that there is first an oxidation removing two
atoms of hydrogen, and then a reduction removing an atom of oxy-
gen. He succeeded in showing that when an aqueous solution of
ammonium carbamate is submitted to electrolysis, and the direc-
tion of the current is changed repeatedly so as to get alternately
reduction and oxidation processes at each pole, some urea is pro-
duced. These facts show the existence of ammonium carbamate
in the body, and the possibility of its conversion to urea. It remains
possible, however, that other salts or compounds of ammonia may
likewise be converted normally to urea by the liver, since it has been
shown experimentally in artificial circulation through this organ
that salts such as ammonium carbonate, or even such complex
ammonia compounds as leucin and glycocoll, may give rise to urea.
Experiments made by Hahn, Pawlow, Massen, and Nencki* 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 con-
tents. 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, and the only blood that the organ received was through
the hepatic artery. If, now, this artery was ligated or the liver
was cut away, as was done in some of the experiments, then the
result was practically an extirpation of the entire organ. The

* " Archiv f. experimentelle Pathologie u. Pharmakologie, " 32, 161, 1893.

KIDNEY AND SKIN AS EXCRETORY ORGANS. 755

animals in these investigations survived this operation for some time,
but they died finally, showing a series of symptoms which indicated
a deep disturbance of the nervous system. It was found that the
symptoms of poisoning in these animals could be brought on before
they developed spontaneously by feeding the dogs upon a rich meat
diet, or with salts of ammonia or carbamic acid. Later investiga-
tions* showed that in normal animals the ammonia contents of the
blood in the portal vein are from three to four times what is found
in the arterial blood, but that after the operation described the
ammonia in the arterial blood increases and at the time of the de-
velopment of the fatal symptoms reaches about the percentage
which is normal to the blood of the portal vein. It would seem
from these investigations that the liver stands between the portal
circulation and the general systemic circulation and protects the
latter from the comparatively large amount of ammonia compounds
contained in the portal blood by converting these compounds to
urea. If the liver is thrown out of function, ammonia compounds
accumulate in the blood and cause death. Similar ammonia salts
are probably formed in other active proteid tissues, since the per-
centage of ammonia in the tissues is considerably greater than in
the blood, and these compounds also are doubtless converted to
urea in the liver, in part at least. As to the origin of the ammonia
compounds, there is little direct evidence. They come, in the long
run, of course, from the nitrogenous foodstuffs, — proteids and al-
buminoids. Drechsel supposes that the proteids first undergo hydro-
lytic cleavage, with the formation of amido-bodies, such as leucin,
tyrosin, aspartic acid, glycocoll, etc.; that these bodies undergo
oxidation in the tissues, with the formation of NH3, C02, and H20;
and that the NH2 and C03 then unite synthetically to form am-
monium carbamate, which is carried to the liver and changed to
urea. It is a very significant fact that the relative and absolute
amount of urea nitrogen in the urine varies directly with the amount
of proteid 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,f and suggests,
therefore, that most of the urea may come directly from proteid of
the food which is hydrolyzed during digestion and absorption (action
of trypsin and erepsin) into simpler amido-acids. These amido-
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 b}^ the liver without entering into tissue

* Nencki, Pawlow, and Zaleski, ibid., 37, 26, 1895; also Nencki and
Pawlow, "Archives des sciences biologiques, " 5, 213.

t Folin, "American Journal of Physiology," 13, 117, 1905.

9

, ,, 756 * PHJfcSI^LOGY OF DIGESTION AND SECRETION.

all. In this way the large proportion of ammonia
compounds in the portal blood after digestion may be explained.
Granting that a portion, perhaps a large portion, of the urea arises
from this early hydrolysis of the proteid of the food, we must admit
also at present that ammonia compounds may be formed in the tis-
sues of the body generally, probably by a similar process of hydrol-
ysis followed by oxidation.

2. It is stated (Kossel and Dakin*) that a ferment (arginase)
may be extracted from the liver which is capable of splitting arginin
into urea and ornithin (diamido valerianic acid). Since arginin is
one of the diamido-bodies formed by the hydrolysis of the proteids
during digestion, it is possible that some of the urea has this origin.
The fact lends some probability to the view suggested above that
much of the nitrogen of proteid food may be converted to urea before
entering the general circulation.

3. Even after the removal of the liver some urea is still found in
the urine. This fact proves that other organs have the power of
forming urea, but what these other organs are and by what process
they make urea are points as yet undecided. 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) . — 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

I I >

N — C — W

hydrogen compound of this nucleus would be designated as purin,

N = CH

and would have the formula: HC C— NH , C5H4N4. Addi-

l| II \PTT
N — C — N^CH

tion of an atom of oxygen gives hypoxanthin, C5H4N40:
HN — CO

HC C — NH

11 J! ^CH. Addition of two* atoms of oxygen gives xan-
N — C — N^

HN — CO

thin, C5H4N402: CO C — NH

HN — C — N/°H' AnC* adcution °f tnree atoms
* Kossel and Dakin, "Zeitschrift f. physiol. Chemie," 42, 181, 1904.

R A F

KIDNEY AND SKIN AS EXCRETORY ORGAl

HN — CO ^"<^U

of oxygen gives uric acid, C5H4N403: 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 amido-group, NH2, the com-
pound, adenin (C5H5N5), is obtained, and the further addition of oxy-
gen gives guanin (C5H5N50). Moreover, caffein, the active principle
of coffee and tea, and theobromin, the active principle of cocoa, are re-
spectively trimethyl and dimethyl compounds of purin. Uric acid,
xanthin, hypoxanthin, and in smaller amounts other members of this
group are found constantly in the urine. 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 ma-
terial. A portion of the amount daily secreted comes, however,
from a metabolism of the proteid 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 liv-
ing tissues, that goes on independently, in great measure, of the
mere oxidation of food. The view generally adopted at present is
that first proposed by Horbaczewsky,f — namely, that the purin
bodies are the end-product, so far as the nitrogen is concerned, of
the physiological oxidation of the nuclein (see appendix) found in
the nuclei of the cells, and especially perhaps of the nuclein of the
leucocytes. On this view the purin bodies give a measure of the
extent of metabolism in the cell-nuclei. The actual amount of these
substances found in the urine does not in all probability represent
the entire amount formed in the body. It is found that when
xanthin, hypoxanthin, uric acid, or materials such as liver or thymus
rich in purin bodies are fed, only about half of the material is ex-
creted as such in the urine, and it seems probable that the same
fate occurs to a part of the endogenous purin material normally
formed in the body. Among birds and reptiles uric acid represents
the chief nitrogenous excretion of the urine, taking physiologically
the place held by urea in the mammalia. In the birds it has been
shown that the uric acid is formed in the liver. Extirpation of the
kidneys in these animals leads to an accumulation of uric acid in

* See Burian and Schur, " Archiv f . die gesammte Physioloeie, " 94, 273.
1903.

t See Minkowski, "Archiv f. exper. Pathol, u. Pharmakol.," 41, 375.

structural formula is given as NHC/ and its chemical re-

758 PHYSIOLOGY OF DIGESTION AND SECRETION.

the blood and tissues, while removal of the liver, on the contrary,
causes a decrease in the excretion of uric acid and an increase in
the ammonia contents of the urine. It may be concluded, there-
fore, that in birds uric acid is formed in part at least in the liver
from ammonia compounds. Whether the liver takes a part in the
formation of the endogenous uric acid in mammals has not been
positively shown.

Origin and Significance of the Creatinin. — Creatinin (C4H7-
N30) is derived from the creatin (C4H9N302) found in muscle. Its

/NH — CO

v

^N(CH3

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(CHJCHPOOH - NHC^H$)CHjC00H

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. The fol-
lowing facts, however, are significant and throw some light on its
origin. Like the purin bodies, the amount present in the urine is
probably partly of an exogenous and partly of an endogenous origin,
— that is, part is formed in the body and part arises from the creatin
contained in the meats and soups used as food. The endogenous
portion, which, of course, is the part that is interesting physio-
logically, shows a tendency to remain constant under constant con-
tions of life, and this fact indicates (Folin) that the creatinin repre-
sents an end-product of the metabolism of living or organized pro-
teid tissue rather than one of the results of the metabolism of the
food proteid. Everything would indicate also that this substance
originates in the muscular tissue. Creatin is a constant and consider-
able 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 creat-
inin. 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

KIDNEY AND SKIN AS EXCRETORY ORGANS. 759

the food is eliminated as 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 in-
creases the amount of creatinin in the urine,* 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. Kochf has suggested, on account of the methyl groups
present, that a part of the creatinin may arise from a metabolism
of the lecithin.

Hippuric Acid. — This substance has the formula C9H9N03. 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-amido-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. is 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 J 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 proteid putrefaction that occurs in the large intestine.

The Conjugated Sulphates and the Sulphur Excretion. —
The sulphur excretion of the urine possesses an importance similar

* Gregor, " Zeitschrift f. physiol. Chemie, " 31, 98, 1900.
t " American Journal of Physiology, " 13, xix, 1905.
j Bashford and Cramer, "Zeitschrift f. physiolog. Chemie," 35, 324.
1902.

760 PHYSIOLOGY OF DIGESTION AND SECRETION.

to that of nitrogen. Sulphur constitutes an element in most of the
proteids, and in some form, therefore, it will be represented in the
end-products of proteid metabolism. The sulphur elimination in
the urine, like the nitrogen elimination, has been taken as a measure
of the amount of proteid destruction. In the urine the sulphur
occurs in three forms: (1) In an oxidized form as inorganic sulphates.
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 proteids. (2)
The so-called conjugated or ethereal sulphates are combinations be-
tween sulphuric acid and indoxyl, skatoxyl, phenol, and cresol, giving
us phenolsulphuric acid (C6H5OS02OH), cresolsulphuric acid (C7H7-
OS02OH), indoxylsulphuric acid or indican (C8H6NOS02OH), and
skatoxylsulphuric acid (C9H8NOS02OH). The indol, skatol, phe-
nol, 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 glucuronic acid
(C6H10O7), 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 proteid 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. 761

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, which salts are eliminated from the blood by the kid-
ney in the water secretion, and in part they are formed in the de-
structive metabolism that takes place in the body, particularly
that involving the proteids 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 are 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

* " Pfliiger's Archiv f. die gesammte Physiologie, " 2, 243, 1869, and 4, 33.

762 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. ex per. Pathologie und Pharmakologie," 32, 241, 1893.

KIDNEY AND SKIN AS EXCRETORY ORGANS. 763

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 vesica? 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 urethral. 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

764 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 Pellacanit 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 biologie, " 1, 1882.

KIDNEY AND SKIN AS EXCRETORY ORGANS. 765

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 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,f 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. 142).

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.J

*" Journal of Physiology," 19, 71, 1895.

t"Archiv f. die gesammte Physiologie, " 49, 141, 1891.

% See Stewart, " American Journal of Physiology, " 2, 182, 1899.

766 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 oh Nutrition and
Circulation. In the female, during the period of lactation, the mam-
mary glands, which must be reckoned amoM the organs of the
skin, form an important secretion, the milkj^Be physiology of this
gland is referred to in the section on ReprocMrction. In this section
we are concerned with the physiology of me 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, and 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. Physiologie, " 1893, 116; see also Willebrand, "Skandi-
navisches Archiv f. Physiologie," 13, 337, 1902.

KIDNEY AND SKIN AS EXCRETORY ORGANS. 767

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 C02 eliminated from
the skin. It is possible that the sudden increase in C02 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.

768 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, proceed-
ing 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. 769

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 th'e 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
49

770 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 prceputii; 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, 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 C02 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, or the liver. 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.

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-

771

772 PHYSIOLOGY OF DIGESTION AND SECRETION.

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 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 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 animal 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

SECRETION OF THE DUCTLESS GLANDS. 773

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 edematous condition
of the skin, loss of hair, etc. Schiff 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 proteid 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
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,t Gley,§ and Vassale and Generate, || 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

* For a general account of the development of the subject and the liter-
ature see " Transactions of the Congress of American Physicians and Surgeons"
(Howell, Chittenden, Adami, Putnam, Kinnicutt, Osier), 1897, and Jean-
delize, " Insuffisance thyroidienne et parathyroidienne, " Nancy, 1902.

t "Zeitschrift f. physiolog. Chemie," 21, 319, and 481, 1896.

% Moussu, " Proc. Fourth International Physiolog. Congress, " 1898.

§Gley, "Pfliiger's Archiv," 66, 308, 1897.

|| Vassale and Generate, " Archives italiennes de biologie, " 33, 1900.

774 PHYSIOLOGY OF DIGESTION AND SECRETION.

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. Assuming, however,
that the distinction made by Moussu and others is well founded,
the interesting question arises as to the functional relationship be-
tween the thyroids and the parathyroids. Myxedema, cretinism,
and similar conditions in man may be referred to an atrophy or loss
of functions of the thyroids, but there is no knowledge of effects
attributable to pathological changes in the parathyroids. The old
view that the parathyroids represent embryonic thyroid tissue which
after removal of the thyroids replaces the functions of the latter
is not supported by experimental or histological evidence. The
two bodies represent different structures, histologically, embryo-
logically, and physiologically, and yet there seems to be some cor-
relation in function between them. The parathyroids, like the thy-
roids, contain a large percentage of iodin; when the parathyroids
are removed the thyroids exhibit a change in structure in that the
colloid material disappears from the vesicles, and finally the tetany
following removal of the parathyroids may be ameliorated by sub-
sequent excision of the thyroids. The exact nature of the functional
connection between these two organs is, however, as yet quite un-
explained; there is need for further investigation.

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-
* Vincent and Jolly, " Journal of Physiology, " 32, 65, 1904.

SECRETION OF THE DUCTLESS GLANDS. 775

ism. According to the other point of view, less generally held, the
function of these bodies is to neutralize 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.

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-
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 physiologie, "
1898, p. 618.

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
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,| 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-

* " Journal of Physiology, " 18, 230, 1895.

t " Archiv f. die gesammte Physiologie, " 64, 97, 1896.

776 PHYSIOLOGY OF DIGESTION AND SECRETION.

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. 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
possess secretory nerve fibers. Abelf 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. iH20 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.

Other crystalline products, adrenalin (C9H13N03), suprarenalin,
etc., have been prepared from the gland and show a most marked
influence in constricting the blood-vessels. These substances are
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 peripheral nerve fibers dis-
tributed 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 adrenal extracts or so-
lutions of adrenalin do not act upon all varieties of plain muscle,
but only on those innervated by nerve fibers originating in the sym-
pathetic chain of ganglia. It has been proposed, therefore, to use
these solutions to determine whether or not given vascular areas,

* " American Journal of Physiology, " 2, 203, 1899.

f Abel, " Berichte d. deut. chem. Gesellschaft, " 37, 368, 1904.

SECRETION OF THE DUCTLESS GLANDS. 777

such as those of the brain or lungs, are provided with vasocon-
strictor nerve fibers. When adrenalin is injected into a normal
animal it may have an influence upon the nerve centers of the vaso-
motor nerves as well as upon the peripheral endings. Meltzer* has
shown that moderate doses under such conditions may cause a dila-
tation, while in parts whose connection with the nerve center is
destroyed only a constriction is obtained. Under normal condi-
tions at least these extracts when injected into the circulation soon
lose their effect. This fact may explain why injection of the ex-
tracts 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 thyroidectomy, it has been suggested that grafts of the adre-
nals under the skin or into the peritoneal cavity may prove more
effective. Results by this method, however, have also been chiefly
negative, owing apparently to the fact that in such grafts the medul-
lary substance, which contains the material that causes constric-
tion of the blood-vessels, readily undergoes atrophy and absorp-
tion. It seems probable that, if the method of grafting is perfected
so as to preserve the medulla intact, this procedure may prove
effective as a therapeutical means in the treatment of Addison's
disease.

The Physiological Rdle 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.

Pituitary Body. — This body is usually described as consisting

*S. J. and Clara Meltzer, "American Journal of Physiology," 9, 252,
1903.

778 PHYSIOLOGY OF DIGESTION AND SECRETION.

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. Howell f and
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
blood-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 has been generally
assumed, but produces a peculiar substance, an internal secretion,
that may have a distinct physiological value. A number of ob-
servers, especially Vassale and Sacchi, have succeeded in remov-
ing 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 pituitary body may be related in
function to the thyroids and may be able to assume vicariously
the functions of the latter after thyroidectomy. There is no satis-
factory evidence, however, in support of this view. On the patho-
logical 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 pitu-
itary body is, however, very uncertain, and is not supported by any
definite clinical or experimental facts.

Testis and Ovary. — Some of the earliest work upon the effect
of the internal secretions of the glands was done upon the repro-
ductive glands, especially the testis, by Brown-Sequard.t 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

* 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.

% " Archives de physiologie normale et pathologique, " 1889-92.

SECRETION OF THE DUCTLESS GLANDS. 779

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
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

* "Zeitschrift f. klinische Medicin," 26, 133, 1894.

t"Pfluger's Archiv f. die gesammte Physiologie," 62, 335, 1896; also
69, 386, 1897.

% Ibid., p. 379. § Morris, " Medical Record," 1901, p. 83.

|| Glass, " Medical News," 1899, p. 523.

