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A TEXT-BOOK

OF

PHYSIOLOGY

FOR

MEDICAL STUDENTS AND PHYSICIANS ,

BY

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

PROFESSOR OF PHYSIOLOC^Y IN THE JOHNS HOPKINS UNIVERSITY, BALTIMORE

GblrD JEfcition, aborougblE TReviseO

PHILADELPHIA AND LONDON

W. B. SAUNDERS COMPANY

1910

a

Set up, electrotyped, printed, and copyrighted September, 1905. Reprinted Feb-
ruary-, 1906, September, 1906, and January, 1907. Revised, reprinted,
and recopyrighted August, 1907. Reprinted January,
1908, and October, 1908. Revised, reprinted,
and recopyrighted August, 1909.

Copyright, 1909, by W. B. Saunders Company.

red at Stationers' Hall, London, England.
Reprinted January, 1910.

D IN AMERICA

W. 0. ".AUNOEHJ COMPANY
PHILADELPHIA

PREFACE TO THE THIRD EDITION.

In the short interval of two years which has elapsed since the
preparation of the second edition of this text-book a large amount
of new material has been added to the literature. To the author
it has seemed, in fact, that there has been an unusual wealth of
contributions to our knowledge, both as regards facts and new
points of view. This material is scattered through a wide range
of publications, for the tendency toward the multiplication of
special journals shows no signs of abatement. No one would be
justified in claiming that he had winnowed all of this extensive
field. The author has attempted to scrutinize the sources of
information which are recognized as specifically physiological,
but he is conscious that much of direct interest to physiology now
appears in journals nominally devoted to other subjects, and which,
therefore, is liable to be overlooked for a time by the professional
physiologist. As it is, the labor of revision has been very great,
and numerous additions and corrections have been made in many
parts of the book. In the second edition most of the changes
incorporated were made necessary by the valuable results follow-
ing upon the extensive application of chemical methods of investi-
gation. In the present edition, the new facts that have been
added, as a consequence of improvements in the methods of so-
called physical physiology, are perhaps as important as those that
we owe to the use of the chemical methods. It requires but
little acquaintance with the development of physiology as a whole
to realize that all good methods of investigation, whether physical,
'chemical, or anatomical, have now as formerly an abundant
opportunity of attaining results of the greatest importance.
While most of the changes made in the present edition have been
of the nature of the correction or modification of former statements,
or the addition of new facts, the author has not hesitated at times
to include also brief mention of new theories or points of view,
which, while possibly of only temporary importance, are at least
characteristic of the present stage of development of the subject.

l

2 PREFACE.

It may not be amiss to call especial attention to the new and sug-
gestive contribution made by Rubner to the difficult subject of
growth and senescence. This work is particularly interesting
as indicating the benefits that may be expected from the applica-
tion of the special methods of physiology to the study of a subject
which heretofore has been investigated mainly from morphological
and statistical standpoints.

PREFACE.

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

The fundamental facts of physiology, its principles and modes

3

4 PREFACE.

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

Some critics have contended that only those facts or conclu-

about which there is no difference of opinion should be pre-
sented to medical students. Those who are acquainted with

llbject, however, understand that hooks 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

book for medical students should aim to present only those
conclusions that have crystallized out of the controversies of other

, 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 Jhe 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 approximate^ 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 op Contraction 17

The Histological' Structure of the Muscle Fiber, 18. — Its Appearance by
Polarized Light, 19. — The Extensibility and Elasticity of Muscular Tissue,
20. — The Independent Irritability of Muscle, 22. — Definition and Enumeration
of Artificial Stimuli, 24. — The Duration of the Simple Muscle Contraction, 25. —
The Curve of a Simple Muscle Contraction, 26. — The Latent Period, 27. — The
Phases of Shortening and Relaxation, 27. — Isotonic and Isometric Contrac-
tions, 27. — Maximal and SubmaximalContractions, 28. — Effect of Temperature
upon the Simple Contraction, 29. — Effect of Yeratrin on the Simple Contraction,
31. — Contracture, 32. — Fatigue, the Treppe, and Effect of Rapidly Repeated
Stimulation, 34. — The Wave of Contraction and Means of Measuring, 35. — ■
Idiomuscular Contractions, 36.— The Energy Liberated During a Muscular
Contraction, 36. — The Proportional Amount of this Energy LTtilized in Work,
37. — The Curve of Work and the Absolute Power of a Muscle, 38. — Definition
of Tetanus or Compound Contraction, 40. — The Summation of Contractions,
42. — Discontinuity of the Processes of Contraction in Tetanus, 43.— The
Muscle-tone, 43. — The Rate of Stimulation Necessary for Complete Tetanus,
44. — The Tetanic Nature of Yoluntary Contractions, 44. — The Ergograph, 47. —
Results of Ergographic Experiments, 49. — Sense of Fatigue, 50. — Muscle
Tonus, 50. — Rigor Mortis and Rigor Caloris, 51. — The Occurrence and Struc-
ture of Plain Muscle Tissue, 54. — Distinctive Properties of Plain Muscle, 55. —
The General Properties of Cardiac Muscular Tissue, 57. — The Contractility of
Cilia and Their General Properties, 57.

Chapter II. — The Chemical Composition of Muscle and the Chem-
ical Changes of Contraction and of Rigor Mortis 60

The Composition of Muscle Plasma, 60. — The Proteins of Muscle, 61. — The
Carbohydrates of Muscle, 62. — Phosphocarnic Acid, 63. — Lactic Acid in Muscle,
63. — The Nitrogenous Extractives of Muscle, 64. — Pigments of Muscle, 64. —
Enzymes of Muscle, 64. — Inorganic Constituents of Muscle, 65. — The Chemi-
cal Changes in Muscle during Contraction, 65. — The Chemical Changes during
Rigor Mortis, 69. — The Relation of the Waste Products to Fatigue, the Chemical
Theory of Fatigue, 69. — Theories of the Mechanism of the Contraction of
Muscle, 71.

Chapter III. — The Phenomenon of Conduction. Properties of

the Nerve Fiber 76

General Statement Regarding Property of Conductivity, 76. — Structure of
the Nerve Fiber, 76. — Function of the Myelin Sheath, 77. — Chemistry of the
Nerve Fiber, 78. — The Nerve Trunk an Anatomical Unit Only, SO. — Definition
of Afferent and Efferent Nerve Fibers, 80. — Classification of Nerve Fibers,
80. — The Bell-Magendie Law of the Composition of the Anterior and the
Posterior Roots of the Spinal Nerves, 82. — Cells of Origin of the Anterior and
Posterior Root Fibers, 83. — Origin of the Afferent and Efferent Fibers in the
Cranial Nerves, 84. — Independent Irritability of Nerve Fibers, Artificial Nerve
Stimuli, 85. — Du Bois-Reymond's Law of Stimulation by the Galvanic Current,
87. — Electrotonus, 88. — Pfliiger's Law of Stimulation, S9. — The Opening and
the Closing Tetanus, 91. — Mode of Stimulating Nerves in Man, 91. — 5lotor
Points of Muscles, 92. — Physical and Physiological Poles, 94.

Chapter IV. — The Electrical Phenomena Shown by Nerve and

Muscle 96

The Demarcation Current, 96. — Construction of the Galvanometer. 97. — Con-
struction of the Capillary Electrometer, 101. — Non-polarizable Electrodes,
101. — Action Current or Negative Variation, 103. — Monophasic and Diphasic
Action Currents, 104. — The Rheoscopic Frog Preparation, 106. — Relation of
Action Current to the Contraction Wave and Nerve Impulse, 10i . — The Elec-
trotonic Currents, 108. — The Core-model, 109.

b TABLE OF CONTEXTS.

PAGE

Chapter V. — The Nature of the Nerve Impulse and the Nutri-
tive Relations of Nerve Fibeb and Nerve Cell Ill

Historical, 111. — Velocity of the Nerve Impulse, 112. — Relation of the Nerve
Impulse to the Wave of Negativity, 114. — Direction of Conduction in the
Nerve, lb">. — Effect of Various Influences on the Nerve Impulse, 117. — The
Fatigue of Nerve Fibers, US. — The Metabolism of the Nerve Fiber during
Functional Activity, 120. — Theories of the Nerve Impulse. 121. — Qualitative
Differences in Nerve Impulses, 121. — Doctrine of Specific Nerve Energies,
124. — Nutritive Relations of Nerve Fibers and Nerve Cells. 12.">. — Nerve Degen-
eration and Regeneration, 127. — Degenerative Changes in the Central End
of the Neuron. 129

SECTION II.

THE PHYSIOLOGY OF THE CENTRAL NERVOUS SYSTEM.

Chapter VI.- Structure and General Properties of the Nerve

Cell 131

The Neuron Doctrine, 131. — The Varieties of Neurons, 133.— Internal St rueture
of the Nerve Cell, 136. — General Physiology of the Nerve Cell, 137. — Sum-
mation i.f Stimuli in Nerve Cells, 139. — Response of the Nerve Cell to Varying
Rates of Stimulation, 140. — The Refractory Period of the Nerve Cell, 141.

Chapter VII. — Reflex Actions 1 12

Definition and Historical, 142.— The Reflex Are, 142.— The Reflex Frog, 144.—
Spinal Reflex Movements, H4. 1 heory of Co-ordinated Reflexes, 140. — Spinal
Reflexes in Mammal-, [47.— Dependence of Co-ordinated Reflexes upon the
Excitation of the Sensory Endings, 149. — Reflex Time, 148. — Inhibition of
Reflexes, 149. — Influence of the Condition of the Cord on its Reflex Act ivit ies,
151.— Reflexes from other Parts of the Nervous System, 151.— Reflexes
Through Peripheral Ganglia, Axon Reflexes, 152. — The Tonic Activity of t he
Spinal Cord, 154.- Effects of the Removal of the Spinal Cord, 155. — Knee-jerk,
150. — Reinforcement of the Knee-jerk, 156. — Is the Knee-jerk a Reflex Act?
158. — Conditions Influencing the Extent of the Knee-jerk. 159. — The Knee-
jerk and Spinal Reflexes as Diagnostic Signs, 160. — Other Spinal Reflexes,
101.

Chapter YIH. — The Spinal Cord as a Path of Conduction 1(53

Arrangement and Classification of the Nerve Cells in the Cord, 103. — General
Relations Of the Gray and White Matter in the Cord. 165. — The Methods

of Determining the Tracts of the Cord, 165. — General Classification of the

Tracts of the Cord, 100.— The Names and I. ocat ions of t he Long Tracts, 168. —

The [termination in the Cord of the libers of the Posterior Root, 169.— Ascend-
ing or Afferent Paths in the Posterior Funiculi, 170. — Ascending or Afferent
Paths in the Lateral Funiculi, 173. — The Spinal Paths for the Cutaneous
Senses 'Touch. Pain, Temperature), 175. The Homolateral or Contralateral

Conduction of the Cutaneous Impulses, 170. — The Descending or Efferent

Paths in the Anf rolateral Columns (Pyramidal System), 177. — Less Well-
known Tracts in the Cord, 179.

Chapter IX. The Gi neral Physiology of the Cerebrum and Its

Motor Fi motions 182

The Histology of the Cortex, 183, 'l he Classification of the Systems of libers
in the Cerebrum (Projection, Association, and Commissural), L84. Physio-
logical Deductions from the Histology of the Cortex, L86.— Extirpation of the
brum, 188. Localization of Functions in the Cerebrum, Historical, 190.
Motoi Vrea of the Cortex, 193. Differences in Paralysis from Injury
to the Spinal Neuron and the Pyramidal Neuron, 195. Voluntary Motor
Path* Othei than the Pyramidal Tract, 195. The Crossed Control of the
Muscle and Bilateral Motoi Representation in the Cortex, 196. Arc the
Motoi Vrea I clusi elj Motoi ? 197.

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

L99

Tl,. Vrea, 200, ["heCourseof the Lemniscus, 201, TheCenterfor

Vision, 203 lb tol igical Evidence of the Coui e of the Optic Fibers, 204.
The Decu ation in the Chia ma, 206. The Projection of the Retina on the

206 The Function of the Lower Visual Centers, 209.
4 he Auditory ('enter, 209. Coui e of the Cochlear Nerve, 211, ["he Phj io
logical .-. ol the Lowei Vuditorj Centers, 212. Motoi Responses

from tl,.- Audi'. Cor! 113 Th< Olfactory Center, 213. The Olfactorj
Bulb and it- Connection . 2U The Cortical Centei for Smell, 215. The
Cortical Centei foi Taste, 215. Vpha ia, 215 Sen or} Vpha ia, 218, The
\ ociation An ubdivi ion ol the \ ociation Vrea . 221 pie

D< elnpment of the Cortical Vrea !22 Histological Differentiation in Coi
tical stiu.iuie, 225, Phj ioloin ol the Corpus Callosum, 220. Physiology
of the Corpora Striata and fhafami, 227.

TABLE OF CONTENTS. 9

PAGE

Chapter XL — The Functions of the Cerebellum, the Pons, and

the Medulla 229

Anatomical Structure and Relations of the Cerebellum, 229. — General State-
ment of Theories Regarding the Cerebellum, 233. — Experiments upon Ablation
of the Cerebellum, 234. — Interpretation of the Experimental and Clinical
Results, 235. — Conclusions as to the General Functions of the Cerebellum,
237. — The Psychical Functions of the Cerebellum, 239. — Localization of Func-
tion in the Cerebellum, 239. — The Functions of the Medulla Oblongata, 240. —
The Nuclei of Origin and the Functions of the Cranial Nerves, 241.

Chapter XII. — The Sympathetic or Autonomic Nervous System.. 246

General Statements, 246. — Autonomic Nervous System, 247. — The Use of
the Nicotin Method, 248. — General Course of the Autonomic Fibers Arising
from the Cord, 248. — General Course of the Fibers Arising from the Brain,
249. — -General Course of the Fibers Arising from the Sacral Cord, 251. — Normal
Mode of Stimulation of Autonomic Nerve Fibers, 251.

Chapter XIII. — The Physiology of Sleep 253

General Statements, 253. — Physiological Relations during Sleep, 253. — The
Intensity of Sleep, 254. — Changes in the Circulation during Sleep, 256. — Effect
of Sensory Stimulation, 259. — Theories of Sleep, 260. — Hypnotic Sleep, 263.

SECTION III.

THE SPECIAL SENSES.

Chapter XIV. — Classification of the Senses and General State-
ments 264

Classification of the Senses, 264. — The Doctrine of Specific Nerve Energies,
266.— The Weber-Fechner Psychophysical Law, 268.

Chapter XV. — Cutaneous and Internal Sensations 271

General Classification, 271. — The Punctiform Distribution of the Cutaneous
Senses, 272. — Specific Nerve Energies of the Cutaneous Nerves, 274. — The
Temperature Senses, 275. — The Sense of Pressure, 276. — The Threshold Stimu-
lus and the Localizing Power, 276. — The Pain Sense, 279. — Localization or
Projection of Pain Sensations, 280. — Reflected or Misreferred Pains, 280. —
Muscular or Deep Sensibility, 2S0. — The Qualitv of the Muscular Sensibility,
282.— Sensations of Hunger and Thirst, 283.— The Sense of Thirst, 285.

Chapter XVI. — Sensations of Taste and Smell 286

The Nerves of Taste, 286. — The End-organ of the Taste Fibers, 288.— Classi-
fication of Taste Sensations, 288. — Distribution and Specific Energy of the
Fundamental Taste Sensations, 289. — Method of Sapid Stimulation, 290. —
The Threshold Stimulus for Taste, 291.— The Olfactory Organ, 291.— The
Mechanism of Smelling, 292. — Nature of the Olfactory Stimulus, 293.— The
Qualities of the Olfactory Sensations, 293. — Fatigue of the Olfactory Apparatus,
295. — Delicacy of the Olfactory Sense, 295. — Conflict of Olfactory Sensations,
297. — Olfactory Associations, 297.

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

of the Eye 298

Formation of an Image by a Biconvex Lens, 298. — Formation of an Image
in the Eye, 301. — The Inversion of the Image on the Retina, 303. — The Size
of the Retinal Image, 304. — Accommodation of the Eye, 305. — Limit of the
Power of Accommodation and Near Point of Distinct Vision, 308. — Far Point
of Distinct Vision, 309. — The Refractive Power of the Surfaces in the Eye,
309. — Optical Defects of the Normal Eye, 310. — Spherical Aberration, 311. —
Abnormalities in the Refraction of the Eye, Myopia, 311. — Hypermetropia,
312. — Presbyopia, 313. — Astigmatism, 314. — Innervation and Control of
the Ciliary Muscle and the Muscles of the Iris, 316. — The Accommodation
Reflex and the Light Reflex, 318. — Action of Drugs upon the Iris, 320. —
The Antagonism of the Sphincter and Dilator Muscles of the Iris, 321. —
Intraocular Pressure, 322. — The Ophthalmoscope, 323. — Retinoscope, 325. —
Ophthalmometer, 326.

Chapter XVI 1 1. — The Properties of the Retina. Visual Stimuli

and Visual Sensations 328

The Portion of the Retina Stimulated by Light, 328. — The Action Current
Caused by Stimulation of the Retina, 329. — The Visual Purple, Rhodopsin,
330. — Extent of the Visual Field, Perimetry, 332. — Central and Peripheral
Fields of Vision, 333. — Visual Acuity, 335. — Relation Between Stimulus and
Sensation, Threshold Stimulus, 337. — The Light Adapted and the Dark
Adapted Eye, 338. — Luminosity or Brightness, 339. — Qualities of Visual

10 TABLE OF CONTENTS.

PAGH

Sensations, 340.— The Achromatic Series. 341. — The Chromatic Series, 311. —
Color Saturation and Color Fusion, 341. — The Fundamental Colors, 342. —
The Complementary Color-, 343. — After Images, Positive and Negative, 343. —
Color Contrasts, 344. — Color Blindness, 345. — Dichromatic Vision, 346. —
Tests for Color Blindness, 347. — Monochromatic Vision, 34S. — Distribution
of Color Sense in the Retina. 348. — Functions of the Rods and Cones, 349. —
Theories of Color Vision, 352. — Entoptic Phenomena, 357. — Shadows of
Corpuscles and Blood-vessels, 357. — Shadows from Lens and Vitreous Humor,
358.

Chapter XLX.— Binocular Vision 359

Movements of the Eyeballs, 359. — Co-ordination of the Eye Muscles, Muscular
Insufficiency and Strabismus, 361. — The Binocular Field of Vision, 362.

idmg or Identical Points, 362. — Physiological Diplopia, 364. — The
Horopter, 365. — Suppression of Visual Images, 365. — Struggle of the Visual
Fields, :'.tit>. — Judgments of Solidity, 306. — Monocular Perspective, 367. —
Binocular Perspective, 368. — Stereoscopic Vision, 369. — Explanation of Binoc-
ular Perspective, 371. — Judgments of Distance and Size, 371. — Optical Decep-
tion-, 372.

Chapter XX.— The Eak as an Organ for Sound Sensations 375

The Pinna or Auricle, 376. — The Tympanic Membrane, 376. — The Ear Bones,
377. — Mode of Action of the Ear Bones, 378. — Muscles of the Middle Ear,
380. — The Eustachian Tube, 381. — Projection of the Auditory Sensations.
382 Sensory Epithelium of the Cochlea, 382. — Nature and Action of the
Sound Waves, 3S3. — Classification and Properties of Musical Sounds, 384. —
Upper Harmonics or Overtones. 386. — Sympathetic Vibrations and Resonance,
388. — Functions of the Cochlea, 388. — Sensations of Harmony and Discord,
391. —Limits of Hearing, 392.

Chapter XXL— Functions of the Semicircular Canals and the

Vestibule 394

Position and Structure of the Semicircular Canals, 394. — Flouren's Experi-
ments upon the Semicircular Canals, 395. — Temporary and Permanent Effects
of the Operations, 396. — Effect of Direct Stimulation of the Canals, 397. —
Kffcct of Section of the Ampullary or the Acoustic Nerve, 397. — Is the Effect
of Section of the Canals Due to Stimulation? 397. — Theories of the Functions
of the Semicircular Canals, 398. — Summary of the Views upon the Function
of the Semicircular Canals, 400. — Functions of the Utriculus and Sacculus, 402.

SECTION IV.

BLOOD AND LYMPH.

Chapter XXII. — General Properties of Blood. Physiology OP

the Corpuscles 404

Histological Structure of Blood, 404.— Reaction of the Blood, 405. — Specific
Gravity of the Blood, 407.— The lied Corpuscles, 408. Condition of the
Hemoglobin in the Corpuscles, 408. Hemolysis, 409. Hemolysis Due to

\aiia1ion in I) i.Hilic Pressure, 410.- Hemolysis Due to Action of Hemoly-
tic -Nature ami \ ml of Hemoglobin. III. Compounds of Hemo-
globin with Oxygen and Other < rases, 416.- The I ion in the I Icmoglobin, I 17. —
Crystals of Hemoglobin, 418.— Absorption Spectra of Hemoglobin and Oxy-
hemoglobin, 419.- Derivative Compounds ot Hei dobin, 423. origin and

Fate of the Red Corpuscles, 125. variations in the Number of Red Corpuscles,
127. Physiology of the Blood Leucocytes, 429. — Variations in Number
of the Leucocytes, 431.- Functions of the Leucocytes, 431. — Physiology of
the Blood Plates, 432.

Chapter XXIII. Chemical Composition op the Blood Plasma;
Coagulation; Quantiti of Blood; Regeneration after

1 1 BMORRH \i;i. 434

Compo it ion of tin- I 'la ma and Corpuscles. 134. Proteins of the Blood Plasma,
436. Serum Albumin, 436 Paraglobulm (Serum Globulin), 437. Fibrino-
gen, 138. Le Well-known Proteins of the Blood, 440. Coagulation of
Blood, MO. Theorie of Clotting, I il'. Preparation of Solutions of Fibrino-
gen, 142. Preparation of Thrombin. 443. The factors of Coagulation,
ii .: Propertie and Origin of Thrombin, in Summary, I M'>. The Con-

vi-i ion of Fibrinogen to Fibrin, 447. whj Bl I Hoc. n,,i Clot Within

the Vessels. 44 culai Clotting, 149 Means of Ha tening or of

Rel ulaiion. 160, Total Quantity of Blood in the Body, 462. —

• ration "i the Blood after Hemorrhage, 453. Blood Transfusion, 155

Chapter XXIV. Composition \m» Formation of Lymph 466

eral S atement 156 Formation, of Lymph, 157. Lymphagpgues of the

First CI 169 I I the Second Class, 160, Bummary of

tin- Factoi Controlling the Mow of Lymph, i<>~.

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 465

The Circulation as Seen under the Microscope, 465. — The Velocity of the
Blood Flow, 466. — Mean Velocity in the Arteries, Veins, and Capillaries, 469. —
Cause of the Variations in Velocity, 471. — Variations of Velocity with the
Heart Beat or Changes in the Blood-vessels, 471. — Time Necessary for a Com-
plete Circulation of the Blood, 472. — The Pressure Relations in the Vascular
System, 473. — Methods of Recording Blood-pressure, 473. — Systolic, Dias-
tolic, and Mean Arterial Pressure, 479. — Method of Measuring Systolic and
Diastolic Pressure in Animals, 479. — Data as to the Mean Pressure in Arteries,
Veins, and Capillaries, 481. — Methods of Determining Blood-pressure in the
Large Arteries of Man, 485. — Normal Arterial Pressure in Man and Its Varia-
tions, 490. — The Method of Determining Venous Pressures and Capillary
Pressures in Man, 491.

Chapter XXVI. — The Physical Factors Concerned in the Produc-
tion op Blood-pressure and Blood-velocity 495

Side Pressure and Velocity Pressure, 495. — The Factors Concerned in Pro-
ducing Normal Pressure and Velocity, 498. — General Conditions Influencing
Blood-pressure and Blood-velocity, 499. — The Hydrostatic Effect, 500. —
Accessory Factors Aiding the Circulation, 502. — The Conditions of Pressure
and Velocity in the Pulmonary Circulation, 503. — Variations of Pressure in
the Pulmonary Circuit, 503.

Chapter XXVII.— The Pulse 505

General Statement, 505. — Velocity of the Pulse Wave, 506. — Form of the
Pulse Wave, Sphygmography, 508. — Explanation of the Catacrotic Waves,
510. — Anacrotic Waves, 511. — The Kinds of Pulse in Health and Disease,
512.— Venous Pulse, 513.

Chapter XXVIIL— The Heart Beat 518

General Statement, 518. — Musculature of the Auricles and Ventricles, 519. —
The Auriculoventricular Bundle, 520. — Contraction Wave of the Heart, 521. —
The Electrical Variation, 522. — Change of Form during Systole, 523. — The
Apex Beat, 524.— Cardiogram, 525. — Intraventricular Pressure during Sys-
tole, 526. — The Volume Curve and the Ventricular Output, 528.— The Heart
Sounds, 531. — The Third Heart Sound, 533. — Events occurring during a
cardiac cycle, 534. — Time Relations of Systole and Diastole, 535. — Normal
Capacity of Ventricle and Work Done by the Heart, 535.— Coronary Cir-
culation during the Heart-beat, 537. — Suction-pump Action of the Heart,
539. — Occlusion of the Coronary Vessels, 541. — Fibrillar Contractions of
Heart Muscle, 541.

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

Properties of the Heart Muscle 543

General Statement, 543. — The Neurogenic Theory of the Heart Beat, 545. —
Myogenic Theory, 546. — Automaticity of the Heart, 548. — Action of Calcium,
Potassium, and Sodium Ions on the Heart, 549.— Connection of Inorganic
Salts with the Causation of the Beat, 550. — Maximal Contractions of the Heart,
552. — Refractory Period of the Heart Beat, 552. — The Compensatory Pause,
554. — Normal Sequence of the Heart Beat, 554. — Tonicity of the Heart
Muscle, 558.

Chapter XXX. — The Cardiac Nerves and Their Physiological

Action 561

Course of the Cardiac Nerves, 561. — Action of the Inhibitory Fibers, 561. —
Analysis of the Inhibitory Action, 563. — Effect of Vagus on the Aur cle and
the Ventricle, 565. — Escape from Inhibition, 566. — Reflex Inhibition of the
Heart Beat, the Cardio-inhibitory Center, 566. — The Tonic Activity of the
Cardio-inhibitorv Center, 567. — The Action of Drugs on the Inhibitory Appara-
tus, 559. — The Nature of Inhibition, 569. — Course of the Accelerator Fibers,
571. — Action of the Accelerator Fibers, 573. — Tonicity of the Accelerators
and Reflex Acceleration, 573. — The Accelerator Center, 575.

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

under Normal Conditions 576

Variations in Rate with Sex, Size, and Age, 576. — Variations through the
Extrinsic Cardiac Nerves, 557. — Variations with Blood-pressure, 577. — With
Muscular Exercise, 578. — With the Gases of the Blood, 579. — With Tempera-
ture of the Blood, 579.

12 TABLE OF CONTENTS.

PAGE

Chapter XXXII. — The Vasomotor Nerves and Theih Physiological

ACTIVITY 582

Historical, 582.— Methods Used to Determine Vasomotor Action, 583. — The
Plethysmograph, oS4. — General Distribution and Course of the Vasoconstrictor
Conic Activity of the Vasoconstrictors, 589. — Ihe \ aso-
constrictor Center, 589. — Vasoconstrictor Reflexes. Pressor and Depressor
Fibers, 591. — Depressor Nerve of the Heart, 594. — Vasoconstrictor Centers in
the Spinal Cord, 595. — Rhythmical Activity of the Vasoconstrictor Center,
595. — Course and Distribution of the Dilator Fibers, 596.— General Properties
of Vasodilator Fibers, 597. — Vasodilator Cepter and Reflexes, 597.— Vasodila-
tation Due to Antidromic Impulses, o'.ui. — Regulation of the Blood-supply
by Chemical and Mechanical Stimuli, Gnu.

Chapter XXXIII. — Thk Vasomotor Supply of the Different

( Irgans 601

Vasomotors of the Heart, 601. — Vasomotors of the Pulmonary Arteries, 602. —
Circulation in the Brain and Its Regulation, 603. — Arterial Supply, tio3. —
Venous Supply, 604. — The Meningeal Spaces, 605. — Intracranial Pressure,
0i>7. — Effect of Changes in Arterial Pressure upon the Blood-How through
the Brain, 60S. — The Regulation of the Brain Circulation, 610— Vasomotor
Nerves ,,f the Head Region, 612. — Of the Trunk and the Limbs, 613. — Of the
Abdominal » Organs, 613. -Of the Genital Organs, 014.— Of the Skeletal Muscles,
614.— The Vasomotor Nerves to the Veins, 615. — The Circulation of the
Lymph, tilt;.

SECTION VI.
PHYSIOLOGY OF RESPIRATION.

Chapter XXXIV. — Historical Statement. The Organs of Exter-
nal Respiration and the Respiratory Movements 618

Historical, 618. — Anatomy of Organs of Respiration, 622. — Thorax as a Closed
Cavity, 622.— Normal Position of the Thorax. 623. Inspiration by ( ontraction
of the Diaphragm, 024. — Inspiration by Elevation of the Ribs, 625.— The
Muscles of Inspiration, 626.— Muscles of Expiration, 626.— Quiet and Forced
piratory Movements, Eupnea and Dsypnea, 0: 7. — Costal and Abdominal
types of Respiration, 628.— Accessory Respiratory Movements, 629.—
Registration of the Respiratory Movements, 629. Volumes of Air Respired
Vital Capacity, Tidal Air, Complemental Air, Supplemental Air, Residual
Minimal Air. 631. — Size of the Bronchial Tree, 633.— Artiluial Respira-
tion, 633.

Chapter XX XV- The Pressure Conditions in the Lungs and

Thorax and Their Enfli ence opon the Circulation 635

The [ntrapulmonic Pressure and Its Variation 635. [ntrathroacic Pressure,
Lriations of, with Forced and Cnu-ual Respirations, 637. -Origin ..I

theN Pn ure in the Thorax. 638. Pneumothorax, o.U) \spuatory

Action of the Thorax. 639. Re piratory Waves of Blood-pressure, 640.

Chapter XXXVI. The Chemical and Physical Changes i\ the Air

wi, ! hi. Blood Caused by Respir \n<>\ b44

1 and Expired \i,. 644. rPhysical Changes in the Expir. ,d Air,

644 [niii i Vction of Expired Vir, 645. Ventilation, 64 flhe Oases

of he PI I. 648 The Pre I Ga es, 651. Abeoi p to .n o G

Liauids, 651 The Tension of Ga«e« in Solul ,, • The Conchtwn o

.„ in the Blood 654 Condition of Oxygen m.theBl I, 655. Con-

Stion^fCarWDfoxidin the HI 1.656 Tfie Phy si. a 'I heory ■■•;■;•'•',.

Hon, 858 Ga « tl • I ling 6 f I change wea in tn<

I . ., -,,-i,, i- Activity of Lung . 661 •

ChapterXXXVII [nnbrvation of the Respirators Movements.

The i ' iter, 662 Spinal Re piratory Centei 663.( -Automatic

tv of the R« piraton Centei 864 Reflex Stimulation of the V®"^!;

Vfferenl Relation! of the Vagu to the Center, 866. [he inspirators

and [nhibil of the Vagu . 668 Reepiraton Reflexei Fro"1 the

i \,, ,. B6fl Voluntary Control of the Re piratorj

Nature ol the Re piratory Center, 870 Re piraton I en

n the Midbrain 672 Automatic Stimulus to the Ri piratpr; Center,

I Re piratoi M ■• • D: a, Hyperpnea,

..,,,,! Apnea 676 Innervation ol the Bronchial Mu culature, <>78.

(162

TABLE OF CONTENTS. 13

PAGE

Chapter XXXVIII. — The Influence of Various Conditions upon

the Respiration 680

Effect of Muscular Work on the Respiratory Movements, 680. — Effect of
Variations in the Composition of the Air, 680. — High and Low Barometric
Pressures, Mountain Sickness, Caisson Disease, 682. — The Respiratory Quotient
and Its Variations, 6S4. — Modified Respiratory Movements, 686.

SECTION VII.

PHYSIOLOGY OF DIGESTION AND SECRETION.
Chapter XXXIX. — Movements of the Alimentary Canal 689

Mastication, 689. — Deglutition, 689. — Nervous Control of Deglutition, 693. —
Anatomy of the Stomach, 694. — Musculature of the Stomach, 695. — Move-
ments of the Stomach, 696. — Effect of the Nerves on the Movements of the
Stomach, 699. — Movements of the Intestines, 700. — Peristaltic and Pendular
Movements of the Intestines, 700. — Nervous Control of the Intestinal Move-
ments, 703. — Effect of Various Conditions on the Intestinal Movements, 704. —
Movements of the Large Intestines, 705. — Defecation, 706. — Vomiting, 709. —
Nervous Mechanism of Vomiting, 710.

Chapter XL. — General Consideration of the Composition of the

Food and the Action of Enzymes 712

Foods and Foodstuffs, 712. — Accessory Articles of Diet, 714. — Enzymes,
Historical, 715. — Reversible Reactions, 717. — Specificity of Enzymes, 719. —
Definition and Classification of Enzymes, 720. — General Properties of Enzymes,
721. — Partial List of Enzymes, 722. — Chemical Composition of the Enzymes,
723.

Chapter XLI. — The Salivary Glands and Their Digestive Action 724

Anatomy of the Salivary Glands, 724. — Histological Structure, 726. — Com-
position of the Secretion, 727. — The Secretory Nerves, 728. — Trophic and
Secretory Nerve Fibers, 730. — Histological Changes during Activity, 734. —
Action of Drugs upon the Secretory Nerves, 734. — Paralytic Secretion, 735. —
Normal Mechanism of Salivary Secretion, 736. — Electrical Changes in Glands,
737. — Digestive Action of Saliva, Ptyalin, 737. — Conditions Influencing the
Action of Ptyalin, 738. — Functions of the Saliva, 739.

Chapter XLIL— Digestion and Absorption in the Stomach 740

Structure of the Gastric Glands, 740. — Histological Changes during Secretion,
741. — Method of Obtaining the Gastric Secretion and Its Normal Composition,
742. — The Acid of Gastric Juice, 744. — Origin of the HC1, 745. — Secretory
Nerves of the Gastric Glands, 746. — Normal Mechanism of the Secretion of
the Gastric Juice, 747. — Nature and Properties of Pepsin, 749. — Artificial
Gastric Juice, 751. — Pepsin-hydrochloric Digestion, 751. — The Rennin En-
zyme, 753. — Digestive Changes in the Stomach, 755. — Absorption in the
Stomach, 756.

Chapter XLlII. — Digestion and Absorption in the Intestines. . . 759

Structure of the Pancreas, 759. — Composition of the Secretion, 760. — Secre-
tory Nerve Fibers to the Pancreas, 760. — The Curve of Secretion, 761. — Nor-
mal Mechanism of Pancreatic Secretion, 762. — Secretin, 763. — Enterokinase,
763. — Digestive Action of Pancreatic Juice, 764. — Significance of Tryptic Diges-
tion, 766. — Action of the Diastatic Enzyme (Amylase), 768. — Action of the
Lipolytic Enzyme (Lipase, Steapsin), 768. — The Intestinal Secretion (Succus
Entericus), 770.— Absorption in the Small Intestine, 771. — Absorption of
Carbohydrates, 773. — Absorption of Fats, 774. — Absorption of Proteins, 775.—
Digestion and Absorption in the Large Intestine. 777. — Bacterial Action in
the Small Intestine, 778. — Bacterial Action in the Large Intestine, 779. —
Physiological Importance of Intestinal Putrefaction, 779. — Composition of
the Feces, 780.

Chapter XLIV. — Physiology of the Liver and Spleen 782

Structure of the Liver, 782.— Composition of Bile, 783. — The Bile Pigments,
784. — The Bile Acids, 785. — Cholesterin, 787. — Lecithin. Fats, and Nucleo-
albumins, 787. — Secretion of the Bile, 788. — Ejection of the Bile — Function of
the Gall-bladder, 789. — Occlusion of the Bile-ducts, 791. — Physiological
Importance of Bile, 791. — Occurrence of Glycogen, 792. — Origin of Glycogen,
793. — Function of Glycogen, Glycogenic Theory. 795. — Glycogen in the Muscles
and Other Tissue, 797. — Conditions Affecting the Supply of Glycogen, 798. —
Formation of Urea in the Liver, 798. — Physiology of the Spleen, 799.

14 TABLE OF CONTEXTS.

PAGE

Chapter XLY. — The Kidney and Skin as Excretory Organs 802

Structure of ihe Kidney, SU2. — The Secretion of Urine, 803. — Function of
the Glomerulus, 805.— Function of the Convoluted Tubule, 807. — Action of
Diuretics. 809. — The Blood-flow Through the Kidneys, 809. — The Composi-
tion of Urine, 812. — The Nitrogenous Excreta in the Urine, 813.- — Origin and
Significance of Urea, 814. — Origin and Significance of the Turin Bodies ^'ric
Acid, Xanthin. Hypoxanthin), 817. — Orighi and Significance of the Creatinin
and Creatin, 820.- Hippuric Acid, 821. — The Conjugated Sulphates and the
Sulphur Excretion, S22. — Secretion of the Water and Inorganic Salts, 823. —
Micturition. 824.— Contractions of the Bladder, S25. — Nervous Mechanism
of Micturition. 827. — Excretory Functions of the Skin, 828. — Composition of
Sweat, 829. — Secretory Fibers of Sweat (Hands. 830. — Sweat Centers, 832. —
Sebaceous Secretion, S32. — Excretion of Carbon Dioxid through the Skin, 833.

Chapter XLYI. — Secretion of the Ductless Glands — Internal

Secretion 834

Internal Secretion of Liver, 835. — Internal Secretion of the Thyroid Tissues,
835. — Extirpation of Thyroids and Parathyroids, 836. — Function of the Para-
thyroids, 836. — Function of the Thyroid. 838. — Cyon's View of Function of
Thyroid, 840. — Function of Thymus, S40. — Structure and Properties of
Adrenal Bodies, 841. — General Function of Adrenals, 843. — Pituitary Body,
844. — Internal Secretion of Testis and Ovary, 847. — Internal Secretion of
Pancreas, 849. — Internal Secretion of Kidney, 851.

SECTION VIII.

NUTRITION AND HEAT PRODUCTION AND REGULATION.

Chapter XLVII. — General Methods. History of the Protein

Food 852

General Statement, 852.— Nitrogen Equilibrium, 852. — Carbon Equilibrium
and Body Equilibrium, 854. — Balance Experiments, 854. — Respiration Cham-
ber, 855. — Effect of Non-protein Food on Nitrogen Equilibrium, 855. —
Nutritive History of the Protein Food, 856. — Tissue Protein and Circulating
Protein, 856. — Amount of Protein Necessary in Normal Nutrition, 858. —
Specific Character of Protein Metabolism, 861. — Specific Dynamic Action of
Proteins, 864. — Nutritive Value of Albuminoids, 865.

Chapter XLVIII. — Nutritive History of Carbohydrates and Fats 868

The Carbohydrate Supply of the Body, SOS. — Intermediary Metabolism of the
Carbohydrate in the Body, 869. — Regulation of the Sugar Supply of the Body,
870.— Functions of the Carbohydrate Fond. 873. — Nutritive Value of Fats,
874.— Fate of Fats in the Tissues, 875.— Origin of Body Fat, 877.— Origin of
Body Fat from Food Fat, 878. — Origin of Body Fat from Carbohydrates,
878. Source of 1 -at in Ordinary Diets, 879. Cause of the Formation of Fat,
Obesity, 879.— General Functions of Fat, 880.

Chapter KLIX. Ni trh i\ e Yam b of the Inorganic Salts ind the

Accessory Articles of Diet 881

The Inorganic Salts of the Body. 881.— Effect of Ash-free and Ash-poor Diets,
882.- Bpecial Importance of Sodium Chlorid, Calcium, and Iron Sails, 882. —
The Condiment , Flavors, and Stimulants, 885.— Physiological Effects of
Alcohol, 886.

Chapter I.. Effect oi Muscular Work i.nd Temperature on Body

Metabolism; Beao Energi oi Foods; Dietetics. 890

The Effect of Muscular Worl ,890 Effect of Sleep, 892.- Effect of Variations
remperature, 893. Effect of Starvation, 893.- The Potential Energj of
I ood, 896 Di< tetic , 898.

Chapter i.i The Production oi Hi m m the Body; Its Measure-
d Regulation; Bodi Temperature; Calorimetryj
Physiological Oxidations ■,"'1

lb torical Account of Theorie of Animal Heat, 904. Body Temperature in

Man, 906 Cal 907 Heat Regulation, 912. Regulation <<f Heat

I ., 912 Regulation of Heat Production. 915 Existence of Heat Centers

and Heat 116 Theorie oi Physiological Oxidations, 918.

TABLE OF CONTENTS. 15

SECTION IX.
PHYSIOLOGY OF REPRODUCTION.

PAGE

Chapter LII. — Physiology of the Female Reproductive Organs.. 925

General Statement, 925. — The Graafian Follicle and the Corpus Luteum, 925. —
Menstruation and Puberty, 927. — Structural Changes in the Uterus during
Menstruation, 928. — The Phenomenon of Heat in Lower Animals, 928. —
The Relation of the Ovaries to Menstruation, 929. — Physiological Significance
of Menstruation, 931. — Effect of the Menstrual Cycle on Other Functions,
932. — Passage of the Ovum into the Uterus, 933. — Maturation of the Ovum,
934. — Fertilization of the Ovum, 936. — Implantation of the Ovum, 938. —
Nutrition of the Ovum — Physiology of the Placenta, 939.— Changes in the
Maternal Organism during Pregnancy, 941. — Parturition, 942.- — The Mammary
Glands, 942. — Connection between the Uterus and the Mammary Glands,
943.— Composition of Milk, 945.

Chapter LIII. — Physiology of the Male Reproductive Organs... 947

Sexual Life of Male, 947. — Properties of the Spermatozoa, 947. — Chemistry
of the Spermatozoa, 949. — The Act of Erection, 950. — Reflex Apparatus of
Erection and Ejaculation, 951.

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

Senescence 953

Definition of Heredity, 953. — Evolution and Epigenesis, 953. — Theory of Mu-
tations, 955. — The Mendelian Law, 956. — Determination of Sex, 957. — Growth
and Senescence, 960.

APPENDIX.

I. — Proteins and Their Classification 965

Definition and General Structure of Proteins, 965. — Reactions of Proteins,
967.— Classification of Proteins, 969.— The Albumins, 969.— The Globulins,
970.— The Glutelins, 970.— Alcohol-soluble Proteins (Protamines), 970.—
Albuminoids, 970. — Protamins and Histons, 970. — The Conjugated Proteins,
971.— The Derived Proteins, 971.

II. — Diffusion and Osmosis 972

Diffusion, Dialysis, and Osmosis, 972. — Osmotic Pressure, 973. — Electrolytes,
974. — Gram-molecular Solutions, 974. — Calculation of Osmotic Pressure in
Solutions, 974. — Determination of Osmotic Pressure by the Freezing Point,
975. — Application to Physiological Processes, 975. — Osmotic Pressure of
Proteins, 976. — Isotonic, Hypertonic, and Hypotonic Solutions, 976. — Diffu-
sion or Dialysis of Soluble Constituents, 977. — Diffusion of Proteins, 977.

Index 979

A TEXT-BOOK

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 rapidity of
contraction, and this variation goes hand in hand with an obvious
difference in histological structure. 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

IS

THE PHYSIOLOGY OF MUSCLE AND NERVE.

The Structure of Skeletal Muscle. — This tissue makes up the
essential part vi 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 Kiihne* which seems
to demonstrate the fluid nature of the living muscle substance. He hap-
pened, on one occasion, to find a frog's muscle fiber containing a nematode
worm within the sarcolemma. The animal swam readily from one end of
the fiber to the other, pushing aside the cross bands, which fell into place

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

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

again after the animal had passed. At one end, where the fiber had been
injured, the worm was unable to force its way. The muscle substance at
tin- point was dead and apparently had passed into a solid condition. The
fad thai the cross hands 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 arc long and thread-like and

run the length of the fiber, and the intervening sarcoplasm. The
fibrils consisi of alternating dim and light discs or segments, which,
falling together in the different fibrils, give the cross-striation
thai i- characteristic. In mammalian muscles the fibrils are grouped
more or less distinctly into bundles or columns (sarcostyles),
between which lies the scuii i y sarcoplasm. The relative amount
of sarcoplasm to fibrillar substance varies greatly in the striped
muscles of different :iiiim:ils, as is indicated in the accompanying

* Kuhne, "Archiv fur pathologische Anatomie, " 26, 222, L863.

THE PHENOMENON OF CONTRACTION.

19

illustrations. The evidence from comparative physiology indi-
cates that the fibrils are the contractile element of the fiber,
while the sarcoplasm, it may be assumed, possesses a general
nutritive function. Among mammals there are certain muscles
in which the amount of sarcoplasm within
each fiber is relatively large, and this sar-
coplasm, having the granular structure
common to undifferentiated protoplasm,
interferes with the clearness of striation of
the fibers. Fibers of this latter sort are
usually of a deeper color than those in which
the sarcoplasm is less abundant, and the
two varieties have been designated as the
red (more abundant sarcoplasm) and the
pale fibers. Muscles containing chiefly the
less clearly striated red fibers, for example,
the diaphragm and the heart, are charac-
terized physiologically by a slower rate of
contraction and an ability to maintain
their activity without fatigue. The so-
called red and pale fibers may occur in the
same muscle. The separate fibrils, like the
entire fiber, show two kinds of substance,
the alternating dim and light bands, 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, and that in the dim
bands as anisotropous. The anisotropic
material of the dim bands contains 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 conclu-
sion is supported by the fact that during contraction the size

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 fibril
(beetle) in which the lower
portion has been fixed in a
condition of contraction. —
{Engelmann.)

20

THE PHYSIOLOGY OF MUSCLE AND NERVE.

of the dim bands increases at the expense of the material in the
light bands.* As shown in the schema given in Fig. 3, the band
exhibiting the property of double refraction seems, during the
phase of contraction, to absorb or imbibe material from the
isotropic substance constituting the so-called light band. This
observation, if beyond doubt, would have the greatest signifi-
cance in revealing the location and mode of action of the real
contractile material of the fibers. It has, however, been called
into question by recent work (see p. 75).