780 PHYSIOLOGY OF DIGESTION AND SECRETION.

of the operation was a return of menstruation and sexual desire,
and a marked alleviation of the disagreeable symptoms following the
artificial menopause. 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.
The probability of an effect of the ovaries on general nutrition is
indicated also by the interesting fact that in cases of osteomalacia,
a disease characterized 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 verifi-
cation in a research by Loewy and Richter* made upon dogs.
These observers found that complete removal of the ovaries, al-
though 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 increas-
ing the oxidations of the body.

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 f 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
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
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,

* Loewy and Richter, " Archiv f . Physiologie," 1899, suppl. volume, p. 174.
t Minkowski, "Archiv f. exper. Pathologie u. Pharmakologie, " 31, 85,
1893.

SECRETION OF THE DUCTLESS GLANDS. 781

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 in 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 may
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.
This conclusion is strengthened by reports from the pathological
side. A number of recent observers (Opie, Ssbolew, Herzog, et al.)
find that in diabetes mellitus in man the islands are markedly af-
fected. They show signs of hyaline degeneration or atrophy or in
severe cases may be absent altogether.

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-
*"Virchow's Archiv," 168, 91, 1902.

782 PHYSIOLOGY OF DIGESTION AND SECRETION.

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. Cohnheim* 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
name "rennin," is normally secreted by the kidney into the renal
blood, and that this substance causes a vasoconstriction.

* Cohnheim, "Zeitschrift f. physiolog. Chemie," 39, 336, 1903; also 1904.
f " Skandinavisches Archiv f . Physiologie, " 8, 223, 1898 ; see also Brad-
ford, "Proceedings of the Royal Society, " 1892.

SECTION VIII.

NUTRITION AND HEAT PRODUCTION AND
REGULATION.

CHAPTER XLVII.
GENERAL METHODS-HISTORY OF THE PROTEID 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 proteids,
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-
teids (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 proteid 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 is

783

>■

o
784

NUTRITION AND HEAT REGULATION.

KB

J

usuSJli neglected except in observations upon conditions in which
musgJar activity has been a prominent feature. As a rule, the
amouilt of nitrogen is determined by some modification of the Kjel-
daK^ method. In principle this method consists in heating the
rngtefrial to be analyzed with strong sulphuric acid. The nitrogen

" ereby converted to ammonia, which is distilled off and caught
i§^ standardized solution of sulphuric acid. By titration the amount
f ammonia can be determined, and from this the amount of nitrogen
is estimated. Nitrogen forms a definite percentage of the proteid
molecule (about 16 per cent.) ; so that if the weight of nitrogen is
multiplied by 6.25 the weight of proteid from which it is derived
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 proteid) 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 proteid tissue, while if the
balance is minus the body must be losing proteid. During the period
of growth, in convalescence, etc., the body does store proteid, 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 conditions, involving,
for instance, a special diet, it often becomes necessary to make
the analyses for nitrogen in order to determine whether or not the
individual is losing or gaining proteid or is in equilibrium.

It is important also to bear in mind that nitrogen or proteid
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 proteid in this diet is doubled?
Our experience teaches us that the extra 10 gms. of nitrogen or
62.5 gms. of proteid is not stored in the body indefinitely. As a
matter of fact, the extra proteid is metabolized in the body and
nitrogen equilibrium becomes established at a higher level. Whereas
under the first condition 62.5 gms. of proteid were eaten and 62.5
gms. of proteid were lost from the body either in the form of nitrog-
enous excreta or in the feces as undigested proteid, under the
second condition 125 gms. of proteid are eaten and 125 gms. of pro-
teid are lost. The total mass of proteid 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 proteid which just suffices to maintain
nitrogen equilibrium, and between this level and the capacity of

GENERAL METHODS — HISTORY OF PROTBID EOOD. 785

the body to digest and absorb proteid food rutrogOT^raibtti^art'rCVj^,
may be maintained upon any given amount of proteid.

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 proteids may just be covered
by the proteids of the food, the consumption of non-proteid 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 equilibrium.
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. — Ac-
cording 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 proteids, fats, and carbohydrates eaten as
food and the proteids, 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 C02 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 C02. From the figures thus
obtained it was possible to estimate the entire C02 given off during
the period of observation. Knowing the total nitrogen and C02
eliminated, it is possible to estimate the amount of proteid and
fat or carbohydrate destroyed in the body. If the carbon belong-
ing to the amount of proteid 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 Physiologie, " vol. vi, 1881.
50

786 NUTRITION AND HEAT REGULATION.

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. 823) 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-proteid Food on Nitrogen Equilibrium. —
By use of the methods referred to above the general influence of
the non-proteid foods (fats, carbohydrates, albuminoids) upon the
proteid consumption of the body has been made evident. An ani-
mal may be brought into nitrogen equilibrium on proteid food alone,
the amount of proteid required being relatively large. If now the
proteid food is mixed with any of the non-proteid foodstuffs it is
found that the amount of proteid necessary to maintain nitrogen
equilibrium may be reduced correspondingly. With reference to
the consumption of proteid in the body the non-proteid foods are
all proteid-sparers, and herein lies one great peculiarity of their nu-
tritional value. On a mixed diet of proteid and non-proteid 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 proteid tissue from
the body. This fact is explained by the consideration that the pro-
teid of our food fulfills two general functions: Its metabolism or
its oxidation furnishes energy, especially heat energy to the body,
and, moreover, a portion of it is used to reconstruct the living proto-
plasm that breaks down in the functional activity of the tissues.
The non-proteid food also furnishes heat energy and work energy,
and to a large extent at least can replace this part of the function
fulfilled by the proteid.

The Nutritive History of the Proteid Food. — The digestive
changes undergone by proteid 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.

GENERAL METHODS — HISTORY OF PROTEID FOOD. 787

that the products of proteid 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 proteid. 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 proteid, before or after absorption, being
converted into what we might call a body proteid characteristic of
the animal. Although it is not specifically stated, the assumption
seems to be that this body proteid is the serum-albumin of the
animal's blood.

Accepting this general assumption, one theory, advocated by
Pfluger, 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 proteid
that subserves this function is designated as tissue proteid. It is
obvious that this function can not be replaced by the non-proteid —
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 proteid that undergoes this fate
is designated as the circulating proteid on the hypothesis that it
enters the circulating liquids of the body, the blood and lymph, and
is carried around in them until destroyed by the tissues.

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 proteid digestion,
the monamido- and diamido-bodies — leucin, tyrosin, arginin, etc. —
are not wholly built up into a new body proteid. 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. 708), there is some evidence that a portion of the proteid mole-
cule during digestion is not broken up into the ultimate split prod-

788 NUTRITION AND HEAT REGULATION.

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 proteid 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 proteid, — the am-
monia, the leucin, etc., — when circulated through the liver, give
rise to urea. Since the split products of proteid 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, wThile a portion of the rest of the mole-
cules from which the nitrogen is thus removed is retained in the
body to be subsequently oxidized and 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 proteid food is promptly
converted to urea and is eliminated before becoming a part either
of the living proteid or the circulating proteid of the body. This
view seems to be opposed to our conceptions of the importance of
proteid foods, but it is in harmony with the surprising fact that the
digestive enzymes are adapted to split the proteid molecule into
what we may call its ultimate products, the relatively simple amido-
bodies, and moreover that most of the proteid 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 proteid food. Upon an average diet containing 16 to
17 gms. of nitrogen (100 to 106 gms. of usable proteid) the urea
forms 87 to 88 per cent, of the total nitrogen of the urine, while when
the proteid 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 proteid
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 the nitrogen of that por-
tion of the proteid food which, from the present point of view, is
hydrolyzed during digestion into the split products and is changed
to urea in the liver.

The Amount of Proteid Necessary for Normal Nutrition —
Luxus Consumption. — As was stated above, nitrogen equilibrium
may be maintained on different amounts of proteid food. It is

* Folin, "American Journal of Physiology," 13, 45, 66, and 117, 1905.

GENERAL METHODS — HISTORY OF PROTEID FOOD. 789

important, from a scientific and from an economic standpoint, to
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-
teid in the diet. Examination of the dietaries of civilized races
shows that, on the average, 100 to 120 gms. of proteid are used
daily by an adult man. Voit gives 118 gms. of proteid 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-proteid portion of the diet is increased. The question is
whether the large excess of proteid 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 one side,
we have the following facts: Some observers (Munk, Rosenheim),
from experiments made upon dogs, state that when a low proteid
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 proteid food
must also be allowed to have considerable weight. With our im-
perfect 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 proteids 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 that a proteid 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 proteid instead of 118 gms.
These observers believe that the excess of proteid usually employed
is undesirable in that it increases the amount of injurious nitrog-
enous waste products, that it throws an unnecessary amount of
labor upon the excretory organs, and that it increases the pos-

* Consult Chittenden, " Physiological Economy in Nutrition," New York,
1905, for discussion and literature.

790 NUTRITION AND HEAT REGULATION.

sibility of the formation of toxic products in the intestines 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 upon a low proteid diet, they
do not demonstrate satisfactorily that a larger proteid diet is
actually attended by evil consequences.

The Specific Character of the Proteid Metabolism.— From
the fact that the nitrogen is eliminated from the body in various
forms — ammonia compounds, urea, creatinin, purin bodies, etc. —
we may infer that the specific metabolism varies in the different
tissues and under different conditions. The steps or stages of this
metabolism are not completely known in any case, but the follow-
ing suggestions have been developed by experimental work. Urea
arises in part in the liver by a conversion of ammonia salts, — for ex-
ample, ammonium carbamate or carbonate (p. 754). The ammonia
salts in turn may arise in the tissues by a process of hydrolytic
cleavage giving origin to amido-bodies, — leucin, glycocoll, etc.,—
which are subsequently oxidized to ammonia, carbon dioxid, and
water. The ammonia and carbon dioxid unite to form ammonium

carbamate, CO\f)]sjfr > which is then dehydrated, directly or in-

4

directly, by the liver to form urea. Or, as previously described,
some of the amido-bodies formed from the proteid during digestion
may be carried to the liver, and the amido-group be split off to form
urea. The general idea, therefore, is that the nitrogen of the pro-
teid is by processes of hydrolysis or by hydrolysis and oxidation
converted to ammonia salts and then to urea. Ammonia com-
pounds are found in the blood, particularly in that of the portal
vein, and these compounds increase in quantity when the liver is
removed.*

Uric acid and the other purin bodies arise probably from a
metabolism of the nuclein material contained in the nucleoproteids of
the body, but the processes involved are not known. Presumably
they are formed from nuclein by processes of hydrolysis caused by
specific enzymes or by the more direct influence of the living tissue.
In the laboratory the nucleins may be split by the hydrolytic action
of acids with the formation of purin bases.

The creatinin of the urine is formed from the creatin found in
muscular tissue. Presumably this creatin is derived from a metab-
olism of the living muscular tissue. There is evidence to show
that increased muscular activity may be associated with an in-
creased formation of creatin (p. 759).

* See Nencki, Pawlow, and Zaleski, " Archiv f . exp. Pathologie u. Phar-
makologie," 37, 26, 1895; and Nencki and Pawlow, "Archives des sciences
biologiques," 5, 213.

GENERAL METHODS — HISTORY OF PROTEID FOOD. 791

With regard to the non-nitrogenous portion of the proteid mole-
cule the evidence to show that it may be converted to glycogen
(sugar) has already been given (p. 733), while the views regarding
its conversion to fat will be referred to in the following chapter under
the head of Origin of the Body Fat.

Nutritive Value of Albuminoids. — The albuminoid most fre-
quently occurring in food is gelatin. It is derived from collagen
of the connective tissues. 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 proteid molecule closely in percentage composition, and it would
seem that the tissues might use it as they do proteid 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. Gelatin,
however, is readily digested, gelatoses and gelatin peptones and event-
ually some split products being formed; these are absorbed and
oxidized in the body, with the formation of C02, H20, and urea or
some related nitrogenous product. 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 proteid necessary for the maintenance of nitrogen
equilibrium may be reduced greatly. Actual experiments have
shown that gelatin is more efficacious than either fats or carbohy-
drates in protecting the proteid in the body. The relative value
of fats, carbohydrates, and gelatin in protecting proteid from de-
struction in the body is illustrated by an experiment reported by
Voit: A dog weighing 32 kgms. was fed alternately upon proteid
and sugar, proteid and fat, and proteid and gelatin, with the follow-
ing 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 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. Munk. has attempted to determine how far the

792 NUTRITION AND HEAT REGULATION.

proteids of food may be replaced by gelatin. In his experiments
a dog was brought into a condition of nitrogenous equilibrium upon
a diet of meat, rice, and lard, containing 9.73 gms. of nitrogen.
During the period this diet was continued the animal, whose weight
was 16.5 kgms., was oxidizing in its body 3.7 gms. of proteid daily
for each kilogram of weight. In a second period lasting four days
the quantities of rice and lard were the same as before, but the pro-
teid in the diet was reduced to 8.2 gms., or 1.3 gms. of nitrogen; the
balance of the necessary nitrogen was supplied in the form of gela-
tin, so that in round numbers only one-seventh of the required daily
amount of nitrogen was given as proteid. The result was that the
animal maintained its nitrogen equilibrium for the short period
stated. It was found that the experiments could not be continued
longer than four days, owing to the growing dislike of the animal
for the gelatin food. During the second period the animal was
receiving in its food and burning in its body only 0.5 gm. of pro-
teid daily for each kilogram of weight, as against 3.7 gms. upon
a normal diet.

CHAPTER XLVIII.
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 proteid tissues of the body, and
possibly also from the body fat, although this latter source is
doubtful. The supply of glycogen under normal conditions is main-
tained chiefly by the carbohydrate food. As was explained in the
section on digestion, the starches, sugars, gums, etc., which con-
stitute 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 proteids 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 con-
verted to glycogen in the liver. Others hold that only those pro-
teids, such as egg-albumin, which contain a carbohydrate grouping
in the molecule are capable of yielding glycogen in the body.*
Whether the fats of the food may serve as a source of glycogen is
also an open question, but the balance of evidence is probably
against such a view. The store of glycogen in the body is about
equally divided between the liver and the muscular tissues, but the
regulation 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 abnomal 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.

The Final Fate of the Carbohydrate of the Body. — Eventually

* See Pfluger, in " Archiv f. die gesammte Physiologie, " 96, 1, 1903, for
literature and discussion.

793

794 NUTRITION AND HEAT REGULATION.

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 (islands of Langerhans)
is necessary to this process. 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. While
the matter is still one for investigation, the trend of recent work
indicates that the sugar is broken down and oxidized by the suc-
cessive action of a number of enzymes, with the formation, there-
fore, of a number of intermediate products.* The first step seems
to be a conversion to lactic acid

CcH1206 = 2C3Hfl03

Sugar. Lactic acid.

under the influence of an enzyme (lactolase or zymase). The lactic
acid is then split into alcohol and carbon dioxid

C3H603 = C02 + C2H5OH

Lactic acid. Ethyl-alcohol.

by the action of another enzyme (alcoholase or lactacidase), and
finally by the action of one or more oxidizing enzymes the alcohol
is oxidized to carbon dioxid and water. Whether or not this specific
process takes place in normal metabolism must be determined by
future work. 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, either in the way indi-
cated above or in controlling the activity of the enzyme in the
liver which converts the glycogen to sugar.

The Temporary Fate of the Carbohydrate in the Tissues. —
The sugar absorbed from the alimentary canal may be stored in
the body in two forms : First, as explained above, it may be changed
to glycogen; or, second, it may be converted into fat and thus be
stored in more permanent form. Nutritive experiments, described
below, leave no doubt that the fat of the body may be formed from
carbohydrate food. It is stated that the fat that has this origin,
carbohydrate fat, is of a more solid consistency — that is, has a larger
percentage of palmitin and stearin — than the fat coming from other
sources.

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

* See Buchner and Meisenheimer, " Berichte d. deutsch. chem. Gesell-
schaft," 38, 620, 1905; and Stoklase, ibid., p. 664.

CARBOHYDRATES AND FATS. 795

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 proteid of the body. Attention has already been
called to the fact that an animal may be kept in nitrogen equilibrium
on a much smaller proteid diet provided carbohydrates (or fats)
are also eaten. One may say, in fact, that as the carbohydrate food
is increased the proteid food may be diminished, down to a certain
irreducible minimum. From the chemical composition of carbo-
hydrates it is evident that they alone can not serve to build up pro-
toplasm. Some proteid food is absolutely necessary for the repair
of tissue or the production of new tissue during growth. An ani-
mal fed on carbohydrate food alone, no matter how abundant the
supply, would eventually starve to death. Within the limits speci-
fied, however, the carbohydrates are proteid-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 proteid from consumption and
enables us to reduce the proteid material in our diet. The im-
portance of the carbohydrates in nutrition is illustrated in a strik-
ing way by the facts in diabetes. Diabetes occurs in man (diabetes
mellitus) as a pathological condition which in some cases at least
is referable to a lesion of the pancreas. As already described, it
may also be produced in dogs and other animals by removal of the
pancreas (pancreatic diabetes). Under both conditions when com-
plete the carbohydrates eaten are not oxidized in the body, but are
eliminated as sugar in the urine. Corresponding to the loss of this
source of energy an increased amount of proteid is necessary in the
diet, and adding carbohydrate to the food in such cases does not

796 NUTRITION AND HEAT REGULATION.

alter the nitrogen elimination in the urine. The diabetic condition
may be produced in other ways the most interesting of which is by
the administration of phloridzin, — a vegetable glucosid obtained
from the roots of certain trees (apple, pear). The cause of phlo-
ridzin diabetes is not entirely known, but the general view is that
the glucosid acts upon the kidney and renders it more permeable,
so that the sugar of the blood escapes into the urine, or, on the
other hand, it may affect the condition of the sugar in the blood so
as to make it pass through the kidney more easily. The diabetes
in this case has obviously a different cause from that of pancreatic
diabetes, but by repeated use of the drug the loss of carbohydrate
to the body may be made complete. If the animal is fed only on
proteid, proteid and fat, or is starved so that he is living on the
proteid and fat of his own body the drug still causes the appear-
ance of large quantities of sugar in the urine. Lusk* finds under
such conditions that the amount of dextrose in the urine bears a
definite ratio to the amount of nitrogen, — D : N :: 3.65 : 1. He
believes that the establishment of this ratio is an indication of a
complete inability of the tissues to use sugar. A similar ratio has
been obtained in the urine of individuals suffering from a severe
and eventually fatal form of diabetes mellitus. Assuming that
the sugar is these cases comes entirely from the proteid of the food
or of the tissues, this ratio would indicate that 58.4 per cent, of the
proteid molecule may be converted to sugar in the body.

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, C02 and H20 — 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 proteids or the carbohydrates. In a
well-nourished animal a large amount of fat is found normally in
adipose tissues, particularly in the so-called "panniculusadiposus"
beneath the skin, and 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

* See Lusk and coworkers, "American Journal of Physiology," vols, i,
iii, and x; also " Deutsches Archiv f. klin. Med.," 81, 472, 1904.

CARBOHYDRATES AND FATS. 797

body proteids and fats; the larger the supply of fat, the more
effectively will the proteid 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
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 not 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. 660). 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.

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
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

798 NUTRITION AND HEAT REGULATION.

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 proteid of the food, the carbohydrate and the fat of the diet
being useful only to protect a part of this proteid 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 -$- 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-
teid 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, f 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 proteid 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.

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

* Pfliiger, "Archiv f. die gesammte Physiologie, " 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. 799

period was 2.55 gms., which indicated a metabolism, therefore, of
16 gms. (2.55 X 6.25) of body proteid. Making the improbable
assumption that all of the carbon of this proteid was retained in
the -body, this would account for 8.32 gms. C (16 X 0.52); so that
3.6 + 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 or by assuming with Voit that it
originated from the proteid. The combined testimony of these
experiments have satisfied physiologists that the fat tissues can
produce fat from sugar. The chemistry of the change is not under-
stood and can not 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 originates most easily from the fat or from the carbohydrate
of the food. While the question is one to which a positive answer
can not 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 may 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
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 proteid. A diet, there-
fore, which will give such an excess to one individual may in the

* Consult Rosenfeld, " Ergebnisse der Physiologie, " vol. i, parti, 1902.
Complete literature.

800 NUTRITION AND HEAT REGULATION.

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 increasing 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 ac-
cumulate fat to a noticeable degree. So also the use of alcoholic
beverages may indirectly favor accumulation of fat, presumably by
depressing 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. Extreme obesity may be
counteracted by altering the mode of life, especially by . taking
much muscular exercise, or more directly by dieting. The diet for
such purposes should be reduced in amount, and should be as free as
possible from fats and carbohydrates, consisting of such material
as eggs, fish, lean meat, salads, fruits, etc. The well-known
Banting diet, devised by a London physician (1864) for the cure
of obesity, makes use of this latter principle.*

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
of cold regions choose a diet rich in fat. (3) It is a proteid-saver.
Like the carbohydrate food, its oxidation protects the proteid from
consumption. In starvation, therefore, the amount of proteid
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 proteid necessary for maintaining 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 probably to the greater difficulty
of oxidation of the fatty material.

* For practical directions concerning the treatment of obesity by dieting
see Gautier, " L'alimentation et les regimes." Paris, 1904.

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, on the contrary, 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 sufficient 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 im-
portant 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 irritability. Even the proteids 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
proteids 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.
51 801

802 NUTRITION AND HEAT REGULATION.

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, " Physiologie des Menschen, "
vol. ii, p. 103, 1901.

INORGANIC SALTS, STIMULANTS, AND CONDIMENTS. 803

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. 501).
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. He estimates it at less
than 0.002 gm. CaO daily. 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 gins, of dry substance contains 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

804 NUTRITION AND HEAT REGULATION.

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, takes place
probably in the liver, but the final excretion of the iron is made
in some form 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 lies in 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 acid condiments, — vinegar, citron, pickles, etc. (5)
The salty condiments, such as table salt. (6) The sugar condiments.

INORGANIC SALTS, STIMULANTS, AND CONDIMENTS. 805

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. 689.) 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 proteid, 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

II XCH

II //Lti

1 ii ^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 proteids, 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.

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-

806 NUTRITION AND HEAT REGULATION.

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 noticeable 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 than f 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.

INORGANIC SALTS, STIMULANTS, AND CONDIMENTS. 807

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 proteid — 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 proteid and non-pro teid foodstuffs, or whether it
protects and takes the place of the latter. With regard to the
non-proteids 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:

Atwater and Benedict / A1cohol-free days. . 251.9 gms. carbon.
Atwater and Benedict j Alcohol days 238.5 "

— 13.4 "
r>- „„ /Alcohol-free days. .212.58 gms. carbon.
^jerre \ Alcohol days 220.84 "

4- 8.26 "
ni .. /Alcohol-free days. .214.83 gms. carbon.
ulopatt \ Alcohol days 22CL87 " " *

+ 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 C02, while
1.7 gms. of sugar yield 2.77 gms. C02, and 0.75 gm. of fat, 2.13 gms. of C02.

* See Atwater and Benedict, Bulletin 69, United States Department of
Agriculture, 1899.

808 NUTRITION AND HEAT REGULATION.

If fat were replaced by the alcohol the amount of C02 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
proteid 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 proteid 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 proteid it was found that less proteid 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 proteid but actually caused an increased proteid
consumption.* Other observers (Neumann, Rosemannf) have
found that, although the effect 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 proteid
tissue, and may even lay on proteid. 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 proteid metabolism. { 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 Physiologie, " 86, 307, 1901,
and 100, 348, 1903, for discussion and literature.

% 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 — proteids. It seemed to follow, from this
generalization, that muscular tissue in activity should use proteid
material, and it was believed at that time that the metabolism of
proteid furnishes 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 proteid of the body.
Nevertheless, when the urine was collected and the urea estimated
it was found that the energy contained in the proteid 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

809

810 NUTRITION AND HEAT REGULATION.

the experiment has been accepted as showing conclusively that the
total energy of muscular work does not come necessarily from the
oxidation of proteid. 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
potential energy of the proteid simultaneously oxidized, but that
the performance of muscular work within certain limits does not
affect at all the amount of proteid 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 that undoubtedly occurs during muscular activity must affect
only the non-proteid 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 proteid 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-proteid
material, and that if the supply of this material had been sufficient
there would not have been any increase in proteid metabolism.
These experiments were repeated in various forms by many ob-
servers (Zuntz, Speck, et al.), 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 proteid, and
the Voit theory, that it comes only from the oxidation of non-pro-
teid material. It has been found that in muscular work carried to
the ordinary extent proteid material, in excess of that destroyed in
conditions of rest, may or may not be used according to the amount
of fats and carbohydrates in the diet. If these latter elements are
in sufficient quantity they furnish the energy required, and proteid
metabolism is not increased by work. If, however, the non-pro-

* Argutinsky, u Pfluger's Archiv f . die gesammte Physiologie, " 46, 552,
1890.

EFFECT OF MUSCULAR WORK AND TEMPERATURE. 811

teids are not sufficient in quantity some of the energy is obtained
at the expense of the proteid of the body, and there is an in-
crease 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 proteids. 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 proteids or fats or both. The
Voit theory is correct to the extent that on an abundant non-proteid
diet much muscular work may be done without any increase in the
consumption of proteid tissue. The muscle is a proteid machine
for the accomplishment of work, and the fuel supplied may be pro-
teid or non-proteid, 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 proteid apparatus itself, and
this idea is borne out by the fact that under similar conditions
other observers have detected an increase in the creatinin excre-
tion, the nitrogenous waste that is peculiar to the muscle. The
effect of muscular work on the carbon excretion, carbon dioxid, is,
of course, marked and invariable. Some extra material must be
oxidized to furnish the energy, and since this material is usually or
exclusively sugar, or sugar and fat, or the non-nitrogenous portion
of the proteid 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 proteid metabolism; on the
contrary, the C02 eliminated and the oxygen absorbed are unques-
tionably diminished. This latter fact finds its simplest explana-
tion 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

•'h

BR ARY

r , ,. 812 .A\NyrfRITION AND HEAT REGULATION.

u nu I Effect 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-proteid 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-proteid 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 C02 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 temperature
nerves of the skin are affected by a fall in outside temperature,
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 mus-
cular tension no increase in the C02 excretion results. This fact
suffices 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
consumption of non-proteid material falls in, therefore, with the
conception 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, proteid
as well as non-proteid, 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 in-
creased production of urea as well as of C02.

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 proteid, 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 proteid 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. Physiologie," 7, 123, 1897.

EFFECT OF MUSCULAR WORK AND TEMPERATURE.

Loss TO
Supposed Weight Actual Loss Each 100 Gmsj .
of Organs Before of Organs of Fresh Org/n^ I
Starvation. in Gms. (Percentage TJo&b).

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 1

Pancreas 6.5 1.1 17.0 .J . , . 4| s.

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 \< /\ A

Brain and cord .... 40.7 1.3 3.2 \ ;> J /

Skin and hair 432.8 89.3 20.6 VT

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 (429 gms.), 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 proteid 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 proteid 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 proteid" derived from its previous food, and
that after this is metabolized the animal lives entirely, so far as
proteid consumption is concerned, upon its "tissue proteid." 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 proteid (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 proteid consumed may
increase, 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 proteids alone.
The general fact that the loss of proteid is greatest during the first
one or two days of starvation has been confirmed recently 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,

814 NUTRITION AND HEAT REGULATION.

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 proteid molecule, after the splitting off of the nitrogen,
may also undergo oxidation and furnish heat. In Liebig 's sense,
therefore, the proteids 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 proteid, 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 can not 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 of general nutrition.
The latter may give rise to heat or possibly absorb heat, but 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
Hungern," 1890. See also Weber, " Ergebnisse der Physiologie, " vol. i,
part i, 1902.

HEAT ENERGY OF FOODS. 815

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
proteid 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-
teid, 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 proteid 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 proteid when burnt outside 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-
teid appears as urea and that 1 gm. of proteid yields J gm. of urea,
then the available heat energy of a gram of proteid 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-

816

NUTRITION AND HEAT REGULATION.

portion is given off in the feces. Rubner has calculated the avail-
able heat energy of proteids by direct experiments upon animals.
In these experiments the heat value of the proteid fed was directly
determined by burning a sample in a calorimeter. Then after feed-
ing a known amount of the proteid 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 proteid fed and
the heat value lost in its excreted products in the feces and urine
gave the actual heat energy obtained from the proteid by the ani-
mal body. Results obtained by this method give an average value
for 1 gm. proteid of 4100 calories (4.1 C), or, since proteid contains
an average of 16 per cent, of nitrogen, we may say that 1 gm. of ni-
trogen ingested as proteid 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

Ash.

0.8
1.2
4.0
1.1
1.3
0.9
1.3
0.8

o: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

22.0

* Selected from Atwater and Bryant, Bulletin 28 (revised edition),
United States Department of Agriculture, 1899.

DIETETICS. 817

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 equi-
librium 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 experiments
prove that this object may be accomplished by proteid 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 indi-
rectly. It will be remembered that a pure meat diet is not entirely
proteid, since all flesh contains some fats and carbohydrates, (glyco-
gen). The functions of a diet are accomplished more easily and
more economically when it is composed of proteids and fats, or pro-
teids and carbohydrates, or, as is almost universally the case, of
proteids, 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 proteids, 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."
52

818 NUTRITION AND HEAT REGULATION.

This fact is illustrated in a general way by the different diets recom-
mended by various physiologists, as follows :

AVERAGE DIETS AND THEIR HEAT VALUES.

MOLESCHOTT. RaNKE. VoiT.

Calories. Calories. Calories.

Proteid 130 gms . . . 533,000 100 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 proteid 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, and 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

* Bulletin 98, United States Department of Agriculture, 1901.
t Chittenden, " Physiological Economy in Nutrition, " 1905.

DIETETICS. 819

familiar articles of food would be necessary, if taken alone, to supply
the requisite daily amount of proteid or non-proteid food ; his esti-
mates are based upon the percentage composition of the foods and
upon experimental data snowing the extent of absorption of the
foodstuffs in each food. In this table he supposes that the daily
diet should contain 110 gms. of proteid=17.5 gms. of N, and non-
proteids sufficient to contain 270 gms. of C:

For 110 Gms. Proteid
(17.5 Gms. N).

Milk 2900 gms.

Meat (lean) 540 "

Hen's eggs 18 eggs.

Wheat flour 800 gms.

Wheat bread 1650 "

Rye bread 1900 "

Rice 1870 "

Corn 990 "

Peas 520 "

Potatoes 4500 "

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 proteids, 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 proteid was distributed as follows:

For 270 Gms. C.

3800
2000

gms.
u

37

670
1000

eggs,
gms.

u

1100

u

750

(I

660

a

750

(i

2550

t(

300 gms. meat

=

63.08 gms.

proteid

=

9.78 gms. N

666.3 c.c. milk

=

18.74 "

a

=

2.905 " "

100 gms. rice

=

7.74 "

a

=

1.2 " "

100 " bread

=

11.32 "

a

=

1.755 " "

500 c.c. wine

1.17 "

0.182 gm. "

102.05 "

15.868 gms. "

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-

820

BODY TEMPERATURE. 821

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
because their oxidations are more rapid and they possess 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 inter-
mediate 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-

822 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. (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 physiologie et de pathol. generate, " 1902,
249.

CALORIMETRY. 823

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 means used for this purpose is
the method of 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.

824

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
and which is filled with oxygen under high pressure. The combus-
tion of the foodstuff is initiated by means of a spiral of platinum

CT\ \ENT

Fig. 266. — Reichert's water calorimeter.

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 calorim-
eter 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

CALORIMETRY. 825

is placed in the inner box and the heat given off is absorbed by the
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. A recent form of this
variety of calorimeter used in this country by Reichert is shown in
Fig. 266. It consists of two concentric boxes of metal with a space
between them of about one and a half 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 $ 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 animal's 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)

826

NUTRITION AND HEAT REGULATION.

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
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-

iHf=n

Fig. 267. — D'Arsonval'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. 267, 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

CALORIMETRY. 827

resultant may be recorded upon smoked paper, as indicated in the
figure.*

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-
teid, 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.f By means of this apparatus many inter-
esting and important experiments have been made upon the nu-
trition of man under special conditions. Such results as the follow-
ing 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:

Income : Potential energy of material metabolized in body = 5459 Cal.
Outeo •! Energy given off from the body as heat .... 4833 Cal.
g \ Heat equivalent of muscular work 602 Cal.

5435 Cal. 5435 Cal.

Experimental error 24 Cal.

* For detailed accounts of special forms of air calorimeters see Rubner,
u Calorimetrische Methodik," 1891; and Rosenthal, "Archiv f. Physiol-
ogie, " 1897, p. 170.

f See Atwater and Rosa, Bulletin 63, United States Department of Agri-
culture, 1899; and for recent improvements, Atwater and Benedict, 1905.

828 NUTRITION AND HEAT REGULATION.

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.

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.

*See Rubner, " Zeitschrift. f. Biologie," 19, 535, 1883; and Richet, " La
chaleur animale," 1889, p. 224.

REGULATION OF THE HEAT LOSS. 829

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

In man this loss of heat is regulated chiefly by controlling the im-
portant factors 3 and 4. We accomplish this end in part deliber-
ately 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.
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

* Zuntz, " Deutsche medizinal-Zeitung, " 1903, No. 25.

830 NUTRITION AND HEAT REGULATION.

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
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-
* Pfliiger, " Archiv f. die gesammte Physiologie, " 18, 255, 1878.

REGULATION OF HEAT PRODUCTION. 831

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 normal animals (dogs) that the body temperature, as we
know, remains constant when the outside temperature is changed,
but that the heat production is increased as the outside tempera-
ture is lowered. Finally, Johannson* has shown that the increased
oxidations that occur under the influence of outside cold, as meas-
ured by the C02 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 inten-
sity. 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

* Johannson, " Skandinavisches Archiv f. Physiologie, " 7, 123, 1897.
t See Wood, " Fever, " " Smithsonian Contributions to Knowledge. "
Washington, 1880.

832 NUTRITION AND HEAT REGULATION.

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
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

*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.

PHYSIOLOGICAL OXIDATIONS. 833

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-
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 :

f 1. The sweat centers and sweat nerves.

„ , ,. . ,. ) 2. The vasoconstrictor center and the vasoconstrictor
Heat dissipation < nerye fibers tQ the gkin

v. 3. The respiratory center.

f 1. The motor nerve centers and the motor nerve fibers

„ , ' +• ) to the skeletal muscles.

Meat production i % The quantity and character of the food as deter-

v 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, proteids — 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 the
metabolism of material in the body by means of which its heat
energy is produced is at bottom comparable to ordinary combus-
tions. Oxvgen is absolutely necessary to the process in each case;
53

834 NUTRITION AND HEAT REGULATION.

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
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 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

* See Engler and Weissberg, " Kritische Studien iiber die Vorgange der
Autoxydation, " 1904.