The Extensibility and Elasticity of Muscular Tissue. — Muscular
tissue, when acted upon by a weight, extends quite readily, and
when the weight is removed it regains its original form by virtue

am — — ■

Hi

Ffa. 4. — a, Curve of extension of a rubber band, to show the equal extensions for equal
increments of weight. The band had an initial load of 17 cms., and this was increased
by increments of :} urns, in each of the nine extensions, the final load being 44 gms. The
In;, joining the ends of the ordinates is a straight line, b, Curve of extension of a frog's
tun cle ' gasf rocnemius). 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 <*ri< I -^ of the ordinates is curved.

of its elasticity. In our bodies the muscles stretched from bone
to bone are, in fact, in a state of elastic tension, [f a muscle is
severed by an incision across its belly the ends retract. The
extensibility and elasticity of the muscles add to the effective-
of the muscular-skeletal machinery. A muscle that is in a
state of elastic tension contracts more promptly and more effec
fcively for h given stimulus than one which is entirely relaxed.
Moreover, in our joints the arrangement of antagonists flexors
and exten or i- such thai the contraction of one moves the
bone against the pull of the extensible and elastic antagonist.
It would seem thai the movements of the skeleton must gain

* Biedermann, "Electro-physiology," vol, i, translated l>y Welby, and
Engelmann, "Archiv f ur die gesammte Physiologic, " 18, L.

THE PHENOMENON OF CONTRACTION.

21

much in smoothness and delicacy by this arrangement. The
physical advantages of the extensibility and elasticity of mus-
cular tissue are evident not only in the contractions of our volun-
tary 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 by the elastic tension of the distended
arteries. The extensibility of muscular tissue has been studied
in comparison with the extensibility 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 relationship may be
represented as shown in the accom-
panying figure, the equal increments
in weight being indicated by laying off
equal distances on the abscissa, and
the resulting extensions by the height
of the orclinates dropped from each
point. If the ends of the orclinates
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 ex-
tension is greatest in the beginning
and decreases proportionately with
new increments of weight. If the
results of such an experiment are
plotted, as above, representing the
equal increments of weight by equal
distances along the abscissa and the resulting extensions by ordi-
nates dropped from these points, then upon joining the ends of
the orclinates we obtain a curve concave to the abscissa. At
first the muscle shows a relatively large extension, 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 increased 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

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

22 THE PHYSIOLOGY OF MUSCLE AND NERVE.

with increasing increments of weight up to the point of rupture,
as shown in the accompanying curve* (Fig. 5). Hayeraftf calls
attention to the fact that under normal conditions the physio-
logical 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 deformation 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
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.
l\' 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
cent nil nervous system and to cause t he swelling of a muscle during
contraction by flowing to it along the connecting nerve. Bui i<>
remove a mu jele from t lie 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

tin- endings of the nerve in the muscle an; still intact, and if may
be thai the BtimuhlS acts only on them and thus affects the muscle

indirectly. In ,-i number of ways, however, physiologists have
found thai the muscle substance can be made to contract by a

* Sir- \I.ii< v, " l)n mouvemenl dans lea f emotions de In, vie," L868, \>. 284
i Haycraft, " Journal of Physiology," 31, 392, 1904.

THE PHENOMENON OF CONTRACTION. 23

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.
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
is ineffective. Direct stimulation of the muscle substance, on the
contrary, causes a contraction, f We are justified, therefore, in
saying that skeletal muscle possesses the properties of independ-
ent contractility (Haller) and independent irritability (Ber-
nard). By the former term we mean that the shortening of the
muscle is due to active processes developed in its own tissue,
by the latter we mean that the muscular tissue may be made
to enter into contraction by artificial stimuli applied directly
to its own substance. This latter property cannot be said to
hold for all the tissues. Whether a nerve cell or a gland cell
may be made to enter into its specific form of activity by the
direct application of an artificial stimulus is still an undetermined
question.

* See Foster's "History of Physiology," p. 287.

f "Lemons sur les effets des substances toxiques et medicamenteuses,"
1857, pp. 238 et seq.

24

THE PHYSIOLOGY OF MUSCLE AND NERVE.

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 mechani-

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 cod 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.

cal 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, how-
ever, only the last form of stimulus is found to be convenient. The

Fig. 7. — Schema of induction apparatus, (Lombard.) b represents 'lie galvanic
' connected by wires to the primary coil, A. On the course of one of these wires

is a key (A) to make and break the current, B shows the principle of the secondary
coil, and the connection of its two ends with the nerve of a nerve-muscle preparation.
When the battery current is closed or made in A, a brief current of high intensitj is
induced in H. This is known as the making or cloBmg shock. When the battery current

w broken in A, < econd brief induction current i arou ed in B,
breaking or opening shock.

This is known as the

mechanical and thermal stimuli cannol be well applied without at
t Ik- same t ime injuring I he muscle subsl ance, and I he same is prob-
ably true of chemical stimuli, which possess the disadvantage, more-
over, of iioi exciting simultaneously the differenl fibres of which
the mu cle i composed. Electrical stimuli, on the contrary, are

THE PHENOMENON OF CONTRACTION. 25

applied easily, are readily controlled as regards their intensity, and
affect all the fibers simultaneously, thus giving a co-ordinated
contraction of the entire bundle, as is the case with the normal
stimulus. For electrical stimulation we may use the galvanic
current taken directly from the battery, or the induced or so-called
faradic current obtained from an induction coil. Under most
conditions the latter is more convenient, since it gives brief shocks,
the strength and number of which can be controlled readily. The
form in which this instrument is used in experimental work in
physiology we owe to du Bois-Reymond (1849-); hence it is
frequently known as the du Bois-Reymond induction coil. Experi-
mental physiology owes a great deal to this simple and serviceable
instrument. A figure and brief description of the apparatus is
appended (Figs. 6 and 7).

Simple Contraction of Muscle. — Experiments may be made
upon the muscles of various animals, but ordinarily in physiolog-
ical 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 a
general idea of the range of rapidity of contraction:

DURATION OF A SIMPLE MUSCULAR CONTRACTION.

Insect 0.003 sec.

Rabbit (Marey) 0.070 "

Frog 0.100 "

Terrapin 1.000 "

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

The involuntary muscle (mammal) 10.00

Foot muscle of slugf (Ariolimax) 20.00

The duration of the simple contraction varies considerably
in the muscles of different parts of the same animal. Thus,
according to Cash, the hyoglossal muscle in the frog requires
0.205 to 0.3 second, while the gastrocnemius takes 0.12 second;
in the tortoise the pectoralis major requires 1.8 seconds, the
omohyoid only 0.55 second; in the rabbit the soleus (a red

* Cash, "Archiv f. Anat. u. Physiol.," 1880, suppl. volume, p. 147.
t Carlson, "American Journal of Pysiology," 10, 418, 1904.

2o THE PHYSIOLOGY OF MUSCLE AND NERVE.

muscle) requires 1 second, the gastrocnemius (a pale muscle)
0.2."> second. On examining into these differences it may lie
shown that the variations bear a relation to the special functions
of the muscles. Rapidity of contraction and maintenance of
contraction are two properties which are capable of being altered
by the processes of adaptation, either together or independently,
to suit the needs of the organism. The distribution of the pale
and red muscles in such an animal as the rabbit bears out this
idea. It will be remembered also that these two varieties show
a difference in histological structure (p. 19).

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.

Fig. 8. — Curve of simple muscular contraction.

will indicate ao\ only the full extent of the shortening, but also
the amount of shortening or subsequent relaxation at any moment

during the entire period. To obtain such records from the rapidly

contracting frog's muscle ii is evidenl that the recording surface
nni-i move with considerable rapidity and with a uniform velocity.
A curve of this kind is represented in Fig. s. C represents

the axis Of abscissas and gives the factor of time. A vertical
Ordinate erected at any point on C .uives the extent of shortening
at that moment. I'.clou the curve of the muscle is the record
of the vibration- of a tuning fork giving 100 doulile vibrations

econd; thai i-. the di tance from cresl t<> crest represents an

interval of ,,',,, of a second. Three principal facts are brought out

by an analysis of the curve: b The latent period. By this is

THE PHENOMENON OF CONTRACTION. 27

meant that the muscle does not begin to shorten until a certain
time after the stimulus is applied. On the curve the stimulus
enters the muscle at S, and the distance between this point and the
beginning of the rise of the curve, interpreted in time, is the latent
period. II. The phase of shortening, which has a definite course
and at its end immediately passes into III., the phase of relaxation.

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

The Phases of Shortening and of Relaxation. — In the normal
frog's muscle the phase of shortening for a simple contraction occu-
pies about 0.04 second, while the relaxation may be a trifle longer,
0.05 sec. In muscles whose duration of contraction differs from
that of the frog the time values for the shortening and the relaxation
exhibit corresponding differences. As we have seen, the appearance
of the muscle fiber when viewed by polarized light indicates that
during the phase of shortening some of the material in the light
bands is imbibed into the substance composing the dim bands.
The process is evidently a reversible one; during the phase of
relaxation the absorbed or imbibed material passes back to the
light band. Many conditions, some of which will be described
below, alter the time necessary for these processes, that is, the
duration of the simple contraction. It is noteworthy that it is
the phase of relaxation which may be most easily prolonged or
shortened by varying conditions.

Isotonic and Isometric Contractions. — In the method of recording the
shortening of the muscle that is described above the muscle is supposed to con-
tract against a constant load which it can lift. Such a contraction is spoken
of as an isotonic contraction. If the muscle is allowed to contract against

28 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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
siidik) until maximum contractions were obtained. The stimuli were then decreased ID
strength and the contractions fell off through a series of gradually decreasing submaximal
contractions. '1 ho 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 greal 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 aiinimal are designated as sub-
minimal. If one increases gradually the intensity of the electrical
current used ae a stimulus without altering its duration, beginning
with a stimulus Bufficienl to cause a minimal contraction, the result-
ing contraction! increase proportionally up to a certain maximum
beyond which furl her increase of si imulus, ol her condit ions remain-
ing the same, causes no greater extent of shortening. Contrac-
tion! between the minimal and the maximal are designated as
submaximal.* (Sei I ig. 9.)

* Kick, "i ntersuchungen liber elektrische Nfervenreizung," Braun-

• ig, i sm.

THE PHENOMENON OF CONTRACTION.

29

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

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

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

30

THE PHYSIOLOGY OF MUSCLE AND .NERVE.

more and more depressed. The point of optimum effect is not iden-
tical for the different tissues of the same animal, much less so for
those of different animals, but the fart may be emphasized that in
no case do protoplasmic tissues withstand a very high temperature.

rr

g' 16'

Fig. 11. — Curve to show the effect of a
temperature from 0° C. to 38° C. upon
the height of con tract ion of frog's muscle.
The fir.-t maximum at 9° C, the second at
28° C. Beyond 38° C. the muscle lost its
irritability and went into rigor mortis.

§>

Ctx

S° 10' 15' 10- 2J- JO- Jtf- 3f jr ir

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 ordinate.?.

Functional activity is lost usually at -l.r)°(\ or below. The duration

of the contraction shows usually in frogs' muscles a simple relation-
ship to the changes of temperature. At low temperatures, 4 or 5° (■.,
the contractions are enormously prolonged, particularly in the phase
of relaxation ; bu1 as the temperature is raised the duration of the
contractions diminishes, a1 first rapidly, then more slowly, to a
certain point aboul 18° to 20° ( '.. beyond \\ hich LI remains more or
constanl in spite of the changes in extent, of shortening. The
relationship between duration of contraction and temperature may
therefore be expre ed by such a curve as is shown in l"\£. 12, in
which the heights of the ordinates represent the relative durations
ot the contractions. Muscles from different frogs show considerable
minor variations in their reactions to changes in temperature, and
we may Buppose that these variations depend upon differences in

THE PHENOMENON OP CONTRACTION. 31

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

Pig. 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.
26, 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
action of glycerin. We have in such substances reagents that affect
one phase of the contraction process without materially influencing
the other. As regards the veratrin effect, it becomes less and less
marked if the muscle is made to give repeated contractions, but
reappears after a suitable period of rest. The peculiar action of
the veratrin is, threrefore, antagonized seemingty by the chemical
products formed during contraction.

* "Journal de la physiol. et de la path, generate," 1899.

32

THE PHYSIOLOGY OF MUSCLE AND NERVE.

Contracture. — The prolonged relaxation that is so character-
istic of the veratrinized muscles may be observed in frog's muscle
under other circumstances, and is described usually as a con-

>.J3

01 £

tea
"E-S

C w

dit ion of contracture. By contracture we mean a slate of
maintained contraction or, Looking al it from the other point of

view, a state of retarded relaxation.

THE PHENOMENON OF CONTRACTION. 33

This condition is often exhibited in a most interesting way when a muscle
is repeatedly stimulated. In some cases it develops at the beginning of a
series of contractions, as is represented in Fig. 14, which pictures the phenome-
non as it was first described.* In other cases it appears later on in the curve,

3 ■B'SlSS!

fa WMiXuW'Wm

! WmmMm^

THB

pw$IK

",'■. '''A, •*•■■' ■■■;' ■

:Smmm»

JSrTOSSBMlllMBUi

jhk^^^fll

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.

preceding or following the development of the state of fatigue. Whenever
it occurs the effect is to hold the muscle in a state of maintained contraction,
on which is superposed the series of quick contractions and relaxations due
to the separate stimuli. When the condition develops early in the functional
activity of the muscle (Fig. 14) further activity usually causes it to disappear,

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.

and the condition of the muscle as a mechanism for prompt shortening and
relaxation is improved. We have in this fact apparently an indication of
one way in which the "warming up" exercise before athletic contests may be
of value. When the contraction appears late in the series of contractions

* Tiegel, "Pfliiger's Archivfur die gesammte Physiologie, " etc., 13, 71, 1876.
3

34 THE PHYSIOLOGY OF MUSCLE AND NERVE.

it is usually permanent, that is to say, it wears off only as the muscle relaxes
slowly from fatigue. Toward the end of such a series the muscle is often
practically in a state of continuous contraction, a condition which would
nullify its ordinary use in locomotion. It seems possible that certain
conditions of tonic spasm or cramps which occur during life may involve this
process, for example, the temporary cram]) that sometimes attacks a player
in athletic games, or the curious spasmodic condition known as intermittent
claudication, in which, apparently as a result of insufficient circulation, the
muscles on exercise are thrown into a state of tonic contraction. From the
physiological standpoint the phenomenon of contracture when compared
with that of the simple contraction indicates the possibility that two different
contraction processes may take place in muscle, one involving the state of
tone and. therefore, the length and hardness of the muscle, the other con-
trolling the movements proper. This suggestion has been made by a number
of authors* on various grounds, and is of interest as indicating a point of
view different from that usually held in regard to muscular contraction.

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. According to Lee,f
the " treppe " in muscle is due to an initial augmenting effect of
the chemical products formed during contraction.

.'). ( 'on Intel lire. This phenomenon of maintained contraction
Ij.i- been described above. In frog's muscles Stimulated repeat-
edly it makes its appearance, as a rule, sooner or Later in llie
Series of contractions; but there is a curious amount of variation

in the muscles of different individuals in this respect.

• See especially [Texkull, "Zentralblatl f. Physiologie," L908, 22, 33; also
Guenther, "American Journal of Physiology," L905, L4, 7.'!.
t Bee "American Journal of Physiology," 1907, L8, 267.

THE PHENOMENON OF CONTRACTION. 35

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 and in Chapter II. The
curve obtained in an experiment of this kind illustrates in a
striking way one of the general characteristics of living matter,
namely, that every effective stimulus applied to it leaves a record,
so to speak. The muscle in this case is in a changed condition
after each stimulus, as is indicated by the difference in its re-
sponse to the succeeding stimulus. While it cannot be said that
a similar effect has been shown in all tissues, still the evidence in
general points that way, and some of the complicated phenomena
exhibited by living matter, such as memory, habits, immunity,
etc., are referable in the long run to this underlying peculiarity.

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

The Contraction Wave. — Under ordinary conditions the fibers
of a muscle when stimulated contract simultaneously or nearly so,
and the whole extent of the muscle is practically in the same phase
of contraction at a given instant. It is comparatively easy to
show, however, that the process of contraction spreads over the
fibers, from the point stimulated, in the form of a wave which moves
with a definite velocity. In a long muscle with parallel fibers one
may prove, by proper recording apparatus, that if the muscle is
stimulated at one end a point near this end enters into contraction
before a point farther off. Knowing the difference in time between
the appearance of the contraction at the two points and the dis-
tance apart of the latter, 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. Knowing the time it takes this wave to pass a given
point (d) and its velocity (v), its entire length is given by the
formula I = 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 (3000X0.1=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

36 THE PHYSIOLOGY OF MUSCLE AND NERVE.

two or more motor plates, giving two or more points of stimula-
tion. 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 the muscle of a dying or recently dead animal by localized
mechanical stimulation, as by drawing a blunt instrument e. </., the handle
of a scalpel — across the belly of the muscle. The point thus stimulated stands
out as a wheal, owing to the idiomuscular contraction.

The Energy Liberated in the Contraction. — When a muscle
contracts, energy is, as we say, liberated in several forms, and
can be measured quantitatively. First there is a production of
heat, which is indicated by a rise in temperature of the muscle.
According to 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-
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
caloric The fact that muscular exercise increases the produc-
tion of heat in the body is a matter of general observal ion. Second.
Some electrical energy is developed •luring the contraction. The
means of detecting and measuring this energy will be described
in a subsequent chapter. Considered quantitatively, the amount
us -mall. Third. Work is done if the muscle; is allowed to shorten

during the contraction. By work is meant external or useful
worl: thai IS, the muscle lifts a weight or overcomes an opposing

ince. [f a muscle contracts against a weight too heavy

THE PHENOMENON OF CONTRACTION. 37

to be lifted or a resistance too strong to be overcome it does no
external work, although, of course, much energy is liberated as
heat or, as it is sometimes called, internal work. The work done
by a muscle during contraction is measured in the usual mechanical
units, by the product of the load into the lift. That is, if a muscle
lifts a weight of 40 grams to a height of 10 millimeters, the work
done is 40 X 10 = 400 gram-millimeters, or 0.4 grammeter. We
can in calculations convert external work into heat or internal
work by making use of the ascertained mechanical equivalent of
heat, according to which 1 calorie = 426.5 grammeters of work.
The work, 0.4 grammeter, supposed to be done in the above
experiment would be equivalent, therefore, to 0.4 + 426, 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. The chemical changes occurring in the
muscle during contraction are complex and not entirely understood,
but the significant ones from our present standpoint are oxidations
which destroy some of the material in the muscle, with the forma-
tion of carbon dioxid and water and the liberation of heat. It is
a matter of interest to inquire as to the proportion of the total
heat energy which may be converted into useful work and the
conditions under which the optimum amount of work may be
realized. Regarded from this standpoint, the muscle may be
considered as a piece of machinery comparable, let us say, to a gas
engine. In the latter the heat generated by the explosive chemical
change is converted partially into external work by a properly
adapted mechanism — and in a well-constructed engine as much
as 15 to 25 per cent, of the total energy may be obtained as work.
In the muscle there is also a mechanism of some kind, not as yet
understood, by means of which a part of the energy liberated
may be converted into work. Experiments made by Fick with
frogs' muscles indicate that the proportion of the total energy
which under optimum conditions may be utilized as work is, in
round numbers, from 25 to 30 per cent. Chauveau,* in experiments
made upon the elevator of the upper lip in the horse, found a pro-
portion of only 12 to 15 per cent. The last observer points out
that this proportion must vary greatly for different muscles and
for muscles in different animals, while for the same muscle it will
* Chauveau, " Le travail musculaire, etc.," Paris, 1891.

38 THE PHYSIOLOGY OF MUSCLE AND NERVE.

vary with the extent and duration of the contractions and other
conditions. From experiments made upon dogs in which a meas-
ured amount of work was done and in which the energy changes
were estimated from the oxygen absorbed and carbon dioxid
eliminated. Zuntz * calculates that somewhat more than ^ of the
total chemical energy liberated in the muscles may be applied to
external work, the other § taking the form of heat. Similar ex-
periments made by the same observer f 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 performed 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, and
Zuntz has shown, in the work previously referred to, that this
efficiency may be increased by training; that is, by the repeated
use of a group of muscles a more economical application may be
made of the liberated heat in the performance of work.

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

Work

Dune in (I'nnii millimeters.

/,(»/// iii Qrams.

Lift in. \l ill i iiu hri:.

Load Lift,

5

27.6

L38.0

15

25. 1

376.5

25

11.45

286.25

:;:,

<;.:*

22().f)

* Zuntz, "Archiv f. d. gesammte Phjrsiologie," 'is, 191, L897.

t Zutit/. and Bchumberg, " Physiologic dee Marsches," Berlin, 1901.

THE PHENOMENON OF CONTRACTION.

39

A series of experiments of this kind furnishes data for con-
structing a curve of work by plotting off along the abscissa at equal

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.

IBBBBKBBI IIBHBHBBBBI

BHHnir""-—
ssnsss

BBBBBBBflfll

■nnenam
iflMjHiiBiie

■■—■■■■■■■
■■■■■■■■«r
bbbbbbbbbbi

■■■■■■■■■■!

BBSIlBflflflBBBBBBBBB
BBBBBBBBBflflBBBBHB
BBBBBgBBBflBBBBBHB
BBBBBBBBBBBBBBBBB
nBBHflBBKBBBBBBBBfl

BBflflBBBKBBBflflBB!

BBBBP BBHBBBBBBB

... 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.

intervals the equal increments in load and erecting over each load
an ordinate showing the proportional amount of work done. The

40 THE PHYSIOLOGY OF MUSCLE AXD NERVE.

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 = LH, 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
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 6.2 1 kilograms. Taken as a whole, the human muscle is a better
machine for work, but it seems possible, although exact figures are
lacking, thai 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 conl Taction as
long :i- ilf stimuli are sent, in or until it loses its irritability from

the effecl of fatigue. A contraction of this character is described
compound contraction or tetanus. If the stimuli follow each

THE PHENOMENON OF CONTRACTION.

41

other with sufficient rapidity the muscle shows no external sign of
relaxation in the intervals between stimuli, and if its contractions

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.

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,

42

THE PHYSIOLOGY OF MUSCLE AND XERYE.

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

jifOple- iTiuscie contract ion_

and Sii*niT\aiior{

Fiic. 20.— Summation of two successive contractions. Curve 1 shows a simple con-
i raction ;lw<- to ■■> single stimulu . the latent period being indicated at the beginning of the
contraction. Curve - show- th ti in due to two succeeding stimuli.

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 t he firs! conl racl ion is maximal, I tie muscle will shorten
si ill farther; the firsl and second contractions are summated, giv-
ing .-i total shortening greater than can be obtained by a single stim-
ulus (see Fig. 20). The extenl of the summation in such cases
varie ■'. 1 ' h b n umbel- of conditions, such as the intervals bel ween the

THE PHENOMENON OF CONTRACTION. 43

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
at proper intervals, a still further summation occurs. In this way
the total extent of shortening in a muscle completely tetanized may
be several times as great as that of a single maximal contraction.

The Discontinuous Character of the Tetanic Contraction
— The Muscle-tone. — In complete tetanus the muscle seems to
be in a condition of continuous uniform contraction; the re-
corded curve shows no sign of relaxation between stimuli and no
external indication, in fact, that the separate stimuli do more than
maintain a state of uniform contraction. It can be shown, how-
ever, that in reality each stimulus has its own effect, and that the
chemical changes underlying the phenomenon of contraction
form an interrupted series corresponding, within limits, to the
series of stimuli sent in. The clearest proof for this belief
is found in the electrical changes that result from each stimulus,
and the facts relating to this side of the question will be stated
subsequently in the chapter on The Electrical Phenomena
of Muscle and Nerve. Another proof is found in the phenome-
non 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 rhuscle the rate of which corresponds with that of the
stimulation. The series of electrical changes corresponding with the
series of stimuli sent in may be made audible by applying a telephone
to the muscle. Making use of this method, Wedenskif has shown
that the ability of the muscle to respond isorhythmically to the
rate of stimulation is limited. In frog's muscle the pitch of the

* Von Kries, "Archiv fur Physiologie," 1888, p. 537.
t Wedenski, " Du rhythme musculaire dans la contraction normale,"
"Archives de physiologie," 1891, p. 58.

44 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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
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 emit met ions, 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 indie., led in the accompanying diagram (Fig. 21). If in ordi-
nary voluntary movements the muscular contractions are tetanic,

we imi-i 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,

THE PHENOMENON OF CONTRACTION.

45

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.

in various ways to ascertain whether there is any objective indi-
cation 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 graphically
by levers or tambours. The records thus obtained show that our
usual contractions are not entirely complete tetani — that is, there
is an indication in some part
of the curve of the single con-
tractions that are being fused.
According to most observers,*
these records show that our
normal contractions are com-
pounded of single contrac-
tions 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 was formerly assumed that this note
does not represent the actual rate of stimulation of the muscle,
since the number is higher than that obtained by some other
methods. A rate of 35 to 40 vibrations per second corresponds
to the resonance tone of the external ear and it is possible that the
real muscle tone may have a lower pitch, and that the ear picks
out by its own resonance one of the overtones. Helmholtz made
use of a simple and direct method to determine this point. He
utilized the principle 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 con-
tractions and that the tone that is heard, 40 vibrations per
second, represents the first overtone. The whole subject has
been reinvestigated more recently by employing the "string
galvanometer" (see p. 100) to record the number of electrical
*Horsley and Schafer, "Journal of Physiology," 7, 96, 1886.

46 THE PHYSIOLOGY OF MUSCLE AND NERVE.

variations occurring during a voluntary contraction. Since
each separate stimulus to a muscle causes a distinct electrical
variation, it is evident that if we can record the number of such
variations per second we shall have almost conclusive evidence
as regards the number of simple contractions which enter into
the production of voluntary tetanus. The string galvanometer
lends itself to this purpose better than any form of electrometer
yet devised, and Piper,* by the use of this instrument, finds that
in voluntary contractions of the flexor muscles of the arms or
fingers the number of electrical variations follow at the rate of

47 to 50 per second. Increase in strength of contraction in

,

•U-.

Wmi. m

Fig. 22. — I'he upper curve shows the vibrations of the "'string" of the string gal-
vanometer during voluntary contraction of the flexor of the fingers. Each vibration is
due to an electrical oscillation in the muscle (action current). These oscillations occur at
the rate of 50 per second, as may be seen by reference to the lower curve, the breaks in which
indicate fifths of a second. This fact would indicate, therefore, that in the voluntary con-
traction we have a tetanus composed of single contractions following at the rate of 50 per
second. — (From Piper.)

these muscles causes no change in rate, although a corresponding
variation in the intensity of the electrical changes is observed.
When different muscles are studied by this method, quite a
marked difference in rate is obtained. Piper reports such
observations as the following: M. deltoideus, 58 to 62; M. gas-
trocnemius and M. tibialis anterior, 42 to 44; M. quadriceps
femoris, 38 to 41; M. masseter, 88 to 100, and M. temporalis, SO
to 86. Assuming that these figures represent the rate of dis-
charge of nerve impulses per second by the nerve cells from
which arise the motor fibers to the muscles named, it is evident
that the various spinal and cranial motor centers may possess
quite widely different rhythms, although for each particular
center the rate is more or less fixed. Among the motor centers
thus far studied it will be noted that the cells of the N. trigeminus
possess the highest rate of discharge. There lias been much
discussion as to whether or not we can obtain simple as well as

* Piper, PflOger'a "Archiv f. d. ges Physiologic," L907, 119,301. Also
"Zeitachrifl f. Biologic," L908, 60, 393, and 504.

THE PHENOMENON OF CONTRACTION.

47

compound contractions by voluntary stimulation of our muscles.
It has been pointed out that in very rapid contractions, such as
occur in the trilling movements of the fingers in playing the
piano, the duration of the separate contractions is so brief as to
suggest that they may be of the order of simple contractions.
Direct investigation of such movements by the older method
of recording with levers (von Kries) or by the newer method of
photographing the electrical oscillations shows, on the contrary,
that even the shortest possible voluntary contractions are brief
tetani made up of a short lasting series of contractions fused
together. In all probability, therefore, our motor centers, when-
ever they are stimulated by a so-called act of the will, discharge
rhythmically a series of nerve impulses. As we shall see later,
it is possible that certain of these centers, when stimulated
reflexly, may discharge a single nerve impulse and thus arouse
a simple muscular contraction (see Knee-kick).

Fig. 23. — 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.

The Ergograph. — Voluntary contractions in man may be re-
corded in a great many ways, but Mosso has devised a special in-
strument for this purpose, known as the ergograph. It has been
much used in quantitative investigations upon muscular work
and the conditions influencing it. The apparatus is shown and
described in Fig. 23. The person experimented upon makes a
series of short contractions of the flexor muscle of the middle
finger, thereby lifting a known weight to a definite height
which is recorded upon a drum. In a set of experiments the

48

THE PHYSIOLOGY OF MUSCLE AND NERVE.

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. 24.
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

1 ig, _' t . — Norm al fatigue curve of the flexors of the middle finger of right hand.
'.i kilograms, contractions at intervals of two seconds. — (Matjgiora.)

Weight

obtained, some of which will be referred to specifically.* It should
be borne in mind, however, thai the ergograph in this form does
not enable ufi to compute the total work that the muscle is capable
of performing. It is obvious thai when the poinl of complete
fatigue is reached, as Illustrated in the record, Fig. 23, the muscle is
still capable of doing work, thai 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

*Mosso, " \rrliivc-. italiennee de biologic," L3, 187, L890; :ils<> "Archivf.
JM.y aologie," 1899, p. L91, 342. Lombard, " Journal of Physiology," 13, I, 1892.

f Franz, " American Journal of Physiology," 4, .'i is, moo; ulso Hough,
(bid., ■',. 240, 1901.

THE PHENOMENON OF CONTRACTION. 49

spring ergograph every muscular contraction is recorded and the
entire work done may be calculated, it also possesses certain theo-
retical and practical disadvantages, for a discussion of which refer-
ence must be made to the authors quoted.

The weight ergograph has, so far at least, given us the most sug-
gestive results. Among these the following may be mentioned:
(1) If a sufficient interval is allowed between contractions no fatigue
is apparent. With a load of 6 kilograms, for instance, the flexor
muscle (M. flexor digitorum sublimis) showed no fatigue when a
rest of 10 seconds was given between contractions. (2) After
complete fatigue with a given load a very long interval (two
hours) is necessary for the muscle to make a complete recovery
and give a second record as extensive as the first. (3) After
complete fatigue efforts to still further contract the muscle
greatly prolong this period of complete recovery, — a fact that
demonstrates the injurious effect of straining a fatigued muscle.
(4) The power of a muscle to do work is diminished by conditions
that depress the general nutritive state of the body or the local
nutrition of the muscle used; for instance, by loss of sleep,
hunger, mental activity, anemia of the muscle, etc. (5) On the
contrary, improved circulation in the muscle — produced by
massage, for example — 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 con-
nection with the use of the ergograph calls for a few words of special mention.
Mosso found that if a muscle — e. g., the flexor digitorum sublimis — is stimu-
lated directly by the electrical current and its contractions are recorded by
the ergograph, it will give a curve similar to that figured above for the volun-
tary contractions, except that the contractions are not so extensive. Under
these conditions the muscle, when completely fatigued to electrical stimula-
tion, will respond to voluntary stimulation from the nerve centers. It
seems likely, as suggested by Hough, that this result is due mainly to the
fact that the electrical current cannot be applied to a muscle in its normal
position so as to excite uniformly all the constituent muscle fibers, although
it is also possible that what we call the normal or voluntary stimulus is more
effective or, to use a physiological term, more adequate to the muscle fibers
than the electrical shock. On the other hand, after fatigue from a series
of voluntary contractions it has been observed that the muscle will still

* Schumberg, "Archiv f. Physiol.," 1899, suppl. volume, p. 289.
4

50 THE PHYSIOLOGY OF MUSCLE AND NERVE.

give contractions If stimulated directly by electricity. This fact has been
interpreted to mean that, in the neuromuscular complex involved in a mus-
cular contraction — namely, motor nerve cell, motor nerve fiber, and muscle
fiber — the first named fatigues most easily, and that the ordinary fatigue
curve obtained from the ergograph does not represent pure muscle fatigue,
but fatigue of the neuromuscular apparatus as a whole, the point of complete
fatigue being reached in the neural component of the mechanism before
the muscle itself loses its power of contraction. This interpretation, however,
is not entirely certain. Wedenski has called attention to the fact that in
the neuromuscular apparatus the motor end-plate is a sensitive link in the
chain, and that, when the nerve is stimulated strongly with artificial stimuli
at least, this structure falls into a condition in which it fails to conduct the
nerve impulse to the muscle. It may be, therefore, that in sustained volun-
tary contractions the end-plate fails first, and thus is directly responsible
for the failure of the apparatus to perform further work. That the fatigue in
ordinary voluntary contractions affects the muscles before the motor nerve
centers is indicated by the experiments of Storey.* Making use of a weight
ergograph and experimenting tipon the abductor indicis he found that after
fatiguing this muscle to voluntary contractions with a certain weight, re-
moval of the weight enabled the individual to make contractions as high and
as rapid as before the fatigue. On the other hand, if after removing the
weight the muscle was stimulated electrically the contractions were lower and
slower than before the fatigue. So far as our knowledge goes, therefore,
fatigue as it appears in sustained voluntary contractions is due probably
primarily to a loss of irritability in the muscle and in the motor end-plates.
The motor nerve fibers do not fatigue, and as regards the motor nerve centers
it is not possible as yet to say what may be their relative susceptibility to
fatigue.

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

Muscle Tonus, — In addition to the conditions of contraction
and of relaxation the living muscle exhibits the phenomenon of
"tone." By muscle tone we mean a state of continuous shortening
or contraction which under normal conditions is slight in extent
and varies from time to time. This condition is dependent upon
the connection of the muscle with the nerve centers, and we may
assume that under normal circumstances the motor centers are
continually discharging subminimal nerve impulses into the muscles
which cause chemical changes similar in kind to those set up by
an ordinary voluntary effort, but less in degree; the result being
thai the muscles enter into a, slate of contraction which, while

slight in exlent , is more or less continuous. According lo this view,

the whole neuromuscular apparatus is in a condition of tonic ac-
tivity, and this slide may be referred in Hie long run to the con-
t inual inflow of sensory impulses into the centra] nervous system.

That is, I lie tonus <>f the skeletal muscles is not. only dependent
* Story, "American Journal of Physiology," L903, 8, '■'<-^>.

THE PHENOMENON OF CONTRACTION. 51

on the nerve centers (neurogenic), but is in reality an example
of reflex stimulation of these centers. The tone of any particular
muscle or group of muscles may be destroyed, therefore, by cut-
ting its motor nerve, or less completely by severing the sensory
paths from the same region. If, for instance, 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. The underlying cause of tone is poorly
understood. It may be, as implied above, simply a condition of
subdued tetanus due to a constantly acting series of sub-minimal
stimuli, or it may be an order of contraction quite different
from the usual visible movements; that is to say, the shortening
in the case of tonus may be due to a substance or mechanism
in the muscle-fibers different from that which subserves the
ordinary quick movements which we designate as contractions.
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 muscle
tone varies with many conditions, the most important of which,
perhaps, are external temperature and mental activity. With
regard to the first, it is known that, as the external temperature
falls and the skin becomes chilled, the sensory stimulation thus
produced acts upon the nerve centers and leads to an increased
discharge along the motor paths to the muscle. The tone of the
muscles increases and may pass into the visible movements of
shivering. By this means the production of heat within the body
is increased automatically. Similarly, an increase in mental
activity, so-called mental concentration, whether of an emotional
or an intellectual kind, leads, by its effect on the spinal motor
centers, to a state of greater muscle tonus, the increased muscular
tension being, indeed, visible to our eyes.

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

52 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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

Pig. 25. — Curve of normal rigor mortis, gastrocnemius muscle of frog. The curve
was obtained upon a kymographion making one revolution in eight days. The murks on
the line below the curve indicate interval, of six hours. It will be seen that the shortening
required eighteen hours, the relaxation about seventy-two hours.

rigor, which in this case is of a more feeble character and shorter
duration. The development of rigor is very much hastened by many
drugs that bring about the rapid death of the muscle substance, such
as veratrin, hydrocyanic acid, caffein, and chloroform. A frog's mus-
cle exposed to chloroform vapor goes into rigor at once and shortens
to a remarkable extent. Rigor is said also to occur more rapidly
in a muscle si ill connected with the central nervous system than
in one whose molor nerve has been severed. After a certain
interval, which also varies greatly,— Iron i one to six days in human
beings,— the rigidity passes off, the muscles again become soft ;nid
flexible; this phenomenon is known as the release from rigor. In
the cold-blooded animals the development of rigor is very much

slower than in warm-blooded animals, Upon an isolated frog's

muscle the most striking fact regarding rigor mortis is the shortening
that the muscle undergoes. This shortening or contraction comes
on lowly, as is shown in the accompanying figure, bul in extent
ii exceed the simple contraction obtainable from the living muscle
by mean- of a maxima] stimulus. This pari of the phenomenon
i . however, much less marked apparently in mammalian muscle,

THE PHENOMENON OF CONTRACTION. 53

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

* "American Journal of Physiology," 9, 374, 1903.
f Kiihne, " Archiv f. Physiologie," 1859, p. 788.
X Latimer, "American Journal of Physiology," 2, 29, 1899.
§ Brodie and Richardson, "Philosophical Trans., Roy. Soc," London,
1899, 191, p. 127; also Inagaki, "Zeitschrift f. Biol.," 1906, 48, 313.
|| Vrooman, "Bio-chemical Journal," 1907, 2, 363.

54 THE PHYSIOLOGY OF MUSCLE AND NERVE.

that when a frog's muscle is gradually heated, only two really
distinct contractions are obtained, one at 39° C. (38° to 40°)
or slightly lower, and one at 50° C. (49° to 51°). Mammalian
muscle gives also two contractions when heated, one at 47° C.
(46° to 50°) and one at 62° C. (61° to 64°). In each of these
cases the second contraction is due to the action of heat on the
connective-tissue elements of the muscle. The first contraction is,
therefore, the one that is characteristic of the muscular substance
proper and the one that marks the occurrence of heat rigor.
At the tempertures stated, 39° C. for frog's muscle and 47° C.
for mammalian muscle, the viscous material within the sarco-
lemma coagulates. While the end result in this case, that is,
the coagulation, is the same as occurs in death rigor due to the
interruption of the normal blood-supply, nevertheless the causes
bringing about the coagulation are different and possibly the
properties of the coagulum formed may be different. Ordinary
death rigor passes off after a certain interval even if putrefactive
processes are excluded; the rigor from heat or from chloroform,
on the contrary, shows no release. With regard to the specific
cause of the coagulation of death rigor nothing final can be. said.
The interesting researches of Fletcher and Hopkins* indicate
that during the survival period between the loss of the normal
circulation and the appearance of rigor chemical changes are
going on in the living substance which result in the formation
and accumulation of lactic acid. When the process of production
of the lactic acid ceases, the muscle has lost its irritability and
then soon enters into the state of rigor. If during this survival
period the muscle is kept well supplied with oxygen no lactic
acid accumulates in the muscle, and when the muscle finally
loses its irritability no rigor occurs. These facts would seem to
implicate the lactic acid in some way in the process of clotting
and of rigor. Rigor of muscles may be caused, of course, by
other specific conditions which kill the muscle and bring on
coagulation of the muscle-substance; by the action of distilled
water, for example, the so-called water rigor, or by the action
of .in excess of calcium salts, calcium rigor.

PLAIN OR SMOOTH MUSCULAR TISSUE.

Occurrence and Innervation.- Plain or long striated mus-
cular ii 3Ue 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

* Fletcher and Bopkina, "journal of Phyaiology," 1907, 35, 247.

THE PHENOMENON OF CONTRACTION. 55

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.
26). 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
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

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

56 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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 (neurogenic tonus), but the muscle, when completely
isolated from the 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, after separation of its extrinsic nerves, depend
upon a property of the muscle itself (myogenic tonus) or upon
their intrinsic nerve cells. Most observers adopt the former

J id. 26. — Curve of simple contraction of plain muscle. The middle line is the time
record, marking intervals of a second. The lowermost line indicates at the break the mo-
ment of stimulation (short-lasting, tetanizing current). It will be seen that the latent period
between beginning of stimulation and beginning of contraction is equal to about three

seconds.

view. The importance of this property of tone in the plain
muscle tissues will be made fully apparent in the description
of the physiology of the organs of circulation and digestion.
Plain muscle may exhibit also the phenomenon of rhythmical
activity — that is, under proper conditions it may contract
and relax rhythmically like heart tissue.* Such movements
have been observed and studied upon the plain muscle of the ureter,
the bladder, the esophagus, stomach, and other portions of the
alimentary canal, the spleen, the blood-vessels, etc. This property
seems to be very unequally distributed among the different kinds

ol plain muscle found in the same or different, animals, but this

fact erves only to illustrate the point, already sufficiently empha-
sized, thai grouping one kind of tissue e. </., plain muscle— into

a common class does not signify that the properties of all the mem-
ber of I he group are idenl ical. The question as to how far the phe-

* Engelmann, "Archiv I', d. gea. Physiologic," 2, 243, L869. Stiles,
"Amer. Jour, of Physiologie," 5, 338, L901.

THE PHENOMENON OF CONTRACTION. 57

nomenon of rhythmical contraction is entirely muscular and how far
it depends upon intrinsic nerve cells is a complex one; the answer
will probably vary for different organs, and the subject will therefore
be considered in the organs as they are treated.

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

Ciliated Cells. — In the mammalian body the phenomenon of
contractility is exhibited not only by the well-defined muscular
tissue, but also by the leucocytes and especially by the cilia of the
ciliated epithelium. Epithelium with motile cilia is found lining
the mucous membrane of the air-passages in the trachea, larynx,
bronchi, and nose, in the lacrimal duct and sac, in the genital pas-
sages, uterus and Fallopian tubes and the tubules of the epididymis,
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
demonstrated to be motile in the frog, and according to an old
observation by Purkinje* the same is true for the mammalian
(sheep) embryo. So also in the neck of the uriniferous tubule
ciliated cells are said to occur, but whether they are motile or not has
not been demonstrated. In the internal ear and the olfactory mucous
membrane the so-called sense cells are also ciliated, but here at least
the cilia are probably not motile. Ordinarily each ciliated epithelial
cell carries a bunch of cilia, all of which contract together, but
motile protoplasmic prolongations of the cell may occur singly, as
is illustrated in the spermatozoa, for instance, and in many of the
protozoa and plant cells. In the lower forms of life cilia play
obviously a very important role in locomotion, the capture of food,
and respiration, and their form and manner of movement vary
greatly. The form of movement or manner of contraction was
formerly described under four heads, — the hook form, the pendular,
the undulatory or wave-like, and the funnel form or infundibulary.
With the exception of the spermatozoa, the cilia found in mam-
mals show the first form of contraction. The little processes are
contracted quickly in one direction, so as to take a hook shape,
* Purkinje, "Muller's Archiv," 1836.

5S THE PHYSIOLOGY OF MUSCLE AND NERVE.

and then relax more slowly, the relaxation taking several times
as long as the contraction. The whole movement is rhythmical and
very rapid. The cilia of the epithelium of the frog's pharynx and
esophagus, which have been the most frequently studied in the
higher animals, contract, according to Engelmann, at the rate
of 12 times per second. When a field of epithelium is observed
under the microscope the contractions pass over it in a definite
direction, but so rapidly that the eye is not able to analyze them;
one obtains the impression simply of a swiftly flowing current.
As the cilia begin to die, their movements become less rapid, and
the nature of the contractions and their progress from cell to cell
can be satisfactorily determined. In the mammalia the function
of the ciliated epithelium is supposed to be entirely mechanical,—
that is, they move along substances lying upon them. In the
oviducts they move or help to move the ovum toward the uterus,
and in this latter organ their motion is supposed to guide the
spermatozoa from the uterus toward the oviducts, — that is,
the resistance offered to the motile spermatozoa guides their move-
ments. So in the respiratory passages foreign particles of various
sorts, together with the secretion of the mucous glands, are moved
toward the mouth, the effect being to protect 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 adequately
explain one will doubtless be applicable to the other. Many
interesting facts have been established regarding ciliary move-
ments. The contractions of the cilia in any Riven field — the
trachea, for instance — follow in a definite sequence and are co-
ordinated. The waves of contraction progress in a definite direction.
This tact increases greatly the effectiveness of the cilia in per-
forming work. Thus, in spite of their extremely minute size, it
i- climated that an area of a square centimeter is capable of
moving a load of 336 gms. The contractions are automatic, —
thai is, the stimulus causing them is not dependent upon a con-
nection with the nervous system, hut upon processes arising within
the cell itself; the cilia of a single completely isolated cell may
continue to contract vigorously. The movement may continue
for -'vcial days after i fie 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 if 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.
'I he ciliary movement is affected by variations in temperature, and

THE PHENOMENON OF CONTRACTION. 59

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-
ogie," 1902, vol. ii, part n; Engelmann, article, "Cils vibratils," in Richet's
" Dictionnaire de Physiologie," vol. iii, 1898.

CHAPTER II.

THE CHEMICAL COMPOSITION OF MUSCLE AND THE

CHEMICAL CHANGES OF CONTRACTION AND

OF RIGOR MORTIS.

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

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

The constituents in addition to water that are known to occur
in muscle are very numerous indeed, and difficult to classify. They
may be grouped under the following heads: (1) Proteins. (2) Car-
bohydrates and fats. (3) Nitrogenous waste products. (4) Special
substances, such as lactic acid, inosite, phosphocarnic acid.
(5) Pigments. (6) Ferments. (7) Inorganic, suits. Very little
thai is positive can be stated regarding the physiological r61e
of most of these constituents, the interest, that attaches to them
at present being largely on the chemical side.

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

: Halliburton, "Journal of Physiology," 8, L33. 1888.

t Von Fiirth, "Arehiv f. exper. Path. u. Pharmakol." 36, 231, 1X05. See
also Halliburton, "Journal of Physiology," 8, L33, 1888; and Stewart and
Bollman, ibid , '24, 427, 1899.

60

THE CHEMISTRY OF MUSCLE. 61

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

Myosin. Myogen.

y y

Myosin fibrin. Soluble myogen fibrin.

t
Myogen fibrin.

It may be doubted whether these proteins exist as such in
the living muscle. Extracts must of necessity be made after
the muscle plasma is dead and probably coagulated. Myogen is
said not to occur in the muscles of the invertebrates. It should

62 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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

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

C6HI2()8-H20 = C„III0O5.

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

♦ Vincenl and Lewis, " Journal of Physiology," 26, 445, 1901 ; also "Zeit-
Bchrifl f. physiolog. Chemie," 34, 417, L901-2; Stewart and Sollman, loc. cit.;
Hofmeister's Beitrage," 1906, ix., 1.