PHYSIOLOGICAL OXIDATIONS. 835

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
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, proteid, 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 proteid 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, —

836 NUTRITION AND HEAT REGULATION.

that is, they induce splitting or decomposition of the material by
the introduction of water. The supposition has naturally been
made that probably the oxidations of the body are effected also by
enzymes which in some way activate the oxygen. Enz}rmes of this
character have been found; they are designated in general as oxi-
dases 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 hydrogen peroxid. The most conspicuous of
the oxidases found in the animal body is the one capable of oxidiz-
ing aldehydes (salicylic or benzoic aldehyde) 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 tyrosinase, first found in plant juice, has also
been isolated from animal tissues. It oxidizes ty rosin 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 act-
ing singly or in combination or in sequence with the hydrolytic
enzymes. As a matter of fact, however, such an hypothesis is
not by any means demonstrated. Oxidases capable of destroying
proteid, fat, and carbohydrate material have not been actually iso-
lated, but the idea seems to be a fruitful one.

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 — proteid, 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 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. 794) : 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

* For further details see Oppenheimer, " Die Fermente und ihre Wir-
kungen, " second edition, 1903.

PHYSIOLOGICAL OXIDATIONS. 837

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 important also to bear in mind the general view advo-
cated by Speck and others, — namely, that the chemical changes
or metabolism of the body may be divided into two general classes :
first, the heat-producing 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 prob-
ably in the different tissues; it is concerned with the building up
and breaking down of the living machinery and may be 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 physiological oxidations to the body.
It may be supposed that these oxidations furnish the energy neces-
sary for the nutritive metabolism of living matter. In those or-
ganisms or cells that lead an anaerobic existence — that is, an exis-
tence in the absence of free oxygen — the energy necessary for the
process is obtained perhaps by 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 accessory 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-

838

THE FEMALE REPRODUCTIVE ORGANS. 839

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 LII.

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 membrdna 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

JBRARV. J

iff: 840 , n\VtJ*E PHYSIOLOGY OF REPRODUCTION.

■<^ ?) ;;)1V^>^

surtaceTtforms 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.

D N

\

THE FEMALE REPRODUCTIVE ORGAZ&Js/' 841

The majority of writers seem to favor the latter view,
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 in 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
menstruation, and it is not infrequently associated with psychical
and physical disturbances of a serious character. If at any time

842 THE PHYSIOLOGY OF REPRODUCTION.

during sexual life the ovaries are completely removed by surgical
operation menstruation is brought to a close, this condition being
designated as the 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 in Lower Mammals. — The phenom-
enon 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. This condition lasts, as a rule, for
several days, and in the female is accompanied by changes which
recall those of menstruation. The external genital organs become

THE FEMALE REPRODUCTIVE ORGANS. 843

swollen and in many animals there is a discharge of mucus or
mucus and blood from the uterus. Histologically the mucous mem-
brane of the uterus undergoes changes similar to those of menstrua-
tion,— that is, the membrane increases in size and becomes con-
gested with blood, — and it exhibits a phase of degeneration
during which some of the epithelial lining may be cast off and some
hemorrhage occur. 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 re-
currence of the period under these circumstances suggests at once
the essential resemblance to the monthly periods of women. Ac-
cording 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
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. f In the human being Morris and Glass ob-
tained similar results. J: An ovary or a piece of an ovary trans-
planted into the uterus itself or the broad ligament caused a re-

* Heape, " Philosophical Transactions, Royal Society, " 185 (B), 1894,
and 188 (B), 1897.

t Halban, "Deutsche Gesellschaft f. Gynakol.," 9, 1901.

t Glass, "Medical News," 523, 1899; Morris, "Medical Record," 83,
1901.

844 THE PHYSIOLOGY OF REPRODUCTION.

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 does not,
however, accord with the facts. Goltz and Rein* 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
most fully perhaps by Fraenkel,t 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

* Rein, " Archiv f . die gesammte Physiologie, " vol. xxiii.

f Fraenkel, ' Archiv f. Gynakologie," 68, 2, 1903. See also Ihm, " Monats-
schrift f. Geburtshulfe u. Gynakol.," 21, 515, 1905, for discussion and exten-
sive literature.

THE FEMALE REPRODUCTIVE ORGANS. 845

luteum furnishes the secretion which stimulates the uterus to the
augmented growth that takes place in the premenstrual period.
This view, as well as other most important functions which this
author attributes to the specific tissue of the corpus luteum, have
not been conclusively demonstrated. At present perhaps it is
wiser to adopt the more cautious theory that some element in the
ovary furnishes an internal secretion which is normally necessary
to the nutrition of the uterus, and whose augmentation during the
growth of a Graafian follicle leads to the greater metabolism charac-
teristic of the premenstrual period.

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.* This view is
probably the one most generally accepted to-day, and falls in with
the belief that ovulation normally precedes menstruation 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 menstrua-
tion occurs before the ovum reaches the uterus and that its physio-
logical 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 some support in the fact
that in some of the lower animals (dogs) the flow of blood precedes
fertilization.

The Effect of the Menstrual Cycle on Other Functions.— It
is natural to suppose that such marked changes as occur in the

* This view finds expression in the aphorisms : " Women menstruate
because they do not conceive," Powers, and " The menstrual crisis is the physi-
ological homologue of parturition," Jacobi.

846 THE PHYSIOLOGY OF REPRODUCTION.

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 sort of erection of the
fimbriae. 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 movement of the ovum. Attention has been called
to the fact that in animals with a bicornuate uterus the ova may
be liberated from the ovary on one side, as shown by the presence
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
* Mosher, "The Johns Hopkins Hospital Bulletin," 1901

THE FEMALE REPRODUCTIVE ORGANS.

847

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
guided in their movements
very probably by the oppos-
ing force of the ciliary con-
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
this direction, but the
spermatozoa, being moved
by 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-
rounded by a layer of follicular epithelium forming the corona ra-
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. 268) . Before or after the egg reaches the Fallopian

Fig. 268. — Human ovum (Lee, modified from
Nagel) : n, Nucleus (germinal vesicle) containing
the ameboid nucleolus (germinal spot) ; d, deu-
toplasmic zone; p, protoplasmic zone; z, zona
radiata; s, perivitellin space.

848 THE PHYSIOLOGY OF REPRODUCTION.

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. 269. 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
both a quantitative and 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
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. 270. 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

* For details see Wilson, " The Cell in Development and Inheritance."
Second edition, 1900, New York.

x^3*^

io^

2£^

5.^

//.

Fig. 269. — Schematic representation of the processes occurring during cell division.

(Boveri.)

THE FEMALE REPRODUCTIVE ORGANS. 849

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 throw much light upon the necessity of
fertilization by the male cell. The spermatozoon before it is ripe
undergoes a process of maturation essentially similar to that des-
cribed for the ovum. Two cell divisions take place with the for-
mation of four spermatozoa, each of which, however, is a functional
spermatozoon. In the process of division the number of chromo-
somes in each cell is reduced 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 sub-

Ovarian egg.

-First polar body.

Mature egg WMW • • • Abortive ova resulting

^H|r from division of first

! polar body.

Second polar body (abortive ovum).
Fig. 270. — Schema to indicate the process of maturation of the ovum. — (Boveri.)

stance 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 centro-
some by the matured egg is interpreted by Boveri as follows : * This
minute structure is the instrument by which the mechanical
process of cell division is initiated and completed. Its loss by the
matured ovum prevents this cell from further development, but
in the act of fertilization the spermatozoon brings into the egg a
new centrosome, or causes the formation of a new centrosome after
its entrance, and thus immediately starts the process of cell mul-
tiplication. From this standpoint the loss of the centrosome

* For a popular presentation see Boveri, " Das Problem der Befruchtung. "
Jena, 1902.
54

850 THE PHYSIOLOGY OF REPRODUCTION.

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
paternal chromosomes, and thus shares the hereditary characteris-
tics of each parent. This view is represented in a schematic way
by Fig. 271, 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 chromatin for a nucleus, and a large cell body,

Fig. 271. — 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. 851

cytoplasm, rich in nutritive material, but it lacks a centrosome,
so that it can not multiply. 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 em-
bryo 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 purpura tus), 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 larvae. 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
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,

* Loeb, "University of California Publications," 2, pp. 83, 89, and 113,
1905. See also Wilson, "Archiv f. entwick. Mechanik," 12, 1901.

852 THE PHYSIOLOGY OF REPRODUCTION.

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.

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 burrow 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 papillae 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 walls of
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 wray 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-
* See Minot, " Transactions of the American Gynecological Society," 1904.

THE FEMALE REPRODUCTIVE ORGANS. 853

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 activities which can
not be wholly explained, but which without doubt are due to the
chemical and physical properties of the substance oi* 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
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

854 THE PHYSIOLOGY OF REPRODUCTION.

the maternal organism digests and prepares the food for the embryo,
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,
through some chemical stimulus which it gives to the organ. The
effect of the presence and growth of the ovum 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 proteid, — 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*), — a result which may be due to some interference
with the normal functions of the liver.

Parturition. — The fetus "comes to term" usually in the tenth
menstrual period after conception, — that is, about 280 days after

* Slemmons, "The Johns Hopkins Hospital Reports," 12, 111, 1904.

THE FEMALE REPRODUCTIVE ORGANS. 855

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 primiparse, ten to twenty hours or more, than in multip-
ara?. 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

856 THE PHYSIOLOGY OF REPRODUCTION.

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
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-

THE FEMALE REPRODUCTIVE ORGANS. 857

jected to adverse criticism — and they can not, therefore, be ac-
cepted unhesitatingly.

Mironow* reports a number of interesting experiments made
upon goats. He found that artificial stimulation of sensory nerves
causes a diminution in the amount of secretion, thus confirming
the opinion, based upon observations upon the human being,
that in some way the central nervous system exerts an influence
on the mammary gland. When the mammary glands are com-
pletely isolated from their connections with the central nervous
system, stimulation of an afferent nerve no longer influences the
secretion. Mironow states also that, although section of the ex-
ternal spermatic on one side does not influence the secretion, sec-
tion of this nerve on both sides is followed by a marked diminu-
tion, and the same result is obtained when the gland on one side
is completely isolated from all nervous connections. The dimi-
nution of the secretion in these cases comes on very slowly, —
after a number of days, — so that the effect can not be attributed
to the removal of definite secretory fibers. Moreover, after ap-
parently 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 operations
of this kind upon pregnant animals the glands increase in size
during pregnancy and become functional after the act of par-
turition. This latter 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 a se-
cretory nerve, Baschf reports that extirpation of the celiac gan-
glion 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 vasomotor fibers,
but that it is essentially an automatic organ. The bond of con-
nection between it and the uterus seems to be, in part if not entirely,
through the blood rather than through the nervous system. It
should be added that a definite connection between the nerve
fibers and the epithelial cells of the gland has been described. {
If this fact is corroborated it would amount to an histological
proof of the existence of special secretory fibers, but the physio-
logical evidence for the same fact is unsatisfactory.

As was said in speaking of the histology of the gland, the se-

* " Archives des sciences biologiques," St. Petersburg, 3, 353, 1894;
t Basch, "Ergebnisse der Physiologie," vol. ii, part i, 1903.
J Arnstein, " Anatomischer y\nzeiger," 10, 410, 1895.

858 THE PHYSIOLOGY OF REPRODUCTION.

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 ; lactose or milk-sugar ; lecithin, cholesterin,
phosphocarnic acid, urea, creatin, citric acid, enzymes, and min-
eral salts. It is well known also that many foreign substances —
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
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.

K20 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

Fe203....- °-34 014 012

P20- 39.8 37.5 5.9

CI 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

THE FEMALE REPRODUCTIVE ORGANS. 859

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

860

THE MALE REPRODUCTIVE OR&tfJ^ 861

a schema similar to that used in the case of thech««^;s^a]$Dt^rn'>
(Fig. 272). In the case of the ovum four ova are produce(
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 probably 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 the centrosome, —
the two necessary factors in cell 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
millions of these cells. The
adult ripe spermatozoon is
characterized as an independ-
ent cell by its great motility,
due to the cilia-like contrac-
tions of its tail. Its power of
movement or its vitality is
retained under favorable con-
ditions for very long periods.
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, " Archivf. d. gesammte Physiologic," 56, 1894, and Walker,
"Archiv'f. Anatomie u. Physiologic," 1899, p. 313.

Primary
spermatocyte.

Secondary
spermatocytes.

Spermatids.

— Spermatozoa.

Fig. 272. — Schema to indicate the proc-
ess of maturation of the spermatozoa. —
(Boveri).

862 THE PHYSIOLOGY OF REPRODUCTION.

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, salts 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. 850).
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 constitute
the substance which conveys the hereditary characteristics of the
father. Whatever progress may be made in the understanding
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 Kossel and his pupils.* The head of the
spermatozoon, the male pronucleus in fertilization, might 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.

THE MALE REPRODUCTIVE ORGANS. 863

alkali, and they are precipitated by most of the general precipitants
of proteids, such as the neutral salts, the alkaloidal reagents, etc.
Their solutions, however, are not coagulated by heat. The molec-
ular formula for salmin is given as C30H57N17O6. When decom-
posed by the action of acids they yield simpler basic products,
the so-called hexon bases or diamido-acids, and particularly the
base arginin (C6H14N402), which is contained in the protamin of
the spermatozoa in greater abundance than in any other proteid.
The protamins differ from most other proteid compounds by their
relative simplicity; they contain no cystin grouping, therefore no
sulphur; no carbohydrate grouping in most of the compounds
examined; and no tyrosin 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 proteids.
It should be added that these albuminous bases, protamins, have
been obtained so far only from the spermatozoa of the fishes and
some of the invertebrates. Efforts to obtain similar compounds
from the sperm of mammals have been so far unsuccessful. The
nucleic acid component 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 C40H56-
N14P4026. 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.

. 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 trabecular 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 * 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
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

* Eckhard, " Beitrage zur Anatomie und Physiologie," 3, 123, 1863, and
4, 69, 1869.

864 THE PHYSIOLOGY OF REPRODUCTION.

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 organs. 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 of the organ is
aided also by a partial occlusion of the venous outflow, which is
effected by a compression of the dorsal vein by means of the
muscle of Houston. This explanation of the act of erection, while
no doubt correct so far as it goes, leaves undetermined the means
by which the dilatation of the small arteries is produced. Vaso-
dilator nerve fibers in general are assumed to produce 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 pudic nerve or the hypogastric (pelvic)
plexus. No such result of their section is reported and it seems that
in the matter of erection the actual mechanism of the great dilata-
tion caused by the nervi erigentes still remains to be investigated.
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
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

THE MALE REPRODUCTIVE ORGANS. 865

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 urethra?.
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.

55

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. It is this last
peculiarity which is included under the term heredity. 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-

866

HEREDITY. 867

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 offered to such a point
of view are apparent at once. In this, as in other similar problems,
experimental work is gradually accumulating facts which throw
some light upon the matter and may eventually lead us to the right
point of view. 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.

868 THE PHYSIOLOGY OF REPRODUCTION.

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 which 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 chromatin (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. Many 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 biologie generate, " 1903.

% For recent accounts of the various theories and discussion see Mor-
gan, "Popular Science Monthly," December, 1903; Lenhossek, "Das Problem
der geschlechtsbestimmenden Ursachen," 1903.

DETERMINATION OF SEX. 869

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 Hofacker-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 according to the Hofacker-Sadler law 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, however, tends to oppose an older view founded largely
upon experiments on frogs, bees, and wasps, according to which
the sex is not determined at or before fertilization, but is con-
trolled 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. The general opinion at present seems to be that
the sex of the embryo is determined in the egg before fertilization
or at the time of fertilization. This view assumes substantially

870 THE PHYSIOLOGY OF REPRODUCTION.

that there are male and female eggs to begin with, and 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 part henogene tic 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 speaks strongly in favor of the view that
the sex may be predetermined in the ovum, which may be either
male or female. However, if we grant the fundamental fact, so
for as the ova are concerned, that they are either male or female
at the time of formation 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 entirely 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 unfertilized it develops into a male, but, if fer-
tilized, into a female, thus indicating a determining influence upon
the part of the male element. If, on the basis of this fact, 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. Our problem still remains
unsolved, although reduced to a narrower field for observation

GROWTH AND SENESCENCE. 871

and experiment. It may be stated, in conclusion, that Morgan
advocates a conservative view according to which the egg, as
far as sex is concerned, is in a sort of balanced condition and may
be thrown to the side of male development or female development
according to the nature of the stimulus received. Fertilization
by the spermatozoon presumably, on this view, is only one of
a number of stimuli which may determine the direction of sex
development.

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-
reous, the crystalline lens gradually loses its elasticity, the muscles
lose their vigor, the hairs their pigment, the nuclei of the nerve

* 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.

872 THE PHYSIOLOGY OF REPRODUCTION.

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 u 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* 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-
pler forms of life, such as the ameba. This latter phase of his theory
has been the subject of much interesting investigation,! but con-

* Weissmann, " Essays upon Heredity and Kindred Biological Prob-
lems"; also " Germ-plasm " in the " Contemporary Science Series."

t See Maupas, " Archives de zoologie experimentale et generale," 6,
165, 1888; Joukowsky, "Inaugural Dissertation," Heidelberg, 1898; Gotte,
" Ueber den Ursprung des Todes," 1883.