THE CHEMISTRY OF MUSCLE. 63

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

Phosphocarnic Acid (Nucleon). — A peculiar substance containing phos-
phorus was discovered by Siegfried in the muscle extracts.* This substance
seems to resemble the proteins, but has a complex and peculiar structure, as
is shown by its split products when hydrolyzed by boiling with baryta water.
Under these conditions there are formed carbon dioxid, phosphoric acid,
a carbohydrate body, succinic and lactic acids, and a crystallizable nitrogen-
ous acid body which is designated as carnic acid (C10Hi5N5O;j). Siegfried
assumes that this latter substance is identical with one of the peptones
(antipeptone) formed during digestion, and conceives, therefore, that his
phosphocarnic acid is a complex substance built up from a peptone and a
phosphorus-containing compound. Compounds of simple proteins with
phosphorus-containing bodies (nucleic acids) are designated usually as
nucleins ; for this compound of a peptone with a phosphorus-containing com-
plex Siegfried suggests the name of nucleon. By the addition of ferric
chlorid the nucleon is precipitated readily from muscle extracts as an iron
compound, carniferrin, and under this name has come into the market as a
presumably efficient therapeutic preparation of iron. The discoverer of
nucleon has attributed to it a very great physiological importance, as a source
of energy to the muscle, and as an efficient means of transportation of iron,
calcium, potassium, and magnesium into the muscle substance, particularly
in such articles of diet as soups, bouillons, meat extracts, etc. It must be
stated, however, that there still remains doubt as to the chemical individuality
of the nucleon or the nucleons, their existence in normal muscle, and their
physiological role. The substance, whether a well-defined chemical individual
or not, is most interesting. Its properties are such as would aid in explaining
the occurrence of some of the known products of the chemical changes during
contraction; but obviously further investigation is 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 found in sour milk in that it ro-
tates the plane of polarized light to the right. The lactic acid in
sour milk is produced by bacterial fermentation, and is inactive to
polarized light, because it exists in racemic form ; that is, it con-
sists of equal amounts of the right-handed form which turns the
plane of polarization to the right and of the left-handed form
which turns it to the left. In the muscle the right-handed form

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

64 THE PHYSIOLOGY OF MUSCLE AND NERVE.

is found mainly or only, and this form, therefore, is frequently
designated as sarcolactic (or paralactic) acid. Recent work
indicates that in the perfectly resting muscle lactic acid is
present only in traces. The amount is greatly increased during
contraction or in the processes leading to rigor. This substance
would seem, therefore, to represent an intermediary product in
the metabolism of contraction and in the metabolism of dying.

The Nitrogenous Extractives (Nitrogenous Wastes). — Muscle
extracts contain numerous crystallizable nitrogenous substances
which are regarded as the end-products of the disassimilation
or catabolism of the living protein material of the muscle.
The number of these substances that have been found in traces or
weighable quantities is rather large. They have aroused great
interest because their structure throws some light on the nature
of protein catabolism. The one that occurs in largest amount is
creatin, C.lH!)N302, or methyl-guanidin-acetic acid, NHCNH,-
NCH3CH,COOH. Creatin may be present in amounts equal to
0.3 per cent, of the weight of the muscle. It has been supposed
to be 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 (see p. 820). 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 (Cr,H4N403),
xanthin (C5H4N402), hypoxanthin (C5H4N40), guanin (C5H5N56),
adenin (C6H5N5), 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 products are found in the
various meat extracts and meat juices used in dietetics. While
they possess no direct nutritive value, it seems probable (see
chapter on Gastric Digestion) that they may be very effective
indirectly by stimulating the secretion of the gastric glands.

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

property it takes part in the absorption of oxygen by the muscular
i issue.

Enzymes. — A number of unorganized ferments or enzymes

have been described by one observer or another. In this tissue
as in others the processes of nutrition seem to be connected with

THE CHEMISTRY OF MUSCLE. 65

the development of special enzymes. A proteolytic enzyme capable
of digesting proteins has been described by Brucke and others;
an amylolytic enzyme capable of converting the glycogen to sugar
by Nasse; a glycolytic enzyme capable of destroying the sugars
by 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. In frog's muscle the entire ash constitutes about 0.88
per cent, of the dry material of the muscle, and of this ash the
potassium and the phosphoric acid together make up more
than 80 per cent. (Urano). 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 surrounding 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 explained 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

* Hermann, " Untersuchungen liber den Stoffwechsel der Muskeln, etc.,"
Berlin, 1867.
5

66 THE PHYSIOLOGY OF MUSCLE AND NERVE.

off more carbon dioxide than a resting muscle when their contained
gases are extracted by a gas pump. This COa 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 stages the
changes in the muscle are equivalent in those of ordinary combus-
tion at high temperatures, the burning of wood or fats, for
instance. Moreover, the formation of the CO., 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. Fletcher* has discovered the
significant fact that the increased elimination of C02 following
upon contraction is clearly shown only when the muscle is well
supplied with oxygen. In the absence of oxygen contraction
may cause no increase in the CO, given off. This fact seems to
be in accord with prevalent ideas regarding the nature of the
muscular metabolism, according to which the chemical processes
take place in two stages. In the first the complex energy-
yielding material, sugar, for example, undergoes a splitting
process which results in the formation of intermediary products,
such as lactic acid. In the second stage these intermediary
products are oxidized, provided, as Fletcher points out, there
is an adequate supply of oxygen. Under normal conditions a
sufficient amount of oxygen is furnished by the circulating
blood, but under pathological conditions and in the excised
muscle the supply may not be adequate, and as a result the
intermediary products are not oxidized completely. Under
such conditions less heat is produced in the muscle, ami the
intermediary products accumulate in the tissue unless carried
off as such in the blood.

The fact that a muscle will continue to contract on stimulation even
when in an atmosphere tree from oxygen was formerly interpreted to mean
thai some oxygen had been stored previously by the muscle and thai con
tractions were possible only as long as this supply held out. Bui since it has
been Found that the contractions under these circumstances are not accom-
panied by an output of carbon di-oxid, this supposition lias been rendered
doubtful. It ha- been suggested, on the contrary, that t he energy for the
contraction* in these cases may be obtained from other than oxidative changes,

for example, from the small amount of heat-energy liberated in the splitting
of BUgar into lad ic acid.

DUapp arance of the Glycogen. — An equally positive chemical
change in the muscle during contraction is the disappearance of its
emit ained glycogen. 8a1 isfactory proof has been furnished I ha1 I lie
amounl of glycogen in a muscle disappears more or less in propor-
tion to the extent and dn ration of I he con I ractions, ami (hat after
prolonged muscular activity, especially in the starving animal, Hie

♦ Fletcher, •'.Journal of Physiology," L902, 28, 474.

THE CHEMISTRY OP MUSCLE. 67

supply may be exhausted entirely. In what way the glycogen is
consumed is not completely known; the matter is discussed in the
section on Nutrition. The most probable view is that the glycogen
is first converted to sugar (dextrose) by the action of an amylolytic
enzyme, and the sugar in turn is destroyed by the serial action of
several enzymes. The first step, probably, is a conversion to lactic
acid. (C6H120,; = 2C3H603), and the lactic acid then undergoes
oxidation, with the production of C02 and H20, under the influence
of an oxidizing enzyme, either directly or after conversion to still
lower members of the fatty acid series (acetic or formic acid).
It is in the last step, that of oxidation, that most of the heat
energy is given off. 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 absolutely
necessary for the chemical changes of contraction. It is stated
that the muscle will continue to contract after all its glycogen is
used up*; still it must be borne in mind that the using up of the
local store of glycogen does not mean that all the sugar supply
of the body is consumed. After the most prolonged starvation
the blood contains its normal supply of sugar, and we can only
suppose that this sugar comes from the material of the body
itself, probably from its proteins, and it remains quite possible
that a constant supply of sugar from some source is necessary to
the chemical changes that occur in normal contractions.

The Formation of Lactic Acid. — The lactic acid that is present
in the muscle is believed to be increased in quantity by muscular
activity. Attention was first called to this point by du Bois-
Reymond, who showed that the reaction of the tetanized muscle
is distinctly acid, while that of the resting muscle is neutral or
slightly alkaline. This fact can be demonstrated by the use of
litmus paper, but perhaps more strikingly by the use of acid fuchsin.f
If a solution of acid fuchsin is injected under the skin of a frog it
is gradually absorbed and distributed to the body without injuring
the tissues. In the normal media of the body this solution remains
colorless or nearly so. If now one of the legs is tetanized the
muscles take on a red color, showing that an acid is produced locally.
The supposition generally made is that the acidity during activity
is due to an increased production of sarcolactic acid. Experiments
have been made by a number of observers to determine quantita-
tively the amount of lactic acid in the resting and the worked
muscle respectively. Several have stated that the amount is act-
ually less in the worked muscle; others have found an increase.
The balance of evidence seems to show that there is an increased

* Jensen, "Zeitsehrift f. physiol. Chemie, " 35, 525.
f Dreser, " Centralblatt fur Physiologie, " 1, 195, 1887.

68 THE PHYSIOLOGY OF MUSCLE AND NERVE.

production, but that this increase may be obscured in the living
animal by the fact that the acid is removed by oxidation or by
the circulating blood. This conclusion has been confirmed in a
satisfactory way by the striking experiments of Fletcher and
Hopkins.* These observers have shown in the first place that
injury to a muscle causes a production of lactic acid, and that,
therefore, the usual method of determining the amount of this
substance in supposedly resting muscle has given fallacious
results owing to the injury inflicted during the process of extrac-
tion. By the adoption of a new method they have avoided this
error, and they find that in resting muscle lactic acid exists in
traces only (0.03 per cent.) or perhaps is absent altogether.
An appreciable amount is formed when the excised muscle is
well tetanized (0.22 per cent.), also after injury, and especially
in the development of rigor. In heat-rigor a maximum yield
of 0.3 to 0.5 per cent, is obtained in the frog's muscle. In a
muscle removed from the body and deprived, therefore, of its
supply of oxygen, lactic acid develops rapidly, reaching finally
an amount equal to that observed in heat-rigor. As long as
such a surviving muscle shows irritability toward artificial stim-
ulation, lactic acid continues to form. When irritability is lost,
no further production of acid can be detected and the muscle
soon goes into death-rigor. On the contrary, if the muscle is
supplied abundantly with oxygen, no accumulation of lactic acid
can be detected. It is evident from these observations that
lactic, acid is formed in the muscle as a result of the chemical
changes underlying contraction, and also of the changes that
occur during dying. The interpretation of this fact and also
of the further fact that the lactic acid does not appear when
oxygen is freely supplied to the muscle is surrounded with
difficulties owing to our hick of knowledge of certain details.
The simplest explanation at present is that already mentioned,
namely, that the lactic acid is an intermediary product formed
from the sugar by enzyme action, and that if subsequently,
in the presence of oxygen, undergoes oxidation under the influ-
ence of ut her enzymes. From tin's point of view it- is necessary

to assume thai when oxygen is freely supplied to an excised
muscle lactic acid does not accumulate because it- is removed by

oxidation as rapid!)' as if is formed. This explanation of the
significance and origin of the lactic acid agrees well with (lie fact,
that in 1 he contracting muscle glycogen disappears as the luetic
acid appears. In rigor mortis, however, although lactic acid is

formed in considerable quantity, if is still a question whether or
* Fletcher and Hopkins, "Journal of Physiology, " L907, 35, 217.

THE CHEMISTRY OF MUSCLE. 69

not glycogen disappears proportionately from the muscle.*
In view of this and similar difficulties it is necessary that the
view given above shall be considered as tentative until further
knowledge is obtained.

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

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

3. There is a production of 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 wTorked 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 post-mortem fermentation, f

The Relation of the Chemical Changes during Contraction
to Fatigue; Chemical Theory of Fatigue. — As we have seen, a
muscle kept in continuous contraction soon shows fatigue ; it
relaxes more and more until, in spite of constant stimulation, it
becomes completely unirritable. We may define fatigue, there-
fore, as a more or less complete loss of irritability and contractility
brought on by functional activity. But even when the fatigue is
complete and the muscle fails to respond at all to maximal
stimulation, a very short interval of rest is sufficient to bring about

* Bohm, "Pfluger's Archiv f. d. gesammte Physiologie, " 23, 44, 1880.
f Kisch, Hofmeister's "Beitrage zur chem. Physiol, u. Pathol.," 8, 210,
1906.

70 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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 is thus deprived of its
circulation and its proper supply of oxygen, fatigue appears
more rapidly and is recovered from less completely. Ranke,*
to whom we owe the first thorough investigation of this subject,
was led to believe that as a result of the chemical changes occur-
ring in the muscle during contraction certain substances are
formed which depress or inhibit the power of contraction. In
support of this view he found that extracts made from the
fatigued muscles of one frog when injected into the circulation
of another fresh frog would bring on the appearance of fatigue
in the latter. Control experiments made with extracts of
unfatigued muscles gave no such result. He designated these
inhibitory products as fatigue substances and made experiments
to prove that they consist of the known products of muscular
metabolism, namely, lactic acid, carbon di-oxide, and possibly
also acid potassium phosphate (KH2P04). These results have
been confirmed by other observers, and we may accept, therefore,
the view that the products of muscular activity, if they are
allowed to accumulate in the muscle, serve to diminish or sup-
press its contractility. We know that when muscular activity
is prolonged, or is carried out under conditions which imply a
lessened supply of oxygen, an accumulation of some of these
products does actually occur. It is possible, of course, that
other intermediary substances are formed which may have a
similar effect. Thus Weichardtf has stated that muscular
contractions give rise to a definite toxin, derived from the
protein material of the muscle, which, in his opinion, is the chief
agent in causing fatigue, lie claims to have isolated this
fatigue toxin (kenotoxin) to the extent at least of having freed
it from the above-mentioned fatigue substances of Ranke.
When injected into the circulation of a fresh animal, it brings
on fatigue "i- even death. Moreover, by injecting it in suitable
doses, the body may form :ui antitoxin, and this latter substance,
when given to a fresh animal, may confer upon if an unusual
capacity for performing muscular work. It is not advisable,
however, to accept these statements until the facts have been
corroborated by other observers and further experiments. At
ni we are justified only in laying emphasis upon the known
products <>f muscular metabolism, particularly the lactic acid.
When t his substance accumulates in the muscle it may be carried

* Ranke, "Tetanus," Leipzig, 1865.

I Weitchardt, "Archiv f. Anat. u. Physiol, (physiol. Abth.)," 1905,219;
also"Mttnchenermed. WoehenBchrift," L904, L905, L906.

THE CHEMISTRY OF MUSCLE. 71

off in the blood and thus influence other organs. On such a
supposition we may explain the fact, brought out by ergographic
experiments, that marked exercise of one set of muscles, for
example, those of the legs in walking or climbing, may diminish
the amount of work obtainable from other unused muscles, such
as those of the arms. So also the effect of muscular exercise
upon the rate of the respiratory movements and upon the heart-
rate is explained, as we shall see, in a similar way. It should
be added that Lee,* confirming an older observation by Ranke,
has published experiments which indicate that the first effect of
the so-called fatigue substances is to increase the irritability of
the muscle, while the later effect is to diminish the irritability or
to suppress it altogether. In this initial favoring influence Lee
finds an explanation of the phenomenon of Treppe (see p. 34).
The theory of fatigue substances does not, however, explain all
the phenomena, particularly the after-results. As was stated in
describing the experiments made with the ergograph, a very
short rest suffices to make the muscle again capable of lifting its
load, but a very long interval of rest, two hours, may be required
before the muscle is restored entirely to its normal condition.
Such a long interval is probably not necessary* for the removal
of the metabolic 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 assimila-
tion 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 must be received by the muscle. We must
suppose, therefore, that two factors, accumulation of the products
of metabolism and exhaustion of energy-yielding material, co-
operate to produce the conditions actually observed; but the
former of these, the formation of metabolic products, seems to be
a protective mechanism that is especially adapted to save the
muscle from complete exhaustion. In what way these products
depress the irritability and contractility of the muscles is not
known.

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

* For discussion and experiments, see Lee; Harvey Lectures, 1905-06,
Philadelphia, 1906; also Journal of the American Medical Association, May
19, 1906, and American Journal of Physiology, 18, 267, 1907.

72

THE PHYSIOLOGY OF MUSCLE AND NERVE.

molecules are reduced to smaller and more stable ones, such as
H,0 and the CO_, and lactic acid which we recognize among the
products. This reaction is exothermic — that is, some of the
chemical or internal energy of the complex compound is liberated
as heat. Both of these results are so frequently observed in
other chemical reactions that they call for no special comment
in this case. The particular problem regarding the muscle is
how this chemical reaction leads to the shortening of the muscle
and thereby makes it do mechanical work. We must assume

that there is some mechanism
in the muscle by means of
which the energy liberated
during the chemical change
is utilized in causing move-
ment, somewhat in the same
way as the heat enery de-
veloped in a gas-engine is
converted by a mechanism
into mechanical movement,
or the electrical energy in
the coils of a motor is util-
ized by a device to develop
movement. Regarding the
means used in the muscle to
transform the original chem-
ical or internal energy to me-
chanical movement we have
no or very little positive
knowledge. Numerous theo-
ries of a more or less specu-
lative character have been
proposed. It lias been sug-
gested (Weber) that the mus-
cular force is essentially due
to the elasticity of tin; mus-
cle. It is known Unit the
elasticity of substances may change with conditions, and it is

med that after stimulation the physical condition of the
muscle is changed and thai the increased elastic attraction bc-

1 ween the particles gives it the form of the contracted muscle.

According to others (Fick), the mechanical contraction is a direct
re hIi of an increased chemical affinity, while others (Muller)
find an explanation in supposed electrical charges upon the
doubly refractive particles of the muscle, in consequence of which
there are developed electrical attractions and repulsions at the

Fin. '-7. — FnKelmann's artificial muscle.
The artificial muscle is represented by the
catgut r^t rintc, m. This is surrounded by a

Coil of platinum wire, w, through which all

electrical current may I"- sent. The catgut
i atl:irlici| iii .-i lever, //, whose fulcrum ia at
c. The catgut ia immersed in a beaker of
water at 50 to 65° ('., and "stimulated"
by the sudden increase in temperature oaui ed

by lli<- i ■ ■■! i current through the coil.

— (After Engelmann.)

THE CHEMISTRY OF MUSCLE. 73

different poles. The most specific and comprehensible hypothesis
advanced is that formulated by Engelmann.* This author has
shown that all contractile tissues contain doubly refractive
particles, that in the striped muscle fiber these particles are
arranged in discs, — the dim bands, — with the singly refracting
material forming the light bands on either side. During con-
traction it has been shown that the material of this latter struc-
ture is absorbed by the doubly refractive substance. Engelmann
has shown, moreover, that dead substances, which contain
doubly refractive particles and possess the property of imbibi-
tion, 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 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,
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. 27. 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
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. 28 and 29). The model may be
used to show the effect of temperature upon the extent and dura-

* Engelmann, "Ueber den Ursprung der Muskelkraft, " Leipzig, 1893;
see also "Pfliiger's Archiv," 7, 155, 1873; and "Archiv f. Physiologic, "
1907, 25.

74 THE PHYSIOLOGY OF MUSCLE AND XERYE.

Fig. 28. — 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.

I ii' 29. [nutation 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
-iiir-li beating cause la s i is ra 1 1- eon i r.iH ion, and these contractions are summated as in the
tetanic rijnir.icli'.ii of muscle.

THE CHEMISTRY OF MUSCLE. 75

tion of the contractions, the effect of variations in strength of
stimulus as expressed in the amount of current used, the sum-
mation of successive stimuli, etc. Under all of these conditions
it imitates closely the behavior of plain muscular tissue.

Another somewhat similar explanation of the mechanics of contraction
has been suggested by McDougall* and has obtained support from several
observers. According to this view the change in form of the muscle is due
to the passage of liquid from the surrounding sarcoplasm into the fibrillse
(or sarcostyles) . This imbibition of liquid by the sarcostyles may be referred
to the increase of osmotic pressure within them caused by the chemical
changes following stimulation. The sarcostyles are divided transversely by
the Krause membranes into sarcomeres, which have the form of elongated
cylinders. By the absorption of water their form is changed to that of a
flattened cylinder, hence the shortening.

* McDougall, "Journal of Anatomy and Physiology," 1897, 31, 410, and
1898, 32, 187. See also Meigs, "Zeit. f. allgemeine Physiologie, " 1908, 8, 81.

CHAPTER III.

THE PHENOMENON OF CONDUCTION— PROPERTIES
OF THE NERVE FIBER.

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

e find it in the nerve trunks and nerve plexuses of the body,

may he either medullated or non-medullated. All the nerve fibers

76

THE PHENOMENON OF CONDUCTION. 77

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
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

78 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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.

Chemistry of the Nerve Fiber. — Our knowledge of the chem-
ist iv of the nerve fibers is very incomplete. The myelin sheath
i composed largely of bodies such us lecithin and eholesterin,
to which the general name of "lipoids" has been applied, the
name having reference to their solubilities and not to their
composition. By extraction of myelin with hot alcohol a
complex phosphorus-containing substance known as protagon
may he obtained in crystalline form. This substance is, how-
ever, believed now to be a mixture rather than ;i definite chem-
ical individual. The mosl important substances isolated from
the myelin are lecithin, cholesterin, and the cerebrosides.
* Langley, "Journal of Physiology, " :'><>, 221, L903; 20, 55, 1890.

THE PHENOMENON OF CONDUCTION. 79

Lecithin (C4,HS4NP09) is a waxy hygroscopic yellowish sub-
stance containing about 4 per cent, of phosphorus. When de-
composed by the action of alkalies it yields as split products
glycerophosphoric acid, a nitrogenous base, cholin (C5H15N02),
and some of the higher fatty acids, such as oleic, palmitic, or
stearic. It is probable that there are a number of different
lecithines varying somewhat in their composition, for instance,
in the character of the fatty acid contained in the molecule.
These lecithin bodies or phosphatids, as they are sometimes
named, are widely distributed in the tissues and liquids of the
body, but are especially characteristic of the white matter of
the nervous system. They combine easily with other substances,
such as proteins, glucosides, etc., and it is probable that lecithin
exists in some such combination in the myelin. The decom-
position of the lecithin referred to above occurs in the body
when nerves undergo degeneration. The presence of the fatty
acid liberated under such circumstances is demonstrated by the
well-known reaction with osmic acid used to detect degenerated
nerve fibers, while the existence of cholin has been shown by
Halliburton* in the liquids of the body not only after nerve-
degeneration produced by experimental lesions, but in the case
of degenerative diseases of the nervous system.

Cholesterin (C27H460) is a white crystalline substance con-
taining, as its formula shows, neither nitrogen nor phosphorus.
It is widely distributed among the tissues of the body, and in an
isomeric form phytocholesterin occurs also in plants. In the
animal body it is especially abundant in the white matter of
the nerves. The chemical nature of cholesterin has long been a
matter of uncertainty, but recent work indicates that it belongs
to the group of "terpenes" heretofore supposed to be confined
to the plant kingdom. The fact that lecithin and cholesterin
usually occur together has suggested that they may have some
physiological connection. The chief fact indicating such a
connection is the discovery that the hemolytic action of cobra
venom on red blood corpuscles is made effective by activation
of the toxin by lecithin (Kyes), while cholesterin, on the other
hand, antagonizes this action of the lecithin. No application of
this antagonistic relationship is possible at present in the case
of the myelin sheath.

Cerebrosides. — This name is given to a group of bodies con-
taining nitrogen, but no phosphorus. In the myelin they are
found in connection with and possibly in combination with the

* Halliburton, "British Medical Journal," 1907, May 4 and 11. Also
"Folia Neuro-Biologica, " 1907, i., 38, and " Biochemistry of Muscle and
Nerve," Philadelphia, 1904.

SO THE PHYSIOLOGY OF MUSCLE AND NERVE.

lecithin. They belong to the group of glucosides, that is, on
hydrolytic decomposition the}' give rise to a carbohydrate group,
in this case galactose. Fatty acids and a nitrogen base also re-
sult from this decomposition. The cerebroside material obtained
from the white matter has been named specificially cerebrin or
phrenosin, but little is known of its exact structure.

Union of Nerve Fibers into Nerves or Nerve Trunks. — The
assembling of nerve fibers into larger or smaller nerve trunks re-
sembles 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
physiological unit. On the other hand, the hundreds or thou-
sands of nerve fibers found in a nerve may form groups which are
entirely independent in their physiological activity. In the
vagus nerve, for instance, we have nerve fibers running side by
side, some of which supply the heart, some the muscles of the
larynx, some the muscles of the stomach or intestines, some the
glands of the 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 filters 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 fillers 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

THE PHENOMENON OF CONDUCTION.

81

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-
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

Motor

Secretory

Inhibito-mo-

tor
Inhibito-se-

cretorv

Sensory

1 Reflex

Inhibitory <

Inhibito-re-
flex

f Motor.

Vasomotor.

Cardiomotor.

Visceromotor.

Pilomotor.

Salivary.

Gastric.

Pancreatic.

Sweat.

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

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

Visual.

Auditory.

Olfactory.

Gustatory.

Pressu re.

Temperature.

Pain.

Hunger.

Thirst, etc.

According to the efferent fibers affected.

Inhibitory effects upon the conscious sensations are
not demonstrated.

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

82 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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 is sutured
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 (hat the fibers in
question do not really belong to the anterior root, — that is, they do
not emerge from the cord with the roof fibers; they are, in fact,
iry 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 quest ion whet her t heir law applies to all afferent and

* Langley, "Journal of Physiology," 23, 240, L898; ibid., 30, 439, L904;
" Proceedings Royal Society,'' 7:;, L904,

THE PHENOMENON OF CONDUCTION. 83

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 posterioi
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, an}*- 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

* Bayliss, "Journal of Physiology," 26, 173, 1901, and 28, 276, 1902.
t Herring, "Journal of Physiology,''' 29, 2S2, 1903.

84 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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-
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
onl)r 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 I rasseriarj or a posterior root ganglion. Its nerve cells send off
processes which divide in T and constitute afferent fibers in the

THE PHENOMENON OF CONDUCTION. 85

so-called nervus intermedius or nerve of Wrisberg. The eighth
nerve consists only of afferent fibers which arise from the nerve
cells in the spiral ganglion of the cochlea, cochlear branch, and from
those 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
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

86 THE PHYSIOLOGY OF MUSCLE AND NERVE.

difficult}- lies in controlling this pressure so that it shall not actually
destroy the nerve fiber by rupturing the delicate axis cylinder.
Various instruments have been devised by means of which light
blows may be given to the nerve, sufficient to arouse an impulse,
but insufficient to permanently injure the fibers. The results ob-
tained by this method have been very valuable in physiology as con-
trols for the experiments made by the usual method of electrical
stimulation. It may be mentioned also that under certain condi-
tions— for instance, at one stage in the regeneration of injured
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. .'JO. — Stimulating (catheter) electrodes for nerves: b. Binding posts for attachment
of wires from the secondary coil; «, insulating sheath of hard rubber; p, platinum points
laid upon the nerve.

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

4. Electrical stimuli. Some form of the electrical current is be-
yond quest ion 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. 30.) By this means the platinum ends which nov

THE PHENOMENON OF CONDUCTION.

87

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
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-ReymonaV 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 b}^ the mak-

Fig. 31. — 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.

88 THE PHYSIOLOGY OF MUSCLE AXD NERVE.

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

Electrotonus. — The altered physiological condition of the nerve
at the poles during the passage of the galvanic current is designated
as electrotonus, the condition round the anode being known as
anelectrotonus, thai round the cathode as catelectrotonus. Elec-
i n.t onus expresses itself as a change in the electrical condition of
the nerve which gives rise to currents known as the electrotonic
currents, a brief description of these currents will he given in
the next chapter, — and also by a change in irritability and con-
ductivity. The latter changes were first carefully investigated

by Pflliger, who showed that when 1 he galvanic current, or, as it is

usually called in this connection, the polarizing current, is not too
strong there is ;ui increase in irritability and conductivity in the
neighborhood of the cathode, the so-called catelectrotonic increase
of irritability, while in the region of the anode there is an anelec-
trotonic decrease in irritability and conductivity. These opposite
variations in the state of the nerve are represented in the accom-
panying diagram. Between the two poles that is, in the intrapolar

THE PHENOMENON OF CONDUCTION. 89

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 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.

Pflilger'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. 32. — Electrotcnic 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 a:1
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
Vs, 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,

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

90 THE PHYSIOLOGY OF MUSCLE AXD NERVE.

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
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.
Pfliiger'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. 33. — Schema to Hhow the arrangement of apparatus for an ascending and a descending
current: PI, ascending; D, descending.

Ascending Current. Descending Current.
Making, Brcakinu. Making. Breaking,

Very weak currents .. C 0 C O

Moderate " . . . .C C C C

Very strong " 0 C C O

The effects obtained with the strong currents are readily under-
stood if we bear in mind the fads stated above regarding cleetro-
tonus. When the current is ascending the stimulus on making
Mails from the cathode, but cannot reach the muscle because it
is blocked by a region of anelectrotonus in which the conduc-

THE PHENOMENON OF CONDUCTION. 91

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

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

Stimulation of the Nerves in Man. — For therapeutic as well
as diagnostic and experimental purposes it often becomes desirable
to stimulate the nerves, particularly the motor nerves, in man.
We may use for this purpose either the induced (faradic, alternat-
ing) current or the direct battery current (galvanic or continuous
current) . In such cases the electrodes cannot be applied, of course,
directly to the nerve; it becomes necessary to stimulate through
the skin, and the so-called unipolar method is employed. The
unipolar method consists in placing one electrode, the active or
stimulating electrode, over the nerve at the point which it is desired
to stimulate, while the other electrode, the inactive or indifferent
electrode, is applied to the skin at some more or less remote part,
usually at the back of the neck. The indifferent electrode is made
large enough to cover several square centimeters of the skin, and one

92

THE PHYSIOLOGY OF MUSCLE AND NERVE.

may conceive the threads of current passing from it into the moist
tissues of the body and thence to the active electrode. As the
threads of current condense to this latter electrode they pass through
the motor nerve which lies under it, and if sufficiently intense -will
stimulate the nerve. The arrangement is represented in the accom-
panying schema (Fig. 34), 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
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

Fig. 34.— Schema to tihaw the unipolar method of stimulation in man. The anode,
+, IH r'rj.i r- ented aa t i • »; Stimulating pole, applied over t lie median nerve. The cathode,

— , ia the indifferent pole. t

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

THE PHENOMENON OF CONDUCTION.

93

that is necessary, when the induced current is used, is to bring the
active electrode as nearly as possible over the spot at which the
muscle receives its motor branch. A diagram showing these
motor points for the arm is given in Fig. 35. 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 is made between the cathodic and
anodic effects. When, however, the battery current is employed

U. flexor carpi ulnaris

tferv. musculacutaneuM
M. biceps brachil
M. brach. interacts

Tvf, flexor digitor. suljliro.

M. abductor pollic. brer.
M. opponens pollicis

M. flex. poll. brev.

M. adductor pollic, brtT-

Fig. 35. — Motor points in upper extremity.

one may make the stimulating electrode either anode or cathode,
and under these circumstances a marked difference is observed
in the strength of the current that it is necessary to use to
get a response. With the battery or galvanic current, in fact,
one may distinguish four stimuli, the closing and the open-
ing shock when the stimulating electrode is cathode and the
closing and the opening shock when it is anode. The con-
tractions resulting from these four stimuli are designated usually
as follows: The cathoclol closing contraction, C C C; the cathodal

94

THE PHYSIOLOGY OF MUSCLE AND NERVE.

opening contraction, C 0 C; the anodal closing contraction,
ACC; and the anodal opening contraction, A O C. If the minimal
amount of current necessary to give each of these contractions
is measured in milliamperes by means of a suitable ammeter,
it will be found that the four stimuli are of different efficiencies.
The usual relationship is expressed by the sequence C C C >
ACC > A 0 C >COC, although this sequence is subject to some
individual variation. Certain pathological or traumatic lesions
that cause the degeneration of the nerves may be revealed
by the use of these methods of stimulation. The nerve trunk
under such circumstances fails to respond to either form of
stimulus, induced or galvanic. The muscle, on the other hand,
while it fails to respond to induction shocks, is stimulated by the
galvanic current and, indeed, may show an increased irritability
toward this form of stimulus, although the contractions are
more sluggish in character than in a muscle with a normal nerve
supply. Certain qualitative changes in the reaction of the
muscle to the galvanic current may also be noticed, for instance,
the A C C is sometimes obtained with less current than the C C C.
This qualitative and quantitative change in reaction to the
galvanic current, and the loss of irritability to the induced cur-
rent, constitute what is known as the reaction of degeneration.

(0$~

—L^fC

yd- j a. ia.

Fig. 38. — Two schemata to show the relation between the physical and the physio-
logical electrodes or pole . Kach schema represents the forearm with the median nerve,
M . In / the tim illation electrode is I lie cathode; the tine: ids of current which have started
from the anode (the inditfcient electrode) placed elsewhere, conver«e to this pole. Where
these thread eater the nerve we have a series of physiological anodes, a ; where they leave,
a erie of physiological cathode , c. In // the stimulating electrode is the anode. The
thread of current leave thi 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 anode and cathode-., now, however, on the opposite sides of the nerve.

Distinction between Physical and Physiological Poles. — The
facte stated above 3eem to show, at first sight, that by the
unipolar method we may obtain both an opening and a closing
shock at cit Iter the cathode or anode, a result which is in

THE PHENOMENON OF CONTRACTION. 95

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. 36).

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,
when one tendinous end is cut off, it is found that the cut end has
an electrical potential differing from that of the uninjured longi-
tudinal surface of the preparation. Following the usual nomen-
clature, the cut end is electronegative as regards the longitudinal
surface. If, therefore, the longitudinal surface is connected by
a conductor with the cut surface a current will flow from the former
to the latter, as is indicated in the accompanying diagram,

+

Fig. 37. — 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 liber thierische Elektricitfit," <lu Bois-Reymond,
1848-1860.

96

ELECTRICAL PHENOMENA.

97

0

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

A current of this character from an excised nerve or muscle
is, of course, small in amount and to detect it one must make
use of a delicate electrometer of some sort (see below). Du Bois-
Reymond considered that the difference in electrical potential
which gives rise to this current exists normally in the muscle,
although masked by an opposite condition in the tendinous ends,
and he therefore spoke of the currents as the natural muscle or
natural nerve currents. It has since been shown by Hermann
that this view is incorrect; that the
perfectly normal uninjured muscle or
nerve has the same electrical potential
throughout and will therefore give no
current when any two points are con-
nected by a conductor. Moreover, the
completely dead muscle or nerve shows
no current. The difference in poten-
tial that is found in the excised
nerve or muscle is due, according to
Hermann, to the fact that at the cut
end the nerve or muscle is injured. The
chemical changes that take place as a
result of the injury make the tissue
electronegative as regards the un-
changed living substance elsewhere.
For this reason Hermann described
the current as a demarcation current;
others have called it the current of
injury.

The nature of the changes at the injured end are not known. It is inter-
esting to note that Bernstein * has shown that the electromotive force of the
muscle current increases with the temperature, a fact which leads him to
conclude that the difference in potential between the longitudinal and cut
surface of the muscle depends upon a difference in concentration of the
electrolytes. The muscle, in fact, acts after the manner of a "concentration
cell." Such a difference in concentration may pre-exist in the normal mus-
cle, or, according to the view adopted above, is developed as the result of
injuring one end of the muscle. It may be supposed that the injury causes
changes which result in the formation of new organic or inorganic electro-
lytes and thus increases the concentration at that point. From what is
known of the chemical changes in muscle it is safe to assert that there is an
increased production of lactic acid at the injured end, and it is probable
that other electrolytes may be liberated in diffusible form. With this increased
concentration at the injured area a development of electric potential might
be expected, owing to the probability that the cations (H, K, Na, Mg, Ca)
will diffuse off more rapidly and thus leave the injured end with a negative,
charge. Experiments made by Urano and von Frey on muscle juice squeezed
out of the muscle fibers under high pressure have shown that when it is diffused
against sugar solutions it loses its K and Mg more rapidly than the P04 and S04.
* "Pfliiger's Archiv," 1902, 92, 521.
7

Fig. 38. — 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.

9S

THE PHYSIOLOGY OF MUSCLE AND NERVE.

Means of Demonstrating the Muscle Current. — The demarcation
current and other electrical conditions to be described require especial appara-
tus for their study. To detect the existence of a current physiologists use
either a galvanometer or a capillary electrometer. The galvanometers employed
are of several types, the Kelvin reflecting galvanometer, the d'Arsonval form,
and more recently the "string-galvanometer" of Einthoven. 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. If a magnetic
needle is swung by a delicate thread so as to move easily, it will come to rest
in the magnetic meridian with its north pole pointing north. If now a wire is
curved round it, as shown in the accompanying diagram (Fig. 38), 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 direc-
tion. The movement 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

Fi«. 39.— D'Arsonval galvanometer as modified by Rowland.

the amount of deflection caused by a standard battery. The effect of the
current Upon the needle increases with the number iif turns of wire, so that

delicate galvanometers constructed upon (his principle are spoken of as high

nee Lr:i I vanomel ers, the great length of wire used making, of course, a.

high resistance. Instead of having the coil through which the current passes

kept in ;i fixed position and the magnet delicately Swung or poised, the reverse

arrangemenl may be used that is, the coil may be swung between the poles
of a fixed magnet. Under 1 hese 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
tin' physiologist who first employed this arrangement. In the d'Arsonval
form the magnel is fixed while the coil of wire through which the current:

f;:i e i swung by a very delicate thread of quartz, silk fiber, or phosphor-
ironze. The principle of the arrangement is shown in the accompanying
diagram 'I \<ri. I'm and one form of a complete instrument, in Fig. 3!). A large

l,i,i i hoe magnel <», 8) is fixed permanently and between the poles is swung

a coil (c) of delicate wire, t he I wo ends of t lie u ire being connected with binding
posts in the frame of the instrument. The coil is held in place below by a,
delicate piral. In Fig, 40 it- will be seen that the delicate thread suspending

ELECTRICAL PHENOMENA.

99

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. 39 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

Fig. 40. — 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 — in) 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. 41. — 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; f, 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.

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.

The movable system of this galvanometer possesses considerable 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.

100

THE PHYSIOLOGY OF MUSCLE AND NERVE.

For purposes of this kind the string-galvanometer or the instrument known
as the capillary electrometer is employed.

The String-galvanometer. — In this instrument a very delicate thread
of silvered quartz or of platinum is stretched between the poles of a strong
magnet, as is represented in the diagrams given in Figs. 42 and 43. The

Fig. 42. — One form of the string-galvanometer : E, The electromagnet; b, the projection
microscope; F, a screw for varying the tension of the thread. — (Edelmann's Catalogue.)

u

Fig. 43. — Schema i<> Bhow tin- relation <>f the thread to the magnets in the string-
galvanometei l I, The delicate thread of silvered quartz or of platinum, stretched between
1 1 ■ ' ■ polai piece {PP) of an electromagnet, When a current passes through .1 A , the thread
b movement. The ends of the magnets are pierced by holes, Been in /'i, through
which the movements "I the thread may !><■ watched by means of a microscope! or he pro-
jected upon ,-i photographic plate. (After Einthoven.)

metal poles of the magnel are pierced by boles, so that the thread may be
illuminated by an eled ric light < Nernsl la nip) from one i ide, and on the other
the Bhadow of the thread may be thrown upon a screen after being magnified

by a microscope (see Fig. 42). With this arrangement the thread shows a

ELECTRICAL PHENOMENA.

101

--3

lateral movement whenever a current is passed through it. The instrument
may be made of great delicacy so as to detect very minute currents, and,
moreover, it has the very great advantage of responding accurately to rapid
changes in potential. If the shadow of the thread is allowed to fall upon
sensitized paper properly adjusted upon a rotating surf ace, its movements may
be photographed and a permanent record be thus obtained (see Fig. 22 for
an example of such a photographic record showing the electrical changes in
a contracting muscle) .

The Capillary Electrometer. — The principle of the construction of
the capillary electrometer is illustrated in Fig. 41. A glass tube, a, is drawn
out at one end into a very fine capillary, the end of which dips into some
diluted sulphuric acid contained in the vessel (/). At the bottom of this
vessel is a layer of mercury connecting with a wire, g, fused into the glass
vessel. The tube a is partially filled with redistilled mercury, which pene-
trates for a short distance into the capillary. By means of pressure applied
from above c, the mercury can be forced through the capillary. Then by
diminishing the pressure the mercury can be brought back into the capillary
a certain distance, drawing after it some of the dilute
sulphuric acid. The mercury in tube a is connected
with the other pole of the battery by a wire fused into
its wall and dipping into the mercury. By regulating
the pressure on the mercury the point of contact be-
tween the thread of mercury and the sulphuric acid
in the capillary, d, can be brought to any desired
position. 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 sulphuric
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 mer-
cury at a certain point in the capillary is disturbed,
the end of the mercury 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 current be passed in the opposite direction the
mercury will move downward a certain distance. The
meniscus of contact moves up or down with the direc-
tion 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 mercury 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 capillaries be brought into focus
at the meniscus, as shown in d, Fig. 41. By means of
proper apparatus the movement can be photographed
and thus a permanent record be obtained of the direc-
tion and extent of movement of the mercury.

Non-polarizable Electrodes. — In connecting a muscle or nerve to an elec-
trometer or galvanometer it is necessary that the leading off electrodes — that
is, the point of contact between the wires and the muscle or nerve — shall be
iso-electrical and non-polarizable. By iso-electrical is meant that the two
electrodes shall have the same electrical potential, and it is obvious that the
leading off electrodes must fulfil this condition approximately at least, since
otherwise the current obtained from the muscle or nerve could not be attrib-
uted 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 fulfil this condition. A more serious difficulty is found in

Fig. 44.— 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.

102

THE PHYSIOLOGY OF MUSCLE AND NERVE.

the polarization of metallic electrodes. Whenever a metal conductor and a
liquid conductor come into contact there is apt to be polarization. What
takes place may be represented by the following diagram, in which a current
is supposed to be passing

+

+

Na

+

Na

+

Na

+
Na

A

CI

CI

CI

CI

~~

—

—

between the poles A and C through a solution of sodium chlorid. During
the passage of the current the cations, Na, with their positive charges
move toward the cathode; at the cathode the free sodium ion acts upon
the water, HHO, forming NaOH and liberating hydrogen, which gives
its charge to the cathode and accumulates upon it in the form of gas. The
anions, CI, with their negative charges move toward the anode; there the
chlorin acts upon the water, forming HC1 and liberating oxygen. In conse-
quences of these chemical actions at the poles an electromotive force is de-
veloped at the cathode which diminishes the current passing from A to C.
It is obvious that in quantitative studies of the electrical currents of animal
tissues polarization will destroy the accuracy of the results; the demarcation
current will show a diminution due not to changes in the nerve, but to physi-
cochemical changes at the leading off electrodes. To prevent polarization
du Bois-Reymond devised the non-polarizable electrodes consisting of zinc
terminals immersed in zinc sulphate. Theoretically any metal in a solution
of one of its salts may be used, but experience shows that the zinc-zinc sulphate
electrode is most nearly perfect. Each electrode where it comes into contact
with the tissue is made of one of these combinations. Various devices have
been used. For instance, the electrode may be constructed as shown in the
diagram (Fig. 44). A short glass tube of a bore of about 4 mms. is well
cleaned — one end, which is to come into contact with the nerve — is filled, as
■shown, by a plug of kaolin made into a stiff putty with physiological saline
solution of NaCl (0.7 per cent.). The kaolin should have a neutral reaction
and unless good kaolin is obtainable it is better to use a plug made of clean
filter paper macerated in physiological saline and packed tightly into the end
of the tube. Above this plug the tube is filled in for a part of its length with
a saturated solution of zinc sulphate into which is immersed a bar of amal-
gamated zinc with a copper wire soldered to its end. With a pair of such
electrodes the conduction of the current through the nerve or muscle to the
hi i't;tllic part of the circuit may be represented as follows:

Zn

+
Zn

+
Zn

+
Na

+

Na

+

Na

+
Zn

+
Zn

SO., SO, CI CI CI so4 so4

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 Zu cation instead of acting upon the water and liberating hydrogen,
deposits itself upon the zinc electrode; at the anode the sulphion (S< )4)
attacks the zinc instead of the water, forming ZnS( ).,. ]n 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, Sucfa electrodes are indispensable in studying the electrical phe-
nomena of living tissues, and also in all investigations bearing upon I, he polar

effect 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.

ELECTRICAL PHENOMENA. 103

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
the example given, relative to that of the demarcation current is
as 10 to 50. Frequently the phenomenon of the negative varia-
tion is known also as the action current. The explanation given
for this action current is that the nerve or muscle when excited
takes on an electrical condition which is negative as regards any
unexcited or less excited portion of the nerve. The effect upon the
demarcation current is illustrated in the accompanying diagram.

The demarcation current in a nerve is led off to a galvanometer
by electrodes placed at 6 and c. When the nerve is stimulated at
a the excitation set up passes along the nerve, and wherever it may
be that portion of the nerve is thrown into an electronegative condi-
tion. When this condition reaches a point at which it can influence
the galvanometer — that is, when it reaches 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 Fig 45.— Schema to indicate the method of detecting
maximum and then ^e action current in a stimulated excised nerve: b and c,
the leading on 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
, „ . , . , negative condition, — which passes along the nerve ; when
definite VelOClty this reaches bit causes a partial reversal of the demarca-
t_ • 1 • • 1 tion current, giving the negative variation or action cur-

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

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

104 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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 witl a definite velocity, just as water
waves radiate from the spot at which a stone is thrown into a quiet
pool. A similar phenomenon occurs in muscle fibers when stimu-
lated, but the negative condition travels over the muscle fiber at a
slower speed, 3 to 4 meters per second in frog's muscle, and with a
wave length, according to Bernstein, of only 10 nuns. This wave
of negativity in the muscle begins during the latent period and,
therefore, precedes the actual shortening at any point, as shown
in Fig. 48.

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

Herzen lias claimed that under certain conditions of local narcosis the
nerve fibers when stimulated may give an action current, hut 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

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

tGriitzner, "Pfliiger's Archiv," 25, 2.r,r,, L881.

X Boruttau, " Pfliiger's Archiv," si and 90, 1001-1902.

ELECTRICAL PHENOMENA. 105

conditions offers more difficulties, because it is diaphasic, as will
be seen from the accompanying diagram (Fig. 46). The figure
represents 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 galvanometer. If the nerve is stimulated at a by a single
stimulus, a negative condition or charge passes along the nerve.
When it reaches the point b, there will be a momentary current
through the galvanometer 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 current through the galvanometer in the other
direction. The diphasic current that occurs under these con-
ditions cannot be detected by the ordinary 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 string-galvanometer or capillary electrometer
the diphasic currents have been demonstrated successfully. In
laboratory investigations one of the leading off electrodes, c,
is usually placed on the cut end of the nerve. Under this con-
dition the action current becomes monophasic and shows itself
as a negative variation of the demarcation current. This
difference is due to the fact that a negative condition upon
excitation depends upon a living condition of the nerve, and it
cannot, 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 usual galvanometer,
provided a series of stimuli is thrown in at a.

Fig. 46. — 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

106 THE PHYSIOLOGY OF MUSCLE \XD 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
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

lie. 17. Si-licma to .show (lie arrangement of a rheoscopic muscle-nerve preparation:
b, The rheoscopic muscle-nerve preparation, the nerve being; arranged to touch the out but-
jape and the longitudinal mrface of the musole, a, whose action ourrenta are to !»■ detected.

When I be nerve Of a is stimulal'd cadi cun t.r:ifl inn of tliis muscle in followed l>y u contrac-
tion of I), .since each conl rail ion of a is accompanied by an action current wliich passes
throuicli the nerve of b ami 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.

ELECTRICAL PHENOMENA.

107

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. When
studied by means of the string-galvanometer it would seem,
according to the curve reproduced in Fig. 48, that in a simple

Fig. 48. — Photograph of the electrical variation in the frog's gastrocnemius muscle
■during a simple contraction, as given by the string-galvanometer : a. The electrical curve,
showing two waves ; b (retouched to make it distinct), occurring during the latent period.
This is followed by a smaller but longer wave, which begins at the moment of shortening
of the muscle ; c, the break in this line indicates the moment of stimulation ; d, the curve
of contraction of the muscle ; k, vibrations of a tuning-fork at the rate of 100 per second. —
(Judin.)

muscular contraction two electrical waves pass over the muscle:
first, a quick extensive change in potential which occurs during
the latent period and marks probably the passage of the wave
of excitation; second, a slower wave accompanying the proc-
ess of shortening. Paying attention only to the first of these
waves, we may suppose 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

10S

THE PHYSIOLOGY OF MUSCLE AND NERVE.

conduct an excitation (muscle impulse), although unable to con-
tract, and the same fact has been demonstrated by Engelmann
for the heart muscle. In the nerve the action current, or the
negative change causing it, has been considered as simultaneous
with or possibly identical with the nerve impulse. The velocity
of the two is identical; the action current is given whenever the
nerve is stimulated, and, so far as experiments have gone, the
nerve cannot enter into activity without showing an action
current. — that is. without showing a moving electrical charge.
Whether this electrical charge constitutes the nerve impulse or
is simply an accompanying phenomenon will be discussed briefly
in the paragraph upon the nature of the nerve impulse in the
following chapter.

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

to the fact that the
condition of the
nerve is altered at
each pole. At the
anode there is a con-
dition of decreased
irritability and con-
ductivity known as
anelectrotonus ; a t
the cathode, in the
beginning, at least,
a condition of in-
creased irritability
known as catelec-
trotonus. In addi-
tion to these changes in the physiological properties of the nerve
there is a change also in its electrical condition at each pole, of
such a character that if the nerve is led off from two points on
the anode side a current will be indicated. The current can be
obtained at a considerable distance from the anode, and is known
as the anelectrotonic current, while the electrical condition in the
nerve fchat makes it possible is designated as anelectrotonus. A
similar current can be led off from the nerve on the cathode side
for a considerable distance beyond the cathode; this is known as
the catelectrotonic current, and the electrical condition leading
to its production as catelectrotonus. Within the nerve these

electrotonic currents have the same direction as the battery or

polarizing current, as is shown in the diagram (Fig. 49), The
terms anelectrotonus and catelectrotonus are used, therefore,
in physiology to designate both the physiological and the elec-

Fig. 49. — 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; o\ 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.

ELECTRICAL PHENOMENA.

109

trical changes around the poles when a battery current is led

into a nerve. Whether the physiological and the electrical changes

have a causal connection or are two independent phenomena is

at present undecided.

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

Fig. 50. — To show the action of the core-model: p, The polarizing current; g' and
g, the galvanometers with leading off electrodes to detect the anelectrotonic and catelec*
trotonic currents, respectively.

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

Another explanation of the electrotonic currents which has been much
discussed is that first developed by Hermann. f 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-B, through the middle of which is stretched a
platinum wire, P, the rest of the tube being filled with a saturated solution
of zinc sulphate. The glass tube is provided with vertical branches by means
of which a polarizing current, p, can be sent into the solution of zinc sulphate
and the electrotonic currents be led off to galvanometers, g', g, on
each side. Under these conditions a current similar to the anelectrotonic
current can be detected on the side of the anode {g') and one equivalent to
the catelectrotonic current on the side of the cathode (g). The explanation
given to these currents is that as the threads of current pass into the platinum
core there is a polarization at the surface between the core and the zinc sul-
phate solution which extends to a considerable distance on each side of the
electrodes and causes diffusion currents from sheath to core. It is these
threads of current that may be led off as electrotonic currents. Hermann
suggested that hi 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 corre-
sponding to the zinc sulphate solution. Others (Boruttau) have suggested that

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

f Hermann, " Handbuch der Physiologie," vol. ii, p. 174.

110 THE PHYSIOLOGY OF MUSCLE AND NERVE.

the neurofibrils in the axis cylinder may represent the core or cores and the sur-
rounding neuroplasm the sheath, thus providing for the possibility of electro-
tonic currents in non-medullated fibers. As a matter of fact, the non-medul-
lated fibers in mammals give very slight electrotonic currents compared with
the medullated fibers.*

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

CHAPTER V.

THE NATURE OF THE NERVE IMPULSE AND THE

NUTRITIVE RELATIONS OF NERVE FIBER

AND NERVE CELL.

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

111

112 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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. 51. — 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 mu-.rle the -ennui ill) 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 curses measured on the line x. The value of this distance in time Ls obtained
rence to the record of a tuning fork vibrating 100 times per second, which is given
on the lower line. In the experiment the length of a tuning fork wave (0.01 sec.) was L'l
nuns., the .li-lan«-e l.ct^-een the two muscular contractions was 3.35 mms., and the dis-
tance between the point i stimulated upon the nerve was 19 mms. Hence the velocity of the
nerveimpul e in thi experiment was 49 divided by (^'Wo ;X ,,',,,) oiiiiiTHimms. Cio.Tltim.)
per second.

and, second, near its origin from the cord, and measuring the time
fli.it 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 .'ill oilier 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, "Miiller'a Archiv f. \...-.t. u. Physiol.," L852, p. 199.

NATURE OF THE NERVE IMPULSE. 113

panying figure the record of a laboratory experiment of this kind
is reproduced. Knowing the difference in time and also the length
of nerve between the points stimulated, the data are at hand to
calculate the velocity of the impulse. The velocity varies with the
temperature. According to Helmholtz, this variation lies between
24.6 and 38.4 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 have been
made upon man and other mammals. Helmholtz stimulated
the median nerve in man at two different points and recorded
the resulting contractions of the muscles of the thumb. By
this means he obtained an average velocity of 34 m. per second,
but others, making use of the same method, have reported
varying results. Quite recently Piper* has applied the string-
galvanometer to the investigation of this point. Using the
unipolar method, he stimulated the median nerve with induction
shocks, the active electrode being applied at the elbow and at
the axilla at a distance apart of from 160 to 170 mm. The
muscular response was recorded not by registering the con-
traction, but by means of its action current When the stimulus
was applied at the elbow the interval between the stimulation
and the electrical response averaged 0.00442 second; at the
axilla the interval was 0.00578 second. The difference, namely,
0.00136 second, gave the time necessary for the impulse to travel
over 160 to 170 mm. of nerve, and indicated a velocity of 117
to 125 m. per second.

It is interesting to recall that only six years before Helmholtz's first pub-
lication Johannes Muller 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 (" Midler'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-Rej-mond 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 materia)
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.

* Piper, "Archiv f. d. ges. Physiologic," 1908, 124, 591.

114 THK PHYSIOLOGY OF MUSCLE AND NERVE.

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
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 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, -g- meter, and in the
anodon, only tttt 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
si jiiiiil.il ion. 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 t hat when light falls upon the living retina an electrical distur-
bance i produced by the visible rays of the spectrum,* and there
is ever, 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 t he central nervous system are accompanied
♦ Consult Gotch, "Journal of Physiology," 31, I, L904.

NATURE OF THE NERVE IMPULSE. 115

by a wave of electrical potential. This fact may be shown by
stimulating the motor areas in the cerebral cortex and testing the
efferent nerves, such as the sciatic, for an action current; or by
stimulating a posterior root on one side in the lumbar region and
testing the sciatic nerve on the other side with a galvanometer.*
Moreover, all influences that alter the velocity or strength of the
nerve impulse affect the intensity of the action current in the same
manner. It is believed generally, therefore, that the electrical
charge is an invariable accompaniment of the excitatory wave,
and the demonstration of an action current in a nerve is tantamount
to a proof of the passage of a nerve impulse.

Direction of Conduction in the Nerve. — The fact that under
normal conditions the motor fibers conduct impulses only in one
direction — i. e.f 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-
ment of the nerve Fig. 52.— Schema to show the arrangement for proving
. T . the propagation of the negative charge in both directions:
impulse. It IS not a. The stimulating electrodes; g and g', galvanometers
t rr- ill i l with leading off electrodes arranged to show the negative
difficult to shOW by variation on each side.

means of a galva-
nometer that when a nerve trunk is stimulated the negative
charge spreads in both directions from the point stimulated and

* Gotch and Horsley, "Phil. Trans., Royal Soc," London, 1891, vol.
182 (B), and Boruttau, " Pfluger's Archiv," 1901.

116 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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
the new ones that are eventually formed in their place are out-
growths from the lingual stump, or at least are not the old efferent
fibers, and hence experiments of this kind are not so conclusive
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 — Temperature. — The strength of the impulse and its
velocity may be modified in various ways: by the action of
temperature, narcotics, pressure, etc. Variations of tempera-
ture, 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 irritability as well as the con-
ductivity of the nerve fiber is influenced markedly by tem-
perature. 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
fiher.s show somewhat different reactions in this respect,; but,
speaking generally, the limits of conductivity in relation to
temperature Lie between 0° C. and 50° ('. Cooling a nerve to

n C. will in most cases suspend the conductivity, but this
function returns promptly upon warming.* By this means
we can Mock the nerve impulses in a nerve trunk for any desired
lengl h of i ime. The exact relai ionship between the temperature
of the nerve and the velocity of the impulse has been studied

carefully with the object of determining the temperature coejji-
* Howell, Budgett, and Leonard, "Journal of Physiology," 16, 298, L894.

NATURE OF THE NERVE IMPULSE.

117

dent. It has been shown by van't Hoff that the velocity of

chemical reactions is increased twofold or more for each rise of

10 degrees in temperature, that is, the temperature coefficient

for chemical reactions lies between 2 and 3. On the other hand,

with most physical processes the temperature coefficient for the

same range of temperature lies around 1 or between 1 and

2. Snyder* finds, on comparing the velocities of the impulse

at different temperatures, that they follow van't Hoff's law for

chemical reactions, that is, the velocity is approximately doubled

by a rise of 10° C. in temperature within physiological limits,

, • i + velocity at fn + 10 9 T, •
or, expressed in more general terms, — -. — r- -j =2. 1 nis

effect of temperature on the velocity of the impulse is shown
graphically in Fig. 53. Anesthetics and narcotics, J such as ether,

Fig. 53. — Figure to show the effect of temperature on the velocity of the nerve impulse.
At each temperature two contractions of the gastrocnemius were recorded, one when the
nerve was stimulated close to the muscle, one when it was stimulated further away (44 mm.).
The horizontal distance between the curves as they rise can be expressed in time by refer-
ence to the tuning-fork vibrations (200 per second) given below. For intervals of 10° C.
it will be seen that the velocity, as indicated by the reciprocals of the distances between
the pairs of curves, indicates a coefficient of two. — (Snyder.)

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 interesting fact that the conductivity of
the nerve may be suspended also by deprivation of oxygen, J —
that is, by local suffocation or asphyxia. A nerve fiber sur-
rounded 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,

* Snyder, "American Journal of Physiology, " 22, 179, 1908.
fFrohlich, "Zeitschrift f. allgemeine Physiol.," 3, 75, 1903.
t Baeyers, ibid., 2, 169, 1903.

118

THE PHYSIOLOGY OF MUSCLE AND NERVE.

as was explained in a preceding chapter, the conductivity of the
nerve may be increased or decreased or suspended entirety by the
action of a galvanic (polarizing) current. This method of sus-
pending conductivity temporarily has been frequently employed
for experimental purposes, the arrangement being as represented
in Fig. 54.

"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
consumption of the en-
ergy-yielding material in
them. Functional activ-
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-
* Wedenski, "Pfluger'a Arehiv," 100, 1, 1904.

Fig. 54. — Schema to show the method of block-
ing the nerve impulse by means of a polarizing cur-
rent: a. The stimulating electrodes; 6, the battery,
the current of which is led into the nerve. The de-
pressed irritability at both anode, +, and cathode, — ,
prevents the nerve impulse started at a from reaching
the muscle.

NATURE OF THE NERVE IMPULSE. 119

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
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 was under stimulation during this entire time. 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. EdesJ 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

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

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

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

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

12C THE PHYSIOLOGY OF MUSCLE AND XERYE.

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.
It must be remembered, however, that, although the above
experiments demonstrate the practical "unfatigueableness" of
nerve fibers under ordinary conditions of stimulation, there are
some reasons to make us hesitate in supposing that in these
structures functional activity is always without a depressing
effect upon irritability. In the first place it has been shown
that the nerve exhibits the phenomenon of a " refractory period."
That is to say, for a certain brief interval after stimulation it is
in a non-irritable condition. 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 stimulus is ineffective so far as
can be determined by the response of an attached muscle or by
means of a capillary electrometer.* 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 irritability of
the nerve is greatly depressed by narcotics, f this critical interval
is much lengthened; two stimuli with a rate of more than 10 per
second may give an effect only for the first stimulus. Garten
has shown 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
diminishes in extent quite rapidly, and recovers after a short
rest.| So also it has boon found that while a nerve deprived of
oxygen, by keeping it in an atmosphere of nitrogen, loses its
irritability after a certain time, this event occurs much more
rapidly if the nerve is stimulated constantly. § This fact would
suggest, therefore;, that the ability of the nerve under normal
eircumstances to escape the results of fatigue may be due
possibly to the fact that the supply of oxygen is sufficiently
abundant to oxidize the fatigue substances formed during
activity.

Does the Nerve Fiber Show Any Evidence of Metabolism
during Functional Activity? The functional pari of a nerve
filicr 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 t runk is small, and its chemisl ry is bul little known.

'. »tch and Burch, "Journal of Physiology, " 24, 410, L899.
i I rdhlich, "Zeitschrift I', allgemeine Physiol.,"3, 468, L904.
| Quoted from Bierdermann, " Ergebnisse der Phyeiologie, " vol. ii, part ii,
p. 129.

§ Tliorncr, " Zeitechrifl f. flllg. Physiologic," S, 530, 1908.

NATURE OF THE NERVE IMPULSE. 121

The efforts that have been made to prove a metabolism in the
nerve fiber during activity have been directed along the lines
indicated by what is known of muscle metabolism. In a muscle
during contraction heat is produced, the substance of the muscle
shows an acid reaction, and among the products formed carbon
dioxid gas is perhaps the most prominent. Efforts to show similar
reactions in stimulated nerves have been unsuccessful. Rolleston*
investigated the question of heat production with the aid of a
delicate bolometer capable of indicating a difference of temperature
of 5~jot°C. The frog's sciatic was used, but no increase in tem-
perature during stimulation could be demonstrated. No change
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.
More positive evidence for the occurrence of a nerve metabolism
during activity is found in the fact, already alluded to, that
oxygen plays a part in maintaining the irritability of nerves.
An excised frog's nerve loses its irritability in an atmosphere
deprived of oxygen and regains it promptly when oxygen is
again supplied. When stimulated in an atmosphere free from
oxygen the nerve shows signs of fatigue, while in the presence of
oxygen activity is maintained, one may say indefinitely, under
continuous stimulation. These facts warrant the belief that
oxygen is used by the nerve during activity, and presumably it
is used in this as in the other tissues to produce physiological
oxidations. An additional fact which points in the same
direction is the high value of the temperature coefficient for
nerve conduction, which has been referred to above. Bearing
these two general considerations in mind, we can hardly escape
the conviction that the functional activity of the nerve fiber is
connected with a chemical reaction of some kind, most probably a
reaction in which some material in the nerve undergoes oxidation.
Views as to the Nature of the Nerve Impulse. — The older con-
ceptions of the nerve principle, while they varied in detail, were
* Rolleston, "Journal of Physiology," 11, 208, 1890.

122 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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 discover}- that the nerve impulse travels with a relatively slow
velocity and is accompanied by a demonstrable change in the electrical
condition of the nerve, two main views regarding its nature have been
entertained. Many physiologists conceive the nerve impulse
as a progressive wave of chemical change which is started at one
end by the stimulus and is then self-propagated along the fiber.
The conception in general is represented by the transmission of a
spark along a line of gunpowder. The flame applied at one end
causes an explosive chemical change, which is then propagated
from point to point. The analogy is obviously very incomplete,
since in the train of gunpowder the material is entirely consumed,
whereas in the nerve an indefinite series of impulses may be trans-
mitted and with a strength varying with the intensity of the origina-
ting stimulus. This general view implies that a disassimilation or
catabolism occurs in the nerve, a breaking down of complex material
with the liberation of the potential chemical energy; it assumes,
in other words, that the wave of chemical change that sweeps
along a nerve fiber is similar to the wave of chemical change,
contraction wave, that passes over a muscle fiber. As was stated
in preceding paragraphs, there is no direct evidence for this
view, although the opinion seems to be growing that the
conduction of the nerve impulse depends upon an underlying
chemical reaction. On this view the electrical change that
accompanies the impulse is considered as a sort of by-action,
due probably to the formation of electrolytes in the reaction
and the subsequent accumulation of negatively charged ions
(anions). 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
li<|ui<l or the electrical current conveyed through a metallic con-
ductor. This view rests upon the fact, that no consumption of
material can he demonstrated in the acting nerve fiber, and that
apparently the fiber can conduct indefinitely without showing
fatigue. Various suggestions have been offered as to the character
of this physical change, hut the one that is perhaps most worthy
of consideration identifies the nerve impulse with the negative
electrical charge that is known to pass along the fiber. It is as-
sumed that this electrical charge constitutes the nerve impulse*,
and to explain its occurrence and propagation from a physical

NATURE OP THE NERVE IMPULSE. 123

standpoint it has been supposed that the nerve fiber has a struc-
ture essentially similar to the "core conductor" (see p. 109), in
that it contains a central thread surrounded by a liquid sheath
of less conductive material. The central thread may be sup-
posed to be the axis cylinder and the less conductive sheath the
surrounding myelin, or perhaps, to follow another suggestion
that fits the non-medullated as well as the medullated fibers,
the central threads are represented by the neurofibrils within the
axis cylinder and the surrounding sheath by the perifibrillar
substance. That the axis cylinder is a better conductor than
the myelin sheath has been indicated by the microchemical
researches of Macallum. This observer has shown that in the
axis cylinder the chlorids exist in greater concentration than in
the surrounding sheath.* The point of importance is that, with
a core model (see Fig. 50), consisting of a glass tube with a core
of platinum wire and a sheath of solution of sodium chlorid,
0.6 per cent., electrical phenomena can be obtained similar to
those shown by the stimulated nerve. If an induction current,
serving as a stimulus, is sent into one end of such an artificial
nerve and from the other end two leading off electrodes are
connected with a galvanometer, then we can demonstrate by
means of the galvanometer that an electrical charge is propagated
along the model at each application of the stimulus. And, as
such a moving electrical disturbance is the only objective
phenomenon known to occur in the stimulated nerve, it has been
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." Other similar
theories have been proposed in which the negative charge is
accounted for on the view that it is the outcome of a purely
physico-chemical reaction of dissociation in which there is no
permanent destruction of material with liberation of potential
chemical energy. Macdonald,f for example, has shown by
microchemical reactions that the axis cylinder contains potassium
so combined with a colloid material as to form a compound that
does not dissociate. On injury, however, or on stimulation this
compound is dissociated and the potassium may be detected,
being liberated as a positively charged ion, while the colloid

* Macallum, "Proceedings of the Royal Society," 1906, B. Ixxvii., 165.
t Macdonald, "Proceedings of the Royal Society," B. Ixxvi., 322.

124 THE PHYSIOLOGY OF MUSCLE AND NERVE.

constituting the negative ion passes possibly into a gel condition.
The more rapid diffusion of the potassium ions would leave any
portion of the nerve in this condition with a negative charge.
It is further assumed that the process, when initiated by a
stimulus, is a reversible one — after the passage of the impulse
the colloid and potassium again unite to form an electrically
neutral molecule. It should be added that these and, indeed,
all specific theories of the nature of the nerve impulse are, at
present, matters for discussion and experiment among specialists.
We are far from having an explanation of the nerve impulse
resting upon such an experimental basis as to command general
acceptance.*

Qualitative Differences in Nerve Impulses and Doctrine of Spe-
cific Nerve Energies. — Whether or not the nerve impulses in vari-
ous nerve fibers differ in kind is a question of great interest in physi-
ology. The usually accepted view is that they are identical in
character in all fibers and vary only in intensity. According to
this view, a sensory nerve — the auditory nerve, for instance — car-
ries impulses similar in character to those passing along a motor
nerve, and the reason that in one case we get a sensation of hearing
and in the other a contraction of a muscle is found in the manner
of ending of the nerve, one terminating in a special part of the cortex
of the cerebrum, the other in a muscle. From this standpoint
the nerve fibers may be compared to electrical wires. The current
conducted by the wires is similar in all cases, but may give rise to
very different effects according to the way in which the wires ter-
minate, whether in an explosive mixture, an arc light, or solutions
of electrolytes of various kinds. We have in physiology what is
known as the doctrine of specific nerve energies, first formulated
by .Johannes Miiller. This doctrine expresses the fact that nerve
fibers when stimulated give only one kind of reaction, whether
motor or sensory, no matter in what way they may be stimulated.
The optic nerve, for instance, gives us a sensation of light, usually
because light waves fall on the retina and thus stimulate the optic
nerve. But if we apply other forms of stimulation to the nerve
they will also, if effective, give a sensation of light. Cutting (he
optic nerve or stimulating it with electrical currents gives visual
sensations. On the identity theory of the nerve impulses the
specific energies of the various nerves— that is, the fact, that each
only one kind of response -is referred entirely to the charac-
teii-t ics of 1 he t issue in which t he fibers end. If, as has been said,

* For :i summary <>f the literature upon the nature "i the nerve impulse
consult Boruttau, "Zeit. I', allg. Physiologie, " I, I, Sammelreferate, l!>()2;
Biedermann, "Ergebnisse der Physiologie, " vol. ii, part ti, L903; Hering,
"Zur Theone der Nerventh&tigkeit, " L899; Gotch, Scliiifer's "Text-book of
Physiology," vol. ii, L900.

NATURE OF THE NERVE IMPULSE. 125

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. 82).

The Nutritive Relations of the Nerve Fiber and Nerve Cell.
■ — In recent times in accordance with the so-called neuron doctrine
(see p. 131) every axis cylinder has been considered as a process of
a nerve cell, and therefore as a part, morphologically speaking, of
that cell. However this may be, there is excellent experimental
evidence to show that the physiological integrity of the axis cylinder
depends upon its connection with its corresponding nerve cell. This
view dates from the interesting work of Waller,* who showed that
if a nerve be severed the peripheral stump, containing the axis cyl-
inders that are cut off from the cells, will degenerate in a few days.
The process of degeneration brought about in this way is known
as secondary or Wallerian degeneration. The central stump, on
the contrary, remains intact, except for a short region immediately
contiguous to the wound, for a relatively long period, extending
perhaps over years. Waller, therefore, spoke of the nerve cells as
forming the nutritive centers for the nerve fibers, and this belief
is generally accepted. In what way the cell regulates the nutrition
of the nerve fiber throughout its whole length is unknown. Some of
the cells in the lumbar spinal cord, for instance, give rise to fibers of
the sciatic nerve which may extend as far as the foot, and yet
throughout their whole length the nutritive processes in these fibers
are dependent on influences of an unknown kind, emanating from

* Waller, "Miiller's Archiv," 1852, p. 392; and "Comptes rend us de
l'Acad. de la Science," vol. xxxiv., 1S52.

126 THE PHYSIOLOGY OF MUSCLE AND NERVE.

the nerve cells to which they are joined. These influences may
consist simply in the effect of constant activity; that is, in the
conduction of nerve impulses, or there may be some kind of an
actual transferal of material. This latter idea is supported by the
interesting fact, which we owe to Meyer, that tetanus and diph-
theria toxins may be transmitted to the central nervous system
by way of the axis cylinders of the nerve fibers. By means of his
method Waller investigated the location of the nutritive centers
for the motor and sensory fibers of the spinal nerves. If an anterior
root is cut the peripheral ends of the motor fibers degenerate
throughout the length of the nerve, while the fibers in the stump
attached to the cord remain intact; hence the nutritive centers
for the motor fibers must lie in the cord itself. Subsequent histo-
logical work has corroborated this conclusion and shown that the
motor fibers of the spinal nerves take their origin from nerve cells
lying in the anterior horn of gray matter in the cord, the so-called
motor or anterior root cells. If the posterior root is cut between
the ganglion and the cord, the stump attached to the cord degener-
ates; that attached to the ganglion remains intact, and there is no
degeneration in the nerve peripheral to the ganglion (Fig. 55). If,

Fig. 55. — Diagram to show the direction of degeneration on section of the anterior
and the posterior root, respectively. The degenerated portion is represented in black.

however, this root is severed peripherally to the ganglion degenera-
tion takes place only in the spinal nerve beyond the ganglion. The
nutritive '•enter, 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 libers in the
crania] 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
arise from sensory ganglia lying outside the nervous axis,

NATURE OF THE NERVE IMPULSE. 127

such, for instance, as the spiral ganglia of the cochlear nerve, or
the ganglion semihmare (Gasserian ganglion) of the fifth cranial
nerve.

Nerve Degeneration and Regeneration. — When a nerve
trunk is cut or is killed at any point by crushing, heating, or other
means all the fibers peripheral to the point of injury undergo de-
generation. This is an incontestable fact, and it is important to
bear in mind the fact that the definite changes included under
the term degeneration are exhibited only by living fibers. A
dead nerve or the nerves in a dead animal show no such changes.*
The older physiologists thought that if the 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 degeneration 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 degeneration differs somewhat
for the different kinds of fibers found in the animal body. In the
dog and in other mammalia the degeneration begins in a few (four)
days; in the frog it may require from thirty to one hundred and
forty days, depending upon the season of the year, although if the
frog is kept at a high temperature (30° C.) degeneration may
proceed as rapidly as in the mammal. In the dog it proceeds so
quickly that the process seems to be simultaneous throughout the
whole peripheral stump, while in the frog, and, according to Bethe,
in the rabbit, it can be seen clearly that the degenerative changes
begin at the wound and progress peripherally. The fibers break
up into ellipsoidal segments of myelin, each containing a piece of
the axis cylinder, and these segments in turn fragment very irregu-
larly into smaller pieces which eventually are absorbed f (Fig. 56).
The central stump whose fibers are still connected with the nerve
cells undergoes a similar degeneration in the area immediately
contiguous to the wound, but the degenerative processes extend
for only a short distance over an area covering a few internodal
segments. Although the central ends of the fibers remain sub-
stantially intact, it is interesting to find that the nerve cells from
which they originate undergo distinct changes, which show that
they are profoundly affected by the interruption of their norma)
connections (see p. 129). In the peripheral end the process of
regeneration begins almost simultaneously with the degenerative

* See Van Gehuchtea, "Le Nevraxe," 1905, vii., 203.

t See Howell and Huber, "Journal of Physiology," 13, 335, 1892; also
Mott and Halliburton, "Proceedings Royal Society," 1906, B. lxxviii., 259,
and Cajal, "Trabajos del laboratorio de investigaciones biologicas (Univ. of
Madrid)," vol. 4, 119, 1906.

12S THE PHYSIOLOGY OF MUSCLE AND NERVE.

changes; the two proceeding, as it were, hand in hand. The regen-
eration is due to the activity of the nuclei of the neurilemmal sheath.
These nuclei begin to multiply and to form around them a layer of
protoplasm, so that as the fragments of the old fiber disappear
their place is taken by numerous nuclei and their surrounding
cytoplasm. Eventually there is formed in this way a continuous
strand of protoplasm with man}' 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. 57). 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 ehemotaxis 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 tul >es, 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 " ehemotaxis."

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. 58).
It is possible that this result is (\ue to local processes in the
band fiber stimulated by nutritive influences of some kind from
the central stump, but more probably there is an actual down-
growth of the axis cylinders from the central ends. In support
of this hitter view, it may be said thai the outgrowth of the
new axis cylinders from the old ones present in the libers of the
central stump has been followed more or less successfully by a
number of histologists.

From .'] practical standpoint it- re interesting to note that this influence
of the central stump may be exerted months or even years after the injury
to i he aerve. The peripheral si ump after reaching the stage <>f " band fibers "
i ready, &t ii were, for the influence of the central end, and canes are onprecord
in which a secondary Buture was made a Long time after the original injury,
with the resuh thai functional activity was restored to the nerve.

Bethef has thrown some doubl upon this view, for he has shown appar-
ently thai in young mammals (eight days to eighl weeks) the regeneration of

* Forsmanns, "Zeigler's Beitrage," 27, 216, L902.

f Bethe, "Allgemeine Anat. u. Physiologie des Nervensystems, " 190.3.

Fig. 56. — Histology of a degenerating nerve fiber.

Fig. 57. — Embryonic fibers in a regenerating nerve

Fig. 58. — A newly developed fiber in a regenerating nerve fiber,

NATURE OF THE NERVE IMPULSE. 129

the fibers in the peripheral stump does not stop at the stage of " band fibers,"
but progresses until perfectly normal nerve fibers are produced, even though
no connection is made with the central stump. It should be added, however,
that the fibers so formed do not persist indefinitely unless they become con-
nected with the central stump. If this connection fails to take place, the
newly formed fibers will degenerate after an interval of some months. Still,
the fact, if true, that in the young fiber the regeneration is complete seems to
indicate definitely that the axis cylinder may arise independently of the fibers
in the central stump.

Whether or not Bethe's observations upon the autoregeneration of the
axis cylinders in the severed nerves of young animals can be accepted is at
present uncertain, but the balance of evidence seems to indicate that what
he took for autoregenerated fibers were really fibers which grew into the
degenerated trunk from the surrounding tissue. (For discussion with refer-
ences, see Barker, "Journal of the American Medical Assoc," 1906, Stefan-
owska, "Journal de Neurologie," 1906, Nos. 16-19, and Halliburton, "British
Med. Journal," May 11, 1907.)

Degenerative Changes in the Neuron on the Central Side
of the Lesion. — According to the Wallerian law of degeneration,
as originally stated, the nerve fiber on the central side of the injury
and the nerve cell itself do not undergo any change. As a matter
of fact, the central stump immediately contiguous to the lesion
undergoes typical degeneration and regeneration similar to that
described for the fibers of the peripheral stump. The immediate
degenerative changes in the fibers in the central stump were supposed
to extend back only to the first node of Ranvier, — to affect, there-
fore, only the internodal segment actually injured. Later it was
found that the degeneration may extend back over a distance of
several internodal segments. This limited degeneration on the
central side must be considered as traumatic, — that is, it involves
only those portions directly injured by the lesion. The central
end of the fiber in general was supposed to remain intact as long
as its cell of origin was normal. It was thought at first that after
simple section of a nerve trunk, in amputation, for instance, the
nerve cells and central stumps remain normal throughout the life
of the individual. Dickinson, however, in 1869 * showed that in
amputations of long standing the motor cells in the anterior horn
of the cord decrease in number and the fibers in the central stump
become atrophied. This observation has been corroborated by
other observers, and it is now believed that after section of a nerve
chronic degenerative changes ensue in the course of time in the
central fibers and their cells, resulting in their permanent atrophy.
We have, in such cases, what has been called an atrophy from
disuse. A fact that has been discovered more recently and that
is perhaps of more importance is that the nerve cells do undergo
certain definite although usually temporary changes immediately
after the section of the nerve fibers arising from them. It has been
shown that when a nerve is cut the corresponding cells of origin
* " Journakof Anatomy and Physiology," 3, 176, 1869.
9

130 THE PHYSIOLOGY OF MUSCLE AND NERVE.

may show distinct histological changes within the first twenty-four
hours. These changes consist in a circumscribed destruction of
the chromatin material in the cells (chromatolysisV, 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. 63).
The cell also becomes swollen and the nucleus may assume an
excentric position. These retrogressive changes continue for a
certain period (about eighteen days). After reaching their maxi-
mum of intensity the cells usually undergo a process of restitution
and regain their normal appearance, although in some cases the
degeneration is permanent. According to other observers a number
of the cells in the spinal cord and spinal ganglia undergo simple
atrophy after section of their corresponding nerves, and some of
the nerve fibers in the central stumps may also show atrophy,
while others undergo a genuine degeneration, which, however,
comes on much later than in the peripheral stumps. It seems
evident that the behavior of the cells and fibers on the central side
of the section is not uniform; atrophy rather than degeneration is
the change that is prominent, and this atrophy in some neurons
occurs early, while in others it is apparent only after a long interval
of time. An explanation of this variation in the reaction of the
nerve cells and their disconnected central stumps cannot yet be
given. On the peripheral side of the section, as stated above, the de-
generative changes are complete and affect all of the fibers.*

*Nissl, 'Allgemeine Zeitschrift f. Psychiatrie, " 48, 197, 1892. Also
Bethe, loc. cit., and Hanson, "Retrograde Degeneration in t he Spinal Nerves,"
The Journal of Comparative Neurology and Psychology, 1906, xvi., 265.

SECTION II.

THE PHYSIOLOGY OF THE CENTRAL

NERVOUS SYSTEM.

CHAPTER VI.

STRUCTURE AND GENERAL PROPERTIES OF THE
NERVE CELL.

The Neuron Doctrine. — Since the last decade of the nineteenth
century the physiology of the nervous system has been treated
from the standpoint of the neuron. According to this point of
view, the entire nervous system is made up of a series of units,
the neurons, which are not anatomically continuous with each
other, but communicate by contact only. It has been taught also
that each neuron represents from an anatomical and physiological
standpoint a single nerve cell. The typical neuron consists of
a cell body with short, branching processes, the dendrites, and a
single axis cylinder process, the axon or axite, which becomes a
nerve fiber, acquiring its myelin sheath at some distance from the
cell. According to this view, the peripheral nerve fibers are simpry
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

131

132

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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

The neuron doctrine, so far as the name at least is concerned, dates from
a general paper by Waldeyer,* in which the newer work up to that time was
summarized. The main facts upon which the conception rests were furnished
by His (lSSG"), 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
dendrite?, and the mode of connection of one nerve unit with another. The
view that these units are anatomically independent and on the embryological

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

aide are derived each from a single epiblastic cell (neuroblast) has proved
acceptable and mos1 helpful; but the validity of this hypothesis has been
called into question from time to time. As was stated on p. L28, Bethe has
claimed thai in young animals the nuclei of the neurilemma] sheath may
regenerate :i new nerve fiber containing axis cylinder and myelin Bheath, and
this fact, if true, .-it once bring into que tion the hitherto accepted belief
that the axis cylinder can I"- formed only as an outgrowth from a nerve cell.
Bome histologistf Apathy, Bethe, Nissl have also attacked the most
fundamental feature of the neuron doctrine the view, namely, that each
neuron represents an independent anatomical element. These authors
contend thai the neurofibrile of the axi cylinder pass through the nerve cells
and enter by way of a network into direct connection with the neurofibrils

*"Deut. med. Wochenschrift, " A891, p. 50.

PROPERTIES OF THE NERVE CELL. 133

of other neurons (see Fig. 64). The neurofibrils form a continuum through
which nerve impulses pass without a break from neuron to neuron. Ac-
cording to this conception, the ganglion cells play no direct part in the con-
duction 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 con-
tinuity. In the explanation given below of the activities of the nervous
system, the author, following the usual custom, 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 neurons of a definite polarity
as regards conduction were replaced by the more complex schema of inde-
pendent neurofibrils and a central reticulum in which a basis for polarity
and definite paths of conduction is lacking.*

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

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

The typical cell of this group is found in the dorsal root ganglia.
In the adult the two processes arise as one, so that the cell seems to
be unipolar, but at some distance from the cell this process divides
in T, one branch passing into the spinal cord via the posterior
root, the other entering the spinal nerve as a sensory nerve fiber
to be distributed to some sensory surface. Both processes become
medullated and form typical nerve fibers. That these apparently
unipolar cells are really bipolar is shown not only by this division
into two distinct fibers, but also by a study of their development
in the embryo. In early embryonic life the two processes arise
from different poles of the cell, and later become fused into an ap-
parently simple process (Fig. 60). 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.

* For discussion, see Barker, "Journal of the American Medical Associa-
tion," 1906, and Retzius, "Proceedings of the Royal Society," 1908, B.
vol. lxxx., 414.

134 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

The nerve cells found in the sensory ganglia exhibit, as a matter of fact,
a number of different types, some of which possess short dendritic processes.
These histological variations cannot as yet be given a physiological signifi-
cance, but their occurrence certainly seems to indicate a possibility that
the sensory ganglia may have a much more varied physiological activity
than has been attributed to them heretofore. For a recent description of
these ganglia and a classification of their cells under eight different types
consult Oajal in Ergebnisse der Anat. u. Entwickelungsgeschichte, vol. xvi.,
1906.

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 axis of the central nervous system.
It has been a question whether the sensory impulses brought
to the ganglion cells through the peripheral process (sensory

Via. 60. — Bipolar cells in the posterior root ganglion. Section through spinal pan-
glion of newborn mouse (Lenhossek) : a, The spinal ganglion; b, the spinal cord; C, the
posterior, d, the anterior root.

fiber) passes into the body of the cell before going on to the
eord or brain, or whether at the junction of the two processes
it -imply passes on directly to the cord. According to the
histological structure there is no apparent reason why an impulse

should not pass directly from tin; peripheral to the ('(Mitral
process at the junction, but whether or not this really occurs
and the relation of the ganglion cell to the conducting' path are

questions thai musl lie left- unsettled at present.

II. The multipolar cells. The processes of these colls 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. 59). According to the structure of this last,
processl , t his t ype may be classified under t wo heads: ( rolgi cells of

t he firsl and t he second type. The cells of t lie first, type are charac-

PROPERTIES OF THE NERVE CELL.

135

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 coilateralsl, 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
neurons. This kind of nerve
cell is frequently described
as the typical nerve cell.
Golgi supposed that it rep-
resents the motor type of
cell, and this view is, in a
measure, borne out by sub-
sequent investigation. The
distinctly motor cells of the
central nervous system —
such, for instance, as the
pyramidal cells of the cere-
bral cortex, the anterior horn
cells of the spinal cord, the
Pur kin je cells of the cere-
bellum— all belong to this

- _ — —

a-n

w

Fig. 61. — Golgi cell (second type).
The axon, a, divides into a number of
fine branches. — (From Obersteiner, after
Andriezen.)

Fig. 62. — Normal anterior horn cell
(Warrington), showing the Nissl granules in the
cell and dendrites: a, The axon.

type. But within the nerve axis 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. 61) are relatively less
numerous and important. They are characterized by the fact

lo6 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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

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

.--»*. «W?,N ..

j

Fig. 03. — Anterior horn cell fourteen days after section of the anterior root (Warring-
ton) : To .show the change in the nucleus and the Nissl granules, beginning chromatolysis.

presence of a material in the form of granules, rods, or masses
which stains readily with the basic anilin dyes, such as methylene
blue, thionin, or toluidin blue. This latter substance is spoken of
as the " chromophile substance," tigroid, or more frequently as
Nissl's granules, after the histologist who first studied it success-
fully. These masses or granules are found in the dendrites as well
as in the cell, but are absent from the axon (see Tig. G2). Little is
known of their composition or significance1, 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. 63). The non-staining

material Of the cell, according to most recent observers, contains

neurofibrils which are continued out into the processes, dendrites as
well a 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-

PROPERTIES OP THE NERVE CELL.

137

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. 64. 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.

Fig. 64. — 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.

General Physiology of the Nerve Cell. — Modern physiologists
have considered the cell body of the neuron, including the den-
drites, as the source of the energy displayed by the nervous system,
and it has been assumed that this energy arises from chemical
changes in the nerve cell, as the energy liberated by the muscle
arises from the chemical changes in its substance. It would follow
from this standpoint that evidences of chemical activity should be
obtained from the cells and that these elements should exhibit the
phenomenon of fatigue. Regarding this latter point, it is believed
in physiology that the nerve cells do show fatigue. The nerve
centers 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-
cuperation and the rapidity with which functional activity is lost

138 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

on withdrawal of the blood supply. Objectively, also, it has been
shown in the ergographic experiments (see p. 49) that the well-
known fatigue of the neuromuscular apparatus possibly affects
the nerve centers as well as the muscle. Assuming that the nerve
cells are the effective agent in the nerve centers, such facts indicate
that they are susceptible to fatigue. But we have no very direct-
proof that this property is possessed universally by the nerve cells
nor any indication of the probable differences in this regard shown
by nerve cells in different parts of the central nervous system.
It seems probable that under normal conditions — that is, under
the influence of what we may call minimal stimuli — some portions
of the nerve centers remain in more or less constant activity during
the day without showing a marked degree of fatigue, just as our
muscles remain in a more or less continuous state of tonic con-
traction throughout the waking period at least. Doubtless when
the stimulation is stronger the fatigue is more marked, because the
processes of repair in the nerve centers can not then keep pace
with the processes of consumption of material. Evidence of a
probable chemical change in the nerve cells during activity is found
also in the readiness with which the gray matter of the nervous
system takes on an acid reaction.* In the fresh resting state it
is probably alkaline or neutral, but after death it quickly shows an
acid reaction, due, it is said, to the production of lactic acid. Its
resemblance to the muscle in this respect leads to the inference
that in functional activity acid is also produced. Mosso states
that in the brain increased mental activity is accompanied by a
rise in the temperature of the brain. f His experiments were made
upon individuals with an opening in the skull through which a
delicate thermometer could be inserted so as to lie 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 by
a chemical change within the cells, since the excessive activity of
the nerve fells seems to be accompanied by some change in these
granules, and in abnormal conditions associated with loss of func-
tional activity (lie granules undergo chromatolysis,- — that is, the}'
are disintegrated and dissolved. < >bvious histological changes which
imply, of course, a change in chemical si ructure, have been observed
by a number of investigators.} All seem to agree that activity of
tin- tissue, whether normal or induced by artificial stimulation,
may cause visible changes in the appearance of the cell and its

* Langendorff, "Centralbl. f. 'I. med. VViss.," 1886. Bee also Halliburton,
'The Croonian Lecture on 'I \><- Chemical Side of Nervous Activity," 1901.
\]., ■, Dii Temperatui des Gehirns," L894.

pecially Hodge, "Journal of Morphology," 7, !).r», 1S".)2, and
9, 1, 1894.

PROPERTIES OF THE NERVE CELL.

139

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. 65).

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

Fig. 65. — 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.)

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

140 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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,— c. 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 clue to the first stimulus has passed off, the second stimulus,
instead of adding its effect to that of the first, simply has no effect
at all; it finds the nerve unirritable.* According to this result,
we should expe^ that a summation of the effects of rapidly
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 ma}' 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 eells. The motor cells of the brain and cord discharge
their impulses under normal stimulation at a certain rhythm

which was formerly supposed to average about 10 per second,
but is now estimated as varying between certain wide limits,

perhaps from 40 to 100 per second (p. 46). For any particular
group of nerve cells the evidence indicates that it has a practically
constanl rate whatever may be the intensity of the stimulus

and, indeed, when artificial stimulation is used and the rate is

varied, the evidence that we have so far appears to show that
the nerve cells do not discharge in a one to one correspondence
with the rate of stimulation, as is the case, within limits, for
muscle and nerve fibers. On the contrary, under such circum-
• Gotch and Burch, "Journal of Physiology," 24, 410, L899.

PROPERTIES OP THE NERVE CELL, 141

stances the discharge from the nerve cells takes place in a
rhythm characteristic of the cells and independent of that of
the stimulation.* From this point of view we must look upon
the nerve cells as possessing fundamentally a rhythmic activity,
as in the case of the heart.

The Refractory Period of the Nerve Cell. — The peculiar
rhythm of the active nerve cell just referred to in the para-
graph above is explained most satisfactorily by an assumption
first used in connection with the rhythmical beat of the heart. As
will be explained more fully in the section on the physiology of
the heart, it has been found that after the contraction of the
heart begins it is unirritable to artificial stimuli, and that its
irritability is recovered during the period of rest, — the diastole.
The heart has, therefore, alternate periods of irritability and
unirritability. The latter phase, the condition in which the heart
muscle will not respond to stimulation, is known as the refractory
period, or refractory phase. A similar conception has been applied
to the nerve cell, to explain its rhythmic activity. It has been
applied also to a phenomenon of a somewhat different order,
namely, to a loss of irritability exhibited by some of the spinal
centers for a brief period after reflex excitation (Sherrington).
Reasoning from analogy with the muscle, we might suppose
that this temporary loss of irritability is due to some product
of the chemical reaction that is assumed to underlie nervous
activity. Using this terminology, it is probable that the cells
in different parts of the nervous system may have different
refractory periods. In the case of the normal nerve fiber
(see p. 120) it will be recalled that the refractory period is very
brief — say, 0.006 sec. — but varies with the condition of the
fiber, since in the narcotized fiber it may be as much as 0.1 sec.

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

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 arc 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.
Modem interesl in the subject was excited by the numerous works
of Marshal] Hall (1832-57), who contributed a number of new
facts with regard to such acts, and formulated a view, not now
accepted, I hat t hese reflexes are mediated by a special set of fibers -
i he excitomotor fillers.

In describing reflexes the older physiologists had in mind only
reflex movements, but at the present time we recognize that the

reflex act mayaffecl not only the muscles, voluntary, involuntary,

and cardiac, hut also 1 he glands. We have to deal with rellex

Becretions as well as reflex movements.

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

* Sec Eckhard, " Geschichte der Entwickelune der Lehre von den Eteflex-
eiBcheinungen," "Beitr&ge zur Anatomie u. Physiologie," Giessen, 1881, vol.
ix.

I IL'

REFLEX ACTIONS.

143

cording to the neuron theory, therefore, the simplest reflex arc
must consist of two neurons: the sensory neuron, whose cell
body lies in the sensory ganglia of the posterior roots or of
the cranial nerves, 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 reprensented in Fig. 66. 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 is represented in Fig. 67, or they may make
connections with intermediate cells which, in turn, are con-
nected with one or more motor neurons (Fig. 68). According

Fig. 66. — 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

144

PHYSIOLOGY OF CENTKAL NERVOUS SYSTEM.