GROWTH AND SENESCENCE. 873

elusive 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.

APPENDIX.

PROTEIDS AND THEIR CLASSIFICATION.

Definition and General Structure. — Proteids 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 proteids 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 proteid molecule has been
obtained by a study of its decomposition products. When submitted to the
action of proteolytic enzymes, or putrefaction, or acids 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 proteids, yet a number of them are
the same for all proteids. The great variety in the end-products is an in-
dication of the complexity of the molecule, while their similarity is proof
that the various proteids are all built, so to speak, upon a similar plan by the
union of certain groupings which may be more numerous in one proteid than
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 proteid
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 proteids:

1. Amido-acetic acid (glycocoll).

2. Amidopropionic acid (alanin).

3. Amidovalerianic acid.

4. Amidocaproic acid (leucin).

5. Amidosuccinic acid (aspartic acid).

6. Amidoglutaric acid (glutaminic acid).

7. Phenylamidopropionic acid (phenylalanin).

8. Oxyphenylamidopropionic acid (tyrosin).

9. Skatolamido-acetic acid (tryptophan).
10. Guanidinamidovalerianic acid (arginin).
11 Diamidocaproic acid (lysin).

12. Histidin (amidomethyl-dihydropyrimidin-carbonic acid).

13. Amido-oxypropionic acid (serin).

14. Amidothiolactic acid (cystein or cystin).

15. a-pyrrollidin-carbonic acid.

16. Oxy-a-pyrrollidin-carbonic acid.

874

PROTEIDS AND THEIR CLASSIFICATION. 875

These split products are all amido-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 proteids 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 proteids, such as serum-albumin
or casein, a much larger number is found. The a-amido-acids of which these

H

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 amido-
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 amido (NH2) group in another. Thus, two molecules of amido-acetic
acid (glycocoll) may be made to unite to form a compound, glycylglycin, as
follows :

NH2CH2COOH + NH2CH2COOH — H20 = NH2CH2CONHCH2COOH.

Glycocoll. Glycocoll. Glycylglycin.

Compounds of this kind are designated by Fischer as peptids. When formed
from the union of two amido-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 proteids. Some of
them give the biuret reaction, some are acted upon and split by proteolytic
enzymes. It seems justifiable, therefore, to consider proteids as essentially
polypeptid compounds of greater or less complexity, — that is, they are acid-
amids formed by the union of a number of a-amido-acid compounds. This
conception of the structure of the proteid 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 proteids 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 amido-acids some proteids — egg-albumin, for example
— yield a carbohydrate body upon decomposition. The carbohydrate ob-
tained is an amido-sugar compound, usually glucosamin, C6H13N03. It is
detected by its reducing action and by the formation of an osazone. It seems
probable, therefore, that some of the proteids 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 Proteids. — It is evident from what has been
said in the preceding paragraph that proteids may give different reactions
according to the kinds of groupings contained in the molecule. The reac-
tions common to all proteids 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 proteids usually found in the tissues and liquids of the body. These
reactions may be described under two heads: (1) precipitation of the proteid
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.

876 APPENDIX.

I. Precipitants. — For one or another proteid 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. Iodin in solution in 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 proteid.

12. Precipitins. In this connection a brief reference may be made to
the interesting group of bodies known as precipitins. As stated
on p. 387, 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 proteid 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 proteid, when injected
under the skin of an animal, may cause the production of a pre-
cipitin capable of precipitating that particular proteid from its
solutions. The precipitin is not absolutely specific for the proteid
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 proteid 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 proteids.

77. The Color Reactions of Proteids.

1. The biuret reaction. The proteid 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.

PROTEIDS AND THEIR CLASSIFICATION. 877

copper sulphate are added carefully so as to avoid an excess. A
purple color is obtained. Some proteids (peptones) give a red
purple, others a blue purple. If only a blue color, without any
mixture of red, is obtained, no proteid is present. At present
this reaction gives the best single test for proteid. It obtains

CONH
its name from the fact that it is given by biuret HN ^pomtj2? 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 proteid 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 proteids.
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 grouping in the proteid molecule, and
fails, therefore, with those proteids 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 proteid 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
proteid 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 proteid molecule.

5. Liebermann's reaction. Dry proteid purified with alcohol and ether

gives a blue color upon boiling with strong hydrochloric acid.

6. The lead sulphid reaction. The proteid 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 proteid. 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 proteid molecule.

7. The Molisch reaction. A few drops of an alcoholic solution of a-

naphthol are added to the proteid solution and then strong sul-
phuric acid. A violet color is obtained. This reaction is given
by the carbohydrate grouping in the proteid molecule. The strong
acid forms f urfurol from this group, which then reacts with the naph-
thol. The reaction is not given by those proteids that do not con-
tain a carbohydrate group.

Classification of the Proteids. — No classification of the proteids has
been proposed which is entirely satisfactory. Eventually a classification
will be obtained based upon the chemical structure of the various proteids,
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.

Albumins.
Globulins.

Albuminates or derived albumins.
I. Simple proteids I Nucleo-albumins (phosphoproteids).
\ Proteoses and peptones.
Histons.
Protamins.
Coagulated proteids.

878 APPENDIX.

{Chromoproteids (hemoglobin, hemocyanin, etc.).
Glucoproteids.
Nucleoproteids.
r Keratin.
III. Albuminoids (pro- i Elastin.

teid-like bodies) 1 Collagen (gelatin).
v 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 iii
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. — Proteids 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 proteids 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 proteids. The albuminates, on the contrary, are
derived from these native proteids 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 (Phosphoproteids). — This name may be applied
to a group of native proteids which are characterized by containing phos-
phorus, such as casein of milk, vitellin from the yolk of the egg, and va-
rious similar proteids found in the cytoplasm of the cellular elements. They
are often classed with or confounded with the nucleoproteids (or nucleo-
albumins) found in the nuclei of the cells. These latter belong to the com-
pound proteids 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 proteid body.

PROTEIDS AND THEIR CLASSIFICATION. 879

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 phosphoproteids. In addition to phosphorus these proteids.
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 proteids 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. They show the usual proteid 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
satisfactorily that no carbohydrate grouping is present in the molecule.

Proteoses and Peptones. — These names are given to the intermediate
proteids 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 amido-acids already referred to as constituting the end-products of
proteid 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 proteid foods. They consist of smaller and more sol-
uble molecules than those of the proteids from which they are derived.
Many different kinds of proteoses 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 proteid and the
stage of peptones. The so-called peptones are characterized by their solu-
bility and the facts that they are not coagulated by heat and are not pre-
cipitated 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
proteids, 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 some, but relatively few, of the usual
split products of proteids, and these largely the so-called diamido-bodies
(arginin, histidin, lysin) rather than the monamido-acids. Some of the latter
may occur, however, such as alanin, serin, amidovalerianic or a-pyrrollidin-car-
bonic acid. The protamins all give an alkaline reaction, form salts with acids,
and are precipitated easily. Their molecular structure is relatively simple.

APPENDIX.

The molecule contains no sulphur
also by its large percentage of nitrogen. Protamin
must be regarded as the simplest form of proteid occurring normally in the
animal body, a proteid in which many of the groupings, such as cystin, tyro-
sin, carbohydrates, found in the usual proteid molecule are entirely lack-
ing and in which the basic groupings (arginin) predominate. The histons
form a series of compounds intermediate in many ways between the pro-
tamins and the usual proteids. The reaction usually considered as char-
acteristic 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 proteids give a precipitate with these reagents
only in acid solutions, while the protamins give one even in alkaline solutions.
Protamins, histons, and the usual proteids 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; another 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 numer-
ous than in the case of the protamins, — a fact which would indicate that
their molecular structure is correspondingly more complex.

The Compound Proteids. — The chromoproteids may be denned as
consisting of a simple proteid 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).
Glucoproteids are compounds of a carbohydrate group with a simple proteid.
Numerous bodies have been put in this class; some of them contain phos-
phorus (phosphoglucoproteids). Those free from phosphorus fall into two
divisions: one, the mucins, which on decomposition yield the carbohydrate
group in the form of an amido-sugar (glucosamin) , and one, the chondropro-
teids, 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 (CjgH^NSOjy) . True mucin is obtained from the secretion
of the salivary glands and the mucous glands of the various mucous mem-
branes. The nucleoproteids constitute the most interesting of the group
of compound proteids. They are recognized as forming an important con-
stituent of the cell nuclei. They may be defined as consisting of a compound
of simple proteid 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 proteid constituent is more complex. On
digestion with pepsin-hydrochloric acid the more complex nucleoproteids
split, with the formation, first, of a proteid substance and a simpler nucleo-
proteid, 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 des-
cribed, 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 nucleoproteids as distinguished from the phosphorus-containing
simple proteids, the nucleo-albumins or phosphoproteids, such as casein.
The percentage of phosphorus in the nucleoproteids 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

DIFFUSION AND OSMOSIS. V fa 881

connective tissues; the collagen (ossein) of the white, nbrou^yWf^iyj tn~r\t
tissues and bones, from which gelatin is made; and the reticulin of tftosce$ife^*t
ular connective tissues of the lymphatic tissues. They resemble the pro-
teids 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 can not be used
by the body to replace its proteid tissues (see p. 791). 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, " Phvsical 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 Schafer's "Text-book of Physiology," 1898.
56

882 APPENDIX

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 in 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.

DIFFUSION AND OSMOSIS. 883

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 are charged with elec-
tricity, and when an electrical current is led into the solution it is conducted
by the movements of the 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 num-
ber of its molecules become dissociated into a Na ion charged positively
with electricity and a CI ion charged negatively, and the solution becomes
a conductor of the electrical current. Substances that exhibit this property
of dissociation are known as electrolytes, to distinguish them from other
soluble substances, 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 obviously 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 molecule. 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 necessary, 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; CI, 35.5) of the salt to
a liter, while a gram-molecular solution of cane-sugar contains 342 gms.
(Cj-jH^Oh) 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 contains 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 34^ of 22.32 atmospheres, or 0.65 of an atmosphere, which in terms of

884 APPENDIX.

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 6.95 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 —. or o.3. In other words,

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 Proteids. — The osmotic pressure exerted by crys-

DIFFUSION AND OSMOSIS. 885

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 proteid, the blood,
especially, containing over 6 per cent, of this substance. It has been gen-
erally assumed that proteids 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 proteids 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 proteids of serum is equal to about 30 mms. of mercury.
That the osmotic pressure of the serum proteids is so small is not sur-
prising if we remember the very high molecular weight of this substance.
In serum the proteids are present in a concentration of about 7 per cent.,
but owing to their large molecular weight comparatively few proteid mole-
cules are present in a solution of this concentration; and, assuming that
the dissolved proteid follows the laws discovered for crystalloids, its osmotic
pressure would depend upon the number of molecules in solution. By
means of this weak, but constant, osmotic pressure of the indiffusible pro-
teid it is possible to explain theoretically the fact that an isotonic or even
a hypertonic solution of diffusible crystalloid may be completely absorbed
by the blood from the peritoneal cavity. Reidt has given evidence which
indicates that pure proteids 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 pressure formerly attributed to the proteids really
belongs. Since these unknown substances are themselves indiffusible, the
arguments just used still hold for the conditions in the body.

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
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
with 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

* "Journal of Physiology," 24, 317, 1899.
t Reid, "Journal of Physiology," 1905.

886 APPENDIX.

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 proteid 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 which they exert serve to attract water 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 Proteids. — 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 proteids 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
proteid, through the capillary walls. This explanation, however, can not be
said to be satisfactory; and in this respect the purely physical theory of
lymph formation waits upon a clearer knowledge of the nature of the nutri-
tive proteids and their relations to the capillary wall (see Lymph, p. 427).

INDEX.

Abdominal respiration, 572

type of respiration, 576
Absolute power of muscle, 36
Absorption coefficient, 600

in large intestine, 717

in small intestine, 712

in stomach, 698

of carbohydrates, 713

of fats, 714

of proteids, 716

spectra of hemoglobin, 394
Acapnia, 625, 630
Accelerator center for heart, 525

nerves, effect of , on heart rate, 527
of heart, 522
reflex stimulation of, 524
Accessory thyroids, 772
Accommodation in eye, limits of, 292
mechanism of, 289

reflex, 301
Achromatic series of visual sensa-
tions, 320
Achroodextrin, 680
Acid albumin in gastric digestion,
693

ami do-acetic, 706, 874

amidocaproic, 706, 874

amidoglutaric, 874

ami do-oxy propionic, 874

amidopropionic, 874

amidosuccinic, 706, 874,

amidothiolactic, 874

amidovalerianic, 706, 874

cholic, 725

conjugated sulphuric, 760

diamidocaproic, 874

glutaminic, 706, 874

glycocholic, 725

guanidinamidovalerianic, 874

hippuric, 759

lactic, 60

oxypnenylamidopropionic, 874

phenylamidopropionic, 874

phosphocarnic, 60

pyrrolidin-carbonic, 874

taurocholic, 725
Acromegaly, 778
Action current, diphasic, 98
in heart, 480
in muscle, 96
in nerve, 96

Action current in retina, 309
monophasic, 98

relation of, to contraction wave,
100
to nerve impulse, 100

Adamkiewicz's reaction for proteids,
877

Addison's disease, 775

Adenase, 664

Adenin, 61, 757

Adrenal bodies, functions of, 775

Adrenalin, 776

Aerial perspective, 345

Aerotonometer, 601

Afferent fibers in cranial nerves,
79
position of, in posterior roots,
77
nerve fibers, 75

After-images in eye, 323

Air, effect of variations in, on res-
pirations, 627

Alanin, 706, 874

Albumin, properties of, 878 (see
also Proteid)

Albuminates, properties of, 878

Albuminoids, nutritive value of, 791
properties of, 880

Albumon, 414

Alcohol as food, 808

effect of, on gastric absorption, 699
physiological action of, 805

Alimentary canal, movements of, 634
glycosuria, 714
principles of food, 654

Altitude, effect of, on red corpus-
cles, 403

Amboceptors, 388

Ametropia, 295

Amido-acetic acid, 706, 874

Amido-acids as part of proteid mole-
cule, 706

Amidocaproic acid, 706, 874

Amidoglutaric acid, 874

Amido-oxypropionic acid, 874

Amidopropionic acid, 706, 874

Amidosuccinic acid, 706, 874

Amidothiolactic acid, 874

Amidovalerianic acid, 706, 874

Ammonia compounds in urine, 752
salts, relation of, to urea, 755

887

888

INDEX.

Ammonium carbamate as precursor
of urea, 754

carbonate as precursor of urea,
737
Amylolytic enzyme, 662
Amylopsin, 708
Anacrotic pulse, 474, 475
Anaglyph, 347
Anelectrotonic currents, 101
Anelectrotonus, 83
Anisotropous substance in muscle, 19
Anode as stimulus to muscle, 82
to nerve, 82

physical, 89

physiological, 89
Anoxemia, 628
Anterior commissure, 213

marginal bundle, spinal cord, 170

roots of spinal nerves, 77
Antidromic impulses in vasodilator

nerve fibers, 78, 548
Antilytic secretion, 677
Antiparalytic secretion, 677
Antipeptone, 705
Antithrombin, 419
Antrum pylori of stomach, 639
Anus praeternaturalis, 717
Apex beat of heart, 482
Aphasia, motor, 204

sensory, 206
Apnea, 623
Arginase, 756
Arginin, 707, 863, 874
Argyll Robertson pupil, 302
Arterial pressure (see Circulation)
Artificial muscle of Engelmann, 69

respiration, 581

stimuli of nerve fibers, 80
Ascending paths in spinal cord, 161
Aspartic acid, 706, 874
Asphyxia, effect of, on heart-rate,

529
Aspiratory action of thorax, 587
Association areas in brain, 207, 209

system of fibers in cerebrum, 175
Astereognosis, 189
Astigmatism, 297
Atropin, action of, on heart, 520
on iris, 303

on salivary secretion, 676
on sweat secretion, 768
Auditory center in cortex, 198

nerve, course of, in brain, 199
effect of section of, 375

sensations (see Ear)

stria-, 201
Auricle (see Heart)
Auriculoventricular muscle bundle,
479
effect of compressing, 508
Auscultation, 486
Autolysis, 835

Autolytic enzymes, 664
Automaticity of heart beat, 500
Autonomic fibers from brain, 234

from sacral cord, 236

from spinal cord, 233
nerve fibers, normal stimulation of,

236
nervous system, general relations

of, 232
Axial stream in arteries, 435

in veins, 435
Axon reflexes, 142

Bacterial action in intestines, 718
Balance experiments in nutrition,

785
Balloon ascensions, effect of, 630
Banting diet, 800

Barometric pressures, effect of, 629
Bartholin, duct of, 666
Basilar membrane, function of, 367
Bathmotropic nerve fibers to heart,

516
Bell-Magendie law, 77
Bilateral representation in motor

areas, 186
Bile, composition of, 722

curve of secretion of, 729

effect of occluding bile ducts, 730

ejection of, into duodenum, 728

functions of, summary, 730

quantity of, 722

secretion of, 727
Bile-acids, composition of, 725
Bile-pigments, 400, 724
Bile-salts, importance of, in fat

digestion, 715
Bilirubin, 724
Biliverdin, 724
Binocular perspective, 346, 349

vision, 338

horopter in, 343
struggle of visual fields in, 344
value of, in judgments of dis-
tance, 344
in judgments of size, 344
Births, ratio of male and female, 869
Biuret reaction for proteids, 877
Bladder, urinary, movements of, 762
Blind spot in eye, 308
Blood, blood-plates of, physiology
of, 407

circulation of (see Circulation)

coagulation of, 414

condition of carbon dioxid in, 604
of nitrogen in, 602

curve of dissociation of oxyhemo-
globin, 603

defibrinated, 382

gases of, 596

general properties of, 381

INDEX.