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

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

I'ig. 07. — Kolliker's schema to show
the -lireet reflex urc. It .shows the pos-
terior tool IiIkt (black) entering the
oord, dividing in Y. and connecting with
motor i-'il (red) by means of collater-
als.

Fin. OS. — Kolliker's schema to
show the reflex are with intercal-
ated tract cells. Posterior root liber,
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-
tion- in the nervous System are more complex and the relictions

are therefore less simple and less easily kept constant.

Spinal Reflex Movements. The reflex movements obtained

from the spinal cord or from ot her parts of thecentral nervous system

REFLEX ACTIONS. 145

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 Avhich a number of muscles — perhaps all the muscles — are con-
tracted convulsively, without co-ordination and with the pro-
duction of disorderly and useless movements. Of these groups,
the co-ordinated reflexes are by far the most interesting. They
can be obtained to perfection from the reflex frog. In such an
animal no spontaneous movements occur if the sensory surfaces are
entirely protected from stimulation. A sudden stimulus, however,
of sufficient strength applied to any part of the skin will give a
definite and practically invariable response in a movement which
has the appearance of an intentional effort to escape from or remove
the stimulus. If the toe is pinched the foot is withdrawn — in a
gentle manner if the stimulus is light, more rapidly and violently,
but still in a co-ordinated fashion, if the stimulus is strong. If
the animal is suspended and various spots on its skin are stimulated
by the application of bits of paper moistened with dilute acetic
acid the animal will make a neat and skillful movement of the
corresponding leg to remove the stimulating body. The reactions
may be varied in a number of ways, and in all cases the striking
features of the reflex response are, first, the seemingly purposeful
character of the movement, and, second, the almost mechanical
exactness with which a definite stimulus will give a definite response.
This definite relationship holds only for sensory stimulation of the
external integument, the skin and its organs. It is obvious, in
fact, that a muscular response can be effective only for stimuli
originating from the external surface. Stimuli from the interior
of the body exert their reactions, for the most part, upon the plain
musculature and the glands. The convulsive reflexes may be
produced by two different means : (1) By very intense sensory
stimulation. The reflex response in this case overflows, as it were,
into all the motor paths. A variation of this method is seen in the
well-known convulsive reaction that follows tickling. In this case
the stimulus, although not intense from an objective standpoint,
is obviously violent from the standpoint of its effectiveness in
sending into the central nervous system a series of maximal sensory
impulses. (2) By heightening the irritability of the central nervous
system. Upon the reflex frog this effect is obtained most readily
by the use of strychnin. A little strychnin injected under the
10

14G PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

skin is soon absorbed and its effect is shown at first by a greater
sensitiveness to cutaneous stimulation, the slightest touch to
the foot causing its withdrawal. Soon, however, the response,
instead of being orderly and adapted to a useful end, becomes
convulsive. A mere touch of the skin or a current of air will throw
every muscle into contraction, and the extensors being stronger than
the flexors the animal's body becomes rigid in extension at every
stimulation. The explanation usually given for this result is that
the strychnin, acting upon some part of the nerve cells, increases
greatly their irritability, so that when a stimulus is sent into the
central nervous system along any sensory path from the skin it
apparently radiates throughout the cord and acts upon all the
motor cells. This latter supposition leads to the interesting con-
clusion that all the various motor neurons of the cord must be in
physiological connection, either direct or indirect, with all the
neurons supplying the cutaneous surface. The further fact that
under normal conditions the effect of a given sensory stimulus is
manifested only on a limited and practically constant number
of the motor neurons seems to imply, therefore, that normally the
paths to these neurons are more direct and the resistance, if we
may use a somewhat figurative term, is less than that offered by
other possible paths. Muscular spasms are observed under a number
of pathological conditions, l'<>r instance, in hydrophobia. We arc;
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 oiler 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
leas! resistance, as they have been called, are in part preformed
and in pari are laid down by the repeated experiences of the indi-
vidual. Thai is, in each animal a definite structure may be sup-
po ed to exisl in the cord; each sensory neuron is connected with
a group of motor neurons, to some of them more directly than to

others, and we may imagine, therefore, a system of reflex apparatuses

Or mechanisms which when properly stimulated will react, always
in the same way. And, indeed, in spite of the adapted character

of the reflexes under consideration their automaton-like regularity

i an indication ihat their production is due to a fixed mechanical

REFLEX ACTIONS. 147

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

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

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

14S PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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

Reflex Time. — Since nerve centers are involved in a reflex
movement, 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 needed for the processes within
the nerve cells. Helmholtz, who first made experiments of this
kind, stated that the time required within the nerve centers
might be as much as twelve times as great as that estimated
for the conduction along the motor and sensory nerves
involved in the reflex. Most observers state that the time
within the center varies with the strength of the stimulus,
being less, the stronger the stimulus. It varies also with the
condition of the nerve centers, being lengthened by fatigue
and other conditions that depress the irritability of the nerve
cells. By reflex time or reduced reflex time we may designate
the time required for the processes in the center, — that is, the total
time less that required for transmission of the impulse along the
motor and sensory fibers and the latent period of the muscle con-
tract ion. 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 ol her
eye. The total time for the reflex was, on an average, from 0.0578
sec. to 0.0662 ^-i'. Ih; estimated that the time for transmission of
the impulse along the sensory and motor pal lis, together wit h the

latent period of the muscle, amounted to 0.0107 sec So that the

t rue reflex I ime from his determinations varied between 0.0 171 and

0.0555 sec. Mayhew,* using a more elaborate method, obtained

for t he total I ime a mean figure equal to 0.0420 ^'C If Kxner's

correction is applied then the true reflex time according to this de-
termination is equal to 0.0313 see. In a series of experiments
made upon frogs, in which the efferenl response to stimulation

of the afferent fibers Of the sciatic nerve was measured by the

electrical variation in the muscle involved, Buchanan finds that

the delaj in the cord, when the reflex was on the same side, was
* Mayhew, "Journal of Exp. Medicine," 2, 35, L897.

REFLEX ACTIONS. 149

equal to 0.01 to 0.02 sec. If the reflex was on the crossed side
about double this time was consumed in the cord. This delay
of the velocity of transmission of an impulse in the nerve centers
is a factor which must vary somewhat in different parts of the
nervous system. It has been shown that in certain cases, at
least, when strong stimuli are used the latent period of a reflex
is not greater than would be accounted for by transmission
through the nerve fibers and by the latency of the muscular
contraction. Thus Francois Frank, in an experiment in which
the gastrocnemius muscle of one side was made to contract
reflexly by stimulation of the afferent root of a lumbar nerve
on the other side, records a latent period of only 0.017 sec.
Evidently in such a case there was no perceptible delay in
passing through the nerve centers of the lumbar cord.

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-
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 chloricl — 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 centers of respiration and micturition
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 inhibitor}' 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

* Setschenow, " Physiologische Studien iiber d. Hemmungs-Mechanisnien
f. d. Reflexthatigkeit im Gehirn d. Frosches," Berlin, 1S63.

150 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

the time relations, intensity, or quality of the nerve impulses.
Regarding the fact, however, there can be no question, and it
constitutes a most important factor in the interaction of the dif-
ferent parts of the nervous system. It is possible that this factor
explains why a normal frog gives reflexes that are so much less
constant and less predictable than 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 by 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. The importance of the process of inhibition
in the normal movements of the body is illustrated strikingly
by the phenomenon known as reciprocal inner rat ion, which has
been investigated chiefly by Sherrington.* This observer has
found that when a flexor muscle is stimulated reflexly there is
at the same time a relaxation or loss of tone in its antagonistic
extensor, which is explained as being due to an inhibition of the
motor cells of the extensor in the cord. Reflex stimulation of
the extensor is accompanied similarly by an inhibition of the
tone of the antagonistic flexor. This phenomenon has been
demonstrated not only for reflex stimulation of the cord but
also for voluntary movements (Athanasieu) and for electrical
stimulation of the cortical centers. The motor centers of the
muscles surrounding the joints are apparently so connected in
pairs that when one is excited the center of the corresponding
antagonist is inhibited. This reciprocating mechanism dis-
appear- under condil i < > 1 1 s , such as si rychnine-poisoning, in which,
according i<> the usual belief, the irritability of the centers is
greatly increased. A relationship quite comparable' to the
reciprocal innervation, although working in only one direction,
is exhibited by Hie peripheral nerve plexuses in the intestinal

canal in the so-called law of the intestines (see p. 701). A

brief statement of the more or less unsatisfactory theories of

inhibit ion is given in connect ion with t he inhibitory action of the
VagUS nerve "n the heart beat, (see p. 569). It- should be added,
however, in lids Connection, that, stimulation of the cord, and

probably of other parts of the nervous system, from two different

sources may resull not only in an inhibition of the reflex normally

occurring from one of the stimuli, but under some circumstances

* Sherrington, "The Integrative Action of the Nervous System," 1906,
p. 84.

REFLEX ACTIONS. 151

may give an augmentation or reinforcement of the reflex. A
striking example of this augmenting effect is given below in the
paragraph upon the knee-kick.

Influence of the Condition of the Cord on its Reflex Ac-
tivities.— The time and extent of the reflex responses may be
altered greatly by various influences, particularly by the action
of drugs. The effect in such cases is usually upon the nerve centers,
—that is, upon the cells themselves or upon the connections between
the terminal arborization and the dendrites — the process of conduc-
tion within the sensory and motor fibers being less easily affected.
A convenient method of studying such influences is that employed
by Turck. 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
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

152 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

reflex effects upon the important centers in the medulla, such
as the vasomotor center, the respiratory center, and the cardio-
inhibitory center, the winking of the eye, sneezing, the light reflex
upon the sphincter muscle of the iris, and many other similar cases
might be enumerated. All of these reactions will be described
and discussed in their proper places. The conscious reactions of
the brain are not included among the reflexes by virtue of the defi-
nition which lays stress upon the involuntary characteristic of the
reflex response, but it should be remembered that, so far as the
nervous mechanism is concerned, these conscious reactions do not
differ from the true reflexes. When we voluntarily move a limb
the movement is guided and controlled by sensory impulses from the
muscles put into action. The fibers of muscle sense from these
muscles convey sensory impulses through a chain of neurons to
the cortex of the brain and there the impulses doubtless affect and
set into action the motor neurons through which the movement is
effected. So far as we know, the discharges from the efferent
neuron of the brain are not really automatic, but are conditioned
or originated by stimuli from other neurons; so that the activities
of the brain are carried on by a mechanism of one neuron acting
on another, just as in the case of the reflex arc. The added feature
of a psychical factor, a reaction in consciousness, enables us to draw
a line of distinction between these activities and those of so-called
pure reflexes; but the distinction is perhaps one of convenience
only, for, although the extremes may be far enough apart to suit
the definition, many intermediate instances may be found which
an- 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 thai the continual adjustment of certain sensory impulses to

certain co-ordinaled movements results in the formation of a more
or less complex reflex arc, a eel of pal hs of least resistance.

Reflexes through Peripheral Ganglia Axon Reflexes.—
Many attempts have been made by physiologists to ascertain
whether or not reflexes can occur through the peripheral nerve
ganglia, lying outside the central nervous system. With regard
to the posterior root ganglia, it has usually been supposed that
they cannot exhiliit reflexes. When the posterior rool con-
necting auch a ganglion to the cord is severed, then, according
to our usual conception, the cells in the ganglia are cut off
from all connections with the peripheral tissues by efferent

REFLEX ACTIONS.

153

paths. This usual view may not, however, be correct. On
the physiological side we have the fact (see p. 83) that stimu-
lation of certain of the posterior root ganglia undei such cir-
cumstances does give peripheral effects
on the blood-vessels, causing a vascular
dilatation in a certain region. On the
histological side Cajal* and others have
shown that some of these cells are provided
with a pericellular nerve network, which
is an afferent path so far as the cell is con-
cerned, while the axon of the cell con-
stitutes an efferent path. Whether these
cells form a special group of efferent cells
lying within the sensory ganglion, or
whether they are sensory cells discharging
into the cord and stimulated reflexly
through the nerve network as well as
through the peripheral process of the axon,
cannot be said. The subject is one full
of interest to physiology. In the ganglia
of the sympathetic nerve and its appen-
dages 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 possi-
ble that in any ganglion of this type there
might be sensory and motor neurons so
connected as to make the ganglion an
independent reflex center. Numerous

experiments have been made to determine experimentally
whether reflexes can be obtained 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 Fig. 277). 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 clown the other hy-
pogastric nerve; the reaction has every appearance of being a
true reflex. Nevertheless, Langley and Anderson, f who have
studied the matter with especial care, are convinced that in this

* Cajal, "Ergebnisse der Anat. u. Entwickelungsgeschichte, " vol. xvi.,
1906.

t Langley and Anderson, "Journal of Physiology," 16, 410, 1894.

Fig. 69.— 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.

1")4 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

and similar case.-? we have to do with what they call pseudo-
reflexes or axon reflexes. The idea underlying 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. 69, may connect by collaterals with
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 thai 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 :i 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 \&
further emphasized. The idea of a more or less continuous but
vai ■■. ing 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, —

REFLEX ACTIONS. 155

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

In the first place, there was, of course, a total paralysis of volun-
tary movement in the muscles innervated normally through the
parts of the cord removed, and a complete loss of sensation in the
same regions, particularly of cutaneous and muscular sensibility.
In the second place, the visceral organs, including the blood-vessels,
were shown to be much more independent of the direct control of
the central nervous system. While these organs in the experiments
under consideration were still in connection with the sympathetic
ganglia and in part with the brain through the vagi, still their
connections with the central nervous system, particularly as
regards their sensory paths and the innervation of the blood-vessels,
were in largest part destroyed. The immediate effect of this
destruction would have been the death of the animal if the care

* Goltz and Ewald, "Pfl tiger's Archiv fur die gesarnmte Physiologic, " 63,
362, 1896.

156 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

of the observer hud not replaced, in the beginning, the normal
control exercised by the nervous system through the spinal nerves;
but later this careful nursing was not required. While these organs,
therefore, are capable of a certain amount of independent activity

and co-ordination, they are normally controlled through the various
reflex activities of the brain and cord. In the third place, it is
noteworthy that the adaptability of the cordless portion of the
animal was distinctly less than normal. Its power of preserving a
constant body temperature was more limited than in the normal
animal, and the susceptibility to inflammatory disturbances in the
visceral organs was greatly increased. It seems evident, from these
facts, that, although the animal was living, its power of adaptation to
marked changes in the external or internal environment was greatly
lessened, and this fact illustrates well the great general importance
of the spinal cord and brain as reflex 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 ( 'irculat ion.

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. Accord-
ing to Sherrington, the parts of this muscular mass chiefly
concerned are the m. vastus medialis and m. vastus intermedins.
In order to obtain the muscular response it is usually neces-
sary to put the quadriceps under some ten-ion by flexion of the
leg. This end is achieved 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 greal majority of normal persons, and this
fad has made it an im port ant diagnostic sign in many diseases
of the spinal cord. The import mice of 1 he reaction for such

purposes was first brought out by the work of Erb and Westphal*
in 1875.

Reinforcement of the Knee-jerk. It was first shown by
Jendrassik (1883) thai the extent of the jerk may be greatly aug-
mented if, at the time i he blow is si ruck upon the tendon, a si rong
voluntary movement is made by the individual, such as squeezing

the hands together tightly or clenching the jaws. This phenomenon
* Erb and We tphal, "Archiv f. Psychiatrie," L875, vol. v.

REFLEX ACTIONS.

157

was studied carefully in this country by Mitchell and Lewis,* 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 byExner to describe a similar phenom-
enon, is also used. It is found that by a reinforcement the knee-
jerk may be demonstrated in some individuals in whom the ordi-
nary blow upon the tendon fails to elicit a response. Bowditch and
Warrenf 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

Fig. 70. — Showing in millimeters the amount by which the "reinforced" knee-kick
varied from the normal, the level of which is represented by the horizontal line at 0, "nor-
mal." The time intervals elapsing between the clenching of the hands (which constituted
the reinforcement) and the tap on the tendon are marked below. The reinforcement is
greatest when the two events are nearly simultaneous. At an interval of 0.4 sec. it
amounts to nothing; during the next 0.6 sec. the height of the kick is actually diminished,
while after an interval of 1 sec. the negative reinforcement tends to disappear; and when
1.7 sec. is allowed to elapse the height of the kick ceases to be affected by the clenching of
the hands. — (Bowditch and Warren.)

interval of from 0.6 to 0.9 sec. Beyond this point the effect became
less noticeable, and at an interval of 1.7 to 2.5 sec. the reinforcing
act had no influence at all upon the jerk. These relations are
shown in the accompanying curve (Fig. 70). These authors con-

* Mitchell and Lewis, " American Journal of Med. Sciences," 92, 363, 1886.
f Bowditch and Warren, "Journal of Physiology," 2, 25, 1890.

158 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

firmed also i ho 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
functional activity at one part may 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 refiexly 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 reilex 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 reilex 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 femoral
nerve, and pathological lesions upon man as well as direct
experimental investigation upon monkeys prove thai if either the
posterior or anterior roots of the third mid fourth lumbar spinal
nerve- are destroyed the knee-jerk disappears entirely. The oppo-
nents of the redex view explain this fact by the theory that in
order tor the quadriceps to respond it, must be in a condition
oi tonus. This tonus depends upon the reflex arc, the sensory

impulses from l he muscle Serving to keep it in that condition

of subdued contraction known as tone. On this view destruc-
tion of the reflex arc renden the muscle less irritable, so that if,
will not respond by a contraction to the sudden mechanical exten-
sion or pull caused by the blow on the temlon. The adherents of
thi- view lay emphasis upon two facts: First, the knee-jerk is a
* Exner, " Vrchiv f. 'Ii<- gesammte Phy iologie," 27, 112, 1882.

REFLEX ACTIONS. 159

simple contraction, and not a tetanus, and, generally speaking,
the motor centers of the cord discharge a series of impulses when
stimulated. In answer to this objection it may be said that
while muscular contractions produced reflexly are usually
tetanic, it does not follow that this is invariably the case. Sher-
rington* has shown, for instance, that an undoubted reflex
designated by him as the "extensor thrust," which also involves
the extensor muscles of the hind leg, is very short lasting, requir-
ing perhaps only A- sec, and judged by this standard is as much
of a simple contraction as the knee-jerk. The "extensor thrust"
is a sharp contraction of the extensor muscles of the hind leg
aroused by pressure upon the plantar surface of the hind foot.
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
man, from 0.025 to 0.073 sec. 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; Waller and Gotch, using the
rabbit, found the time to be only 0.008 to 0.005 sec Other
figures would appear to indicate that the latent period is shorter
the smaller the animal, a fact which in itself would imply that
some factor other than the latency of the muscle itself enters
into the time required. And if we accept the newer figures in
regard to the velocity of the nerve impulse in mammalian nerves
at the body temperature (see p. 113) there would seem to be
sufficient time in all cases for the impulse to get to the cord and
back. Thus, in the dog, if we take the velocity of the impulse
as 120,000 mm. per second, and the distance to be travelled as
800 mm., only 0.0066 sec. would be necessary to make the circuit,
assuming that there is no appreciable delay in the centers. In
view of these figures it seems quite unjustifiable to conclude
that the knee-jerk is not a reflex simply because the time between
the stimulus and the response is shorter than with some other
known reflexes. It will be remembered in this connection that
one observer (p. 149) records a genuine reflex time for this
region as short as 0.017 sec. So also the fact that under certain
conditions a genuine crossed knee-jerk may be obtained, that
is, an extension of the other leg, speaks in favor of the view that
the usual jerk is a reflex phenomenon.

Conditions Influencing the Extent of the Knee-jerk.: — The
effect of various normal conditions upon the knee-jerk has been

* Sherrington, "The Integrative Action of the Nervous System," 1906.

160

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

studied by a number of observers, particularly by Lombard.* The
results are most interesting in that they indicate very clearly that
the irritability of the spinal cord varies with almost every marked
change in mental activity. During sleep the jerk disappears
and in mental conditions of a restful character its extent is relatively
small. In conditions of mental excitement or irritation, on the
contrary, the jerk becomes markedly increased. Lombard ob-
served also, in his own case, a daily rhythm, which is represented
in the chart given in Fig. 71. It would seem from his experiments

Fig. 71. — Lombard'8 ficure to indicate the daily rhythm in the extent of the knee-

t'erk and the effect of mental stimuli. The ordinate.s (0-110) represent the extent of the
:iek in millimeters. Bach dot represents a .separate kick, while the heavy horizontal line
gives the average extent for the period indicated.

that the extent of the knee-jerk is a sensitive indicator of the
relative state of irrit ability of the nervous system: "The knee-
jerk ifi increased and diminished by whatever increases and di-
mini In- the activity of the central nervous system as a whole."
Tlii- general fact is supported, especially as regards mental activity,
by observations Oil other similar mechanisms, --such, for instance,

as the condition of the nervous centers controlling the bladder.

Use of the Knee-jerk and Spinal Reflexes as Diagnostic
Signs. — Tin- fact thai the knee-jerk depends on the integrity of

the reflex arc in the lumbar cord has made it useful as a diagnostic

indication in Lesions of the cord, particularly, of course, For the

♦Lombard, "The American Journal <>f Psychology," 1887, |>. I, Set;
;il " article "Knee-jerk" (Warren), "Wood'a Etef. Handbook of Med. Sci-
," econd edition, L902.

REFLEX ACTIONS. 161

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
horns of the gray matter will destroy the reflex b3^ 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. 149)
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
explanation is incomplete in that it leaves undecided the question
as to whether this inhibitory influence is exerted through the
ordinary motor paths or through a special set of inhibitory fibers.
Other Spinal Reflexes. — Various other distinctive reflexes
through the spinal cord may be obtained readily, and since the
motor cells concerned lie at different levels in the cord the
presence, absence, or modified character of these reflexes has
been used frequently for diagnostic purposes. In the first
place there are a number of so-called deep reflexes which may
be aroused by sensory stimulation of parts beneath the skin,
such as the tendons, ligaments, and periosteum. Almost any
tendon if stimulated mechanically may give a jerk of the cor-
responding muscle, just as in the case of the knee-kick. Such
reactions have been described and used in the case of the wrist-
jerk, the jaw-jerk, the Achilles-jerk, etc. The last named is
obtained by putting the foot into a position of dorsiflexion and
then tapping the tendo calcaneus (Achillis). The result is a
contraction of the gastrocnemius, causing plantar flexion of the
foot. A variation of this reflex is the phenomenon known as
ankle clonus. This is obtained by giving a quick forcible
dorsiflexion to the foot thus putting the tendon and muscle
under a sudden mechanical strain. In some cases there results
a rhythmical series of contractions of the gastrocnemius. A
second group of reflexes may be obtained by stimulation of
special points on the skin, the cutaneous reflexes. For example,
the plantar reflex, which consists in a flexion of the toes when the
11

162 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

sole of the foot is stimulated by tactile or painful stimuli. Under
pathological conditions which involve a lesion of the pyramidal
tracts in the cord this reflex is altered, the great toe being
extern lei 1 instead of flexed (Babinski's phenomenon). The
cremasteric reflex consists in a contraction of the cremasteric
muscle which raises the testis. It follows from stimulation of
the skin on the inner side of the thigh at the level of the scrotum.
The location of the motor centers of these and other similar
reflexes is shown in the accompanying illustration (Fig. 72).

lit:. , _'. — Diagrammatic representation of the lower portion of the human buTb and
spinal cord.

The cord is divided into its four regions: 1, Medulla cerviealis; 2, medulla dorsalis;
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
thern 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
ciCo-epinale. Reflexus epigastricus, Reflexus abdominalis, Reflexus cremastericus, Reflexus
patellar)*, Heflexus tendo Achillas. Centrum vesicale, Centrum anale (the last two on the
left side of the diagram). (Donaldson, "Amer. Text-book of Physiology," from "looses
Neurologic®," StriimpeU and Jakob.)

Pharynx

Oesophagus
Larynx, Trachea
Infestina

{Thorax. Abdomen)

Regio occipitalis'
Regio colli
Regio nuchae
Regio humeri
Regio Nervi radialis
Regio N. meoiani
N.

Mm. pharyngis. palati
Mm. iai yogis
Mm. linguae
Oesophagus
Sternocleidomastoideus
let i

Diaphragma
Supra-,
Deltoi
Biceps

Pectoralis major (portio ciavicui.)

Teres minor

Extensores carpi et digitor. longi ) §=

iorlportioi

§:. Flexores carpi et digitor. longi

If- lleopsoas
. Sartorius

Quadriceps femoris

Biceps Semitendi— Semimembranosus

Extensores digitorum
Peronei
Flexores digitorum

Fig. 72.

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

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

The Arrangement and Classification of the Nerve Cells
in the Gray Matter of the Cord. — Nerve cells are scattered
throughout the gray matter of the cord, but are arranged more
or less distinctly in groups or, considering the longitudinal aspect
of the cord, in columns the character of which varies somewhat in
the different regions. From the standpoint of physiological anatomy
these cells may be grouped into four classes: (1) The anterior
root cells, clustered in the anterior column of gray matter (1, Fig.
73). The axons of these cells pass out of the cord almost at once
to form the anterior or motor roots of the spinal nerves. (2) The
tract cells, so called because their axons instead of leaving the cord
by the spinal roots enter the white matter and, after passing upward
or downward, help to form the tracts into which this white matter
may be divided (2 and 3 of Fig. 73) . These tract cells are found
throughout the gray matter, and according to the side on which the
axon enters into a tract they may be divided into three subgroups:

163

164

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

(a) Those whose axons enter the white matter on the same side of
the cord, the tautomeric tract cells of Van Gehuchten. (b)
Those whose axons pass through the anterior white commissure
and thus reach the tracts in the white matter of the other side.
These arc known as commissural cells or the heteromeric tract
coll- of Van ( rehuchten. They form one obvious means for crossed
conduction in the cord, (c) Those whose axons divide into two,
one j:>assing 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

Uentral

Fjk. 73. — Schema of the structure of the cord. — After Lenhossek.) On the right the
nerve cells; on tin- left the entering nerve fibers. Right side: 1, Motor cells, anterior
column, giving rise to the fibers "f the anterior root; '-', tract cells whose axons pass into
the white matter of I hi' an t et ior and lateral funiculi; '-, commissural eel Is whose axons pass
chiefly through the anterior commissure to reach the anterior funiculi of the other side;

4, Golgi cells i econd I pe), whose axon do nol leave the may matter; .r>, tract cells whose

;.i into the white matter of the posterior funiculi. Leftside: L, Entering libers

of tin- po terioi io.it, ending, from within outward, as follows: Clarke's column, posterior

Column ol oppo ite id'-, anterior Column -a me side I re Ilex arc), lateral coin i mi of same side,

posterioi column of am.- ide; 'J. collateral-, from fibers in the anterior and lateral funiculi,
■';, collateral ol descending pyramidal fibei ending around motor cells in anterior column.

axons divide into a number of small branches like those of a
dendrite. The axons of those cells, therefore, do not become

medullated nerve fibers; they take no part in the formation of
pinal roots or the tracts of white matter in the cord, but
terminate diffusely within the gray mailer itself. (I) Tin; pos-
terior root cells lying toward the base of I he anterior coin inns.

These cells have l><-<-n demonstrated in some of the lower verte-
brates (petromyzon- chick embryo), but I heir existence in the
mammal i- -till a question in some doubt; their axons pass out
from t he cord by t he posterior root and t hoy form t he anatomical
evidence for the vie^ thai the posterior roots may contain souk;

SPINAL CORD AS A PATH OF CONDUCTION. 165

efferent fibers. Some of the groups of tract cells have been given
special names — such, for instance, as the dorsal nucleus (Clarke's
column). This group of cells lies at the inner angle of the
posterior column of gray matter (5, Fig. 76), 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 funiculi on the same side to con-
stitute an ascending tract of fibers known as the tract of Flechsig,
or the fasciculus cerebellospinalis.

General Relations of the Gray and White Matter in the
Cord. — Cross-sections of the cord at different levels show that
the relative amounts of gray and white matter differ considerably
at different levels, so that it is quite possible to recognize easily
from what region any given section is taken. At the cervical and
the lumbar enlargements the amounts of both gray and white
matter — that is, the total cross-area of the cord — show a sudden

White matter.

Gray matter.

—Entire section.

100

80

eo

^_^- — ^^xComposite

curves based an 4 Cases.

• .. ~^.

■ ---- —

40

so

100

Juinoryvinismi n m rc

y va yn ym k x xi xu

i n jukyi nuiim

Fig. 74. — 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-

106 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

eration) and the method of myelinization. The method of second-
ary degeneration depends upon the fact that, when a fiber is cut
off from its cell of origin, the peripheral end degenerates in a few
days. If, therefore, a lesion, experimental or pathological, is made
in the cord at any level, those fibers that are affected undergo
degeneration: those with their cells below the lesion degenerate up-
ward, and those with their cells above the lesion degenerate down-
ward. According to the law of polarity of conduction in the neuron
a descending degeneration in the cord indicates motor or efferent
paths as regards the brain, and ascending degeneration indicates
sensory or afferent paths. It is obvious that localized lesions can
be used in this way to trace definite groups of fibers through the cord.
If, for instance, one exposes and cuts the posterior roots in one or
more of the lumbar nerves, the portions of the fibers entering the
cord will degenerate, and the path of some of these fibers may be
traced in this way upward to the medulla. The degenerated fibers
may be revealed histologically by the staining methods of Weigert
or of Marchi. The latter method (preservation in Midler'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 fund tonal activity.

General Classification of the Tracts. — The tracts that have
been worked out in the white matter of the cord have been classified
in everal 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 I hose neurons whose axons extend upward toward the

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

SPINAL CORD AS A PATH OP CONDUCTION. 167

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

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

16S

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

these long tracts are more conspicuous and form a larger per-
centage of the total area of the cord. A physiological corollary
of this conclusion should he 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. 147).

Specific Designation of the Long Spinal Tracts. — The tracts
that are most satisfactorily determined for the human spinal cord
are indicated schematically in Fig. 75.

They are named as follows: In the posterior funiculus,

1. The fasciculus gracilis (column of Goll),

2. The fasciculus cuneatus (column of Burdach).

ventral

pd

0

/

*>

g

lit'. 75, Schema of the tracts in the spinal cord (Kolliker) : n. Fasciculus grapihs;
/,. fasciculus cuneatu ; pc, fa ciculus cerebrospinalis lateralis; pd, fasciculus cerebrospinalis
anterioi ; /. fasciculus cerebellospinalis ; gr, fasciculus anterolateral superficialis.

In t lie Lateral funiculus,

1. The fasciculus cerebrospinalis lateralis, known also as the

lateral or crossed pyramidal I ract.

2. The fasciculus cerebellospinalis, known also as Flechsig's
i pad .

:;. The fasciculus anterolateral superficialis, known also as
Gower's trad .

1. The lateral ground bundle (fasciculus lateralis proprius),
made up chiefly of short association fibers.

In t he anterior funiculus,

1. The fasciculus cerebrospinalis anterior, known also as the
direct or anterior pyramidal I rad .

2. The anterior ground bundle (fasciculus anterior proprius).

SPINAL CORD AS A PATH OF CONDUCTION.

169

Of these tracts, the fasciculus gracilis, fasciculus cuneatus,
fasciculus cerebellospinalis, and fasciculus anterolateralis super-
ficialis represent ascending or sensory paths, while the lateral
and anterior cerebrospinal or pyramidal fasciculi form a related
descending or motor path. It will be convenient to describe
first the connections and physiological significance of these
tracts and then refer briefly to the other less definitely estab-
lished ascending and descending paths.

The Termination in the Cord of the Fibers of the Posterior
Root. — All sensory fibers
from the limbs and trunk
enter the cord through the
posterior roots. Inasmuch
as these roots are superfi-
cially connected with the
posterior funiculi, the
older observers naturally
supposed that this portion
of the white matter of the
cord forms the pathway for
sensory impulses passing to
the brain. That this sup-
position is not entirely cor-
rect was proved by experi-
mental physiology. Sec-
tion of the posterior fu-
niculi causes little or no
obvious loss of sensations
in the parts below the
lesion. Histological inves-
tigation has since shown
that only a portion of the
fibers entering through the
posterior root continue up
the cord in the posterior
funiculi; some and indeed
a large proportion of the
whole number enter into
the gray matter and end

around tract cells, whence the path is continued upward by the
axons of these latter cells, mainly in the lateral or anterolateral
funiculi. The several ways in which the posterior root fibers
may end in the cord are indicated in Fig. 76.

The posterior roots contain fibers of different diameters, and
those of smallest size (1) are found collected into an area known

Fig. 76. — Schema to show the terminations
of the entering fibers of the posterior root : 1,
Fibers entering zone of Lissauer and terminating
in posterior column; 2, fiber terminating around a
tract cell whose axon passes into white matter 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 column (reflex arc); 5, fiber terminating
in tract cell of dorsal nucleus; 6, fiber (exog-
enous) passing upward in posterior funiculus to
terminate in the medulla oblongata.

1(0 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

as the zone of Lissauer, lying between the periphery of the cord
and the tip of the posterior column. These fibers enter the gray
matter chiefly in the posterior column 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 column 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 commissure, or in the motor cells of
the anterior column, thus making a typical reflex arc. Some
of the fibers of this group may also pass through the posterior
commissure, to end in the gray matter of the opposite side.
The larger fibers lying nearest to the median line enter the fas-
ciculus cuneatus 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 dorsal nucleus. The axons of the cells in the dorsal
nucleus in turn pass out of the gray matter to constitute the
ascending path in the lateral funiculus, known as the cerebello-
spinal fasciculus.

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 filter in the posterior root is
represented in Fig. 67. 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, therefore, which runs upward in the
fasciculus cuneatus (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 embryo, but we have little
exact information concerning their numerical value in the adult.
The schema given in Fig. 7(i must, therefore, be accepted as an
entirely diagrammatic representation of the chief possibilities
of the mode of ending of the fibers of the posterior roof by way

of their collaterals as well as by way of the main stems.

Ascending (Afferent or Sensory) Paths in the Posterior
Funiculi. The posterior funiculi are composed partly of fibers
derived directly from t he posterior roots (6 in schema) and arising,

therefore, from the cells in the posterior root ganglia, and partly

SPINAL CORD AS A PATH OF CONDUCTION.

171

from fibers that arise from tract cells in
cord itself. It is convenient to speak
of the former group as exogenous fibers,
using this term to designate nerve fibers
which arise from cells placed outside
the cord; and the latter group as endo-
genous fibers — that is, fibers that have
their cells of origin in the gray matter of
the cord. If we omit a consideration
of their collaterals the course of the
exogenous fibers is easily understood.
They come into the cord at every pos-
terior root, enter into the fasciculus
cuneatus, 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 tho-
racic or cervical regions the fasciculus
gracilis is composed mainly of exogenous
fibers that have entered the cord in the
lumbar or sacral region. These fibers
continue upward 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
funiculus gracilis (or nucleus of Goll)
and the nucleus o'f the funiculus cunea-
tus (or nucleus of Burdach). Their
path forward from the medulla is con-
tinued by new neurons arising in these
nuclei, and will be described 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 funiculi are severed in this
region, the degeneration will affect the
exogenous fibers throughout their
course to the medulla, and it will be seen
that in the cervical region the degen-
erated fibers are grouped in the area of
the fasciculus gracilis (see Fig. 77). The

the gray matter of the

4-* Cervical

7tJtDorsal

2^ Lumbar

S-'Lumbi

Fig. 77. — Diagrams to
show course of upward de-
generation of fibers of poste-
rior funiculi 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
fasciculus gracilis.

172 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

endogenous filters, so far as they are ascending, represent afferent
paths in which two or more neurons arc concerned. The pos-
terior root fibers concerned in these paths end in the gray
matter of the cord, and thence the conduction is continued by
one or more tract cells. The conduction by this set 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
physiological value of the ascending fibers in the posterior
funiculi has been investigated by a large number of observers.
The physiologists have employed the direct method of cutting
the funiculi in the thoracic or lumbar region and observing the
effect upon the sensations of the parts below the lesion. The
positive results of these experiments have been difficult to
discover. Most of the older observers found that there was
no detectable change in the sensations 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 funiculi of the cord in the
lu inliar legion are affected and the striking symptom of this
condition is an interference with the power of co-ordinating
properly t lie movements of the lower limbs, particularly in the
ad of maintaining body equilibrium in standing and walking, —
a condition known as Locomotor ataxia. So far as the cutaneous
.lions are concerned, — that is, the sensations of touch
(pressure), pain, and temperature, all observers agree that the
two latter are not affected, while regarding touch, opinions have
differed radically. Schifif contended that touch sensations are
detectable as long as these funiculi are intact and are seriously
interfered with when they are sectioned; bu1 most of the results,

pathological and experimental, indicate thai when the con-
tinuity of these fibers is destroyed the sense of touch is still
en1 in the parts supplied by the cord below the lesion. To
summarize, therefore, we may say thai the evidence at hand
proves that the ascending fihers of the posterior funiculi do not
convey impulses of pain or temperature, that if they convey
touch (pressure) impulses they certainly do not form the

* Borchert. "Archiv f. Physiologic, " L902, 389. Sec also Sherrington,
"Journal of Physiology," 14, 255, L893.

SPINAL CORD AS A PATH OF CONDUCTION.

173

only path of conduction for this sense, and that most probably
their chief function is the conduction of impulses of muscle sense,
— that is, they consist of sensory fibers from the voluntary
muscles and their tendons. 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 funiculi, therefore, while it does not cause paralysis, is
followed by disorderly — that is, ataxic — 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 "lemniscus," 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 Funic-
uli.— The two best known ascending tracts in these funiculi
are those of the cerebellospinal and the superficial anterolateral
fasciculi. The former takes its origin in the upper lumbar
region, and is composed of axons connected with the tract cells
of the dorsal nucleus. The impulses which its fibers convey are
brought into the cord through those fibers of the posterior root
that end around the cells of the dorsal nucleus. A number of
the fibers in this funiculus end doubtless in the gray matter of
the upper regions of the cord,
but most of them continue
upward on the same side,
enter the inferior peduncle of
the cerebellum (rest if or m
body), 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 superficial anterolateral
fasciculus, situated ventrally
to the cerebellospinal fas-
ciculus (gr, Fig. 75), may ex-
tend forward into the anterior
funiculi along the periphery
of the cord. The two bun-
dles may be more or less intermingled at the points of contact.
This tract begins also in the upper lumbar region, its fibers arising
on the same side from tract cells situated in the anterior column
and the so-called intermediate portions of the gray matter.
Many of the fibers in this tract doubtless terminate in the cord

Wave

Fig. 78. — To show the course of the fibers
of the cerebellar tracts of the cord (Molt):
v.a.c, Ventral tract (superficial anterolateral);
d.a.c, dorsal tract (cerebellospinal); s.v.,
superior vermis; P.C.Q., inferior colliculus.

174 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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 peduncle
(brachium conjunctivum) and the anterior medullary velum,
to end in the vermiform lobe chiefly on the same side, but to
some extent on the opposite side* (Fig. 78). Where this tract
separates from the cerebellospinal fasciculus it isstatedf that it
gives off a number of fibers which enter the restiform body with
the cerebellospinal fasciculus to end in the cerebellum. This
and other facts indicate that the two tracts constitute a com-
mon system. Regarding the physiology of these two tracts
there is little experimental and not much clinical evidence.
Some observers have cut the cerebellospinal fasciculus in ani-
mals, but with no very obvious effect except again a slight
degree of ataxia in the movements below the lesion and some
loss of muscular tone. J This result, together with the fact
that the bundle ends in the cerebellum, gives reason for be-
lieving that the fibers mediate muscular sensibility. As we
shall see, much evidence of various kinds connects the cere-
bellum 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 perhaps the joints and other so-called deep sen-
sory parts, and since the fibers of the cerebellospinal fasciculus
end in the cerebellum, and since experimental lesion of them
gives no loss of cutaneous sensibility and some degree of ataxia,
ii seems justifiable to conclude that these fibers are physiolog-
ically muscle-sense libers. The superficial anterolateral fasciculus
has not been the subject of much experimental study from the
physiological side. Clinically, the tract may be involved in
pai hological or traumal ic lesions of t he lateral funiculi. Gowers §
gives a history of some such cases which lead him to believe that
this trad constitutes a pathway for pain impulses, and this view
or the view thai it conducts the impulses of both pain and
temperature has been more or less generally accepted. Little
confidence, however, can be placed in this conclusion, since the
le ions in question were not strictly confined to the fasciculus

■ For the literature upon these tracts, sec Vim Gehuchten, "Le NeVraxe,"
3, 157, 1901.

Bchaefer and Bruce, "Journal <>f Physiology," 1907 ("Proc. Physiol.
-

J Bing, "Archiv fur Physiologie, " 1906, 250.

§ <;.. ■ Lancet," 1886.

SPINAL CORD AS A PATH OF CONDUCTION. 175

in question. The only positive indication that we have con-
cerning the physiological value of these fibers is given by then-
histology in the fact that they end for the most part in the
cerebellum. The cerebellum we know may be removed in dogs
and monkeys without loss of the sensation of pain, temperature,
or touch, and this fact speaks strongly against the view that
either the cerebellospinal or the superficial anterolateral fascicu-
lus is concerned in the conduction of these cutaneous sensations.
From a physiological standpoint we should be inclined to believe
that both of these tracts conduct the impulses of the deeper
sensibilities, particularly the sensations arising from the muscles,
tendons, and joints. It would seem, therefore, that all the
long ascending tracts in the posterior and lateral funiculi of
the cord may be made up of fibers of muscle sense, using this
term in a wide sense to include the deep sensibility of the joints,
tendons, and muscles. The immense importance of muscular
sensibility in the maintenance of life and in defense against
enemies may explain, upon the doctrine of the struggle for
existence, why the long paths should have been 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 two para-
graphs it would seem probable that the spinal paths for touch,
pain, and temperature must be along the short association
tracts of the proper fasciculi of the lateral and anterior funiculi.
There is evidence from the clinical side that the paths of con-
duction for these senses are separate. In the pathological
condition known as syringomyelia, cavities are formed in the
cord affecting chiefly the central gray matter and 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 temperature
(analgesia and thermo-anesthesia), but preserves that of pressure
(touch). Facts of this kind indicate that the paths of conduc-
tion for touch are separate from those for pain and temperature,
but little that is positive is known regarding the exact location of
these paths. The fibers of pain and temperature probably end
in the gray matter of the cord (posterior column) soon after their
entrance, and the path is continued upward by tract cells whose
axons enter the proper fasciculi in the lateral or anterolateral
funiculi, most probably in the lateral funiculi, so far at least as
the lower animals are concerned,* but the number of such
neurons concerned in the conduction as far as the medulla is not
known. Regarding the path for the touch impulses a singular
* For discussion, see Bertholet, " Le Nevraxe," 1906, vii., 283.

17G PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

amount of uncertainty prevails. This sense is not lost or, at
least, is rarely lost in cases of syringomyelia in which the other
cutaneous senses are affected. On the other hand, the posterior
funiculi, 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 funiculi are reported in which the sense of touch was
not lost. Some authors, therefore, have been led to believe
that the touch impulses may be conveyed up the cord by several
paths: by the long association fibers of the posterior funiculi
and by the short association fibers of the lateral funiculi. Such
a view receives little support from the experimental work on
the lower mammals. In these animals the evidence tends to
show that the conduction is by way of the lateral or anterolateral
funiculi, by means of tract cells and short association tracts.
The fact that in man the clinical evidence seems to point to the
posterior funiculi as a possible or, indeed, probable path for these
fibers may serve to exemplify the fact that in these matters
the various mammalia differ more or less according to the degree
of their development. It seems possible also that so far as man
is concerned an explanation of the difference of opinion regard-
ing the spinal paths of the sense of touch is found in the distinc-
tion made by Head and Thompson* between tactile discrimina-
tion and tactile localization. By the former is meant the ability
to discriminate between two stimuli applied simultaneously
to the skin at a certain distance apart, by the latter the ability
to perceive and locate accurately a pressure stimulus applied
to the skin. These two forms of cutaneous touch sensations
are mediated according to these authors by separate systems
of fibers. As the result of a spinal lesion the power of dis-
crimination may be h>st over a given area of skin winch other-
wise is completely sensitive to all cutaneous stimuli. They
find thai the fibers of tactile discrimination travel up the cord
uncrossed in the posterior funiculi, together with some of the
fibers of muscle sense that is, the fibers which give us a sense of

position and movement of the limbs. The libers of tactile local-
ization, on the Contrary, pass upward in the lateral or antero-
lateral funiculi ami cross to the other side before reaching the
medulla.

Homolateral and Contralateral Conduction of the Cuta-
neous Impulses. < Ireal interest, from the medical side, has

been hown in the question of the crossed or uncrossed conduc-
tion of the cutaneous impulses in the cord. The matter is nat-
urally one of importance in diagnosis. In human beings it was
* I lead and Thompson, "I (rain, " 1906,

SPINAL CORD AS A PATH OF CONDUCTION. 177

pointed out by Brown-Sequard* 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 cutaneous
sensory impulses is contralateral. Experimental work on lower
animals, on the contrary, has not supported this view. While
results in this direction have varied, as would be expected from
the intrinsic difficulties connected with the interpretation of
the sensations of an animal, the general outcome has been to
show that the sensory conduction is bilateral, but mainly on
the same side. That is, if the cord is cut on one side only
(hemisected) in the thoracic region, the cutaneous sensibility
of the parts below the lesion is impaired upon the same side,
but not completely abolished, showing that some crossing has
taken place, f It is probable that this crossing is more com-
plete in man than in the lower animals, although later studies
in man of unilateral lesions of the cord (Brown-Sequard paraly-
sis) indicate that the contralateral loss of cutaneous sensibility
affects chiefly the senses of pain and temperature; the loss of
touch is not complete and muscular sensibility, of course, is
affected only on the same side. Head and Thompson, in the
paper previously referred to, conclude upon the basis of extensive
clinical studies that in man all the fibers of cutaneous sense
cross in the cord except those mediating tactile discrimination.
As stated above, these latter pass upward in the posterior funic-
uli together with some of the fibers of muscle sense, and do not
cross until after they reach the medulla. According to their
interpretation, a complete unilateral lesion of the cord in the
cervical region would be followed by a homolateral loss of
motion in the parts below and also of tactile discrimination and
muscle sense, using the latter term to cover the deep sensibility
in regard to position and movements of the limbs. On the
contralateral side there would be a loss of pain, temperature,
and tactile localization in the skin, and also a loss of deep sen-
sibility to touch (see p. 271).

The Descending (Efferent or Motor) Paths in the Antero-
lateral Column. — The main descending path in the cord is the
pyramidal or cerebrospinal system of fibers. In man, as shown
in Fig. 75, there are two fasciculi belonging to this system, —
the anterior and the lateral pyramidal tracts. Both tracts
arise from the anterior pyramids on the ventral face of the

* Brown-Sequard, "Journal de Physiologie, " 6, 124, 232, 581, 1863.
t Mott, "Brain," 1895, 1, and Bertholet, "Le Nevraxe," 1906, vii., 283.
12

17s

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

medulla, whence the name of the pyramidal system. At the
junction of the medulla and curd the fibers of the pyramids
decussate in part, forming a conspicuous feature of the interna]
structure at this point, known as the pyramidal decussation.
According to the general schema of this decussation (see Fig. 79),
the larger number of the fibers in the pyramid of one side pass

over to form the lateral pyramidal
fasciculus of the other side of the
cord (4, 5), while a smaller part
(3) continues down on the same
side to form the anterior pyrami-
dal fasciculus. Eventually, how-
ever, these latter fibers also cross
the mid-line in the anterior white
commissure, not, however, all at
once, as at the pyramidal decussa-
tion, but some at the level of each
spinal nerve. These pyramidal
fibers have their origin in the cor-
tex of the cerebral hemispheres in
large pyramidal cells; some of
them cross the mid-line before
reaching the medulla to end
around the colls 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 columns which
give rise to the motor roots of the
spinal nerves. Both fasciculi, the
lateral and the anterior, con-
tinue throughout, the length of
t he cord, diminishing in area on
the way as some of their fibers
terminate in each segment. This
system of libers is supposed to

represent the mechanism for effecting voluntary movements,

and according to the general schema the voluntary motor path

from cerebrum to muscle comprises two neurons, the pyra-
midal or cerebrospinal neuron and the spinal or the cranial
neuron. Moreover, as represented in the schema, the innerva-
tion is crossed, the right side of the brain controlling the wus-

FIk. 70. Schema representing
the course ol the fibers of tin- pyra-
midal or cerebrospinal system: I,
Fibers to the nuclei of t Uo cranial
nei i '■; 2, uncrossed Bbei - to I he
lateral pyramidal fasciculus; •''.. fibers
to iii<- anterior pyramidal fs ciculu
' in the cord; t and 5, fibers
that oro i in the pyramidal decu a
tion to male the lateral pyramidal
lu of I In- opposite Jide.

SPINAL CORD AS A PATH OF CONDUCTION. 179

culature 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. 79) continue 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 relatively less important
and the anterior fasciculus in the anterior funiculus is lacking
altogether. In the birds what represents the same system is
found in the anterior funiculus (Sandmeyer), while in the frog
the system does not exist at all.

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

Mouse 1.14 per cent.

Guinea pig 3.0 "

Rabbit 5.3

Cat 7.76

Man 11.87

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

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
complete, and the physiological value of which is entirely un-

* Lenhossek, " Bau des Nervensystems," second edition, 1895.
t Rothmann, " Zeitschrift f. klin. med.," vol. xlviii., 1903.

ISO PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

known or at best is a matter of inference from the anatomical
relations.*

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

Descending Tracts in the Anterolateral Funiculus. — The pre-
pyramidal tract, known also as Monakow's bundle, the fasciculus
intermediolateralis, or the rubrospinal tract, is a conspicuous
bundle forming a wedge-shaped or triangular area in the lateral
columns between the lateral pyramidal fasciculus and the
superficial anterolateral fasciculus (Gower's), or, perhaps, more
correctly speaking, forming the anterior portion of the lateral
pyramidal fasciculus; the two systems being more or less inter-
mingled. 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 funiculi, 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 column of gray matter, whose
axons, in 1 urn, 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 con-
nected with the cerebrum, either directly or by way of the
cerebellum, it represents a cerebrospinal motor path in addition
to thai offered by the pyramidal System.

The vestibulospinal fibers lie anterior to the preceding tract
in the anterolateral funiculus; they may extend into the anterior
funiculus as far as the .'interior pyramidal fasciculus. These

fibers originate in the nucleus of Deiters. In the cord the fibers

end around cells in the anterior column. Since the Deiters
nucleus forms a termination for the sensory fibers of the vestibu-
lar branch of the eighth cranial nerve, and since these fibers are

♦ Collier and Buzzard, "Brain," L001, 177; and Fraser, "Journal of
Physiology," 28, 866, 1902. For Bummary and Literature, consult: Van Ge-
hucbten, " Anatomie du systeme aerveux '!<■ I'homme," 4th ed., L906.

SPINAL CORD AS A PATH OF CONDUCTION. 181

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 move-
ments used to maintain equilibrium, their connection in Deiters'
nucleus with a spinal motor path becomes very significant as
furnishing a reflex arc through which sensory impressions from
the vestibular apparatus in the ear may automatically control
the musculature of the body. A number of other descending
paths in the anterior and lateral funiculi have been described,
such as Helweg's bundle or the olivospinal tract, lying on the
margin of the cord at the junction of the anterior and the lateral
funiculi and supposed to arise in the olivary bodies; the anterior
and the lateral reticulospinal tracts arising from cells in the
reticular formation of medulla, pons, and midbrain; and the
continuation into the cord of the important medial longitudinal
fasciculus (post. long, bundle), which extends from the midbrain
through to the cord and connects the motor nuclei of the cranial
nerves with the motor centers of the cord. Concerning these
and similar tracts our physiological knowledge is scanty, and it
is not possible at present to employ them with certainty in
explaining the activity of the neuromuscular apparatus.

CHAPTER IX.

THE GENERAL PHYSIOLOGY OF THE CEREBRUM
AND ITS MOTOR FUNCTIONS.

From the time of Galen in the second century of the Christian
era the brain has been recognized as the organ of intelligence and
conscious sensations. Galen established this view not only by
anatomical dissections, confirming the older work of the Alexandrian
school (third century B.C.) in regard to the origin from the brain
of the cranial nerves, but also by numerous vivisection experiments
upon lower animals. All modern work has confirmed this belief
and has tended to show that in the cerebral hemispheres and, indeed,
in the cortex of gray matter lies the seat of consciousness.
It is perhaps still an open question as to the existence of a
conscious or psychical factor in the activities of other parts of the
nervous system, but there is no doubt that the highest develop-
ment of psychical activity in man is associated with the cortical mat-
ter of the cerebrum. In the young infant the dawn of its mental
powers is connected with and dependent on the development of the
normal cortical structure, while in extreme age the failure in the
mental faculties goes hand in hand with an atrophy of the elements
of the cortex. If this cortex were removed all the intelligence, sen-
sation, and thought that we recognize as characterizing the highest
psychical life of man would be destroyed, and abnormalities in the
structure of this cortical material are accepted as the immediate
causal factor of those perversions in reasoning and in character
which are exhibited by the insane or the degenerate. The cortical
gray matter, therefore, is the chief organ of the psychical life, the
tissue through whose activity the objective? changes in the externa]
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 if is held
that the methods of science are applicable only to the investiga-
tion of the objective that is, the physical and chemical change
wit hin t he nervous mat ter, while i he psychical reaction is of a nature
that cannol be approached through the conceptions or methods
of physical science. In other words, then; is a- physicochemical

IS2

GENERAL PHYSIOLOGY OF THE CEREBRUM. 183

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

The Histology of the Cortex. — The finer structure of the
different regions of the cortex has been the subject of much investi-
gation, but in this connection it is only necessary to recall the
elementary facts so far as they are useful in physiological explana-
tions. Leaving aside minor differences in the shape and stratifica-
tion of the cells, it is an interesting fact that the cortex everywhere
has a similar structure. It consists of four or five layers more or
less clearly distinguishable (see Fig. 80).

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 large pyramidal cells, particularly in the Rolandic area.

184

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

White

Mali

iir hu. To show the
ttructure <.f the cortea oere-
bri r/^, /, rine) : /, The molec-
ular layer; //, the layer of
vertical fu iform eel] ; ///,
thr- layer of small pyramidal
cell : / V , i he l-

i , the luyor
of polymorphic cell ■

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

4. The layer of fusiform or polymor-
phic nerve cells. A small layer of cells
whose form is more irregular than that of
the pyramidal cells, but whose axons also
pass into the medullary portion of the
cerebrum, while their dendrites stretch
externally into the layers of pyramidal
cells. In this layer are found also some
cells belonging to the second type of
Golgi (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. I The fibers in this white matter may
be classified under three heads: First,
the projection system {A, B, C, D, and
E of Fig. SI), comprising those filters,
afferent and efferent, which connect the
cortex with underlying parts of the cen-
tral nervous system, — the spinal cord,
medulla, pons, midbrain, or thalamus.
I'hi-: great projection system emerges, for
the most pari, through the internal cap-
sule and t he peduncles of t lie cerebrum.
Certain parts Of t lie cortex .are seemingly

lacking in a projection system; the fibers

GENERAL PHYSIOLOGY OF THE CEREBRUM.

185

Fig. 81. — 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 (lemniscus) tract ; D, the visual tract ; E, the auditory
tract ; F, the fibers of the superior peduncle of the cerebellum ; G, fibers of the middle pedun-
cle uniting with A in the pons ; H, fibers of the inferior peduncle of the cerebellum ; J, fibers
between the auditory nucleus and the inferior colliculus ; K, motor (pyramidal) decussation
in the bulb ; Vt, fourth ventricle. The numerals refer to the cranial nerves. — (Modified
from Starr.)

Fig. 82. — 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, thalamus.

186 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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. si1'. There are short association tracts (A, A) con-
necting neighboring convolutions and long tracts passing from one
lobe to another. Third, the conimissural system, consisting of as-
sociation fibers that cross the mid-line and connect portions of one
cerebral hemisphere with the cortex of the other. These fibers
make up the commissural bands known in gross anatomy as the
corpus callosum, anterior white commissure, fornix, etc.

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

third place, the central nervous system throughout \\)v verte-
brates i 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 •iiiiil.-irii ■ in :-i met ure in the two cases. The chief difference
thai comparative anatomy is able to show is that iu the higher
' I [,i i .,u .iii mI.y bui la structure du systeme nerveux, etc.,"
Paris, is!) t.

GENERAL PHYSIOLOGY OF THE CEREBRUM.

187

animals the greater mental development is associated with a greater
complexity and richness in the connections of the neurons. As
shown in Figs. 83 and 84, the number of processes, particularly
the dendritic processes, is much greater in the cortical cells
of the higher animals; or, to put this fact in another way, the
number of cells in the cortex of the higher animals is much less
for an area of the same size than in lower animals. The amount
of in-between substance or the richness of the network of processes

Fig. 83.- — 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 ; 6, commencing dendrites ; c, dendrites
further developed; d, first appearance of collateral branches; e, further development of
collaterals and dendrites. — (From Ramon y Cajal.)

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

1SS

PHYSIOLOGY OV 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

1

' " - ' l \
. '•' i .-), >'

' » • .
.,'■>

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' » .''

'■::'/'!'.

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fl ?> c

£ig, B4. Section through cone ponding pari i <>( the cortex in: a, Man; f», <!<>«;
and e, mole, to show the greater eparation o! the aerve cells in the higher animals. -
{Rethe, after

chiefly for their negative results. II' 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, tt maintains a normal posture and shows
no loss at all in its power of equilibration. When placed on its
bach it quickly regains its usual position, [f thrown into water

GENERAL PHYSIOLOGY OF THE CEREBRUM. 189

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

190 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

the other parts of the brain had been destroyed, was, of course,
functionless. In addition, a large part of the corpora striata and
the 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-
culled 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. Xo caressing could arouse signs of pleasure, and no
threatening signs of fear or anger. Like the pigeon, the most con-
spicuous defect in the animal was a lack of intelligent response,—
that is, the responses to sensory stimuli were simple, and evidently
did not involve complex associations with past experiences. His
memory records, for the most part, had been destroyed. Goltz
records that when starved he showed signs of hunger, and that
eventually he learned to feed himself when his nose was brought
into contact with the food, although he was not able to recognize
food placed near him. He would reject food with a disagreeable
taste. When sleeping he gave no signs of dreaming, differing in
this respect from normal dogs.

Localization of Functions in the Cerebrum. — When the
belief was established that the cerebrum is the organ of the higher
psychical activities there arose naturally the question whether dif-
ferent parts of the cortex have different functions corresponding
to the various faculties of the mind, or whether the cerebrum is
functionally equivalent throughout, in the same sense, for instance,
as the liver. This question of the localization of functions in the
brain (cerebrum) has been much debated, but the most interesting
ami important discussions upon the subject belong to the nine-
teen) li 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
hfa chief disciple (Spurzheim), system of phrenology.* (Jail, from his
earl;.- 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 eiirrenl 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
II (and Spurzheim), " Recherche* hi ir In systeme w-rvcux en ^'neml
.1 celtu <lu oerveau en particulier," L810 19.

GENERAL PHYSIOLOGY OF THE CEREBRUM. 191

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

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

192

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

tion is found in the work of Fritsch and Hitzig* (1870), in which
they exposed and stimulated electrically the cortex cerebri in
dogs. They observed that stimulation of certain definite areas,
particularly in the sigmoid gyrus, gave distinct and constant
movements in the limbs, face, etc. (see Fig. 85). This work
was followed quickly by experiments of a similar kind made
by numerous observers, in which the cerebrum was stimulated in

various animals and finally in
man. In addition, the method
of ablation of these areas was
employed with subsequent
study of the animal in regard
to the motor or sensory de-
fects resulting therefrom, and
the results obtained were
further extended by careful
autopsies upon human beings
in whom paralyses of various
kinds and sensory defects were
associated with more or less
definite lesions of the cerebrum.
The first outcome of this work
was to lead to an extreme view
of localization of function in
the brain, in which the differ-
ent motor and sensory areas
were definitely circumscribed
and separated one from the
other, making the cerebrum a
plurality of organs, to use
Gall's term. The more recent
work lias tended to modify
these extreme views of local-
ization and to emphasize the
fact that histologically and
physiologically the entire cere-
brum is connected so inti-
Qiately, part to purl, (hat, although the different regions mediate
different functions, nevertheless an injury or defect in one part
may influence to some extent the functional value of all other
regions in the organ. The general idea of a, localization of func-
tion has been established definitely, but, the modern view is that

the cerebrum is composed of a plurality of orga.ns, not completely

• I ritech and Hitzig, "Archiv f. Anatomic und Physiologic und wiHsen-
jchaftliche Medizin," 1870, 300.

i-'i«. 85. — To show the motor areas in the
dog's brain as originally determined by
Fritsch and Hitzig: «, Sigmoid gyrus; A, center
for the neck muscles; -F, center for the ex-
tensors and adductors of the forelimb; +,
center for th<- flexora and rotation of tore-
limb; 2, center for the bind Limb; 0 — o,

Center for tin; muscles innervated by the
facial.

GENERAL PHYSIOLOGY OF THE CEREBRUM.

193

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
central sulcus of Rolando and extends inward upon the mesial
surface of the cerebrum. Its exact boundaries marked out by

Togs
Ankle ^
Knee.

£lboiu^

Wrists
JTinyers
$T7uwd>

AnjusSfVaguia-

" Sulcus
SCen

Abdotnett-

Ovest

Ear / / 7
Eyelid / Qosun

Sulcus Centralis

ua / Closure , \\~ ±*S <£>ulcusl

Nose °fjai° Obenmg Voea,L Mastication,
ofiOLM cords

Fig. 86. — 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.

careful stimulation of the region in monkeys was more or less
verified upon man, since in operations upon the brain it was
often necessary to stimulate the cortex in order to localize a
given motor area. By these means charts have been made
showing the cortical area for the musculature of each part of
the body. It was found that in general the distribution of
the areas lies along the central sulcus of Rolando and follows
the order of the cranial and spinal nerves. Within each area
smaller centers may be located by careful stimulation; thus,
the hand and arm area may be subdivided into centers for the
wrist, fingers, thumb, etc. More recently Sherrington and
13

194

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

Greenbaum,* 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 central
sulcus, but lie chiefly along the anterior central convolution,
as represented in Figs. S6 and 87, 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 clin-
ical experience has shown that lesions in this part of the cortex
are accompanied by a paralysis of the muscles on the other

Sale. CenCrvl. AntJS, * Vagina.

Sulacalloso \ ^ Sulc.precenCr.rnarg.

marg.-*

Sulc.parieCo
occip.

Sulccalcarin

C.S.S. del.

Fit;. 87. — To show extension of motor areas on to the mesial .surface, brain of chim-
panzee. [Sherrington and Greenbaum). Mesial surface of left hemisphere: Stippled region
marked I, K (J gives the motor area for lower limb; /, «, and h .indicate regions from which
movements were obtained occasionally with strong stimuli; /, foot ami leg; «, shoulder and
chest ; A, thumb and lingers. I he shaded area marked 10 Y K S indicates a region stimulation
of which give- conjugate movements of the eyes.

side, particularly in the limbs. Pathological or experimental
lesions here, moreover, are followed by a degeneration of the
pyramidal neurons, — a degeneration which extends to the ter-.
ruination of the neurons in the cord. With these data, we can con-
struct ;i fairly complete account of the mechanism of voluntary
movements. The Initial outgoing or efferent impulses arise in the

large pyramidal cells of the motor areas and proceed along the
of their neuron- to the motor nuclei of the cranial or spinal

nerves. The neurons of the pyramidal tract constitute the motor
trad for voluntary* movements; a lesion anywhere along this tract.

Causes paralysis, more or less complete and on the other side of

the body in general, if the lesion is anterior to the decussation.

♦ "Report of the Thompson Yates and John on Laboratories," 4, 351,
1902; 5, 55, 1903.

GENERAL PHYSIOLOGY OF THE CEREBRUM. 195

The path of the motor fibers is represented in the schema given
in Fig. 88. Arising in the cortex, they take the following route
(see also Fig. 81, B):

1. Corona radiata.

2 Internal capsule.

3. Peduncle of cerebrum.

4. Pons Varolii, in which they are broken into a number of

smaller bundles by the fibers of the middle peduncle of
the cerebellum (brachium pontis). 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. Anterior and lateral pyramidal fasciculi 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 (cerebrospinal) neurons,
respectively. Lesions of the anterior root cells in the cord
or of the axons arising from them cause complete paratysis of
the corresponding muscles, since these muscles are then re-
moved not only from voluntary control, but also from reflex
effects. The muscles are entirely relaxed and in time exhibit
a more or less complete atrophy. When the pyramidal neurons
are affected, as in the familiar condition of hemiplegia resulting
from a unilateral lesion of the motor cortex, there is paralysis as
regards voluntary control, but, the spinal neuron being intact, the
muscles are still subject to reflex stimulation through the cord,
especially to the so-called tonic impulses. Under these conditions,
especially if the lesion is in the cord, it is frequently noticed that the
paralyzed muscles are thrown into a state of continuous contraction,
contracture, in which they exhibit a spastic rigidity. This fact,
therefore, may be used in diagnosing the general location of the
lesion. A satisfactory explanation of the cause of the contraction
has not been furnished. It may be due to uncontrolled reflex
excitation of the spinal neurons, or, as suggested by Van Gehuchten,
to the action of the indirect motor path by way of the rubrospinal
tract (fasciculus intermediolateralis).

Is the Pyramidal System the Only Means of Voluntary (Cor-
tical) Control of the Muscles? — Much discussion has arisen

196

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

regarding this question. It is, in fact, one of those questions of
nervous mechanism in which experiments upon lower animals
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 devel-
oped, and corresponding with this
fact it is found that the paralysis
from lesion of the motor cortex is
more permanent. In fact, observa-
tions upon men in whom it has
been necessary to remove parts of
the motor area by surgical opera-
tion indicate that the voluntary
control of the muscle is lost or im-
paired permanently. It would seem,
therefore, that even in an animal as
high in the scale as the dog volun-
tary control of the muscles can be
maintained through fibers other
than those belonging to the pyra-
midal system. A system such as
that found in the rubrospinal tract
(p. 180) may be considered as ade-
quate to fulfil such ii function. In
man, however, along with the more
complete development of the pyr-
amidal system, the efficacy of the
phylogenetically older motor sys-
tems is correspondingly reduced.

The Crossed Control of the
Muscles and Bilateral Represen-
tation in the Cortex.— It has been
known from very ancient times that an injury to the brain on
one side is accompanied by a paralysis of voluntary movement
on the other side of the body, a condition known as hemiplegia.
The facta given above regarding the origin and course of the
pyramidal system of libers explain the crossed character of
of tlie paralysis quite satisfactorily. The schema thus pre-
sented to us is, however, not entirely without exception. In

Fij?. 88.- Schema representing
the course of the fibers of the pyra-
midal system: L, Fibers to the nuclei of
the cranial nerve ; 2, uncrossed fibei
to the lateral pyramidal fasciculus ;
■',, fibers <" the anterior pyramidal

Itl ii.. ii, I- in I be curd ; I and

6, fibers thai <-m-- m the pyramidal
decu ation to make the lateral
pyramidal tract of the opposite ide,

GENERAL PHYSIOLOGY OF THE CEREBRUM. 197

cases of hemiplegia in which the whole motor area of one
side is included it is known that the paralysis on the other side
does not involve all the muscles, and, in the second place,
it is said that there is some muscular weakness on the same
side. The paralysis in hemiplegia affects but little, if at all,
those muscles of the trunk which are accustomed to act in
unison, — the muscles of inspiration, for instance, the diaphragm,
abdominal and intercostal muscles, and the muscles of the larynx.
It would appear that these muscles are bilaterally represented in
the cortex; so that if one side of the brain is intact the muscles of
both sides are still under voluntary control. The mechanism of
this bilateral representation is not definitely known; one may
conceive several possibilities. The motor area on each side may
send down a double set of pyramidal fibers, one of which crosses
and the other remains on the same side, or the fibers may
bifurcate. Or it is possible that the bilateral control is due
to commissural connections between the lower centers in the
cord. Some evidence in favor of the former view is found in the
undoubted histological fact brought out by 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 fasciculus in the cord on both sides, show-
ing 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
pyramidal cells that give origin to the fibers of the pyramidal
system 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, that is, in
muscular and cutaneous sensibility, 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 con-
sciousness, the muscular sensations, being mediated perhaps
through cells other than those giving rise to the pyramidal fibers.
Recent physiological and clinical work has, however, not tended
to support this view. The motor areas appear to be confined
to the region in front of the central sulcus of Rolando, while the
cortical area, which gives rise to that kind of consciousness that
we designate in general as body sensibility, extends back of

198 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

this sulcus in the posterior central convolution. 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 myelinization 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. 222 and Fig. 97). On the con-
trary, in an interesting report by Cushing* of two cases in which
the anterior central convolution was stimulated in conscious
patients, it is stated that there was no sensation other than that
arising from the change in position of the muscles which were
thrown into contraction. In the motor area there arc numerous
connections by afferent fibers, association tracts, with other
parts of the brain. By this means the motor area, without
doubt, is brought into relation 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 com-
plexity, that is to say, every movement is preceded or accom-
panied by certain sensations and perceptions which depend
upon sensory stimulations occurring at that time, or upon
experiences derived from conditions of excitation that have
occurred at some previous period — every action is part of a
train of conscious or subconscious processes whose neural medi-
an ism extends over wide regions of the cortex. The mental
processes, the associations, that lead to and originate the motor
discharge, cannot be definitely located in the cortex, but the
immediate origin of the motor impulse lies, most probably, in
the area along the anterior margin of the central sulcus of
Rolando, which constitute the foci, so to speak, in which all
accessory processes are gathered, so far as they affect our mus-
cular acts, and from which emerge the actual efferent stimuli to
the different muscles.

* Cushing, "American Journal of Physiology," L909 ("Proc. Amer.
Physiol. Boc. )•

CHAPTER X.

THE SENSE AREAS AND THE ASSOCIATION AREAS OF
THE CORTEX,

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

199

200 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

The Body -sense Area. — In his early experiments Mimk
insisted that lesions of the cortex involving the area around the
central sulcus are accompanied by a state of anesthesia on the
other side of the body, hemianesthesia, particularly as regards
the tactile and muscular sensations. It is not necessary, perhaps,
to go into the details of the long controversy that arose in
connection with this point. Both the clinical and the experi-
mental evidence has been contradictory 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 central sulcus, the sensory areas concerned with the cutaneous
and muscular sensations extend posterior to this sulcus.* Posi-
tive 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 have been described
in the posterior central and neighboring parietal convolutions
in which there was a hemianesthesia more or less distinctly
marked without any paralysis. As stated above, Cushing,f
in his report upon the stimulation of the cortex in two conscious
patients, states that no sensations were aroused by stimuli
applied to the anterior central convolution, while stimulation
of the posterior convolution aroused distinct sensations of
numbness and of touch. Such cases tend to support the view
that the motor and body sense areas, although contiguous, do
not overlap. Regarding the sensory defects associated with
lesions of the parietal lobe posterior to the central sulcus (pos-
terior 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 affected but little, if at all.
Monakow gives the order in which sensory defects manifest

themselves after such lesions, as follows: The localizing space

and muscle sense-, are chiefly affected, in fact, almost lost, on the
opposite side; the temperature and pressure sense may be
affected, while the pain sense is retained or but slightly affected.
The clinicians have observed that the most positive and invaria-
ble symptom of lesions in this region is a condition of asfereogno-

sis,that is, a diminution in the stereognostic sense or perception.
By the stereognostic perception is meant the power to judge
concerning the form and consistency of external objects when

handled, and it musl be regarded as a perception based upon

* Consult Monakow, "Ergebnisse der Physiologic, " 1902, vol. i, part i,
p, 821. t Cushing, loc. cil ,

SENSE AREAS AND ASSOCIATION AREAS.

201

localized sensations of touch and temperature in combination
with muscular sensibility. On the whole, therefore, we must
infer that the cortex in this postcentral area is concerned with
the finer and more conscious interpretations of the sensations
of pressure, temperature, and muscular conditions, and especially
the higher type of these sensations which we can project or
localize accurately. The definite part of the cortex, if any,

Cen/rai <su/cus

Nucleus of funiculi
gracilis tffun. cunealus

ToCereo
synternal arcuate fibers

<Z?fcinal Cord.

Fig. 89. — Schema representing the origin and course of the fibers of the median fillet, — the
intercentral paths of the fibers of body sense.

concerned in the primary conscious mediation of the sense of
pain has not been definitely localized.

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

202

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

posterior funiculi, after ending in the nucleus of the funiculus
gracilis and the nucleus of the funiculus cuneatus of the medulla.
This path is represented in a schematic way in the accompanying
diagram (Fig. 89). The second sensory neurons arise in the
nuclei mentioned. For the most part, at least, these new neu-
rons run ventrally, as internal arcuate fibers, cross the mid-line,
and then pass forward or anteriorly. The crossing occurs mainly
just in front of — that is, cephalad to — the pyramidal decussa-
tion, forming thus a sensory decussation (decussation of the
lemniscus), which explains the crossed sensoiy control, as the
pyramidal decussation explains the crossed motor control of
the cerebrum in relation to the body. After this decussation

I

Fig. 90. Cro — ection through midbrain (Kolliker) to show the position of the lemniscus
/. /.). \r, The red nucleus; 8n, the substantia nigra; Fp, the peduncle.

the sensory fibers form a longitudinal bundle on each side known

as the median fillet or lemniscus, which in the pons lies jusl
dorsal '<> the pyramidal system of fibers.

The lemniscus filters may be traced forward (see Fig. !)()) as

far as the superior colliculus of the corpora quadrigemina and

the thalamus, the important termination being in the thalamus
(ventral or lateral nucleus). Those neurons that end in the
thalamus are continued forward by a third set of neurons, which

end in t he parietal lobe of the cerebrum (see big. si , < '). On its

way through the medulla and pons f he lemniscus is believed to

receive acce ion- of Bensory fibers from the sensory nuclei of

the cranial nerves of the opposite side. The course of the lem-

niscue hae been traced by various means, but especially by the

SENSE AREAS AND ASSOCIATION AREAS. 203

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

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

The Center for Vision. — The location in the cortex of the
general area for vision has been established by anatomical, physio-
logical, and clinical evidence. The physiologists have experimented
chiefly by the method of ablation. Munk, Ferrier, and later ob-
servers have found that removal of both occipital lobes is followed
by defects in vision. According to Munk, removal of both occip-

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

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

204 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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

brain undergo secondary degeneration and their course; can be
traced microscopically to the brain. By this means it lias been
shown thai in man and 'lie mammalia there is a partial decus-
sation of the optic fibers in the chiasma. The libers from the
Loner side <>f each retina cross at this point to the opposite optic
tract; those from the outer side of the retina do not decussate,

SENSE AREAS AND ASSOCIATION AREAS.

205

but pass into the optic tract of the same side. The fibers of the
optic tract end mainly in the gray matter of the lateral genicu-
late body, but some pass also to the thalamus (pulvinar) and
some to the superior colliculus of the corpora quaclrigemina.
These locations, therefore, particularly the lateral geniculates,
must be considered as the primary optic centers. From these
points the path is continued toward the cortex by new neurons
whose axons constitute a special bundle, the occipitothalamic

Occipital lobe.

Occipito-thalamic radiation.
Superior colliculus.

Lateral geniculate.
Thalamus.

v— Retina.

Fig. 91. — Diagram to indicate the general course of the fibers of the optic nerves and the
bilateral connection between cortex and retina.

radiation, lying in the occipital part of the internal capsule
(see Fig. 81, D). A schema representing this course of the
optic fibers is given in the accompanying diagram (Fig. 91).
According to this schema, the general relations of each occipital
lobe to the retinas of the two eyes is such that the right occip-
ital 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.

206 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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

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

The Amount of Decussation in the Chiasma. — According
to the schema given above, half of the fibers in each optic nerve
decussate in the chiasma. There is, however, no positive proof
that the division of the fibers is so symmetrically made. In the
lower vertebrates, — fishes, amphibia, reptiles, and most birds —
the crossing is said to be complete, while in the mammalia a certain
proportion of the fibers remain in the optic tract of the same side.
In a general way, it would appear that the higher the animal is
in t Ik- 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 if is
also possible "r probable that the extent of decussation in man
shows individual differences. There seems to be no acceptable

suggestion regarding (lie physiological value of (his partial decus-
sation other than i hat, of a probable relation to binocular vision. It
h.i- been used to explain the physiological fact that simultaneous
stimulation of symmetrical points in the two retinas gives us a
single visual sen :it ion.

The Projection or Localization of the Retina on the
Occipital Cortex. — It would seem most probable that the paths
from each -pot iii the retina terminate in a definite region of
the occipital cortex, ami attempl have been made by various
methods o, determine this relation. According to Henschen,* the
* Hen chen; "Brain," L893. 170.

SENSE AREAS AND ASSOCIATION AREAS.

207

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

t . ,, . . ,. LEFT RETINA

end in this region, — according
to some authors (Henschen)
along the anterior third of the
fissure, according to others
(Schmid and LaqueurJ) along
the posterior portion of the
fissure. Moreover, since uni-
lateral lesions of the occipital
lobe, however extensive, do
not cause complete blindness
of the foveal region, it has
been supposed that this im-
portant part of the retina is
bilaterally represented in the
cortex, as indicated in the ac-
companying diagram (Fig. 92),
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-

* Donaldson, "American Journal of Psychology," 1S92, 4.

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

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

cC;piT'xU

Fig. 92. — 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.

Jlls PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

nected with a wide area in this lobe. Those who hold this view
explain the known fact that lesions in the region of the calcarine
fissure give the most permanent condition of hemiopia, on the
view that these lesions involve the underlying fibers of the
occipitothalamic radiation. 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,
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
(lateral 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 stimulation of the occipital cortex.
Stimulation of this kind causes movements of the eyes, and the
movements vary with the place stimulated, f Stimulation of
the upper border of the lobe causes movements of the eyes
downward, stimulation of the lower border movements upward,
and of intermediate regions, movements to the side. Assuming
that the direction of the movement is 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. A definite relationship of this kind is indicated
to some extent by clinical facts, that is to say, lesions of the
lower region of the occipital lobes cause blindness chiefly in the
lower portion of the retina and lesions of the anterior region
in the upper portion of the retina. The fact that stimulation
of the occipital cortex causes definite movements of the eyeballs
seems to imply that there are efferent fibers in the occipitothal-
amic radiation running from t he occipital cortex to the midbrain,
where they make connect ions wit h 1 he motor nuclei of the third,
fourth, and sixth cranial nerves.

* Monakow, loc. cit., also "Ergebnisse d. Physiologic, " MJ07.
fSchafer, "Brain," ll, I, L889, and 13, 165, L890.

SENSE AREAS AND ASSOCIATION AREAS. 209

The Function of the Lower Visual Centers. — The first ending
of the optic fibers lies in the lateral geniculate and to a lesser
extent in the thalamus and superior colliculus. It is conceiv-
able, 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 mechanical 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 medial longitudinal fasciculus through which con-
nections are established with the motor nuclei of other cranial
nerves, furnishes us with a possible reflex arc through which the
visual impulses brought into the lower optic centers, especially
the superior colliculus, may cause co-ordinated movements of
the eyes or of the head. Usually it is assumed that conscious
visual sensations, and especially visual associations and mem-
ories, are aroused only after the impulses reach the occipital
cortex. In the fishes the midbrain forms the final ending of the
optic fibers, and in these animals, therefore, whatever psychical
activity accompanies the visual processes must be mediated
through this portion of the brain. In the higher animals, how-
ever, the development of a cerebral cortex is followed by the
evolution of the occipitothalamic radiation, and as the connec-
tions 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 por-
tions of the brain lying most anteriorly, and doubtless the degree
of consciousness is greatly intensified in the higher animals in cor-
respondence 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
14

210

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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 probable that it lies mainly in the superior temporal
gyrus and the transverse gyri extending from this into the
lateral fissure of the cerebrum (fissure of Sylvius).

The Histological Evidences. — On the histological side the paths
of the auditory fibers have been followed with a large measure of

Posterior nucleus.

Deiters's nucleus.

Dorsal nucleus.
Ventral nucleus.

Cochlear branch.

Vestibular branch.

Semicircular
canals.

Scarpa's ganglion.
Cochlea.
Spiral ganglion.

Mi'- medullary nuclei of the eighth nerve. (From Poireer and Charpy.)

Buccess, although in many details the. opinions of the different
tigators vary considerably. The eighth cranial nerve
springe from the bulb by two roots: the external and the
internal. The former has been shown to supply, mainly at
least, the cochlear portion of the internal ear, and is, there-
lore, the auditory tierve proper. This division is spoken of

ae the cochlear branch. The internal root supplies mainly
the vestibular branch of the internal ear, and is, therefore,
spoken of :> the vestibular branch (see Fig. 93). If seems cer-
tain that the latter i no1 an auditory nerve, but is concerned

SENSE AREAS AND ASSOCIATION AREAS.

211

with peculiar sensations from the semicircular canals and vestibule
that have an important influence on muscular activity, especially
in complex movements. The central course of these two roots is
quite as distinct as their peripheral distribution, — a fact that bears
out the supposition that they mediate different functions. The
vestibular branch ends in the nucleus of Deiters, the nucleus of
Bechterew, and the nucleus fastigii of the cerebellum. Through
these nuclei reflex connections are made with the motor centers
of the cord and midbrain, and probably also with the cerebellum.
The path is not known to be continued lorward to the cerebrum.
The central course of the cochlear branch is indicated schematically
in Figs. 93 and 94. The
fibers constituting this
branch arise from nerve
cells in the modiolus of
the cochlea, — the spiral
ganglion. These cells,
like those in the poste-
rior root ganglia, are bi-
polar. One axon passes
peripherally to end
around the sense cells
of the cochlea, at which
point the sound waves
arouse the nerve im-
pulses. 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 res-
tiform body and known
as the ventral or acces-
sory nuclei (V.n., Fig.

94), and one dorsally, known as the dorsal nucleus or the tuber-
culum 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. 94).

* For literature, see Van Gehuchten, "Le Nevraxe, " 4, 253, 1903, and
8, 127, 1906.

Fig. 94. — Diagram to show central course of
auditory fibers (modified from Van Gehuchten):
D.n., Dorsal nucleus giving rile to the fibers that
form the medullary striae (a.s.); V.n., the ventral
nucleus, giving origin to the fibers of the corpus
trapezoideum {c.tr.); s.o., superior olivary nucleus;
l.f., lateral lemniscus; n.s., nucleus of the lateral
lemniscus; t.g.i.,, the inferior colliculus.

212 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

►Some strike directly across toward the ventral 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 corpus trapezoideum. The
fibers of this cross hand end, according to some observers, in
certain nuclei 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 auditory fibers enter a distinct tract long known to the anat-
omist and designated as the lateral fillet or lateral lemniscus.
Authors differ as to whether the auditory fibers of this tract arise
from nerve cells in the superior olivary and neighboring nuclei,
or are the fibers from the accessory nucleus which pass by the
superior olivary body without ending and then bend to run for-
ward in a longitudinal direction. This last view is represented
in the schema (Fig. 94). 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 form a structure
visible to the eye and known as the medullary or auditory stria?.
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
lemniscus of the other side either with or without ending first
around the cells of the superior olivary nucleus. According to
the descriptioD of some authors, the fibers from the accessory
nucleus and tuberculum acusticum do not all cross the mid-line
to reach the lateral lemniscus of the other side; some of them
pass into the lateral lemniscus of the same side; so that the
relations of the fibers of the cochlear nerves to the lateral lemnis-
cus resemble, in the matter of crossing, the relations of the optic
fiber- to the optic tract. After entering the lateral lemniscus

the auditory fibers puss 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 lemniscus. From this second or third termination

another set of fibers, the auditory r;i,< I ial ion, continues forward
through the inferior extremity of the internal capsule to end

in the mperior temporal gyrus (see Fig. si, E). According to

Plechsig,* who has studied the course of these fibers in the

embryo by the myelinization method, the main group passes

from the median geniculates to the transverse gyri of the tern-

* Flech ig, ' Localisation der geistigen Vorgange," Leipzig, L896.

SENSE AREAS AND ASSOCIATION AREAS. 213

poral lobe within the lateral fissure of the cerebrum (fissure
of Sylvius). The median geniculates, in man at least, have,
therefore, the function of a subordinate auditory center, as the
lateral geniculates have the function of a subordinate visual
center. The median geniculates are connected with the inferior
colliculus, and also, it will be remembered, with each other, by
commissural fibers (Gudden's commissure) that pass along the
optic tracts and the inferior 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 lemniscus, inferior colliculus, median
geniculate, Gudden's commissure, auditory radiation, and
temporal cortex.

The Motor Responses from the Auditory Cortex. — According
to Ferrier, stimulation of the cortex of the temporal lobe (inferior
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 physiolog}^ 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
* See Barker, "The Nervous System," 1899, for references to literature.

214

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

of this tract are widespread, complicated, and in part incom-
pletely known. All those portions of the brain connected with t he
sense of smell are sometimes grouped together as the rhinenceph-
alon. According to von Kolliker, the parts included under this
designation are, in addition to the olfactory bulb and tract, Am-
nion's horn, the fascia dentata, the hippocampal lobe, the fornix, the
septum pellucidum, and the anterior commissure. The schematic
connections of the olfactory fibers are as follows (Fig. 95): After

■ -Diagram of the central course of the olfactory fibers: /, Olfactory bulb;
//, olf < , III, cortex of the hippocampal lobe (gyrus uncinatus): / V, anterioi

Commit lire, olfactory portion; A, olfactory epithelial cells of nose (their fibers, olfactory
nerve libers, terminate in the glomeruli of the bulb)] It, glomeruli 01 olf actory bulb where
the olfactory fibers come in contact with the dendrites ot the mitral cells; c, mitral and
bru-h cells; I, -', 3, axons from the mitral cells constituting the fibers of the olfactory
tract. Fibei •!, which enter the commissure, arise, according to somo observers, from
cells in the olfactory li.ue near the base of the tract.

entering the olfactory lobe the libers terminate in certain globular
bodies, the glomeruli olfactorii (B), whose diameter varies from 0.1 to

0.3mm. Here connections are made by contact with the dendrites
of nerve cells of the olfactory lobe, the mitral and brush cells (Q.
The axons of these cells pass toward the brain iii the olfactory had,.
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
commit jure 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

SENSE AREAS AND ASSOCIATION AREAS. 215

in the gray matter adjacent to the base of the olfactory tract,
the tuberculum olfactorium, whence the path is probably continued
by other neurons to the region of the hippocampal lobe. (3) The
lateral tract, whose fibers seem' to pass to the hippocampal lobe of
the same side. According to Van Gehuchten,* none of the fibers
of the anterior commissure arise from the nerve cells in the olfactory
bulb. He considers that the fibers in the olfactory portion of this
commissure constitute an association system connecting the olfac-
tory lobe of one side with the olfactory bulb of the other side.

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 convolution,
especially its distal portion, the uncus. 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
movements that accompany usually strong olfactory sensations.
On the other hand, ablations of these regions are followed by de-
fects 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. 98).

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

216 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

that is, those who arc 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 arc 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 (1S25) as the result of numerous autopsies.

(It is a curious fact that Bouillaud's observations were inspired by the work
of Gall. Gall having observed, as he thought, that individuals who are fluent
speakers or who have retentive memories are characterized by projecting eyes,
concluded that this peculiarity is due to the larger size of the lower part of the
frontal lobe, and he therefore located the faculty of speech in this region of the
brain. In spite of the vagaries into which he was led by his false methods Gall
made many most important contributions to our knowledge of the anatomy of
the brain and the cord. The discovery of the location of the center of speech,
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 t hese 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 in general confirmed this localization, and what
is designated as the "speech center" has been placed in the
inferior frontal convolution in the gyrus surrounding the anterior
or ascending limb of the lateral fissure (fissure of Sylvius,
»S, Fig. 90). Many authors insist that this localization is too
limited, and thai defects in the power of speech may result not
only from injuries to this region but also from lesions of con-
tiguous areas, including the anterior portion of the island and
the opercular portion of the central convolution. Autopsies
have shown thai in right-handed persons the speech center is

placed or IS functional usually in the left cerebral hemisphere,

while ;n the case of left-handed individuals aphasia and paralysis
are produced by lesions involving the right side of the brain.
This region is not I he dired corl ical motor center for the muscles

of speech. It is possible that aphasia may exist without paralysis
of the e latter muscles. It, is rather the memory center of the

motor innervations necessary to form the appropriate sounds

or words wit h 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

SENSE AREAS AND ASSOCIATION AREAS. 217

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. Motor
aphasia is classified sometimes as complete and incomplete.
In the former case there is entire loss of the power of expression,
including eventually the power to write or to use symbols. The
incomplete form includes a number of varieties and is sometimes
further divided into the subcortical and the transcortical, accord-
ing to the supposed location of the lesion. When the individual
can conceive the words, but is unable to express them in spoken
language or expresses them incompletely, the lesion is supposed
to be subcortical. When, on the contrary, there is inability to
conceive the words, an interference with the inner word-building,
the lesion is supposed to affect the cortex. It does not seem
to be certain whether or not, in the case of complete lesion
of the center on one side, the ability to speak can be again
acquired by education of new centers, f Some recorded cases
seem to indicate that this re-education 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 in
some aphasics the loss of the power of writing, a condition desig-
nated as agraphia, is the characteristic defect, rather than the
loss of the ability to use articulate language. The area in which
the motor associations for the act of writing are located has
been placed in the middle or second frontal convolution con-

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

f See Mills, " Journal of the Amer. Med. Assoc," 1904, xliii.

218

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

tiguous to the cortical motor centers for the muscles of the arm
and hand (11". Fig. 96).

Sensory Aphasia. — In sensory aphasia* the individual suffers
from an inability to understand spoken or written language,
ami as the cortical centers for hearing and seeing are situated
in distinct parts of the brain, we should expect that the mech-
anism 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 under-
stand spoken lan-
guage, or word-deaf-
ness, is, in fact, usually
attributed to a lesion
involving the supe-
rior temporal convo-
lution contiguous to
the cortical sense of
hearing (H, Fig. 96),
while loss of power
to understand written
or printed language,
word - blindness, is
traced to lesions in-
volving the inferior
parietal convolution,
the gyrus angularis,
contiguous to the oc-
cipital visual center
(V, Fig. 96). These two conditions may occur together, bu1 cases
are recorded in which t hey existed independently. 1 1 may be im-
agined thai the individual suffering from word-blindness alone is
r — »-m tally in i lie comlii ion of one who attempts to read a foreign
language. The power of vision exists, but the verbal symbols
have no associal ions, I berefore, no meaning. So one who is word-
deaf alone may be compared to I he normal individual who is
Bpoken to in a foreign tongue. The words are hea.nl, but they

ociations with past experience. Sensory aphasia,

I il.f motor aphasia, may be complete or incomplete. In the com-
plete form there is \vord-de;d'ness as well as word-blindness, but

the individual may be capable of speaking. In the incomplete
type these symptoms are exhibited in milder form. The exact

1 on 'lit Starr, "Aphasia," " Transactions of the Congress of American
Physicians and Burgeons," vol. i, p. :»'j!», L888; also Monakow, "Gehirn*
pathologie," L906.

H

Fig. 90. — Lateral view of a human hemisphere;
cortical area V, damage to which produces 'mind-
blindness" (word-blindness): cortical area //, 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. 219

localization in the cortex of the areas involved in the auditory
and visual associations and perceptions connected with speech
has not been established satisfactorily. The question is a
complex and difficult one, and those who have had the most
experience are perhaps the most cautious in referring word-
blindness or word-deafness to the lesion of circumscribed areas
of the cortex.* It may be said, however, with some certainty,
that the phenomena of sensory aphasia in general are connected
with lesions involving the area along the margins of the pos-
terior portion of the lateral fissure (fissure of Sylvius) and
extending into the parietal lobe as far as the angular gyrus,
and with the cortex within the fissure, including the cortex of
the island.

The general facts regarding aphasia illustrate excellently the
prevalent conception of cerebral localization. The understanding
and the use of spoken or written language is, so to speak, a mental
whole, both from the standpoint of education and of use. To
understand or to express certain conceptions implies the use of
definite words, and our visual, auditory, and motor experiences are
combined in these symbols. Each phase of this complex may be
cultivated more or less separately; in the case of the unlettered
man, for instance, the "written or printed symbols form no part
in the associations connected with his verbal concepts. Corre-
sponding to these facts we have, on the anatomical side, a portion
of the brain in which the auditory memories are organized, — that
is, they are 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 fun-
damentally distinct, they are practically combined in their
activity. Corresponding with this conception it is found from
clinical experience that aphasics, although the lesion may
affect only one of these various centers, suffer a deterioration,
more or less pronounced, of their general intellectual capacity.
We may believe that the varying gifts of individuals, in' the matter
of the use of language, rest partly on the amount of training re-
ceived and partly on the inborn character and completeness of
the nervous machinery in the different centers.

The Association Areas. — According to the views presented
above, it will be seen that the motor and sense areas occupy only

* For a general review, see Monakow, "Ergebnisse der Physiologie, "
1907, 334.