889

Blood, hemoglobin in, 385
amount, 389
nature, 389

hemolysis of red corpuscles, 385

histological structure of, 381

leucocytes of, 404

nucleoproteid in. 414

osmotic pressure of, 386

proteids of, 410, 413

reaction of, 382

reasons for not clotting in vessels,
419

red corpuscles of, 384
fate of, 401
origin of, 401

regeneration of, after hemorrhage,
424
Blood-plasma, composition of, 408
Blood-plates, effect of hemorrhage
upon, 425

part taken by, in coagulation, 417

properties of, 406
Blood-pressure, effect of menstrua-
tion upon, 846

in brain, 556

relation of, to heart rate, 527

respiratory waves of, 588

Traube-Hering waves of, 544
Blood-serum, 382, 409

specific gravity of, 383

total quantity of, 423

transfusion of, 426
Body equilibrium in nutrition, 785

sense area, 188

temperature in man, 821
Bowman's theory of urinary secre-
tion, 743
Brain, association areas of, 207

auditory center in, 198

center for taste, 204
for olfaction, 202

centers affected in aphasia, 204

development of cortical areas, 210

effect of variations in arterial
pressure upon, 557

intracranial pressure in, 556

localization of function in, 181

motor areas of, 183

regulation of circulation in, 559

sensory areas of, 188

vascular supply of, 552
Brightness in visual sensations, 319
Bronchi, capacity of, 581

constrictor and dilator fibers of,
625
Buffy coat of blood, 415
Burdach, column of, 162

Caffein, 757, 805
Caisson disease, 629

Calcarine fissure, relation of, to vision,

195
Calcium salts, effect of, on heart,
501
importance of, in clotting of
blood, 416
in curdling of milk, 696
nutritive value of, 803
of milk, 429
Calorie, definition of, 35, 823
Calorimeters, varieties of, 824
Calorimetric equivalent, 825

measurements, 828
Calorimetry, indirect, 827

principles of, 823
Cannula, washout, 443
Capillary blood-pressure, 452

electrometer, construction of, 94
Carbohydrates, absorption of, 713
as glycogen formers, 732
as source of body fat, 798
fate of, in body, 793
fermentation of, in intestine, 714
general functions of, 794
of muscle, 59
supply of, in body, 793
Carbon dioxid, action on respira-
tory center, 621
condition of, in blood, 604
effect of, in inspired air, 594,

629
excretion of, through skin, 770
in balance experiments, 785
in saliva, 669

production of, in muscle, 62
tension of, in alveolar air, 607
in arterial blood, 608
in tissues, 608
in venous blood, 607
equilibrium, 785
monoxid hemoglobin, 391
Cardiac cycle, 488

glands of stomach, 683
muscle, properties of, 54, 504
nerves (see Heart)
Cardiogram, 482

Cardio-inhibitory center, 517, 518
Carnin, 61
Casein, 695, 879
Catalase, 664
Catalysis, 658

Catelectrotonic currents, 101
Catelectrotonus, 83
Cathode as stimulus, 82

physical and physiological, 89
Centers in cerebrum (see Cerebrum)
Central field of vision, 313
Centrosome, 848

Cerebellum, ending of spinal tracts
in, 164
experimental work upon, 220
general functions of, 219, 223

890

INDEX.

Cerebellum, localization of function
in, 224
paths connecting with other parts

of brain, 218
psychical functions of, 224
structure of, 216
Cerebrospinal liquid, 555
Cerebrum, association areas of, 207
system of fibers in, 175
auditory center in, 198
center for hearing, 198
for olfaction, 202
for vision, 192
centers affected in aphasia, 206
commissural system of fibers in,

175
development of cortical areas in,

210
general physiology of, 171
histology of cortex, 172
localization of function in, 179
motor areas of, 183
projection system of fibers in, 173
results of ablation of, 178
sensory areas of, 188
vasomotor supply of, 552
Cerumen, 770
Chemotaxis, 119
Cheyne-Stokes respiration, 632
Cholesterin, 721, 726, 770
Cholic acid, 725
Cholin, 727

Chorda tympani nerve, 270, 667, 670
Chromatic aberration in eye, 293

visual sensations, 321
Chromatolysis, 121
Chromophile substance in nerve cells,

127
Chromoproteids, 880
Chromosomes, 848, 867
Chronotropic nerve fibers to heart,

516
Chyle fat, 715
Chymosin, 695

Ciliary muscle, action of, in accom-
modation, 291
nerves to, 299
Ciliated epithelium, 54
Circulating proteids, 787
Circulation, accessory factors in, 466
as seen under microscope, 434
curve showing pressures in, 452
data concerning pressures in (man),
458
• mean pressures in, 450
diastole and systole of heart, 477
effect of adrenal extracts upon,
776
of heart beat and size of arteries
upon, 440
explanation of side-pressure in, 460
of velocity changes in, 439

Circulation, explanation of velocity-
pressure in, 460
factors of normal pressure and

velocity in, 463
form of pulse wave, 472
general curve of velocities in, 439
general statement of pressure rela-
tions, 442
hydrostatic effects upon, 465
importance of elasticity of arteries,

463
in brain, 552, 559
in kidneys, 749

means of determining blood-pres-
sure in, 442, 453
velocities in, 435
of lymph, 564

pressures in coronary system, 491
in pulmonary system, 467, 468
pulse pressures in, 446
respiratory waves of pressure in,

588
systole and diastole of heart, 477
systolic, diastolic, and mean pres-
sures in, 446
and mean velocities in, 438
time required for complete, 441
Traube-Hering waves of pressure

in, 544
velocity in capillaries, 438
in coronary system, 491
in man, 438

in pulmonary system, 467, 468
of pulse wave, 470
Clarke's column, 156
Clotting (see Coagulation)
Coagulation, blood, 414
intravascular, 421
means of hastening and retarding,

421
theories of, 415
Cocain, action of, on iris, 303
Cochlea, functions of, 366

sensory epithelium of, 360
Cold spots on skin, 257
Color blindness, 325, 327
contrasts, 324
fusion, 321
saturation, 321
sense of retina, 328
vision, theories of, 331
Combustion equivalents of foods, 815
Comma tract of Schultze, 169
Commissural system of fibers (cere-
brum), 175
Common sensations, 256
Compensatory pause in heart-beat,

506
Complemental air, 580
Complementary colors, 322
Compound muscular contractions, 39
Condiments, 656, 804

INDEX.

891

Conduction as physiological property,
72
direction of, in nerve fibers, 107
Conjugate foci, 283
Conjugated sulphates, 759
Contraction, 17, 32, 33 (see also

Muscle)
Contralateral conduction in cord, 166
Convoluted tubules of kidney, 746
Core-model of nerve, 102
Coronary arteries, effect of occlusion
of, 494
vasomotor supply of, 491
Corpora quadrigemina, relation of, to
visual apparatus, 193, 197
striata, functions of, 214
Corpus callosum, structure and func-
tion, 213
luteum, 840
trapezoideum, 200
Corresponding points of retina, 340
Cortex of cerebrum, general physi-
ology of, 175
histology of, 172
Corti, rods of, 367
Costal respiration, 573, 576
Cowper's glands, 861
Cranial nerves, afferent fibers in, 79
efferent fibers of, 79
nuclei of origin of, 226
Cranioscopy, 180
Creatin, 61, 66, 758
Creatinin, 61, 758
Cresol-sulphuric acid, 719, 760
Cretinism, 773

Curve, contraction, of artificial
muscle, 70
of plain muscle, 53
of skeletal muscle, 25
dissociation of oxyhemoglobin, 603
extensibility and elasticity of

muscle, 19
gastric secretion, 690

intensity of sleep, 240
pancreatic secretion, 702
pressures in vascular system, 452
relations of heart sounds, 487, 488
respiratory movements, 578
secretion of bile, 729
systolic, diastolic, and mean blood-
pressures, 447
velocity of blood-flow, 439
visual acuity of retina, 316
.work of muscle, 36
Cycloplegia, 303
Cystin, 726, 874
Cystinuria, 726

Death rigor, chemical changes dur-
ing, 66
in muscle, 49
theories of, 872

Defecation, 650

Degeneration in nerve fibers, 118, 120

Deglutition, 634

nervous control of, 638
Deiters's cells in cochlea, 368
Demarcation current, muscle and

nerve, 91
Demilunes of salivary glands, 668
Depressor nerve fibers, 540

of heart, 543
Derived albumins, properties of, 878
Descending paths, spinal cord, 167,

169
Deutero-albumoses, 693
Diabetes, 733

mellitus, 780

pancreatic, 780

phloridzin, 795
Dialysis, definition of, 881
Diaphragm, action of, 572
Diaphragmatic respiration, 572
Diastase, 662

discovery of, 657
Diastole, duration of, in heart, 480
Diastolic arterial pressure, 446

method of determining in

animals, 447
method of determining, in
man, 454
Dicrotic pulse wave, 474
Diet, accessory articles of, 656, 804

average daily, 818

Banting's, 800

effect of reduction of salts in,
802
Dietetics, general principles of, 817
Diffusion circles on retina, 289

definition of, 881
Digestion in large intestine, 717

in small intestine, 700

in stomach, 696
Diopter, definition of, 293
Dioptrics of eye, 282
Diplopia, 342

Direct field of vision, eye, 313
Discord, physiological explanation

of, 369
Dissociation of oxyhemoglobin, 603
Diuretics, action of, 748
Dromograph, 437
Dromotropic nerve fibers to heart,

516
Duct of Bartholin, 666

of Rivinus, 666

of Stenson, 666

of Wharton, 666

of Wirsung, 700
Dyspnea, 575, 622

Ear effect of section of auditory
nerves, 375

892

INDEX.

Ear, effect of stimulation of semi-
circular canals, 374
Eustachian tube of, 359
Flourens's experiments on semi-
circular canals, 372
functions in analyzing sound
waves, 365
of cochlea, 366
of ear-bones, 356
of sacculus, 379
of utriculus, 379
intrinsic muscles of, 358
limits of hearing, 370
position of bones in, 355
projection of auditory sensations,

360
semicircular canals of, 372
sensations of discord, 369

of harmony, 369
sensory epithelium in cochlea. 360
structure of, 353

bones of, 355
theories of functions of semicircu-
lar canals of, 375
tympanic membrane of, 354
Eck fistula, 754
Efferent nerve fibers, 75

occurrence in anterior roots, 77
in cranial nerves, 79
Ejaculation of spermatic liquid, 864
Elasticity and extensibility of muscle,

19
Electrical currents during heart beat,

480
Electrodes, non-polarizable, 95

stimulating, 81
Electrolytes, effect of, on osmotic

pressure, 882
Electrotonic currents, 101
Electrotonus, 83
Eleventh cranial nerve, nucleus of,

230
Embryo, nutrition of, 852
Endogenous fibers of spinal cord,

162
Energy of muscular contraction, 34
Enterokinase, 704, 711
Entoptic phenomena, 336
Enzymes, adenase, 664
amylopsin, 708
arginase, 756
chemistry of, 664
classification of, 661
definition of, 661
enterokinase, 704, 711
erepsin, 711

general properties of, 663
glycolytic, 782
guanase, 664

historical account of, 657
intracellular, 835
inverting, 711

Enzymes, lipase, 709

of muscle, 61

oxidases, 836

pepsin, 691

peroxidases, 836

ptyalin, 679

rennin, 695

reversible reactions of, 659

specificity of, 661

thrombin, 416

trypsin, 705
Epigenesis, 866
Epinephrin, 776
Erection, physiology of, 863
Erepsin, 664, 711
Ergograph, 45
Erythroblasts, 402
Erythrocytes (see Red corpuscles)
Erythrodextrin, 680
Eserin, action of, on iris, 303
Esophoria, 340
Ethereal sulphates, 759
Eupnea, 575
Eustachian tube, 359
Evolution, hypothesis of, in heredity,

866
Excretion, 721

Exogenous fibers in spinal cord, 162
Exophoria, 340
Expiration (see also Respiration)

definition of, 571

expiratory center, 619

muscles of, 574
Expired air, composition of, 592

injurious effects of, 593
Extensibility of muscle, 19
External geniculates, 193, 197
Eye, abnormalities in refraction of,
295

accommodation in, 301
mechanism of, 289

action of drugs upon, 303

acuity of vision in, 315

after-images in, 323

as optical instrument, 282

binocular field of vision, 340
perspective, 346

chromatic aberration in, 293

color blindness of, 325
contrasts in, 324
vision in, 321

complementary colors, 322

corresponding points in, 340

dark adapted, 310, 318

diffusion circles in, 289

diplopia in, 342

direct field of vision^ in, 313

entoptic phenomena in, 336

far point of distinct vision, 292

function of cones, 330
of rods, 330

fundamental color sensations, 322

INDEX.

893

Eye, horopter, 343

indirect field of vision in, 313
inversion of image in, 287
light adapted, 310, 318

reflex in, 301
movements of, 338
muscular insufficiency, 339
nature of visual stimuli, 308
near point of distinct vision, 292
nodal point of, 286
ophthalmoscopic examination of,

305
optical defects of, 293

delusions, 350
physics of formation of image in,

282
qualities of visual sensations, 320
reduced schematic (Listing), 286
refractive power of, 293
size of retinal images, 288
spherical aberration in, 294
stereoscopic vision, 347
struggle of visual fields, 344
suppression of visual images, 343
theories of color vision, 331
threshold stimulus of, 317
visual field of, 312

judgments, 349

purple of, 310
Eye-muscles, action of, 338

Facial nerve, dilator fibers in, 545

nucleus of, 229
Far point of distinct vision, 292
Fat, absorption of, 714

as glycogen former, 734

digestion of, 709
in stomach, 699

excessive formation of, in obesity,
799

in bile, 727

metabolism of, in body, 797

nutritive value of, 796

of chyle, 715

origin of, from carbohydrates, 798
in body, 797
Fatigue, in nerve fibers, 110

muscular, 47

of olfactory organs, 279
theories of, 66
Feces, composition of, 720
Fermentation in intestine, 718

of carbohydrates in small intes-
tine, 714
Ferments, historical account of, 657
Fertilization of ovum, 850
Fibrillary contractions of heart, 495
Fibrin factors, 417

ferment, preparation of, 416

globulin, 413, 419

relations to blood-clot, 414

Fibrinogen, 412

preparation of, 416
Fictitious meal (Pawlow), 689
Fifth cranial nerve, 227
Fillet, lateral, 200

median, 190
Fistula, Eck's, 754

gall-bladder, 715

stomach, 686

Thiry-Vella, 710
Flavors, 656

dietary importance of, 804
Flechsig's myelinization method, 157

tracts, 164
Fluorid solution, effect on clotting,

422
Food, composition of, 655

definition of, 654

potential energy of, 814
Foodstuffs, definition of, 654
Fourth cranial nerve, nucleus of, 227
Fovea, center for, in occipital cor-
tex, 196

of retina, size of, 314, 315
Franklin theory of color vision, 334
Freezing point, method of determin-
ing, 884
Fundic glands of stomach, 683
Fundus of stomach, 639

Gall-bladder, functions of, 728

nerves of, 730
Galvanometer, construction of, 92

d'Arsonval, 93
Gases, laws governing absorption
of, 599
of blood, 596
pressure of, 599
tension of, in solution, 601
Gas-pump, 597
Gastric glands, 683

histological changes in, during

secretion, 684
secretory nerves of, 688
secretion, acid of, 687
composition of, 685
curve of, 689
means of obtaining, 685
normal mechanism of, 689
Gelatin, nutritive value of, 791
Genital organs, vasomotor supply of,

562
Germ plasm, definition of, 872
Globin, 389
Globulicidal action of blood-serum,

387
Globulins, general properties of, 878
Glomerulus of kidney, functions of,

744
Glossopharyngeal nerve, dilator fibers
in, 545

894

INDEX.