220 THE PHYSIOLOGY OF MUSCLE AND NERVE.

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
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 mailer 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 v. ith a eerl ain portion of his brain more highly organized than

i Flech ig, Gehirn and Seele, " Leipzig, L896; also, "Archives de Neurol*
ogie," vol. ii, L900.

SEXSE AREAS AND ASSOCIATION AREAS. 221

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 ma}' 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
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. 99), which lies in front of the motor area;
the median or insular, — that is, the cortex of the island of Reil;
and the posterior, which lies back of the body feeling area, extending
to the occipital lobe and also laterally into the temporal lobe.
This area Flechsig suggests may be subdivided into a parietal area,
34, Fig. 99, and a temporal area, 36, Fig. 99. 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

I'l'l THE PHYSIOLOGY OF MUSCLE AND NERVE.

(amentia) or mentally deranged (dementia). It is stated* that
the brain in such eases 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 Roil there are no
tacts sufficiently distinct to warrant a positive statement,
although, as stated above, the data from pathological anatomy
would seem to indicate that this portion of the cortex may form
a part of the speech area both on the motor and the sensory side.
The area is much more developed in man than in the lower mam-
mals, and its connections with other parts of the cortex by means
of association tracts are such as to lead to the supposition that
its general functions are of the higher synthetic character attributed
to the association areas in general. *

By way of caution it should be stated that the general ideas developed
above in accordance with Flechsig's views do not meet with universal accep-
tance. Some of the most experienced observers are unwilling to admit that
such a degree of localization of the psychical activities really exists. They
contend that the whole cortex may be concerned in mediating the highest
mental processes, and quote post-mortem examinations of carefully studied
cases in support of this view. We must recognize, in fact, that the schemata
de.-.i<_rned to show the distribution of the higher psychical activities in the
represent at present only hypotheses which need satisfactory con-
firmation before they can be finally accepted. We may feel considerable
confidence in the localizations of the motor areas and of some, at least, of the
sensory areas, hut in the matter of the more complex mental acts, failure
in which expresses itself in the conditions of aphasia, dementia, perversions,
etc., our knowledge is incomplete, both as regards analysis of the symptoms
and the localities affected in the brain.

The Development of the Cortical Area. — Flechsig * has
published the results of an extensive study of the time of mye-
linization 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 lie gives the name of project it>n anus. The
location of these areas is shown in part in Figs. 97 and 98, 18 (0b, if),
'■ >;. 7 (7,J), .9, IB. TWO areas connected with the olfactory sense
are not shown in these figures; they appear in the anterior per-
forate lamina on the base of the brain and in the uncinate gyrus.

Brain," 1903, p. 215.
t Rech ij.r, "Berichte der mathematisch-physischen Klasse der konigl,
= 0 der Wissenschaften zu Leipzig," 1904. For a summary of
1 1,,, results of this work, see Sabin, " The Johns Hopkins Hospital Bulletin,"
l ebruary, 1906.

SENSE AREAS AND ASSOCIATION AREAS.

223

"-""''"Ir

f

-

■*:>:«

£x&i!'r

Fig. 97. — Lateral surface of the brain, showing the primordial areas, both sensory and
automatic, in dotted zones. — (Flechsig.)

ft

■ '-:;-^v-h^vvA^-''

1S*

$

.9

'■*.

I

Fig. 98. — Same zones on the mesial surface of the brain. — (Flechsig).

224

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

• •:;.- v-;/;'-Vr'A-::";;;' -. Vv«-^v: };,,..

\

>,/•

.PJ

99. — Lateral surfaces of the brain, showing the primordial and marginal zones.
— (Flechsig.)

I

:ir,

33

'/"■

23

tp

36

i ig 100. Same area* <m the me ial urfaoe. {Flechaig-I

SENSE AREAS AND ASSOCIATION AREAS. 225

Later there is developed around these primary zones areas that
Flechsig calls marginal or border zones, which have no projection
fibers, but which are connected by short association fibers with
one or more of the primary projection zones, 14, 16 to S3, in Figs.
99 and 100. 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 #, is to 2h, and 14, ub with 7. Later still
the great association areas — 34, 35, 36, Figs. 99 and 100 — acquire
their myelinated fibers. These latter centers, as indicated above, may
be considered as association areas with more complex connec-
tions, and they serve to mediate, therefore, the higher psychical
activities. Flechsig, in his report, designates these areas from an
anatomical point of view as terminal or central zones. As the
result of his histological work, as far as it has progressed, he distin-
guishes thirty-six areas in the cortex in which the myelinization of
the fibers occurs separately, and in which, therefore, by inference
different physiological activities are mediated. These 36 areas
are subdivided as follows:

I. Primary areas.

la. Primary projection areas (I, 2, 4, 5, 6, 7, 8 {15), seven or
eight in number, and provided with projection fibers —
sensory and motor.

V>. Primary areas without projection fibers {3, 9, 10, 11, 12, 13)
and apparently without association fibers. Functions un-
certain.

II. Association areas.

IIa* Intermediate or border areas, 14, 16-33, provided with
short association fibers.

II Terminal or central areas, 34, 35, 36, provided with long
association fibers.

Histological Differentiation in Cortical Structure. — While
the general structure of the cortex is everywhere similar, detailed
examination has shown differences in the shape of the cells, the
thickness and number of the strata, the calibre of the fibers, etc.,
which are said to be constant for any given region. By this means
it is possible to divide the cerebral cortex into a number of areas
whose structures are sufficiently distinct to be recognized with some
certainty. Reasoning from analogy we should infer that a differen-
tiation in structure implies a subdivision of physiological activity,
and to this extent this recent histological work supports the view
of a localized distribution of function in the cortex. Campbell,*

* Campbell, "Histological Studies on Localisation of Cerebral Functions,"
Cambridge, 1905.

15

226 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

in a very thorough investigation of this kind, has succeeded in
separating some fifteen or sixteen different areas, and the results
obtained by him support in a general way the localizations described
in the preceding pages. Thus the cortex in the postcentral con-
volution (body-sense area) has a structure distinctly different
from that of the precentral convolution (motor area), the latter
being characterized among other things by the presence of giant
pyramidal cells (Betz cells). In the occipital lobes the region
round the calcarine fissure (visuosensory ) has a structure different
from that of the contiguous cortex (visuopsychic), and a similar
difference is claimed for the auditor}- region. Campbell calls
attention to the fact that the extreme end of the frontal lobe
(prefrontal region) has a comparatively undeveloped structure.

Fig. 101. Diagram to show the composition of the corpus callosum aa a system of com-
missural fibers, without projection fibers. — (Cajal.)

The Corpus Callosum. — The corpus callosum is the must
conspicuous of the bands of commissural fibers that connect one
cerebral hemisphere with the other. Similar tracts of the same
general nature are the anterior commissure and the fornix.
The position and great development of the corpus callosum

has made it I lie ol.jert of e\ periinenl al as well as anatomical

invest igat ion. When t he corpus is divided by a section along t he
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 andSchafer) from above, symmetri
cal movements on the two sides of the body may be obtained. If
the motor cortex on one side is removed, stimulation in the lon-
gitudinal fissure causes movements only on the side controlled
by the uninjured cortex. These facts are in harmony with the

SENSE AKEAS AND ASSOCIATION AREAS. 227

results of histological studies, which indicate that the fibers of the
corpus callosum do not enter directly into the internal capsules
to be distributed to underlying portions of the brain, but are truly
commissural and connect portions of the cortex of one hemisphere
with the cortex of the other side. This relation is indicated in the
accompanying diagram (Fig, 101). 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 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 lateral geniculate bodies form part of the optic
path. In addition, however, 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 thalami have
been frequently studied experimentally to ascertain whether
they have specific functions independently of their rela-
tions to the cortex. These efforts have given uncertain results.
Older experiments (Nothnagel), in which the attempt was made to
destroy these nuclei by the localized injection of chromic acid, are
probably unreliable, as the destruction involved also the projection
fibers passing to the cortex. Lesions of the nucleus caudatus are said
to be accompanied always by a rise in body temperature and an
increase in heat production, and stimulation of the same nucleus
gives a very marked rise in blood-pressure. These facts indicate
a possible connection of this nucleus with heat and vasomotor
regulation. Other observers have supposed that these nuclei are
especially concerned in the co-ordination of the muscles employed
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 they would seem to have a physiological im-
portance similar to that of the cortex itself, but experimental

228 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

and clinical facts are at present insufficient to justify any
hypothesis as to their special functions. With regard to the
various nuclei of the thalamus it is known that they form abun-
dant connections with the sensory areas of the cortex cerebri,
and from this standpoint they may be regarded as consisting of
subcenters, with a probability, 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.
102. 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

229

230

PHYSIOUKiY OF CENTRAL XKRYOUS SYSTEM.

parallel to the surface and doubtless make connections with the den-
drites of the Purkinje cells as well as with the cells of the molecular
layer. A few larger nerve cells of Golgi's second type (/) are found
also in the granular layer. In the molecular layer are found two
types of cells: the larger basket cells (6) whose axons terminate in a
group of small branches that inclose the body of the Purkinje cells,
and a number of smaller cells (e), situated more superficially,
whose axons pass longitudinally in the molecular layer and termi-
nate in arborizations or baskets that doubtless make connections
with the dendrites of the Purkinje cells.

I ig. Mil'. Histology of (lie (••■icbclluin. (From ObcrBtviner.)

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 (lie moss and climbing fillers may pass at once to the
Purkinje cells and lead to efferenl discharges, or they may end in
the cells of the granular or molecular layer and thus be distributed
to i lie Purkinje cells in a more indirect way. In addition to the
cortex the cerebellum contains several masses of gray matter in
it- 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

CEREBELLUM, PONS, AND MEDULLA. 231

medullary substance of the vermiform lobe (nucleus fastigii, n.
globosi, and the n. emboliformis). The axons of the Purkinje
cells of the cortex terminate in these subcortical nuclei, and the
efferent path from the cerebellum is then continued by new
neurons. Thus, the fibers of the superior peduncles (brachium
conjunctivum) of the cerebellum arise chiefly from the dentate
nuclei, and only indirectly from the cortex. The anatomical
connections, afferent and efferent, between the cerebellum and
other parts of the nervous system are very complex and not
yet entirely known. Without attempting to recall all of these
connections, which will be found described in works upon anat-
omy or neurology, emphasis may be laid upon those which are
at present helpful in discussing the physiology of the organ.

1. Connections with the Afferent Paths of the Cord. — Through the
inferior peduncles (restiform bodies) the cerebellum receives affer-
ent fibers from the spinal cord and the medulla. The cerebello-
spinal fasciculus undoubtedly terminates in the cerebellum, and
according to some observers the fibers of the posterior funiculi
after ending in the n. gracilis and n. cuneatus are also continued
in part to the cerebellum by nerve fibers passing by way of the
inferior peduncles. This latter view has, however, not found
confirmation in recent work, most authors believing that the
afferent fibers of the posterior funiculi all enter the lemniscus,
after decussating, and pass forward to the thalamus. Ascending-
fibers arising in the reticular formation of the medulla and the
olivary nucleus also take this path to the cerebellum, and, on the
other hand, probably make connections with the sensory tracts
of the cord or the sensory nuclei of the medulla. Another
afferent tract of the cord, that of Gowers (fasciculus anterolater-
als superficialis), ends in the cerebellum, in large part at least,
forming a part, in fact, of the cerebellospinal system. The nature
of the sensory impulses conveyed in this way to the cerebellum
is not entirely understood, but it seems certain that some of
them, at least, are what we designate as impulses of deep sen-
sibility, that is, sensibility of muscle, tendon, and joint, as opposed
to cutaneous sensibility, and this fact, as we shall see, throws
some light on the specific functional importance of the cerebellum.

2. Connections ivith the Vestibular Branch of the Eighth Cran-
ial Nerve. — This branch, arising in the semicircular canals and
utriculus and sacculus, ends in the pons in several nuclei (Deiters',
Bechterew's) and also in the n. fastigii of the cerebellum. These
nuclei, in turn, are connected with other parts of the central
nervous system, but the details, are not yet completely known.
The connections that have been most clearly established are
those made with the motor centers. From Deiters' nucleus the

232

PHYSIOLOGY OF CENTRAL XLRYOUS SYSTEM.

vestibulospinal tract arises and passes to the cord to connect
with the motor centers of the spinal nerves, while Bechterew's

nucleus is said to give origin to a bundle which runs with the
medial longitudinal fasciculus and may make connections with
the motor nuclei of the cranial nerves. In how far the vestibular

L03 Diagram to indicate a possible descending path from cerebrum to cord in ad-
dition i" ill'- pyramidal system, namely, tin- secondary or cerebellar motoi path (Van
Gehuchten). The path i- indirect and comprises tbe following units: I. The cortico
ponto cerebellar path, represented as arising in tin- motoi area <>i the cerebrum and passing
down with 'in- pyramidal ■■ item to end in the pons, thence continued through the middle
peduncles '" tbe cerebellar cortex <>i opposite Bide. 2. i In- path from the cerebellar cortex
in the dentate nucleus. 3. The path from the dentate nucleus to the red nucleus passing
iperior peduncles, brachium conjunctivum. I. The path from the red
nucleui to 'in- motoi cells "i the ptnal cord rubro pinal tract i.

nuclei may make afferenl connections with the cerebellum is
undecided, lmt it seems probable thai such tracts exist, iii view
of the fad thai destruction of the semicircular canal and severe
lesions of the cerebellum cause motor disturbances that are
strikingly similar.

:;. Connections "Hli Other Sensory Nuclei, In addition to the

CEREBELLUM, PONS, AND MEDULLA. 233

special sensory connections just described, it is stated by various
neurologists that the sensory nuclei of the vagus, the trigeminal
and the auditory nerves, send afferent paths into the cerebellum,
and that similar paths extend from the primary end stations
of the optic fibers.*

4. Connections with the Cortex of the Cerebrum. — The cerebellar
cortex is connected with the cerebral cortex by the large system
known as the cortico-ponto-cerebellar tract (see Fig. 81, A). The
fibers of this tract arise in the motor area of the cerebrum or in the
frontal cortex anterior to the motor area, descend in the internal
capsule and cerebral peduncle, and end in the gray matter of
the pons. Thence new axons continue the path across the
mid-line and to the cerebellar cortex by way of the middle
peduncle (brachium pontis). The tract would seem to convey
efferent impulses from the cerebral cortex (motor region) of
one side to the cerebellar cortex of the opposite side. A second
possible connection with the cerebrum is made by way of the
thalamus. Fibers arising in the dentate nucleus emerge by
way of the brachium conjunctivum and connect with the red
nucleus in the subthalamic region and perhaps also with the
thalamus. The latter fibers may be continued forward to the
cortex of the cerebrum and thus constitute an afferent path from
cerebellum to cerebrum. Those fibers, on the contrary, which end
in the red nucleus are brought into reflex connection with the
motor bundle (rubrospinal tract), extending from the red nucleus
to the motor centers in the spinal cord. Making use of the connec-
tions described above, Van Gehuchten pictures an indirect motor
path from the cortex of the cerebrum to the motor nerves by way
of the cerebellum (see Fig. 103). The motor impulses descend by
way of the cortico-ponto-cerebellar path to the cerebellar cortex,
thence to the dentate nucleus, thence to the red nucleus, and then,
by way of the rubrospinal tract, to the motor nuclei of the spinal
nerves.

Theories Concerning the Functions of the Cerebellum.—
Modern views concerning the functions of the cerebellum may be
classified under three general heads: First, those that consider it
a general co-ordinating center or organ for the muscular movements
and especially for those concerned in equilibrium and locomotion.
This view, first proposed essentially by Flourens (1824), has been
adopted by many, perhaps by most, writers since his time. The
manner in which the organ serves to co-ordinate these movements
has been explained in various ways. According to the older ob-
servers, it was supposed so to arrange or group the various motor
impulses that they reached the lower motor centers in the cord
* See Edinger, "Brain," 29, 483, 1906.

'J.'U PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

in the necessary combination for co-ordinated contractions. Ac-
cording to more recent observers, this synergetic action is exor-
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
by many observers, f 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, thcrefoie, 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. Jt 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 buys, and especially, although with important modifica-
tion-, by Luciani.} Some of the details of the work of the latter
observer are given below.

ExperimentalWorkUpon the Cerebellum. — Rolando, and par-
ticularly l-'loureiis, gave (lie direction to modern experimentation
in this subject. '| he latter observer made numerous observations,
e pecially on pigeons, in regard to the effect of removing all or a
part of i In' cerebellum, lie describes in detail the striking results
of auch an operation. When all or a large, pari of the organ isre-

* Lussana. Sec "Journal <!<• la physiol. <!<• I'homme," •">, 418, 1862.
i Bee Lewandowsky, "Archiv f. Physiologic, " L903, L29.
j Ini- the literature of the cerebellum, see Lueiani, " II cervelleto, '' Flor-
1891: German tran lation,"Das EOeinhirn," L893. Also Lueiani,' article
I'm Kleinhirn," in Ergebnie e der Physiologie, " vol. iii, pari n, p. 269,
L904, and van Rynberk, ibid., vii, <>■',:;, L908.

CEREBELLUM, PONS, AND MEDULLA. 235

moved the animal shows a most distressing inability to stand or
move. There seems to be no muscular paralysis, but, at first,
a total lack of power to co-ordinate properly the contractions of the
various muscles involved in maintaining equilibrium. The animal
takes a most abnormal position, with the head retracted and
twisted, and any attempt to move is followed by violent disorderly
contractions that may result in a series of involuntary somersaults.
The animal is totally unable to fly. When the injury to the cere-
bellum is less the effect upon the movements is either too slight
to be noticed or is shown in a greater or less uncertainty in its
movements. When it attempts to walk, for instance, it exhibits
a staggering, drunken gait, a condition designated as cerebellar
ataxia. Similar operations on mammals give in general the same
results. If the operation is unilateral, — that is, affects only one
hemisphere, — the animal (dog) exhibits forced movements, such
as a tendency to roll around the long axis of his body toward the
injured side and subsequently movements in a circle toward the same
side. In man there are several cases on record in which the
organ was shown by autopsy to be largely or completely atro-
phied, and numerous cases of tumors affecting the cerebellum
have also been reported. 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 ex-
hibited, especially when the movements were rapid and forced.
In the ataxic condition resulting from tabetic lesions of the
posterior funiculi 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 movements.

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

236 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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
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 ;i tremor of the muscles
when voluntarily contracted, especially in movements requiring
much exertion. Luciani supposes that tliis tremor is due to an
alteration thai is. ;i slowing of the rhythm of discharges of the
impulses from the motor centers. The functions of the cerebellum
on lii-- theory are expressed, therefore, by saying that if is an aug-
menting organ for the activitj of the neuromuscular apparatus; and
that, so far as this augmenting or si rengl hening activity can be ana-
lyzed, it consists in .'in increase in the energy of (lie motor discharges
(sthenic action), an increase in the tension or tone of the motor
centers and their connected muscles (tonic action), ;md an increase
in the rhythm of the motor impulses (static action) so that nor-

CEREBELLUM, PONS, AND MEDULLA. 237

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 similar fibers of so-called deep
sensibility. 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 mechanism
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
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 necessaiy
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 sensoiy

238 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

nerves to the vestibule of the ear, the muscles, joints, etc., 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
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-
ii n nts 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 fad is clear proof that the cerebellum is not
the only mechanism through which such co-ordination is possible;
bu1 ii is no valid objection to the view that normally this control
i- 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 centen may be \\>«'(\ to replace its functions in part,
at lea '. 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 con cious movements of the body are conl rolled direct ly

* Lewandowsky, " Archiv f. Physiologie," L903, 1~">; see also Kohnstamm,
"Archiv I. d. g< ammte Physiologie," 89, 240, 1902.

CEREBELLUM, PONS, AND MEDULLA. 239

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 apparent loss of sensations after removal of the cerebellum,
but Luciani, Russell, and others state their belief that in some
indefinable way the mentality of the animal is affected by such
operations. Whatever functions of this kind are present we
can define only by the unsatisfactory 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-
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
reverse, 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. There arises, however, the question
whether or not there is a localization of function in the cere-
bellum, that is, whether definite parts of the cerebellar cortex
are in specific relations with separate muscles or groups of
muscles. The possibility of a localization of function was
suggested years ago by experiments made by Ferrier, in which
electrical stimulation of the cortex gave definite movements
of the head, limbs, and especially of the eyes, the movements
varying somewhat according to the part stimulated. These
results were not wholly confirmed by later observers. Horsley
and Clarke* state that such strong stimuli are required to obtain
a decisive effect from the cortex of the cerebellum that it may be
questioned whether in positive cases the result is due to excita-
tion of the cortex itself or to an escape of stimulus to the under-
lying nuclei. Direct stimulation of the dentate nucleus gave
them conjugate movements of the two eyes. These indications
of a localization have been strengthened by the results of com-
parative anatomy and especially by the effects of ablation of
definite parts of the cortex. Earlier experimenters, using the
* Horsley and Clarke, "Brain," 28, 13, 1905.

240 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

method of ablation, obtained quite negative results from the
standpoint of localization, but this seems to have been due to
the fact that a faulty anatomical schema was used; a whole hemi-
sphere, or the entire vermiform lobe, etc., was removed. Later
experimenters* have adopted the newer anatomical schemata,
which take account of the true genetic relations of the various
lobes and lobules of the cerebellum, and they have been rewarded
by obtaining results of a positive character. The newer anatomical
nomenclature is illustrated in Fig. 104, which gives a schematic
representation of the arrangement of the lobules of the cere-
bellum of the dog, according to Bolk. Following this schema
van Rynberk reports that excision of the lobulus simplex is

Lmjj

Fig. 101. Schema of dog's cerebellum to show Bolk's nomenclature for the lobes and
Blllci. Dorsal view : I. a, |c>l his anterior (this lobe is separated from the larger posterior lobe

by the deep primary fissure, Svr) ; Ls, lobulus simplex; Lens, lobulus ansiformis; /./>,
lobulus paramedianus ; /.»i/<, lobulus medianus posterior; AY, format is vermieularis (pars
tonsillaris); C1, cms primum; '"-. crus secundum; Svr, sulcus primarius ; Sp, sulcus
paramedianus ; Si, sulcus intercruralis. — (After van Rynberk.)

followed by movements of the head (head nystagmus), which
indicate an abnormal innervation of the neck muscles. Injury
on on" side of t he crus primum of I he ansiform lobule is followed
by abnormal movements of the forefoot of the same side, while
similar injuries to the crus secundum result in abnormal move-
ments localized to the hind fool. Extirpation of a lobulus
paramedianus causes rolling movements round the long axis
of the body or bending of the body to one side (pleurothotonus).
It i- to be expected thai extension of this work will throw much

lighl upon the Specific relations of the cortex of the cerebellum
tot he musculat ure of I he body.

The Medulla Oblongata. In the medulla oblongata we must
recognize a region of special physiological importance in that it

• Van Rynberk, "General Review in Ergebnisse der Physiologic, " 7,
663, L908.

5 6

FijE. 105 Nuclei of origin of motor and primary terminal sen ory nuclei of cerebral
nerve {Held): Bchematicallj lepresented in a supposedly transparent brain stem viewed
from behind. (Nuclei and rool <>i motor nerves in light red, <>f sensory nerves in
purple. Cochlear nerve in yellow.) 4, nucleus of the third nerve (n. oculomotorii);
."), nucleus of the fourth nerva (n. troehlearis); 6, the fourth nerve; 7, the descending
(motor) nmt of the fifth nerve; 8, the principal motor nucleus of the fifth nerve;
'i, the semilunar ganglion (g. Gasseri); 26, the ascending (sensory) n>"t of the fifth
nerve; 14, nucleus "C the ixth cranial nerve; l">, nucleus of the facial (seventh)
nerve; In, the fm-i.-i I nerve; 34, 33, nucleus "f the vestibular branch of the eighth omnia)
nerve; 32, ventral nucleus of the cochlear branch of the eighth nerve; 27, dorsal nucleus
of the cocnleai branch of the eighth nerve; 19, -'K the glossopharyngeal nerve; 18, 28, the
nerve; 20, motor nuclei r,f vagus and glossopharyngeal (nucleus ambiguus and
nucleus dorsalis); Si. 24, nucleu of the ake cinereas, the solitary bundle and its nuclei] ;
17, the eleventh or spinal accessory nerve; 22. nucleus of the spinal accessory; 21, nucleus
of the hypoglot al nerve, (From SpaUeholz, Human Anatomy.")

CEREBELLUM, PONS, AND MEDULLA. 241

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 tying 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-
nections have been determined by physiological experiments, but
so far it has not been possible to mark out histologically the exact
groups of cells concerned. The position and physiological properties
of these centers are described in the sections on respiration and
circulation. These centers are of especial importance because of
their wide connections with the body, their essentially independent
activity in reference to the higher parts of the brain, and the abso-
lutely necessary character of the regulations they effect. In the
development of the brain the functions originally mediated by the
lower parts have been transferred more and more to the higher
parts, especially in regard to conscious sensation and motion, and
the so-called higher psychical activities. But the unconscious and
involuntary regulation of the organs of circulation and respiration
and to a certain extent of the other visceral organs has been cen-
tralized, as it were, in the medulla. In addition to the control
of the respiration and circulation other important reflex activities
are effected through the medulla by means of the vagus nerve,
which has its nucleus of origin in this part of the brain. Such, for
instance, are the reflex control of the heart through the cardio-
inhibitory center and of the motions and secretions of the alimentary
canal.

The Nuclei of Origin and the Functions of the Cranial
Nerves. — The origin, course, anatomical and physiological relations
of the first or olfactory, second or optic, and eighth or auditor}''
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. Ocidomotorius) . — This nerve arises
from the base of the brain on the median side of the corresponding
pedunculus 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
16

242

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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 sym-
pathetic 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 cen-

Edinger-Westphal nucleus.
Principal nucleus
Median nucleus.

Nucleus of 4th nerve.

Fig. 106. Nuclei of origin of the third and fourth nerves. — (From 1'oirit r nnd Cluirpii.)

tral gray matter of the midbrain at the level of the superior col-
liculus. 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
Fig. 106, namely, the lateral (or principal) nucleus, which gives

origin chiefly to the fibers innervating the extrinsic muscles; the
median nucleus: and t he nucleus of Edinger-Westphal. According
to Bernheimer* the large median nucleus gives rise to the fibers
that innervate the ciliary muscles, while the Edinger-Westphal
nuclei (accessory nuclei) emit nil i he movements of the sphincter
muscle of the iris. Some of the fibers, particularly those from

* Bernheimer, in " Graefe Saemi cb't I iandbuch derges. Augenheilkunde,"
2d ed., I, 41.

CEREBELLUM, PONS, AND MEDULLA.

243

the lateral nucleus to the inferior rectus, the internal rectus, and
the inferior oblique, cross the mid-line and emerge in the nerve
of the opposite side.

Fig. 107. — Diagram showing the average area of distribution of the sensory fibers of the
trigeminal nerve. — (Cushing.)

N. opht,

N. max. sup.

N. max. inf.

Fig. 108. — Nuclei of origin of the fifth cranial nerve. — (From Poirier and Charpy, after

Van Gehuchten.)

The Fourth Cranial Nerve (N. Trochlearis) . — This nerve emerges
from the brain in the anterior medullary velum (valve of Vieussens)
just posterior to the inferior colliculus. It curves around the

244 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

pedunculus cerebri to reach the base of the brain. It is a motor
nerve, and supplies fibers to the superior oblique muscle of the
eyeball. In the interior of the brain the fibers arise from a
nucleus in the central gray matter just posterior to that of the
third nerve (Fig. 106). The fibers pass dorsalward toward the
vein in and make a complete 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,
portions of the ear, mouth, and tongue, and to the dura mater
(Fig. 107). In the interior of the brain the motor portion, portio
minor, arises partly from a small nucleus in the pons and partly
from a long column of cells extending along the lower margin of the
central gray matter throughout the midbrain. This column and
the fibers arising from it constitute the descending motor root of the
fifth nerve (see Fig. 108). 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. 105).

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. 105).

The Seventh Cranial Nerve (N. Facialis). — This nerve appears
on t he base of the brain at i he inferior margin of the p<ms, lateral
and somewhat posterior to t he emergence of t he sixth nerve. It
18 mainly a motor nerve, but carries some sensory fibers (libers of
taste and genera] sensibility) received through the n. intermedins of
Wrisberg. The motor libers 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 libers arise from a

con picuous nucleus in the tegmental region of the pons lying
ventral to the nucleus of the sixth, beneath the middle of the fourth
ventricle (Fig. 105). The sensory libers of the nerve of Wrisberg
originate in I he nerve cell of I he geniculate ganglion.

CEREBELLUM, PONS, AND MEDULLA. 245

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. 105). 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
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 medullar v
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. 105).

The Twelfth Crainal Nerve (N. Hypoglossiis) . — This nerve arises
from the medulla in the furrow between the anterior p}-ramid 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.
105).

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 gan-
glia, the celiac 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
i' in, 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

I uo ledge 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 c<li-
tion, London, L844, |>. '.».

tScli.it'' I' I -hunk of Physiology," 1900, vol. ii ; "10rgcbnis.se der

iologie," 1903, vol. ii, part n, j). 823 ; also "Brain," 1903, vol. xxvi.

240

SYMPATHETIC NERVOUS SYSTEM.

247

c&

Cord ^UC

Qjymjbatkeiic

lion-

Tbst-oanfflion.i(t
fibre.

Plain,
I muscle.

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 the}' possess a certain independ-
ence of the central nervous system. The au-
tonomic system is contrasted physiologically
and anatomically with the efferent spinal and
cranial fibers that supply the striated or volun-
tary muscles: physiologically in the fact that
this latter group of fibers is entirely dependent
upon activities of the central nervous system,
and anatomically in the fact that the auto-
nomic fibers, although arising ultimately from
the central nervous system, all pass to their pe-
ripheral tissues by way of sympathetic nerve
cells. The autonomic path consists of two
neurons : one belonging to the central nervous
system, whose axon emerges in one of the spinal
or cranial nerves and ends around the dendrites
of a sympathetic cell; and one occurring in some
one of the numerous sympathetic ganglia, whose
axon passes to the peripheral tissue. The first
axon is spoken of as the preganglionic fiber, the
second as the postganglionic fiber. Their con-
nections are represented in the accompanying
schema (Fig. 109).

Physiological and anatomical investigations
have shown that autonomic nerve fibers arise
from four regions in the central nervous system
(Fig. 1 10) : First, from the midbrain, emerging

Preganglionic jibre.

Fig. 109. — Schema to show the general relation between
the preganglionic and postganglionic fibers of the autonomic
paths.

Fig. 110.— Illus-
trating the central ori-
gin of the autonomic
fibers. — {Langley.)

248 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

in the third cranial nerve and passing via the ciliary ganglion;
second, from the bulbar region, emerging in the seventh, ninth, and
tenth cranial nerves; third, from the thoracic spinal nerves (first
thoracic to fourth or fifth lumbar) and passing in general via the
ganglia of the sympathetic chain; fourth, from the sacral ' region
by way of the so-called nervus erigens supplying the descending
colon, rectum, anus, and genital organs. The autonomic fibers at
their origin in the central nervous system — that is, while pregan-
glionic fibers — are all possessed of a small medullated sheath,
having a diameter of 1.8 [J. to 4 fx. 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 a
preganglionic fiber will pass through several ganglia before
making final connections with a sympathetic cell. So far, I lie
course of these fibers has been traced most, successfully in the
case of the nerves supplying the sweat-glands, blood-vessels, and
especially the erector muscles of the hairs, the so-called pilomotor
nerve-fibers. The visible result of stimulation in the last case
gives a ready means of determining the presence of the fibers.

General Course of the Autonomic Fibers Arising from the
Spinal Nerves. — It has long been known that the spinal nerves
.in- connected with many of the ganglia of the sympathetic chain
by fine branches known as the rami rommunicantes. 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 (lie fact, that I he white rami are
composed almost entirely of medullated libers, while the gray rami
are largely non-medullated. In the cervical, lower lumbar, and
sacral regions the rami consist only of tin; gray part. Physiological
♦ "Proceedings, Royal Society," 1889, 46, 428.

SYMPATHETIC NERVOUS SYSTEM. 249

experiments show that the white rami consist of preganglionic
fibers that arise from nerve cells in the spinal cord, pass out by
way of the anterior roots, enter the white ramus, and thus reach
the sympathetic chain. On entering this latter the fiber may
not end at once in the ganglion at which it enters, but may pass up
or down in the chain for some distance. Eventually, however, it
ends around a sympathetic nerve cell and the path is then con-
tinued by the axon from this cell as the postganglionic fiber. The
gray rami consist of these latter fibers, which return from the sym-
pathetic chain to the spinal 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. 111). 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,

250

PHYSIOLOGY OF CENTRAL XERYOUS SYSTEM.

tenth, and eleventh cranial nerves.

Fig. 111. — Diagram (riving a schematic
representation of tin- coin e of the autonomic

1«ym jKit hi-i \r) fibers arising from the I boracico-
ombar and acral regions of the cool, i be
preganglionic fiber la represented in red, the
postganglionic in black lines. The arrow in*
dieate the normal direction of tin; nerve im-
i>ui es or nerve conduction, 8.e., Superior
cervical ganglion; l.r., inferior cervical gan-
glion; T, the fii I thoracic ganglion ; 8p., the

splanchnic nerve; ''., tin; .semilunar or celiac

ganglion ; m., t be inferior mesenteric ganglion ;
A., the hypogastric nerves; N.K., the nervu
eriRens. the numerals indicate the corre-
sponding spinal net

Those that emerge in the third
nerve end, as preganglionic fi-
bers, in the ciliary ganglion.
Their postganglionic fibers
leave this ganglion in the short
ciliary nerves and innervate
the plain muscle of the sphinc-
ter of the iris and the ciliary
muscle. The fibers that emerge
in the seventh and ninth
nerves probably supply the
glands and blood-vessels (vaso-
dilator fibers) of the mucous
membrane of the nose and
mouth. Some of these fibers
reach the fifth nerve by way
of anastomosing branches and
are distributed \vith it. Their
preganglionic portion termi-
nates in some of the ganglia
belonging to the sympathetic
typo which arc found in this
region, such as the sphenopal-
atine and otic ganglia, and the
submaxillary and sublingual
ganglia for the fibers dis-
tributed to the glands of the
same name. The autonomic
fibers that arise with the tenth
(and the eleventh) nerves are
distributed through the vagus.
Physiologically these fibers
consist of motor fibers (vis-
ceromotor fibers) to the mus-
culature of the esophagus,
stomach, small intestine, and
large intestine as far as the
descending colon, motor fibers
to the bronchial musculature,
inhibitory fibers to the heart,
and secretory fibers to the
gastric and pancreatic glands.
The ganglia in which the pre-
ganglionic portions end have
not been definitely located,

SYMPATHETIC NERVOUS SYSTEM. 251

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. 111). The autonomic fibers of the nervus erigens
suppl}T vasodilator fibers to the external genital organs, and in
the male constitute the physiological mechanism for erection;
whence the name. They supply, also, vasodilator fibers to rectum
and anus and motor fibers to the plain muscles of the colon de-
scendens, rectum, and anus. The preganglionic parts of these
fibers end in small sympathetic ganglia in the pelvic plexus or in
the neighborhood of the organs supplied.

Normal Mode of Stimulation of the Autonomic Nerve Fibers.
• — In distinction from the nerve fibers innervating the skeletal
muscles practically the whole set of autonomic fibers is removed
'from the control of the will. An apparent exception to this general
statement is found in the fact that the ciliary muscle of the eye is
seemingly under voluntary control. We must suppose that under
normal conditions the autonomic fibers 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 consideration 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, unconsciously, for instance,
the movements of the intestines, the secretion of the digestive
glands, and the contraction and dilatation of the arteries.
The autonomic nerve-fibers control, therefore, the uncon-
scious 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

252 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

paths in the central nervous system. What we designate as vol-
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:

253

254 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

The respirations become slower and deeper and the costal respiration
(respiration by elevation of the ribs) predominates over the ab-
dominal or diaphragmatic respiration as compared with the waking
condition. The respiratory movements also show frequently a
tendency to become periodic, — that is, to increase and decrease
regularly in groups after the manner of the Cheyne-Stokes type
of breathing. The expiration is frequently shorter and more audi-
ble than in the respirations of the waking hours. The eyeballs
roll upward and inward and the pupil is constricted. According
to Lombard's observations, the knee-kick decreases or disappears
entirely during sleep. Some of the constant secretions are dimin-
ished in amount, — as, for instance, the urine, the tears, and the
secretion of the mucous glands in the nasal or pharyngeal mem-
brane. One of the familiar signs of a sleepy condition is the 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 entile cortex docs 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

jcertaining the intensity of th< sensory stimulus necessary to

awaken the sleeper. Kohlschlitter * used for this purpose a pendu-
lum falling againsl a sounding plate. At intervals of a half-hour
during the period of sleep the auditory stimuli thus produced were
increased inintensitj until waking was caused. His results arc

expressed in the curve shown in Fig. I 11^, in which the intensity
* Kohlschutter, "ZeitBchrift f, rationelle Medicin," 1863.

THE PHYSIOLOGY OF SLEEP.

255

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
oelow 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

STRENGTH OF STIMULUS

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Fig. 112. — 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.)

period up to the third hour. That this is the case is perhaps
sufficiently demonstrated by the experience of every one, but
Weygandt has attempted to prove the point by direct experi-
ments. He found that for simple mental acts, such as the ad-
dition of pairs of figures, a short sleep was as effective as a longer
one, but for more difficult mental work, such as memorizing
groups of ten figures, efficiency was distinctly improved in
proportion to the length of sleep. It is probable that the curve
of intensity of sleep varies somewhat with the individual and
also with surrounding conditions. That individual variations
occur is indicated by the results obtained by two other observers,
Monninghoff and Piesbergen,* who used the same general
method as was employed by Koklschiitter. The sleeper was
awakened by auditory stimuli produced by dropping a lead
* Monninghoff and Piesbergen, " Zeitschrift f. Biologie," 19, 1, 1883.

256 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

ball from varying heights upon a lead plate. Only two experi-
ments were made each night, and the curves constructed repre-
sent, therefore, composites from several periods of sleep. One
of the curves obtained is represented in Fig. 113. 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 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. 114. 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; in most cases the maximum
is reached at the first or second hour of slumber, but Michelson
believes that there are two classes of individuals in this respect,
those with morning dispositions in whom the maximum of
mental efficiency occurs early in the day and who upon going to
sleep show a maximum of intensity within an hour, and those
with evening dispositions whose maximum efficiency comes
later in the day and whose curve of sleep reaches its maximum
of intensity with relative slowness (If to 3^ hrs.).

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, Tarchanofrj" has been able to measure
their blood-pressure while sleeping. He finds that (he pressure
in the aorta falls by an amount equal to twenty to fifty millimeters
of mercury during sleep, and that the same general fact is true
for man is shown by the sphygmomanometric observations reported
by Brush and layrrucal her.} Making use of patients with a
trephine hole in the skull, Mosso# has been able to show that during
Bleep the volume of the brain diminishes, while that of the arm
or foot increases. The apparent explanation of this fact is that
the blood-vessels in the body dilate, and receive, therefore, more

* Howell, "Journal of Experimental Medicine," 2, 313, 1897. Michel-
son, "Dissertation," Dorpat, L891.

; Tarchanoff, "Archives italiennes de biologie," 21, 318, L894.

I Bru li ;in<l Payerweather, "American Journal of Physiology," 5, 199,
1901.

Mo o, "Ueberden Kreislauf dee Blutes im menschlichen Gehirn," 1,881.

THE PHYSIOLOGY OF SLEEP.

257

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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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17

25S

PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

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). It should be stated
that in a preliminary communication
by Shepard it is stated that he ob-
tained contrary results from observa-
tions upon two patients with trephine
holes in the skull. The volume of the
brain as well as that of the foot or
hand increased during sleep.* The
authorf has extended Mosso's observa-
tions so as to obtain a plethysmo-
graphy 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.
115. 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 begin-
ning of sleep. 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 doubtless
to the contraction of ils blood-vessels;
so thai at the time of awaking it lias
practically the same volume as at the
beginning of sleep. If, on the basis
of Mosso's experiments, quoted above,
we assume that Hie blood-flow in the
brain stands in a reciprocal relation

to that in the .•nan, this curve may be taken to indicate; that

before and after the onset of sleep the blood-flow through the

♦ Shepard, "American Journal of Physiology," '2'.\, L909 (<rProc. Amer.
Physiol, doc.")- t Howell, loc. dt.

THE PHYSIOLOGY OF SLEEP.

259

brain diminishes rapidly to a certain point and that before
awaking the blood-flow begins to increase again until it reaches
normal proportions.

Effect of Sensory Stimulation. — That sensory stimuli of vari-
ous kinds affect a sleeping individual without entirely awaking
him is shown by the movements that may be caused in this
way, and also by the nature of the dreams which may be pro-
voked. It is very interesting to find from plethysmography
observations that all kinds of sensory stimulations from without
and from within are liable to affect the circulation of the blood
during sleep. As shown by the plethysmography the volume of

Fig. 116. — Sleep: A, effect of external impression (music box), insufficient to awaken
sleeper, — a marked diminution in volume of the arm ; B, effect of external impression
(music box) sufficient to awaken sleeper; a stronger diminution in volume followed by
dilatation as the subject again fell asleep.

the arm diminishes more or less in proportion to the intensity
of the stimulus, and the probable interpretation of this fact is
that the sensory stimulus acts reflexly upon the vasomotor
center in the medulla and causes through it a contraction of
the blood-vessels. In the curve shown in Fig. 115 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 Fig.
116. In these experiments the recorder attached to the plethys-
mograph to register the changes in volume was of a different
kind (tambour) and the record reads in a reverse way to that

260 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

shown in Fig. 115, — 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
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,
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 dining 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-
resull 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 excital ions, menial or sensory.

2. Consumption of the Intramolecular Oxygen. — Pnuger-j1 suggests

thai 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

thai] il '•mi be replaced by the absorption of oxygen from the blood.
The result i- a gradual reduction in irritability; so that when
-nil 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-
cal];, combined by anabolic processes to form the irritable living

mutter i- again replenished.

* Preyer, " Centralblatt f. d. med. Wiss.," 13, 577, 1875; and Obersteiner,
" Allgcmeine Zeitschrifl f. Psychiatric," 29, 224, 1872 7:;.

, PflUger, ^rchiv f . d. gesammte Physiologie, " 10, 168, L875.

THE PHYSIOLOGY OF SLEEP. 261

3. The Neuron Theory. — Duval,* 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 very probable that during sleep there is a diminished
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 Fayer weather, 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

* Duval, "Comptes rendus de la soc. de biol," February, 1895; and Cajal,
"Archiv f. Anat. (u. Physiol.)," 375, 1895.

202 PHYSIOLOGY OF CENTRAL NERVOUS SYSTEM.

of sleep, while others take the opposite view that it follows and
is merely one result of sleep. On the basis of the plethysmography
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
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 lime 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 lias
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 ;i more complete state of inactivity, and the diminution of
blood-flow lo the brain and (he state of unconsciousness is longer
lasting, lasts Indeed, according to the curves of which an example
is given in Fig. 1 15, 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
I he increa-ed flow of blood, is the greater or less fatigue of the
cortical cells themselves alter a day's activity, and their greater
* Howell, "Journal of El cperimental Medicine," 2, 313, L897.

THE PHYSIOLOGY OP SLEEP. 263

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 it's 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
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 undoubtedly associated with a dilatation of the blood-
vessels of the skin of the trunk and extremities. What the
condition in the visceral 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 plethysmography method, f 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.

* Hill, "The Physiology and Pathology of the Cerebral Circulation,"
London, 1896.

f Walden, "American Journal of Physiology," 4, 124, 1900-01.

SECTION III.
THE SPECIAL SENSES.

CHAPTER XIY.

CLASSIFICATION OF THE SENSES AND GENERAL
STATEMENTS.

Under the general term sense organ Ave may include not only
the peripheral organ on which the stimulus acts, but also the sensory
path through which the impulses are conveyed to the central
nervous system and the cortical center by means of which the
reliction in consciousness is mediated.

Classification of the Senses. — In general, we attempt to
distinguish the various sense organs by the differences in their
end reaction in consciousness. Each sense organ gives a different
kind of response, the nature and distinctive features of which
are recognized subjectively. The conscious sensations ;ue 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
t li.it 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 arc doubtless many other sensations whose conscious
reaction la less distinct in quality and lor which our subjective
means of recognition and classification are less satisfactory or

entirely inadequate. Such, for instance, ace tin' sensations from

tin- muscles, from the semicircular canals and (lie vestibular sacs

of the ear, and from many of the visceral organs. For the recogni-
tion and classification of these senses and sense organs if is neces-
sary to fall back upon t he met hods of anatomical and physiological
analysi . methods which in many respects are uncertain. So also

within the limit- of any sensation of a given quality or modality,

we di tinguish certain subqualities. In vision we have manydif-

264

CLASSIFICATION OF THE SENSES. 265

ferent qualities which we designate by special names, — the series
of different colors, for example. In sound sensations we distinguish
different tones and different qualities of tones. But here, again,
the subjective mark is often so indistinct in consciousness
that it cannot be used satisfactorily for purposes of classifica-
tion. In the odor sensations we distinguish many different quali-
ties, each recognizable at the time that it is experienced, but their
characteristics are so fugitive that so far it has not been possible
to name them or group them in any satisfactory way. In studying
the qualities of the various sensations, so far as they are recogniz-
able, the effort of physiology has been to connect them with some
definite anatomical or physiological peculiarity in the sense organs
concerned. The final explanation of the differences in quality
involves a study of the nature and properties of consciousness
itself, — a subject which as yet has not been undertaken by physi-
ology. At present we accept the fact of consciousness and the
fact that there are different kinds or qualities of consciousness,
and our investigations are directed only toward ascertaining
the anatomical, physical, and chemical properties of the organs
involved in the production of these subjective changes.