Glossopharyngeal nerve, nucleus of,

229
Glucoproteids, 880
Glucosamin, 875
Glutaminic acid, 706, 874
Glutolin, 411
Glycocholic acid, 725
Glycocoll, 706, 725, 874
Glycogen, amount of, in liver, 732

discovery of, 731

glycogenic theory, 734

importance of, in embryo, 853

in muscle, 59, 736

loss of, during muscular contrac-
tions, 64

metabolism of, in body, 794

origin of, 732

supply of, in body, 793
Glycolysis of sugars in body, 782
Glycosuria, 733

alimentary, 714
Glycylglycin, 875
Gmelin's reaction for bile pigments,

724
Golgi's nerve cells, second type, 126

pericellular nerve net, 127
Goll, column of, 162
Gowers's tract, 164
Graafian follicle, structure of, 839
Gram-molecular solution, 883
Growth, 871
Guanase, 664
Guanin, 61, 757
Gudden's commissure, 201

Harmony, physiological cause of,

369
Hearing, cortical center of, 198

limits of, 370
Heart, accelerator center for, 525
nerves of, 522

action current of, 480
of inhibitory nerves, 512

analysis of inhibition, 514

apex beat of, 482

automaticity of, 500

capacity of ventricles of, 489

cardiac nerves of, course, 512

cardiogram, 482

cardio-inhibitory center of, 517

causation of beat, 503

change in form of ventricle in
systole, 481

compensatory pause of, 506

contraction wave in, 479

coronary circulation in, 491

course of cardiac nerves, 512

depressor nerve of, 543

diastole and systole of, 477
time relations of, 489

effect of calcium upon, 501

Heart, effect of occlusion of coro-
naries upon, 494
of potassium upon, 501
of sodium upon, 501
escape from inhibition, 517
events of a cardiac cycle, 488
fibrillary contractions, 495
inhibition of auricle, 516

of ventricle, 516
intraventricular systole, 484
intrinsic nerves of, 496
maximal contractions of, 504
musculature of, 478
myogenic theory of beat of, 498
negative pressure in, 493
neurogenic theory of beat of, 497
rate of beat as affected by age, 526
by blood-pressure, 527
by extrinsic nerves, 527
by muscular exercise, 528
by sex, 526
by size, 526
by temperature, 529
reflex acceleration of beat, 524
refractory period of, 504
sequence of beat of, 496, 507
sounds of, 485
suction-pump action of, 492
systole and diastole of, 477

time relations of, 489
systolic plateau of beat, 485
theories of inhibition of, 520
tonic inhibition of, 518
tonicity of muscle of, 510
vasomotors of, 550
ventricle of, in systole, 481
work done bv, 489
Heart-block, 508
Heart-muscle, general properties of,

54
Heat centers, 830

equivalent of foodstuffs, 815

loss of, physiological regulation of,

828
nerves, 830

production, physiological regula-
tion of, 829
puncture, 832

regulation, general statement of,
m 828

rigor of muscle, 51
sexual, in lower animals, 842
Helmholtz theory of color vision, 331
Helweg's bundle, spinal cord, 170
Hematin, 389, 399
Hematoi'din, 724
Hematopoietic tissue, 402
Hematoporphyrin, 400
Hemeralopia (night-blindness), 331
Hemin, 399
Hemipeptone, 705
Hemiplegia, 186

INDEX.

895

Hemochromogen. 389, 400
Hemodromograph, 437
Hemoglobin, absorption spectra of,
394

compounds of, with carbon dioxid,
392
with carbon monoxid, 391
with nitric oxid, 392
with oxygen, 391

condition of, in corpuscles, 385

crystals of, 393

curve of dissociation of oxyhemo-
globin, 603

derivative compounds of, 398

iron in, 392

nature and amount of, 389
Hemolysins, natural and acquired,

387
Hemolysis, 385
Hemorrhage, effect of, 425
Heredity, definition and history, 866
Hering theory of color vision, 333
Heterophoria, 340
Hexon bases, 863
Hippuric acid, 759
Histidin, 707, 874
Histohematins, 400
Histons, 863, 879

effect of, on coagulation of blood,
421
Hofacker-Sadler law, 869
Homoiothermous animals, 821
Homolateral conduction in cord, 166
Horopter, 343
Hunger, sense of, 267
Hydrocele liquid, 411
Hydrochloric acid, function of, in pep-
tic digestion, 693
in gastric juice, 687
Hydrolysis, 662

Hydrostatic factor in circulation, 465
Hypermetropia, 296
Hyperpnea, 622
Hypertonic solutions, 885
Hypnotic sleep, 248
Hypoglossal nerve, nucleus of, 230
Hypophysis cerebri, 778
Hypotonic solutions, 885
Hypoxanthin, 61, 756

Identical points of retina, 340
Identity theory of nerve impulse,

115
Immune body, 388
Indican, 760
Indirect calorimetry, 827

field of vision, eye, 313
Indol group in proteid molecule, 706
Indoxyl sulphuric acid, 719, 760
Induction coil, 23
Inert layer in circulation, 435

Infundibular body, 778
Inhibition, escape from, in heart,
517
of heart, 513, 527
of knee-jerk, 147
of reflexes, 139

of respiratory movements, 616
reflex of heart, 517
theories of, 520
Inotropic nerves to heart, 516
Inspiration (see also Respiration)
definition of, 571
increased heart-rate during, 591
means of producing, 572
muscles of, 574
Inspired air, composition of, 592
Internal secretion, adrenals, 775

definition and historical account,

771
kidney, 782
liver, 771
ovary, 779
pancreas, 780
testis, 778
thyroid tissues, 772
sensations, 256
Intestinal movements, effect of
various conditions upon, 648
secretion, 710
Intestines, bacterial action in, 718
large, movements of, 648
nervous control of movements of,

647
reaction of contents of, 718
small, movements of, 644
Intracellular enzymes, 835
Intracranial pressure 556
Intrapulmonic pressure, 583
Intrathoracic pressure, 584
origin of, 586

variations of, with forced breath-
ing, 585
Intraventricular pressure, 484
Introductory contractions of muscle,

33
Invertase, 664, 711
in stomach, 697
Involuntary muscle, 52
Iodothyrin, 773
Iris, action of drugs upon, 303

antagonistic action of muscles upon,

304
muscles and nerves of, 299
Iron in hemoglobin, 392

salts, source and nutritive impor-
tance of, 803
Irritability, definition of, 22
of muscle, 22
of nerve fibers, 80
Isodynamic equivalent of foodstuffs,

817
Isometric muscular contractions, 27

896

INDEX.

Isotonic muscular contractions, 27

solutions, definition of, 885
Isotropous substance in muscle, 19

Jacobson, nerve of, 666
Judgments, visual, of distance and
size, 349
of perspective or solidity, 345

Kidney, action of diuretics on, 748

blood-flow through, 749

composition of secretion of (urine),
751

function of convoluted tubules, 746
of glomerulus, 744

internal secretion of, 782

secretion of urine in, 742

structure of, 741
Kjeldahl's method for determination

of nitrogen, 752, 784
Knee-jerk, conditions influencing,
149

definition of, 146

explanation of, 148

reinforcement of, 146

use of, as diagnostic sign, 150

Labor, physiology of, 854

Lactic acid in muscle, 60

increase of, during contraction,
64

Laked blood, 385

Langerhans, islands of, 781

Large intestine, digestion and absorp-
tion of food in, 717

Larynx, reflex effects from, on respi-
rations, 617

Latent period of muscular contrac-
tion, 26

Lecithin, 727

Lemniscus, lateral, 200
median, 190

Leucin, 706, 874

Leucocytes, effect of hemorrhage
upon, 425
functions of, 405
in formation of thrombin, 417
structure and classification, 404
variations in number of, 405

Leuconuclein, effect upon blood
coagulation, 421

Liebermann's reaction for proteids,
877

Liebig's classification of foodstuffs,
809

Light-reflex in eye, 301

Lipase, 662

in pancreatic secretion, 709
in stomach, 697

Lipase, reversible reaction of, 660
Listing's law, 339

schematic eye, 286
Liver, bile-pigments of, 724
acids of, 725

defensive action of, in coagulation,
420

formation of urea in, 737

glycogen of, 731

glycogenic action of, 734

internal secretion of, 771

pulse, 476

quantity of bile, 722

secretion of bile, 727
Localization of function in cerebellum,
224
in cerebrum, 179
Localizing power of skin, 260
Locke's solution, 502
Locomotor ataxia, 163
Ludwig's theory of urinary secretion,

743
Luminosity of visual sensations, 319
Lungs, gaseous exchanges in, 606

vasomotors of, 551
Luxus consumption, 788
Lymph, action of lymphagogues, 430

circulation of, 564

formation of, 427

summary of factors concerned in
formation of, 432
Lymphocytes, 404
Lysin, 707, 874

Maltase, 662, 664

Mammary glands, effect of uterus
upon, 856
structure and functions, 855

Manometer, Fick's spring, 448
Hiirthle's, 448

maximum and minimum, 449
use of, for determining blood-pres-
sure, 443

Mast cells, 404

Mastication, 634

Mathematical perspective, 345

Mean blood-pressure, 446

Medulla oblongata, 225

respiratory center in, 610

Medullary striae, 201

Meningeal spaces, 554

Menstruation, 841

effect of, on other functions, 845
physiological significance of, 845

Mercury manometer, use of, for blood-
pressures, 443

Metabolism, definition of, 783

Methemoglobin, 398

Micturition, physiology of, 761

Milk, composition of, 858

Millon's reaction for proteids, 877

INDEX.

897

Minimal air, 580
Miosis, definition of, 303
Molisch reaction for proteids, 877
Monakow's bundle, 169
Motor aphasia, 205
areas of brain,. 183
paths in spinal cordj 167, 169
points in man, 88
Mountain sickness, 629
Movements of alimentary canal, defe-
cation, 650
deglutition, 634
large intestine, 648
mastication, 634
small intestine, 644
stomach, 640
vomiting, 651
Mucin in saliva, 669
Muscarin, action of, on heart, 520
on iris, 303
on sweat glands, 768
Muscle, absolute power of, 36
action current of, 96
artificial stimulation of, 23
carbohydrates of, 59
cardiac, properties of, 54
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
ergographic records from, 45
extensibility and elasticity of, 19
fatigue of, 33, 47, 66
glycogen of, 736
heat rigor of, 49
inorganic salts of, 62
introductory contractions of, 33
isotonic and isometric contrac-
tions of, 27
lactic acid of, 64
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
57

Muscle, proteids of, 57
sarcoplasm, 18
simple contraction of, 24
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, 563
voluntary contractions of, 43
white and red fibers of, 30
Muscle-sense, cortical area for, 189
distribution and characteristics of,

265
importance of, in visual judg-
ments, 346
paths for, in spinal cord, 163, 164,

165
quality of, 266
Muscular insufficiency in movements
of eyeballs, 339
work, effect of, on heart rate, 528
on physiological oxidations,

809
on proteid metabolism, 810
on respiratory movements,
627
source of energy in, 811
Musical sounds, classification and

properties of, 362
Mydriasis, definition of, 303
Myelin sheath of nerve fibers, func-
tion of, 73
Myelinization method of Flechsig, 210
Myogen, 58
fibrin, 58
Myogenic theory of heart beat. 498
Myohematin, 400
Myopia, 295
Myosin, 58
fibrin, 58
Myxedema, 773

Narcosis, effect of, upon nerve im-
pulse, 109

Near point of distinct vision, 292

Negative pressure in thorax, 584, 586
in ventricle, 493
variation in muscle and nerve, 96,
98

Nerve, abducens, nucleus of, 229
auditory, 199
chorda tympani, 270, 667
facial, nucleus of, 229
fourth cranial, nucleus of, 227
glossopharyngeal, nucleus of, 229
hypoglossal, nucleus of, 230
motor and sensory roots of, 77
olfactory, 203

898

INDEX.

Nerve, optic, 194

recurrent sensibility of anterior

roots, 77
spinal accessory, nucleus of, 230
third cranial, nucleus of, 226
trigeminal, nucleus of, 227
twelfth cranial, nucleus of, 230
vagus, nucleus of, 229
Nerve-cell, chromato lysis of, 121

classification of, in spinal cord,
154

degenerative changes in, 120

general physiology of, 128

internal structure of, 126

metabolism in, 129

neuron doctrine, 122

reaction of, 129

refractory period of, 132

summation of stimuli in, 130

varieties of, 124
Nerve-fibers, action current of, 96

afferent and efferent, 75

anodal and cathodal stimula-
tion of, 82

antidromic impulses in, 78

artificial stimuli of, 80

classification of, 75

core model of, 10

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, 116

opening and closing tetanus
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, 115

relation of, to action current,
100, 107

theories of, 113

velocity of, 105

Nervi erigentes, 236, 545
Neurogenic theory of heart beat, 497
Neuron doctrine, 122
Neurons, varieties of, 124
Nicotin, action of, on salivary secre-
tion, 676
on sweaty secretion, 768
use of, in tracing autonomic fibers,
233
Night-blindness, hemeralopia, 331
Ninth cranial nerve, nucleus of, 229
Nissl's granules, 127
Nitric oxid hemoglobin, 392
Nitrogen, condition of, in blood, 602
determination of, 784
equilibrium, 783

effect of non-proteid food on,
786
excretion in urine, 752
Nitrogenous extractives of muscle, 61
Nodal point of eye, 286
Non-polarizable electrodes, 95
Normoblasts, 402

Nucleo-albumin, general properties
of, 878
in bile, 727
Nucleon, 60
Nucleoproteids, 880
in blood, 414

Obesity, physiological cause of, 799
Ohm's law of composition of sound

waves, 365
Olfaction, end-organ for, 275

mechanism of, 276
Olfactometer, 280
Olfactory associations, 281

bulb, histological structure of, 202

center in cortex, 202

nerve, course of fibers of, in brain,

203
organs, fatigue of, 279
sensations, classification of, 278
conflict of, 281
qualities of, 277
threshold stimulus, 280
sense cells, 276
stimuli, nature of, 277
Oncometer, 749
Ophthalmoscope, 305
Opotherapy, 771

Optic chiasma, decussation in, 195
structure of, 194
nerve, course of fibers of, in brain,

193
radiation, 193
thalamus, functions of, 214

in vision, 197
tracts, structure of, 195
Optical deceptions, 350
Optograms on retina, 311

INDEX.

899

Osmosis, definition of, 881
Osmotic pressure, definition of, 882
determination of, 883
of blood, 386
Oval field of Flechsig, 169
Ovaries, internal secretion of, 779
relation of, to menstruation, 843
Overtones, production of, 364
Ovulation, 840, 844
Ovum, fertilization of, 850
implantation of, in uterus, 851
maturation of, 847
passage of, into uterus, 846
Oxalate solutions, effect of, on coagu-
lation, 422
Oxidases, 662, 836
Oxidations, theories of, 833
Oxygen, action of, on respiratory
center, 620
compound of, with hemoglobin,

391
condition of, in blood, 603
effects of, on muscular irritability,
63
varying pressures of, on respira-
tion, 628
tension of, in alveolar air, 607
in tissues, 608
in venous blood, 607
Oxyhemoglobin, 391

Pacchionian bodies of brain, 554
Pain sense, distribution and char-
acteristics of, 262
localization of, 263
path for, in cord, 163, 165
Pancreas, action of lipase in, 709

anatomy of, 700

curve of secretion of, 702

digestive action of secretion, 705
on carbohydrates, 705

internal secretion of, 780

normal mechanism of secretion, 703

secretory nerves of, 701
Paraglobulin, 411
Paralysis (motor), 185
Paralytic secretion (saliva), 677
Parapeptone, 693
Parathyroid, structure and function

of, 772
Parthenogenesis, 851, 870
Parturition, physiologv of, 854
Pendular movements (intestine), 646

sound waves, 363
Pepsin, 664

discovery of, 657

properties of, 691
Pepsin-hydrochloric acid digestion,

693
Peptids, 708, 875
Peptone, 693, 879

Peptone, absorption of, in stomach,
699

effect on clotting of blood, 423

hemi- and anti-, 705
Peptozym, 423
Pericardial liquid, 410
Perimeter, 312
Peripheral field of vision, 313

resistance in circulation, 462
Peristalsis, 644
Peroxidases, 836
Perspiration (see Sweat)
Pettenkofer's reaction, 725
Pfliiger law of stimulation, 84

tetanus, 86
Phagocytes, 405
Phenolsulphuric acid, 719, 760
Phenylalanin, 706, 874
Phloridzin diabetes, 734, 796
Phosphocarnic acid, 60
Phrenology, 180
Physiological diplopia, 342

oxidations, theories of, 820, 833
Lavoisier's work, 569

point (vision), 315

saline, 386, 426
Physostigmin, action of, on iris, 303
Pilocarpin, action of, on heart, 520
on iris, 303

on salivary glands, 676
on sweat glands, 768
Pituitary body, structure and func-
tions of, 777
Placenta, functions of, 852
Plain muscle, 52

Plasma of blood, composition of, 408
Plethysmography, 533
Pneumogastric nerve (see Vagus)
Pneumograph, 577
Pneumothorax, 587
Poikilothermous animals, 821
Polar bodies of ovum, 848
Polypeptid, 708
Positive electrical variation in heart,

521
Posterior columns, descending tracts
of, 169
tracts of, 161

root, termination in cord, 160
cells of, • origin of, 78
Postganglionic nerve fibers, 232
Potassium phosphate in muscle, 65

salts, action of, on heart, 501
Potential energy of food, 814
Precipitins, 876
Predicrotic pulse wave, 474
Preganglionic nerve fibers, 232
Pregnancy, changes in, 854
Prepyramidal tracts, 169
Presbyopia, 292, 297
Pressor nerve fibers, 540
Pressure of gases in solution, 601

900

INDEX.

sure sense, distribution of, 256
localizing power, etc., 260
Primary proteoses, 693
Principal axis of lens, 284

focal distance, 283, 286
Projection system of fibers (brain),

173
Propeptone, 693
Prostate gland, 861
Protalbumoses, 693
Protamins, 862, 879
Proteids, absorption of, in intestine,
716

as glycogen-formers, 733

classification of, 877

definition and structure of, 874

diffusion of, 886

excretion of nitrogen of, 752

general reactions of, 875

in blood-plasma, 410, 413

necessary amount of, in diet, 788

normal metabolism in body, 790

nutritive history of, 787

of muscle, 57

osmotic pressure of, 885

putrefaction of, in large intestine,
719
Proteolytic enzymes, 662
Proteoses, general properties of, 879
Prothrombin, 418
Proximate principles of food, 654
Psychophysical law, 253
Ptyalin, 669

action of, in stomach, 697

digestive action of, 679

effect of various conditions upon,
681
Puberty, 841, 860

Pulmonary arteries, vasomotors of,
551 "

circulation, peculiarities of, 467
variations of pressure in, 468
Pulse, anacrotic waves of, 475

catacrotic waves of, 474

form of wave, 472

general statement, 469

varieties of, in health and disease,
475

velocity of, propagation of, 470

venous, 475
Pulse-pressure, 446
Purin bases, 61, 739, 756, 863
Purkinje, images of, 290

phenomenon, 319
Putrefaction in intestines, 719
Pyloric glands of stomach, 683

secretion of, 692
Pyramidal tract in brain, 184

in spinal cord, 167
Pyrrol compounds in proteid mole-
cule, 706
Pyrrolidin-carbonic acid, 706, 874

Reactions for proteids, 875
Gmelin's, 724
of blood, 382

of contents of small intestine, 718
of urine, 751
Pettenkofer's, 725
Recurrent sensibility of anterior roots.

77
Red blood-corpuscles, chemical com-
position of, 409
condition of hemoglobin in, 385
effect of hemorrhage upon, 425
hemolysis of, 385
influence of spleen upon, 738
number and size of, 384
origin and fate of, 401
variations in number of, 402
Reduced hemoglobin, 391

schematic eye, 286
Reflex actions, axon reflexes, 142
classification of, 136
definition and historical, 133
from parts of brain, 142
influence of condition of cord on,
141
of sensory endings upon, 138
inhibition of, 139

of heart through, 517
knee-jerk, 146

of erection and ejaculation, 864
of respiratory center, 612
of vasomotor nerves, 540
preparation of reflex frog, 135
reflex arc, 133
respiratory, from nose, larynx,

and pharynx, 617
special and deep reflexes of cord,

151
spinal reflexes, 135, 138
theory of, 137

through peripheral ganglia, 142
through vasodilator nerves, 546
time of, 139

Tiirck's method of studying,
141
Refractive power of eye, 293
Refractory period of heart beat, 504

of nerve cell, 132
Regeneration in nerve fibers, 118

of parts of body, 868
Reinforcement of knee-kick, 146
Rennin, 695

of kidney, 782
Reproduction, changes during preg-
nancy, 854
in uterus in menstruation, 842
chemistry of spermatozoa, 862
determination of sex, 868
erection, 863

fertilization of ovum, 850
functions of placenta, 852
general statements, 838

INDEX.

901

Reproduction, growth and senescence,
871

heredity, 866

implantation of ovum, 851

mammary glands, 855

menstruation, 841

nutrition of embryo, 852

ovulation, 840, 844

parturition, 854

properties of spermatozoa, 860

relation of ovaries to menstrua-
tion, 843

structure and functions of corpus
luteum, 840
of Graafian follicles, 839
Residual air, 580

Resonance, importance of, in func-
tions of ear, 366
Respiration, abdominal type, 576

acapnia, 625

accessory centers of, in brain, 619
respiratory movements, 577

anatomy of thorax, 571

apnea, 623

artificial, 581

aspiratory action of, on blood-flow,
587

automatic action of respiratory
center, 612

bronchocon stricter and broncho-
dilator fibers, 625

calorimeter, 827

capacity of the bronchi, 581

chamber, 785

chemical composition of inspired
and expired air, 592

Cheyne-Stokes type of, 632

complemental air, 580

condition of carbon dioxid in blood,
604

costal, 573, 576

definition of inspiration and ex-
piration, 571

dissociation of oxyhemoglobin, 603

dyspnea, 622

effect of changes in barometric
pressure upon, 629
in composition of air, 627
of muscular work upon, 627

exchange of gases in, 608

forced, 575

functional value of nitrogen, 602

gaseous exchange in lungs, 606

gases of blood. 596

history of, 566

hyperpnea, 622

increased heart-rate during inspira-
tion, 591

injurious effect of expired air, 593

intrapulmonic pressure, 583

intrathoracic pressure, 584

mechanism of inspiration, 572

Respiration, methods of recording,

577
minimal air, 580
modified respiratory movementst

633
mountain sickness, 629
muscles of expiration, 574

of inspiration, 574
negative pressure in thorax, 584
normal stimulus of, 619

ventilation of alveoli, 581
of swallowing, 636
origin of negative pressure in

thorax, 586
physical theory of, 606
physiological anatomy of organs

of, 570
pneumothorax, 587
reflex stimulation of respiratory

center, 612
relation of vagus nerve to, 614
residual air, 580
respiratory center, 610, 618

quotient, 631

waves of blood-pressure. 588
secretion of gases in lungs, 608
spinal respiratory centers, 611
supplemental air, 580
tension of gases in alveolar air,
606
in arterial blood, 608
in tissues, 608
in venous blood, 607
tidal air, 580

ventilation, principles of, 595
vital capacity, 579
volumes of air respired, 579
voluntary control of, 618
Respiratory center, 610, 611, 618, 619

automatic activity of, 612

normal stimulus of, 619

reflex stimulation of, 612
quotient, 631

waves of blood-pressure, 588
Retina, action current of, 309
acuity of vision in, 315
after-images from, 323
color blindness of, 325

contrasts in, 324

vision in, 321
corresponding points of, 340
distribution of color sense in, 328
entoptic phenomena, 336
function of rods and cones of, 330
fundamental and complementary

colors, 322
light adapted and dark adapted,

318
portion of, stimulated by light,

308
projection ,of, on. occipital lobes,

LIBRARY

V4/,

902

INDEX.

Retina, qualities of visual sensations
from, 320
size of fovea in, 314, 315
theories of color vision in, 331
threshold stimulus of, 317
visual purple of, 310

Reversible chemical reactions, 659

Rheoscopic frog preparation, 99

Rhodopsin, 310

Ribs, action of, in inspiration, 573

Rigor of muscle, 49, 51, 62, 66

Ringer's solution, 387

Ritter's tetanus, 86

Rivinus, ducts of, 666

Rods and cones of eye, functions of,
330

Sacculus, functions of, 379
Saliva, chorda, 673
composition of, 669
digestive action of, 679
general functions of, 681
secretory nerves for, 670
sympathetic, 673
Sahvarv glands, action of drugs upon,
676
anatomical relations, 666
histological changes during ac-
tivity, 674
structure of, 668
normal stimulation of, 678
secretory center for, 679

nerve fibers of, 672
theory of secretory nerves, 673
Salts, absorption of, in stomach, 698
excretion of, 760

general nutritive importance of,
801
Sarco lactic acid, 60
Sebaceous glands, secretion of, 769
Secondary axes of a lens, 284

degeneration, nerve fibers, 117, 157
proteoses, 693
Secretion, 703, 711
internal, 771
of bile, 727

of sebaceous glands, 769
of sweat, 767
of urine, 742
Secretogogues of gastric glands, 690
Secretory nerves of salivary glands,

671
Semicircular canals, direct stimula-
tion of, 374
Flourens's experiments upon, 372
• structure of, 372
temporary and permanent effects

of operations on, 374
theories of functions of, 375
Seminal vesicles, function of, 861
Senescence, 871

Senses, classification of, 249

cutaneous, 256
Sensory aphasia, 206
areas of cortex, 188
paths in spinal cord, 161
Sequence of heart beat, 507
Serin, 874

Serum, action of foreign, 389
-albumin, 410
-globulin, 411
Seventh cranial nerve, nucleus of.

229
Sex, determination of, 868
Side-pressure in blood-vessels, 460
Sixth cranial nerve, nucleus of, 229
Skatoxylsulphuric acid, 719, 760
Skeletal muscular tissue, physiology

of, 18
Skin, excretory functions of, 766

sweat glands of, 766
Sleep, changes in circulation during,
242
curves of intensity of, 239
effect of sensory stimulation dur-
ing, 243
hypnotic, 248
metabolism during, 811
physiological phenomena of, 238
theories of, 244
Small intestine, absorption in, 712
Smegma prseputii, 770
Smell, center for, in brain, 204

end-organ of, 275
Smelling, mechanism of, 276
Sodium chlorid, nutritive value of,
802
salts, effect of, on heart-beat, 501
Somatoplasm, definition of, 872
Sound, sensations of (see Ear)
waves, nature and action of, 361
overtones of, 364
simple and compound, 363
Specific energy of taste sensations,
273
gravity of blood, 383
nerve energies, doctrine of, 115,
251
of cutaneous nerves, 258
Spectra, absorption, blood, 394
Spectroscope, 395
Spermatozoa, chemistry of, 862
maturation of, 861
properties of, 860
Spermin, 779

Spherical aberration in eye, 294
Sphygmography, 472
Sphygmomanometers for determin-
ing blood-pressure in man, 456
Spinal cord, anterior marginal bundle
of, 170
as path of conduction, 154
classification of tracts in, 157

INDEX.

903

Spinal cord, effect of removing, 144,
651
general relations of gray and

white matter in, 156
groups of cells in, 154
Helweg's bundle in, 170
homolateral and contralateral

conduction in, 166
less well-known tracts of, 169
Monakow's bundle in, 169
paths in, for cutaneous im-
pulses, 165
pyramidal tracts of, 167
reflex activities of, 133, 144
tonic activity of, 144
tracts of, in lateral column, 164
in posterior column, 164
in white matter, 156
ventral longitudinal bundle, 170
vestibulo-spinal tract, 170
reflex movements, 135
reflexes in mammals, 138
respiratory center, 611
Spirometer, 579
Spleen, physiology of, 738
Stannius, first ligature of, 499
Stapedius muscle, function of, 358
Starvation, effect of, on body-metab-
olism, 812
Steapsin (see Lipase)
Stenson's duct, 666
Stereognostic sense, 189
Stereoscopic vision, 347
Stethoscope, 485
Stimulants, 656

nutritive importance of, 805
Stimuli, artificial, of muscle, 23
Stokes- Adams syndrome, 508
Stokes's reducing agent, 397
Stomach, absorption in, 698
anatomy of, 639
automaticity of, 643
digestion in, 696
glands of, 683
histological changes in, during

activity, 684
means of obtaining secretion of, 685
mechanism of gastric secretion,

689
movements of, 640
musculature of, 640
properties of pepsin of, 691
secretory nerves of, 688
Strabismus, 340
Stromuhr, 436
Submaxillary ganglion, 668
Succus entericus, 710
Sugars, absorption of, in stomach,
699
metabolism of, in body, 794
Sulphur, forms in which excreted,
759

Summation of muscular contractions,
39
of stimuli in nerve centers, 130
Superior olivary body, relation of, to

auditory paths, 200
Supplemental air, 580
Suprarenalin, 776
Swallowing, 634

respiration, 636
Sweat, amount and composition of,
766
nerve centers for, 769
secretory fibers of, 767
Sweat-nerves, action of, in heat regu-
lation, 829
Sympathetic nervous system, general
relations, 231
resonance, 366
Syntonin, 693

Systole, duration of, in heart. 489
Systolic arterial pressure, 446

determination of, in animals,
447
in man, 453
plateau of ventricular contraction,
485

Tabes dorsalis, 163
Taste buds, 275

center for, in brain , 204
nerves of, 270

sensations, classification of, 272
specific energy of, 273
threshold stimulus, 275
sense of, 270

stimuli, mode of action, 274
Taurin, 725
Taurocholic acid, 725
Tectorial membrane, 368
Temperature (see Heat)

effect of, on bo&y metabolism, 811
on gases in solution, 600
on heart rate, 529
on muscular contraction, 28
of human body, 822
sense, distribution and character-
istics, 259
path for, in spinal cord, 163, 165
punctiform distribution of, 257
Tension of gases in solution, 601
Tensor tympani muscle, function of,

358
Tenth cranial nerve, nucleus of, 229
Testis, internal secretion of, 778
Tetanus, number of stimuli necessary
for, 42
of artificial muscle, 71
of muscle, 39
opening and closing, 86
Theobromin, 757, 805
Third cranial nerve, nucleus of, 226

904

INDEX.

Thirst, sense of, 267
Thorax, as closed cavity, 571

aspiratory action of, 587

normal position of, 571

origin of negative pressure in, 586
Thrombin, 416
Thrombokinase, 418
Thyroid, extirpation of, 772

function of, 774

internal secretion of, 772

theory of (Cyon), 775
Tidal air, 580

Tigroid substance in nerve cells, 127
Tissue proteid, 787
Tissues, exchange of gases in, 608
Tone (musical) of muscular con-
traction, 41
Tonicity of heart muscle, 510

of muscle, 48

of nerve centers, 144
Touch sense, path of, in cord, 169
Tracts in spinal cord, 157, 169

of Burdach 159

of Flechsig, 159, 164

of Goll, 159

of Gowers, 159, 164
Traube-Hering waves, 544
Treppe of muscular contractions, 33
Trigeminal nerve, area of distribu-
tion of, 228
nucleus of, 227
Trophic nerve fibers, salivary glands,

672
Trypsin, 664, 707
Tryptophan, 707, 874
Tiirck's method for reflex time, 141
Twelfth cranial nerve, nucleus of,

230
Tympanic membrane, 354
Tyrosin, 706, 874

Unipolar method of stimulation, 87
Urea, formation of, in liver, 737

origin and significance of, 753
Ureters, contractions of, 761
Urethra, sphincter of, 763
Uric acid, 61

in spleen, 739
significance of, 757
Urinary bladder, movements of, 762
nerves of, 765

pigments, 400
Urination, physiological mechanism

of, 761
Urine, composition of, 751

nitrogenous excreta of, 752

origin of acidity of, 748

osmotic pressure of, 746

reaction of. 751

secretion of, 742

secretion pressure of, 745

Uterus, changes of, during menstrua-
tion, 842
effect of, on mammary glands, 856
Utriculus, function of, 379

Vagus nerve, action of, on gastric
secretion, 688
on heart, 516 (see also In-
hibition)
on pancreas, 701
as motor nerve to stomach, 643
nucleus of, 229

relations of, to respiratory cen-
ter, 614
Vasomotor fibers, centers for, in cord,
543
in brain, 552

to pulmonary arteries, 551
nerves, action of, in heat regula-
tion, 829
antidromic impulses in, 548
course and distribution, 535, 545
general properties of dilators,

545
history of discovery of, 531
methods used to demonstrate,.

532
of heart, 550
position of constrictor center,

538
reflex actions of, 540
rhythmical action of constric-
tor center, 544
to abdominal organs, 562
to dilator center and reflexes,

546
to genital organs, 562
to head, 561
to kidneys, 749
to skeletal muscles, 563
to trunk and limbs, 562
to veins, 564
tonic activity of, 538
Veins, vasomotor supply of, 564
Velocity of blood-flow (see Circu-
lation)
pressure in blood-vessels, 460
Venous pulse, 475

in brain sinuses, 558
Ventilation, principles of, 595
Ventral longitudinal bundle in spinal

cord, 170
Ventricle (see Heart)
Veratrin, effect of, on heart, 30
Vernix caseosa, 770
Vestibulo-spinal tract of spinal cord,,

170
Vision (see Eye and Retina)
Visual acuity, 315
center in cortex, 192

INDEX.

905

Visual field, binocular, 340
monocular, 312
fields, conflict of, in binocular

vision, 344
purple, 310
Vital capacity, 579
Voluntary muscular contractions, 43
Vomiting, 651

Wallerian degeneration, 117, 157

Warm spots of skin, 257

Water, absorption of, in stomach, 698

excretion of, 760
Weber-Fechner law, 253

Wharton's duct, 666

Wirsung, duct of, 700

Work done by contracting muscle, 37

Xanthin, 61, 756

Xanthoproteic reaction for proteids,

877

Zymogen, 663
granules, 675

Zymoplastic substances in coagula-
tion of blood, 418

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EYE, EAR, NOSE, AND THROAT. 13

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CHEMISTRY, SKIN, AND VENEREAL DISEASES. 15

American Pocket Dictionary rou,Recenuy01;.?edised

The American Pocket Medical Dictionary. Edited by W. A.
Newman Dorland, 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. I
can recommend it to our students without reserve."

Stelwagon's Essentials of Skin 8bH^X\£SSM

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- Comp end Series.
The Medical News

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tain the high standard of excellence for which these question compends have been noted."

Wolffs Medical Chemistry ""S^S^S?*"1

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. In
Saunders' Question- Comp end Series.
New York Medical Journal

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student has enabled him to furnish a valuable aid to the student."

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 Saunders'
Question- Compend Series.
The Medical News

"The best condensation of the subjects of which it treats yet placed before the pro'
fession."

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, #1.25 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. In Saunders' 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.
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Chirurgical College, Philadelphia, etc. Post-octavo, 241 pages, 1 12
illustrations. Cloth, $1.00 net. In Saunders' Question Compends,
The Lancet, London

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Gleason's Diseases of the Ear Third Edition, Revised

Essentials of Diseases of the Ear. By E. B. Gleason, S. B.,
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Phila., etc. Post-octavo volume of 214 pages, with 114 illustra-
tions. Cloth, $ 1. 00 net. In Saunders' Question- Compend Series.

Bristol Medico-Chirurgical Journal

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freshness of style or completeness of information."

Wilcox on Genito-Urinary and Venereal Diseases IssJuued

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 net. Saunders1 Compends.

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