In former times it was customary to divide the sensations into
two different groups, — the special and the common senses,- — the
former including the so-called five senses of man, — namely, sight,
hearing, touch, taste, and smell, — while under the latter were
grouped all other sensations of less distinctive qualities. In physi-
ology the belief that man has only five special senses has, however,
long been abandoned. The sense of touch as ordinarily understood
has been shown to consist of three or more distinct senses, namely,
pressure (in its several varieties), 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 con-
tradistinction to a common sense; so that a classification based
on this nomenclature is unsatisfactory. In one respect, how-
ever, 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 consciousness. But
in no case are we conscious that this is the case. On the
contrary, we project our sensations either to the exterior of
the body or to some peripheral organ in the body, the effort
being apparently to project them to the place where experi-
ence has taught us that the acting stimulus arises. We may
divide the senses, therefore, into two great groups: (1) The

'266 THE SPECIAL SENSES.

external or rather the exterior senses, or those in which the sensa-
tions are projected to the exterior of the body, and which form,
therefore, the means through which we become acquainted with the
outside world. The exterior senses include sight, hearing, taste,
smell, pressure, ami 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 cither 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. Tf
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 Midler (1801-1858). The term
is in some respects unfortunate, as at present in (he 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 <>r

mediates its own specific, quality of sensation, the specific energy of

the optic apparatus being visual sensations, of (lie auditor)- apparatus

sound sensations, etc., and each sensory nerve or apparatus can
give no oilier than its own quality of sensation. Whether this

specificity in die reaction of each sensory nerve is due to some pecu-
liarity in the nerve it-elf <.r iis peripheral end-organ, or to a, pecu

liarity of the part of the brain in which it terminates Midler left,

an open question, although he called attention to the fact that
the central ending is capable of giving its specific effect, in con-

CLASSIFICATION OF THE SENSES. 267

sciousness independently of the conducting nerve fibers. With
regard to this latter question the opinions of physiologists still
differ. Most physiologists, perhaps, adopt the view that the
specific reaction in consciousness is due to the central ending, —
that, in other words, the different sensory parts of the cortex
give different kinds or qualities of consciousness, while the sensory
nerve fibers are simply conductors of nerve impulses, which,
however much they may differ in intensity, are qualitatively
the same in all nerve fibers. According to this view, it would
result, as du Bois-Reymond expressed it, that, if the auditory
nerve fibers were attached to the visual center and the optic
fibers to the auditory center, we would see the thunder and hear
the lightning. Each typical sense-organ from this standpoint
consists of three essential parts: the central ending, which deter-
mines the quality of the sensation; the peripheral end-organ,
retina, cochlea, etc., which determines whether or not any given
form of stimulus shall be effective and which in most cases is con-
structed so as to be responsive to a special form of stimulus desig-
nated as its adequate stimulus; and of connecting neurons whose
only function is to conduct the nerve impulses originating in the
end-organ. The fact, therefore, that the light waves can stimulate
the rods and cones of the retina, but are an inadequate stimulus
probably to the hair cells of the cochlea or the taste buds of the
tongue, is due to a peculiarity in structure of the rods and cones;
but the fact that the impulses conducted by the optic fibers arouse
a peculiar modality of sensation is not due to any peculiarity in
structure in these fibers or in the rods and cones, but to a charac-
teristic structure of the optic centers. The positive experimental
evidence for the correctness of this view is not conclusive, but, on
the whole, is impressive. Such facts as the following may be noted:

1 . When sensory nerve fibers are stimulated otherwise than
through their end-organs each reacts, if it reacts at all, according
to its specific energy, — that is, it produces its own quality of sensa-
tion. When the optic nerve is cut, for instance, the mechanical
stimulus causes a flash of light ; when the chorda tympani is stimu-
lated in the tympanic cavity by mechanical, electrical, or chemical
stimuli sensations of taste are aroused.

2. Mechanical pressure upon the peripheral nerves distributed to
the skin may cause a loss of some of the cutaneous senses in certain
areas of the skin with a retention of others. Thus the senses of
pressure and temperature may be lost and that of pain retained,
or pain may be lost and pressure retained. A similar dissocia-
tion of the sensations of the skin in definite regions may be
observed after localized lesions of the spinal cord, or during the
process of regeneration that follows suture of a severed nerve.
Such facts agree with the view that each sense has its own set

268 THE SPECIAL SENSES.

of nerve-fibers; those that mediate pain cannot by a mere
modification of the stimulus give also a sense of pressure.

3. The only objective manifestation of a nerve impulse that we
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
Hehnholtz 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 light, 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
vrarj in quality .-is well as in intensity, and that therefore one and
the 3ame nerve fiber may arouse different qualities of sensation and

different end effects according to the character of Hie impulse

conveyed. This point, of view is not capable of much discussion,
since there are no positive facts that support- it. It is logically

actory 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

: >lv differ in character.

The Weber-Fechner (Psychophysical) Law.— One difficulty

thai has been encountered in Hie physiological study of sensory

nerve i thai the end reaction cannot be measured with exactness.

With efferenl nervee the end reaction is a contraction or secretion

CLASSIFICATION OF THE SENSES.

269

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
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 -^ — that is, one additional
gram — to make a just perceptible difference in the pressure sensa-

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EXCITATION^.

Fig. 117. — 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 -^ — that is, 2 gms. — to make a just perceptible dif-
ference in sensation. This relationship is known as Weber's law.
While its exactness has often been disputed, it seems to be generally
admitted that for a median range of stimulation the law expresses
the approximate relation between the two variables considered.
Fechner attempted to give this law a more quantitative and ex-
tensive application by assuming that just perceptible differences

270 THE SPECIAL SENSES.

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
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 -3-, a result is obtained such as
is represented in the accompanying figure (Fig. 117). 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, "Bruin," 201, 1895.

CHAPTER XV.
CUTANEOUS AND INTERNAL SENSATIONS.

General Classification. — 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 enumerated
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, fascise, etc. — have only nerves of pain, but no sense
of touch or temperature. Of these cutaneous senses, three —
pressure, warmth, and cold — may be grouped with the exterior
senses, the sensations being projected to the exterior of the
body, into the substance causing the stimulation; although, as
was mentioned above, the temperature sensations under con-
ditions— 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.

Protopathic, Epicritic, and Deep Sensibility. — In the matter
of the classification of the cutaneous senses and, indeed, the
body senses in general, a new point of view has been suggested
by Head and Rivers.* These authors made a careful study of
the loss of sensations after division of the cutaneous nerves,

* Head and Rivers, "Brain," 1905, 99, and 1908, 323.
271

272 THE SPECIAL SENSES.

and of the subsequent gradual and separate return of these
sensations following upon suture of the divided ends. They
find that in skin areas made completely anesthetic there is
present a deep or subcutaneous sensibility to pressure and
movements, a sensibility which must be mediated through
sensory fibers contained in the nerves to the muscles. In the
skin itself there are present two systems of sensory fibers which
regenerate at different times in a nerve that has been severed,
and may be studied separately by this means. One system
convex- sensations of pain and of extreme changes in tempera-
ture, but the sensations are imperfectly localized and the sensi-
bility is low, or, to express the same idea in another way. the
threshold is high. This kind of sensation is found in the viscera
also, and it may be considered from the functional standpoint
as a defensive agency toward pathological changes in the tissues;
it is designated as protopathic sensibility. It is stated that the
glans penis possesses only this kind of sensibility. Protopathic
sensibility comprises three qualities of sensation and presum-
ably three sets of nerve-fibers, namely — for pain, for heat (not
stimulated below 37° C), and for cold (not stimulated above
26° C). The second system of fibers responds to stimulations
by light pressures and small differences in temperature between
26° and 37° C, the range of temperature to which the tem-
perature nerves of the protopathic system are insensitive. These

fibers regenerate after lesions much e slowly than the pro-

topathic variety, and since the sensations mediated by them
are localized very exactly, they furnish us the means for making
fine discriminations of touch and temperature. For this reason
they arc described us ;,n epicritic system, and the corresponding
sensations arc designated as epicritic sensibility. This system
of fibers is not found in the other organs, and it constitutes,
therefore, the special characteristic of the skin area. In this

■ in there are included separate libers for heat, for cold, for
tactile localization, and lor tactile discrimination. It is through
the sensations mediated by these libers thai we recognize the
shape and size of object s.

The Punctiform Distribution of the Cutaneous Senses.
A mo-t interesting fact in regard to the cutaneous senses is that
they arc qoI distributed uniformly over the whole skin, but are
it in discrete points or spots. This fad was first clearly
established by Blix,* although it was discovered independently
by Goldscheider and in this country by Donaldson. These ob-

- paid attention chiefly to the Warm and cold spots. The

Zeitschrifl f. Bioloeie," 20, III, 1884; Donaldson, "Mind," 39,
I, 1886. See also Goldscheider, ?'Archivf. Physiologie, " 1885, suppl. volume.

CUTANEOUS AND INTERNAL SENSATIONS.

273

existence of these spots may be demonstrated easily by anyone
upon himself by moving a metallic point gently over the skin.
If the point has a temperature below that of the skin it will be
noticed that at certain spots it arouses simply a feeling of contact
or pressure, while at other spots it gives a distinct sensation of
coldness. If, on the other hand, the point is warmer than the
skin it will at certain spots give a sensation of warmth. On mark-
ing the cold and warm spots thus obtained it is found that they

•• *

Fig. 118. — 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.

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 or tactile sense and the pain sense
are also distributed in a punctiform manner; they have been
studied most carefully by von Frey.* To determine the loca-

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

274 THE SPECIAL SENSES.

tion of the pressure points he used fine hairs of different diam-
eters fastened to a wooden handle. The cross-areas of these
hairs are determined by measurements under the micro-
scope, 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, J^i2, 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 :i retention of the
pressure sense, — a fact which indicates that these senses have
separate paths and therefore separate nerve-fibers.* Still more
interesting eases of dissociation are reported as the result of the
compression of peripheral nerve trunks. Tims, liarkerf 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 iii t he 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,

.\ .iciii. and eold spot, is supplied by its own nerve fiber, and that
each, when stimulated, reacts, if it reacts at all, only with its own
peculiar quality of sensation. According to this view, artificial

* I'm- many interesting cases of dissociation due i«> spinal lesions, see
Head, ' Brain/' L906, 537.

| Barker, "Journal of Experimental Medicine," 1,348, L896.

CUTANEOUS AND INTERNAL SENSATIONS. 275

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, but
in most of the experiments on record no distinction was made
between protopathic temperature sensations and those mediated
by the epicritic temperature nerves. It is difficult to adapt
the older descriptions to this newer terminology, but when not
otherwise specifically stated it may be assumed that the epicritic
system is referred to. In general, the cold spots are more
numerous than the warm spots, and react more promptly to
their adequate stimulus. The threshold stimulus varies in
different parts of the skin, the tip of the tongue requiring the
smallest stimulus to arouse a sensation, and the eyelids, fore-
head, 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 somewhat radiate arrange-
ment 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

276 THE SPECIAL SENSES.

carbon-dibxid gas a distinct warm sensation will be experienced.
A curious effect of this kind is what is known as the paradoxical
cold reaction. It is produced by applying a very warm object, with
a temperature of 40° to 60° C, to a cold spot. According to
Head and Rivers this reaction is rather characteristic of the
protopathic temperature fibers. It can be obtained, for example,
from the glans penis, which possesses only protopathic sensibility,
or during the course of regeneration of a severed cutaneous
nerve. In this latter condition hot objects applied to a cold
spot give a vivid sensation of cold. The same result may l>e
felt sometimes 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, however, 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 con-
junctiva, where the cold sense is especially prominent or exclu-
sively present.

The (Epicritic) Sense of Pressure or Touch. — The cutaneous
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 haii', indeed, acts like a lever and transmits any pres-
sure applied to if with increased intensity, acting, therefore, as re-
gards the pre—lire organ somewhat: like the eardxines in the case

of the endings of the auditory nerve. In parts of the body nol
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 feel in

whicha delicate sense of pressureis present inspiteof 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 the i pre ure point.-'. These points are close together on those
parts, such as the tongue and fingers, which have a delicate tactile
and more widely scattered where the sense is less developed.
The Threshold Stimulus and the Localizing Power.- The
delicacy of the cue of pressure may be measured by determining

CUTANEOUS AND INTERNAL SENSATIONS. 277

the minimal pressure necessary to arouse a sensation, — that is,
the threshold stimulus, — or it may be estimated in terms of the
power of discriminating two contiguous stimuli, — that is, the mini-
mal distance that two points must be apart in order for the sensa-
tions to be recognized as distinct. The two methods of measure-
ment do not coincide. As determined by the threshold stimulus,
the greatest delicacy is exhibited by the skin of the face, the fore-
head, and temples. According to the older methods of measure-
ment, the forehead will perceive a pressure of 2 mgs., while the skin
of the tips of the fingers needs a pressure of from 5 to 15 mgs. to
arouse a perceptible sensation. The back of the hand or the arm
is more sensitive from this standpoint than the tips of the fingers.
When measured by the power of discriminating two points —
that is, the localizing sense — the tips of the fingers are far more
sensitive than the skin of the face or of the arm. This latter prop-
erty, in fact, stands in relation to the closeness of the pressure
points to one another. The localizing sense may be determined
by Weber's method of using a pair of compasses with blunt points.
For any given area of the skin the power of discrimination or local-
ization is expressed in terms of the number of millimeters between
the two points at which they are just distinguished as two separate
sensations when applied simultaneously to the skin. Instruments
made for this purpose are designated as esthesiometers. They
carry two points the distance of which apart can be readily adjusted
and read off on a scale. The most satisfactory form of esthesiom-
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 S 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

27S THE SPECIAL SENSES.

the tongue as compared with the fingers. From the above data it
is evident also that the whole skin may be imagined as composed
of a mosaic of areas of different sizes, the sensory circles of Weber,
in each of which two or more simultaneous stimulations of the pres-
sure nerves give only one pressure sensation. The size of these
areas, particularly where they are large, may be reduced by practice,
as is shown by the increased tactile sensibility of the blind. The
fact that we can recognize two simultaneous pressure stimuli of the
skin as two distinct sensations implies that the two sensations have
some recognizable difference in consciousness. This difference is
spoken of as the local sign. We may believe that every sensitive
point upon the skin has its own distinctive local sign or quality, and
that by experience we have learned to project each local sign more
or less accurately to its proper place on the skin surface. Two points
on this surface that are a great distance apart are easily recognized
as different; but as we bring the points closer together the difference
becomes less marked and finally disappears when the distance
corresponds to the area of the sensory circle for the part of the skin
investigated, for instance, 1 mm. for the tongue, 22 mms. for the
forehead, etc. The ultimate limit of the power of discrimination
was assumed by Weber to depend upon the area of distribution of
a single nerve fiber. Assuming that each nerve fiber at its termi-
nation spreads over a certain skin area, it was suggested that the
size of this area forms a limit to the power of discrimination,
since two stimuli within it would affect a single fiber and therefore
would give a single sensation.

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.
[f instead of applying the two points simultaneously they are
applied in succession, at an interval of one second, t he 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 sensor} circles on the skin become much
raialler 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
poinl can be obtained, ft seems probable, moreover, that each of
these pressure points is connected to the brain byaseparate nerve
path, possibly a single fiber, and thai this anatomical arrangement

CUTANEOUS AND INTERNAL SENSATIONS. 279

determines the limitation of the localizing sense for different
regions of the skin.

In the newer work of Head and Rivers, which has been referred to several
times, it will be recalled that they distinguish first of all between cutaneous
sensibility to pressure and a deep sense of pressure. When the cutaneous
fibers of a given area are all destroyed by degeneration, the area is still sen-
sitive to pressure applied so as to deform the skin inward. The spot so
stimulated can be localized accurately. This deep sense of pressure is mediated
by the deep nerve fibers which supply the muscles. According to these
authors the cutaneous pressure sensibility is mediated by two sets of fibers,
those which give us the power of tactile discrimination when the compass
points are applied simultaneously to the skin, and those which give us the
power of tactile localization simply. In lesions of the spinal cord one of
these sensibilities may be lost and the other retained over a given skin area.
(Head and Thompson, "Brain," 1906.) In fact, the fibers of tactile discrimi-
nation are stated to pass up the cord (uncrossed) in the posterior funiculi,
while those of tactile localization ascend in the lateral or anterolateral funiculi
and cross before reaching the medulla.

The Pain Sense. — Pain is probably the sense that is most widely
distributed in the body. It is present throughout the skin, and
under certain conditions may be aroused by stimulation of sensory
nerves in the various visceral organs, and indeed in all of the mem-
branes of the body. Our knowledge of the physiological properties
of the end-organs and nerves mediating this sense is chiefly limited
to the skin, and for cutaneous pain at least the evidence, as stated
above, is very strongly in favor of the view that there exists a special
set of fibers which have a specific energy for pain. All recent ob-
servers agree that the pain sense has a punctiform distribution in
the skin, the pain points being even more numerous than the pres-
sure points. The threshold stimulus of these points in various
regions may be determined by von Frey's stimulating hairs, and
experiments of this kind show, as we should expect, that it varies
greatly. The cornea, for instance, gives sensations of pain with
much weaker stimuli than in the case of the finger tips. In general,
however, the threshold stimulus is much higher for the pain than
for the pressure points. Histological examination of the pain points
indicates that there is no special end-organ, the stimulus taking
effect upon the free endings of the nerve fibers. Any of the usual
forms of artificial nerve stimuli may affect these endings if of suf-
ficient intensity, and, as is well known, stimuli applied to sensory
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

280 THE SPECIAL SENSES.

to the training acquired in connection with concomitant (epicritic)
pressure sensations, the latter acting as a guide or aid in the pro-
jection. Thus in the cases referred to above, in which a portion
of the skin had lost the sense of pressure and temperature, but
retained that of pain, it was found that the localization was very
incomplete. Pain arising in the internal organs, on the contrary,
is located very inaccurately. The pain from a severe toothache,
for example, may be projected quite diffusely to the side of the face.
A very interesting fact in this connection is that such pains are
often referred to points on the skin and may be accompanied by
skin areas of tenderness. Pains of this kind that are misreferred
to the surface of the body are designated as reflected pains. It has
been shown by Head * and others that the different visceral organs
have, in this respect, a more or less definite relation to certain
areas of the skin. Pains arising from stimuli acting upon the
intestines are located in the skin of the back, loins, and abdomen
in the area supplied by the ninth, tenth, and eleventh dorsal
spinal nerves; pains from irritations in the stomach are located
in the skin over the ensiform cartilage; those from the heart in the
scapular region, and so on. The explanation offered for this
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 pro-
duced is felt in the part of higher sensibility rather than in the part
of lower sensibility to which the stimulus was actually applied."
It is interesting that affections of the serous cavities — c. g., the
peritoneum— do not cause reflected pains or cutaneous tenderness
as in the case of the viscera. Another notable fact in this connec-
tion is the occurrence of the condition known as allochiria. When
from any cause one or other of the cutaneous senses is depressed
in a given area stimulation in this region may give sensations
which are referred to the symmetrical area on the other side of
1 1n- body, or, it this also is involved, it may be referred to the area

1 1 < ■ . i above or below in the spinal order. The above law,

according to which projection is made to the area of high sensi-
bility most, closely connected with the area of low sensibility,

.-(.•in- to hold in this case also.

Muscular or Deep Sensibility. The existence of a special set
of sensory nerve-fibers distributed to the muscles was clearly

gnized by some of the older physiologists. Charles Bell, f

Head, Brain," Hi, I, 1893, and 24, 345, L901.
i Bell, 'lli'- Nervous System of the Human Body," third edition, Lon-
don, isi 1, p. 200

CUTANEOUS AND INTERNAL SENSATIONS. 281

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 fur-
nished 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
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 funiculi of the cord, and observations
upon the results of pathological lesions of the posterior funiculi
(tabes dorsalis) give results which are interpreted to mean that
fibers of muscular sensibility form the most important group in
the posterior funiculi and constitute, as well, perhaps, the long,
ascending fibers in the cerebellospinal fasciculus in the lateral
funiculi. It is believed, therefore, that our so-called voluntary
muscles are richly supplied with afferent fibers and that the im-
pulses carried by these fibers to the brain are necessary for the
proper contraction of the muscles, and particularly for the ade-
quate 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
* Sherrington, "Journal of Physiology," 17, 237, 1894.

282 THE SPECIAL SENSES.

maintenance of their normal motor connections. Within the
central nervous system the fibers of muscle sense end in part in
the cerebellum and in part pass forward, by way of the median
fillet, to end in the cerebrum. In the cerebrum they end in the
cortex of the parietal lobe in the region of the posterior central
convolution. There is reason to believe that this cortical sense
area of the muscle sense is connected by association fibers with
the motor areas lying anterior to the central 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
thai 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 combinations necessary in locomotion. Through
the circle or arc in the cortex of the cerebrum it may be supposed
that our characteristic voluntary movements are affected, and
it may be doubted whether a so-called voluntary contraction
can be made when this circle is broken on the sensory side.
Whether or not this latter suggestion is true, it seems to be
beyond doubt that adequately controlled voluntary movements
depend for their adaptation upon the inflow of sensory impulses
along the fibers of muscle sense. We have a certain conscious-
ness 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 Muscular Sensibility. -Under the term
muscular sensibility in its wide sense we must understand the
aensibility mediated by the afferent fibers from the muscles,
the tendons, ligaments, and joints. The quality of these deep

sensations is of Beveral kinds we have first. of all the deep

ure sensibility (see p. '-'7!)), which gives a definite conscious
reaction thai is well Localized. It- is usually projected to the
exterior and is ao1 consciously separated from the tactile or

lie sensations of the skin. We probably make much use
of this sensibility in judging the weight and resistance of bodies.
Mu cular sensibility proper is that ill-defined consciousness

which we possess of the condition and position of our muscles

or of the joints or Limbs moved by them. It, includes also the
3en <■ of passive posh ion, and I he sense of effort and of the spatial
relations of t he Limbs in mo1 ion or at rest. The untrained person
scarcely recognizes the exi bence of these sensations, but they

CUTANEOUS AND INTERNAL SENSATIONS. 283

are evident enough upon analysis, and it is most certain that
they take a fundamental part in regulating our movements.
In all our estimations of the extent of the muscular contractions
they form the chief sensory basis, and in this way they may
indirectly furnish us with data for perceptions and judgments
of various kinds. Thus, in the judgments 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 fundamental 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 essential 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. In excessive muscular
effort the quality of the muscle sensation undergoes a change
and becomes strong enough to make a distinct and peculiar
impression upon our consciousness. 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

2S4 THE SPECIAL SENSES.

maintenance of body equilibrium is effected through this sense. Its
striking influence upon the body at large is well illustrated in the case
of animals (pigeons, dogs) deprived of their cerebrum. During the
period of fasting these animals show all the external signs of hunger
and keep in continual, restless movement that seems to imply a con-
stantly acting sensory stimulus. We may assume that appetite
has its sensory origin, its peripheral nerve endings in the stomach,
and that these endings are excited in some unknown way when the
stomach is empty. This gastric hunger, as it might be called,
disappears, or the appetite is appeased when the stomach is filled.
This fact in itself would indicate that the stimulus has a local
origin in the stomach, and is not dependent upon any general
change in the nutritive condition of the body. The appetite is
satisfied by filling the stomach with food long before this food
is actually absorbed and distributed to the tissues. The inges-
tion of totally indigestible material would probably have temporarily
a similar result. The exact nature of the conditions that lead
to or cause a stimulation of the sensory nerves of appetite in the
stomach remains unexplained. The well-known fact that muscular
exercise and low temperatures and particularly a combination of
the two cause a marked augmentation of the appetite would suggest
that the sensory stimulus is influenced by the extent or character
of the oxidations in the muscular tissues, and that, therefore, some
substance may be formed as the result of these oxidations which
affects the sensory nerves of the stomach. The same general sug-
gestion is contained in the fact that diabetics exhibit an abnormal
appetite in spite of abundant feeding. In these individuals the
carbohydrate food escapes oxidation more or less completely, and
the metabolism, particularly in the muscles, involves, therefore,
to a greater exlenl , the oxidation of protein material, — a fact which
may stand iii some relation to the abnormal appetite thai .is observed.
The complexity of the nervous apparatus that controls I he 1 he 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. All animal will

Btarve 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 t his kind indicates that the sensory apparal us 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 i hat follows overfeeding indicates something more than a sim-
ple removal of the sensations of appetite; it implies an active state,

CUTANEOUS AND INTERNAL SENSATIONS. 285

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 f asters," at least, seems to show that, if
water is provided, prolonged deprivation of food is not accompanied
by the intense discomfort or suffering popularly associated with
the idea of complete starvation.

The Sense of Thirst. — Our sensations of thirst are projected
more or less accurately to the pharynx, and the facts that we know
would seem to indicate that the sensory nerves of this region have
the important function of mediating this sense. The water con-
tents of the body are subject to great changes. Through the lungs,
the skin, and the kidneys water is lost continually in amounts that
vary with the conditions of life. This loss affects the blood directly,
but is doubtless made good, so far as this tissue is concerned, by a
call upon the great mass of water contained in the storehouse of the
tissues. To restore the body tissues to their normal equilibrium
in water we ingest large quantities, and the control of this regula-
tion is effected through the sense of thirst. We know little or
nothing about the nervous apparatus involved; but it may be
assumed that when the water content falls below a certain amount
the nerve fibers in the pharyngeal membrane (fibers of the glosso-
pharyngeal nerve) are stimulated and give us the sensation of
thirst. That we have in this membrane a special end-organ of
thirst is indicated, moreover, by the fact that local drying in this
region, from dry or salty food, or dry and dusty air, produces a
sensation of thirst that may be appeased by moistening the mem-
brane with a small amount of water not in itself sufficient to relieve
a genuine water need of the body. Our normal thirst sensations
might be designated, therefore, as pharyngeal thirst, to indicate
the probable origin of the sensory stimuli. Prolonged deprivation
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 si <rlil 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 semilunar 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, thai all the taste fibers originate

Or rather end in the sensory nucleus of the fifth, while ot hers

believe thai 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 semilunar ganglion by a cir-
cuitous route, as is indicated in the diagram given in Fig. 110.
Those thai run in the lingual and chorda tympani nerves are
tned to pass to the ganglion by way of the great superficial
petrosal and Vidian nerves and the sphenopalatine ganglion,

while those thai are contained in the glossopharyngeal reach

286

SENSATIONS OF TASTE . AND SMELL.

287

the same ganglion through the tympanic nerve, the small
superficial petrosal, and the otic ganglion. A recent report
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.

iTros.Su^CT^kiahs minor
I lp«tros .super^ic ■ma.vir

G ■^awieuViGnv

jt-tvjmlpamtys.

(^.betroium. -t°V'

•"fljcui

Fig. 119. — 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.

Regarding the anterior two-thirds of the tongue, the lingual region,
it was found that in some cases there was at first a loss of acuity of
taste or even an entire disappearance of the sense, but subsequently
it returned. It would seem, therefore, that the loss of taste de-
scribed after removal of the Gasserian ganglion is an incidental
result the cause of which is not entirely clear. 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.

288

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,
therefore, that they originate directly in the nerve cells of the
geniculate ganglion and enter the brain with the fibers of the
intermediate nerve (n. intermedins Wrisbergii).

The End-organ of the Taste Fibers. — In the circumvallate
papillae, in some of the fungiform papilla1, and in certain portions
of the fauces, palate, epiglottis, or even the vocal cords there are
found the organs known as taste buds which are believed to act
as peripheral organs of taste. These curious structures are repre-
sented in Fig. 120. 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 lour
primary or fundamental sensations,- namely, sweet, bitter, acid,

and Baity, and thai 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 he resolved into a Blighl odor sensation
and ;i sensation due in stimulation of the fibers of general sensi-
bility, thai is, i< gives no taste sensation proper. The taste of
alum may !><• considered as a combination of ;i salty taste with
common sensibility. Combinations of sweel and acid tastes, sweet,

Fig. 120. — Section through one of the taste
of i Ik- papilla foliata of the rabbit (from
Quoin, after Ranvier), highly magnified: p, Gus-
tatory pore: e, gustatory cell; r, mstentacular
cell; »(. leucocyte containing granules; e, super-
ficial epithelial cell ; /», nerve fibei

SENSATIONS OF TASTE AND SMELL. 289

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 papillse thus examined, 27 gave no reaction at all, although
sensitive to pressure and temperature. In the 98 papilla? that
reacted to the sapid stimulation it was found that 60 gave taste
sensations of all three qualities, 4 gave only sweet and bitter, 7 only
bitter and acid, 12 only sweet and acid, 12 only acid, and 3 only
sweet. None was found to give only a bitter sensation. These
facts bear directly upon the question of the specific energy of the
taste fibers. It is possible that the four fundamental taste qualities
may be mediated by four different end-organs and four separate

* Oehrwal], "Skandinavisches Archiv f. Physiologie," 2, 1, 1S90.
19

290 THE SPECIAL SENSES.

sets of nerve fibers, each giving, when stimulated, only its own
quality of sensation. On the other hand, it is possible that one and
the same nerve fiber might give different qualities of sensation
according to the nature and mode of action of the sapid substances.
The fact, as shown by 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 : give different tastes according to the part of the tongue
upon which the}' are placed. Thus, sodium sulphate (Guyot) may
taste salty upon the tip of the tongue and bitter when placed upon
the posterior part. A better instance still is given by solutions of
a bromin substitution product of saccharin, the chemical name

f CO
for which is parabrom-benzoic sulphinid: C6H3Br 1 ~*~ ^NH.

When this substance is placed upon the tip of the tongue it gives a
sweet sensation, while upon the posterior region it gives only a bitter
taste together with a sensation of astringency (Howell and Kastle).
Extracts of the leaves of a tropical plant, Gymnema silvestre, applied
to the tongue, destroy the sense of taste for sweet and bitter sub-
stances (Shore), and this fact may be explained most satisfactorily
by assuming that this substance exercises a selective action upon
taste terminals in the tongue, paralyzing those for the bitter
and the sweet substances. Finally, the fact that electrical, me-
chanical, or chemical stimulation of the chorda tympani, where it
passes through the tympanic cavity, may arouse taste sensations is
proof that the taste sensation in general is not due to a peculiar kind
of impulse that can be aroused only by the action of sapid bodies
upon the terminals in the tongue, but, on the contrary, that it is a
specific energy of these fibers, and depends for its quality, there-
fore, upon the specific reaction of the terminations in the brain.

Method of Sapid Stimulation. — In order that sapid substances
may react upon the taste terminals il is necessary, in the first place,
thai they shall be in solution. It is impossible to taste with a dry
tongue. We may a aume, therefore, that the stimulation consists
c < m i.'illy in :i 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
qualities can be referred to a definite chemical structure in the

Bapid bodi( , Are there certain chemical groups which posses:: I he

property of reacting specifically with the end-organs? Experience

show- that substances of very different chemical const it ulion may

SENSATIONS OF TASTE AND SMELL. 291

excite the same taste. Thus, sugar, saccharin, and sugar of lead
(lead acetate) all give a sweet taste, while, on the other hand,
starch (soluble starch), which stands so close in structure to the
sugars, has no effect upon the taste terminals. It is interesting
to remember that the taste nerves may be stimulated by sapid sub-
stances dissolved in the blood as well as when applied to the ex-
terior of the tongue. A sweet taste maybe experienced in diabetes
from the sugar in the blood, or a bitter taste in jaundice from the
bile.

The Threshold Stimulus. — The determination of the threshold
stimulus for different sapid substances is made by ascertaining the
minimal concentration of the solution which is capable of arousing
a taste sensation. The delicacy of the sense of taste is influenced,
however, by certain accessory conditions which must be taken into
account. Thus, the temperature of the solution is an important
condition. Very cold or very hot solutions do not react, — that is,
the extremes of temperature seem to diminish or destroy the sensi-
tiveness of the end-organ. A temperature between 10° and 30° C.
gives the optimum reaction. So also the delicacy of the sense of
taste is increased by rubbing the sapid solution against the tongue.
Doubtless this mechanical action facilitates the penetration of the
sapid body into the mucous membrane, but it seems also to in-
crease the irritability of the end-organ. It is our habit in tasting
bodies with the tongue to rub this organ against the hard palate.
With regard to the threshold stimulus such results as the following
are reported:

Salty (sodium chlorid). 0.25 gm. in 100 c.c. 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.
121). At the free edge of the cells there is a limiting membrane
through which the olfactory hairs project. The olfactor}r sense

292

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
hWr ky 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.
213). 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 eells the impulses are con-
ducted along < he olfactory tract to their various terminations in the

Olfactory lobe itself, either of the same or of the opposite side, and

nail, 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 niiydit, be compared with the nerve gan-
glion layer of the retina, and the nerve libers of t he olfactory tract

with the fibers of the optic nerve.

The Mechanism of Smelling. — Odoriferous substances to

Fig 121. Cells of the olfactory region (after
r. Brunn): ", ", Olfactory cells; '», /<, epithelial
eel] , //, a, central proce prolonged :< i an • .1 r .- 1 * ■
tory nerve fibril; I, I, nucleus; c, knob-like clear
termination "i peripheral process; h, h, bunch of

olfactory liair.s.

SENSATIONS OF TASTE AND SMELL. 293

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-
dele jeff, the elements in certain groups are characterized by their
odoriferous properties; for instance, the second, fourth, and sixth
members — sulphur, selenium, and tellurium — of the sixth group.
Moreover, in organic compounds belonging to an homologous series
the smell gradually changes and, indeed, increases in the higher
members of the series, — that is, in those having a more complex
molecular structure.

The Qualities of the Olfactory Sensations. — While we dis-

* For many interesting facts concerning smelling and the literature to
1895 see Zwaardemaker, "Die Physiologie des Geruchs," Leipzig, 1895.
tHaycraft, "Brain," 1888, p. 166.

294 THE SPECIAL SENSES.

tingiiish 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, which
depend upon the presence of ethereal substances or esters.
II. Odores aromatici or aromatic odors, which are typified by camphor
and citron, bitter almond and the resinous bodies. This class is
divided into five Bubgroups.

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 I • t - 1 instance to the bile.
V. Odores alliacei or garlic odors, such as are found in the onion, garlic,

sulphur, selenium and lellurii jompounds. They fall into three

subgroups.
VI. Odores cnipvreumai ici 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 bircmi or goal 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 plante and acani bus.
IX. Odores nauseosi or nauseating or fetid odors, such as are given by feces
and certain plant- 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. 295

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 Shiel els.* In his experiments the vascu-
lar supply to the skin of the arm was determined by plethysmo-
graphic methods, and it was found that both pleasant (heliotrope
perfume) and unpleasant (putrefactive) odors give a similar vascu-
lar reaction. Each class, if it acts at all, causes, as a rule, a con-
striction of the skin vessels, such as is obtained normally from in-
creased mental activity, — a reaction usually interpreted to mean a
greater flow of blood to the brain.

Fatigue of the Olfactory Apparatus. — It is a matter of
common observation that many odors, such as the perfumes of
flowers, quickly cease to give a noticeable sensation when the stimu-
lation is continued. This result is usually attributed to fatigue
of the sense cells in the end-organ and it is noticeable chiefly with
faint odors. One who sits in an ill-ventilated room occupied by
many persons may be quite unconscious of the unpleasant odor
from the vitiated air, while to a newcomer it is most distinct.

Threshold Stimulus — Delicacy of the Olfactory Sense. —
The extraordinary delicacy of the sense of smell in some of the lower
animals is seemingly beyond the power of objective measurement or
* Shields, " Journal of Experimental Medicine," 1, 1896.

296 THE SPECIAL SENSES.

expression. The ability of a dog, for instance, to follow the trail of
a given person depends undoubtedly upon the recognition of the
individual odor, and the actual amount of olfactory material left
upon the ground which serves as the stimulus must be infinitesi-
mally small. Even in ourselves the actual amount of olfactory
material which sui rices 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

Fif!. 122. — 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
th.it can cause a sensation. By this method such figures as the
following are obtained: Camphor is perceived in a dilution of 1 part
to I' 10,000; 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 -jit 7nj*o"mr?r °f a milli-
gram in 1 liter of air or -j-jnnrlnnnro" °f a milligram inSOc.c. of air.
Various methods have been proposed to determine the relative
delicacy <>f the olfactory sense in differenl persons, and these methods
have some application in the clinical diagnosis of certain cases.
Zwaardemaker has devised ;i simple apparatus, the olfactometer,
the principle of which is illustrated in Fig. 122. It consists of an
outside cylinder the olfactory cylinder whose inner surface is of
porous material which can be filled with a known strength of olfac-
tory solution and an inside tube, smelling tube. This latter is
applied to the nose and where it runs inside the cylinder it is gradu-

SENSATIONS OF TASTE AND SMELL. 297

ated in centimeters. It is evident that the further out the inner
tube is pulled the greater will be the amount of olfactory substance
which will be exposed to the incoming air of an inspiration.

Conflict of Olfactory Sensations. — When different odors are
inhaled simultaneously through the two nostrils they may give rise
to the phenomenon of a conflict of the olfactory fields similar to that
described for the visual fields. That is, we perceive first one then
the other without obtaining a fused or compound sensation. The
result depends largely on the odors selected. In some cases one
odor may predominate in consciousness to the entire suppression
of the other, — a phenomenon which also has an analogy in binocular
sensations. It is well known, also, that certain odors antagonize or
neutralize others. It is said, for instance, that the odor of iodoform,
usually so persistent and so disagreeable, may be neutralized by the
addition of Peru balsam, and that the odor of carbolic acid may
destroy that of putrefactive processes. Whether the neutralization
is of a chemical nature or is physiological does not seem to have
been definitely ascertained.

Olfactory Associations. — Personal experience shows clearly
that olfactory sensations arouse numerous associations — our
olfactory memories are good. On the anatomical side the cortical
center in the hippocampal lobe is known to be widely connected
with other parts of the cerebrum, and we have in this fact a basis for
the extensive associations connected with odors. In animals like
the dog, with highly developed olfactory organs, it is evident that
this sense must play a correspondingly large part in the psychical
life. In such animals as well as among the invertebrates it is in-
timately connected with the sexual reflexes, and some remnant of
this relationship is obvious among human beings. Among the so-
called special senses that of smell is perhaps the one most closely
connected with the bodily appetites, and overgratification or over-
indulgence of this sense, according to historical evidence, has at least
been associated with periods of marked decadence of virtue among
civilized nations.

PHYSIOLOGY OF THE EYE.

The eye is the peripheral organ of vision. By means of its
peculiar physical structure rays of light from external objects are
focused upon the retina and there set up nerve impulses that are
transmitted by the fibers of the optic nerve and optic tract to the
visual center in the cortex of the brain. In this last organ is
aroused that reaction in consciousness which we designate as a
visual sensation. In studying the physiology of vision we may
consider the eye. first, as an optical instrument physically adapted
to form an image on the retina and provided with certain physi-
ological mechanisms for its regulation; secondly, we may study
the properties of the retina in relation to its reactions to light.
and lastly, the visual sensations themselves, or the physiology
of the visual center in the brain.

CHAPTER XVII.

THE EYE AS AN OPTICAL INSTRUMENT-DIOPTRICS
OF THE EYE.

Formation of an Image by a Biconvex Lens. — That the re-
fract ive surfaces of the eye form an image of external objects upon
i In' 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 semit ransparent , 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 thai a small, inverted image of external objects is formed
upon the retinal surface, just as an inverted image of the exterior is
formed upon t he ground glass plate of a photographic camera. This
image is formed in the eye by virtue of the refractive surfaces of the

COrnea and t he lens. The curved surfaces of these t ransparent, bodies

nbstanfially like ;i convex glass lens, and the physics of the

formation of an image by such a lens may be used to explain the

refractive processes in the eye. To understand the formation

of. 'in image by a biconvex lens the following physical facts must he

298

DIOPTRICS OF THE EYE.

299

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. 123). This focus for parallel rays is the principal focus and
the distance of this point from the lens is the principal focal dis-
tance. This distance depends upon the curvature of the lens and
its refractive power, as measured by the refractive index of the
material of which it is composed. Parallel rays are given theo-
retically by a source of light at an infinite distance in front of the
lens, but practically objects not nearer than about twenty feet
give rays so little divergent that they may be considered as par-

Fig. 123. — Diagrams to illustrate the refraction of light by a 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.

allel. On the other hand, if a luminous object is placed at F the
rays from it that strike upon the lens will emerge from the other
surface as parallel rays of light. If a luminous point (/, Fig. 123)
is placed in front of such a lens at a distance greater than the
principal focal distance, but not so far as to give practically
parallel rays, the cone of diverging rays from it that impinges
upon the surface of the lens will be brought to a focus (/') further
away than the principal focus. Conversely the rays from a
luminous point at /' will be brought to a focus at /. These points,
/ and /', are therefore spoken of as conjugate foci. All luminous

300

THE SPECIAL SENSES.

points within the limits specified will have their corresponding
conjugate foci, at winch their images will be formed by the lens.
Lastly, if a luminous point is placed at v, Fig. 123, nearer to the
lens than the principal focal distance, the cone of strongly di-
vergent rays that falls upon the lens, although retracted, 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 {p-F, Fig. 123).
All other straight lines passing through the optical center are known
as secondary axes. Rays of light that are coincident with any of these
secondary axes suffer no angular deviation in passing through the
lens; they emerge parallel to their line of entrance and practically
unchanged in direction. Moreover, any luminous point not on the

I ig. I _' I -Diagram t.i illu frate the formation of an image by a biconvex lens: o, For-
mation of the image of a point ; /;, 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 Hie image of such a point
can be determined by the following construction (Fig. 121): Let. I
represenl the luminous poinl in question. It will throw a cone of
rays upon the lens, the limiting rays of which may be represented by
A-l) and A-c. One of these rays, .1-/', will be parallel to the prin-
cipal axi . and will therefore pass through the principal focus, /''.

\i the di tance 18 determined and is indicated properly in the

construction, the line .1-// may be drawn, as indicated, so ;is to
through F after leaving the lens. The point- at, which the

DIOPTRICS OF THE EYE. 301

prolongation of this line cuts the secondary axis, A-o, marks the
conjugate focus of A and gives the position at which all of the
rays will be focused to form the image, a. In calculating the
position of the image of any object in front of the lens the same
method may be followed, the construction being drawn to de-
termine the images for two or more limiting points, as shown
in Fig. 124. 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 — + ~ = ~, 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 term index of refraction expresses the constant ratio between the
angles of incidence and of refraction, or specifically between the sine of the

sine i
angle of incidence and the sine of the angle of refraction: = index of

sine r
refraction.

302

THE SPECIAL SENSES.

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

The three points at which the light is refracted are indicated
in the accompanying schema (Fig. 125). 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. 125.— Diagram to illustrate the surfaces as the 6Ve 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.
126). In this reduced eye the position of the ideal refracting
surface c' lies in the aqueous humor, a1 a distance of 2.1 mms. from
the anterior surface of the
cornea, and the position of
the nodal poinl or optical
center — that is, the center

of curvature of the ideal _ '

refracting surface lies in

the crystalline lens at n, a ^?

distance of 7.:; nuns, from

,:'"- anterior surface of the Fig 126.-Diagram \

QOrnea The principal fo- or schematic eye with a single refracting surface

1 ' eparating two media ol (Efferent densities: <■',

Cal distance for this refract- the ideal refrac Burface situated 2. 1 rums.

.. .. behind the anterior Burface "I real cornea; ",

Urtace lies a1 a UlS- the nodal point, or center of curvature of the

,. ..,, - i • i surface <•', and 15.6 mms. in front of retina.

tance ol &\j.l Dims., wniCil The eyeball i supposed to be filled with a uni-

n.nl,]j u_ ooiiivolonl (n form substance having a refractive index of 1.33,

wr>«i|fl De equivaieni lo equal to that of the vitreou humor.

22.8 mms. (20.7 , 2.1)

From the actual surface of the cornea and 15.5 nuns. (22.8— 7.:;)

from the nodal point. In the eye a1 resl this principal focal

DIOPTRICS OF THE EYE. 303

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 externa) object on the retina
it suffices, therefore, to use a construction such as is represented in
Fig. 127. 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 stimulation of any given point
on the retina to that part
of the external world
from which the stimulus
arises — that is, to the
luminous point giving
origin to the light rays.
According to the physi-
cal principles described
above, the image of such

1 nnint must hp formed FiS- 127- — Diagram to illustrate the construc-

a point niUbt Oe lOimeU t.Qn ne^essary to determine the location and size of

on the retina where the the retinal image,
secondary axis from that

point through the nodal point touches the retina. In pro j ecting 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. 127 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 sensorv 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

304 THE SPECIAL SENSES.

its local sign. The sensations arising from each of these points we
have learned to project outward into the external world along the
line from it to the nodal point of the eye, because under the normal
conditions of life this point is stimulated only by external objects
situated on this line. This law of projection is so firmly fixed that
if a given point in the retina is stimulated in some unusual way
we still project the resulting sensation outward according to the
law, and thus make a false projection and interpretation. For
instance, if the little finger is inserted into the inner and lower angle
of the eye and is pressed upon the eyeball the edge of the retina is
stimulated mechanically. One experiences, in consequence, a
visual sensation, known as a phosphene, consisting of a dark-blue
spot surrounded hy 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. 1-7, the triangles A-n-B and <i->i-bare
symmetrical; consequently we have the ratio:

A-B : a-b : : A-n : a -n or

A-B A-n

— r— = ; lluil is

a I. a-n

Size of object I>i lance of object from nodal point.

Size of lira : Distance of image from nodal point.

As was i tated above, the distance of the image From the nodal
point thai is, the distance of the retina from the nodal point-
inn.' be placed al L5.5or L5mms. 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; i uppo e h is desired to know the size on
tin- retina of the image made by an object 120 feet high at- a distance
of one mile (5280 feet), [f we designate the size of the image as z

DIOPTRICS OF THE EYE. 305

and substitute the known values for the other terms of the equation,

we have — = 4r, ori = 0.341 mm., which is about the cliam-

eter of the fovea centralis. The retinal image of the object in
this case would be, in round numbers, about to-q Vut of the actual
height 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. 128. — 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 awav as the object is brought closer to the
20

306 THE SPECIAL SENSES.

lens. In the eve the same result is obtained by increasing the curva-
ture and therefore the refractive power of the lens. That a change
in the lens is the essential factor in accommodation for near objects
is demonstrated by a simple and conclusive experiment devised by
Helmholtz with the aid of what are known as the images of Pur-
kinje. The principle of this experiment is represented by the dia-
gram given in Fig. 128. The eye to be observed is relaxed;
that is, gazes into the distance. A lighted candle is held to one
side as represented, and the observer places his eye so as to
catch the light of the candle when reflected from the observed eye.
With a little practice and under the right conditions of illumina-
tion the observer will be able to see three images of the candle re-

A B

Fiir. 129. — Reflected images of a candle flame as seen in the pupil of an eye at rest and
accommodated for near objects. — (Williams.)

fleeted from the observed eye as from a mirror: one, the brightest,
is reflected from the convex surface of the cornea (a, Fig. 129, A);
one much dimmer and of larger size is reflected from the convex
surface of the lens {b, Fig. 129, .1). This image; is larger and
hunter because the reflecting surface is less curved. The third
image (c, Fig. 129, .1) is inverted and is smaller and brighter
than the second. This image is reflected from the posterior
surface of the lens, which acts, in this instance, like a concave
mirror. If now the observed eye gazes at a near object, it will
he noted (Fig. 120. H) t hat the first image does not change at
all, the third image also remains practically the same, but the
middle image (b) becomes smaller and approaches nearer to the

fii'-t (a). This result can only menu th;it in the net of accom-

modation the anterior surface of the lens becomes more convex.
In this w:iv its refractive power is increased mid the more diver

gent rays from the near object are focused on the retina. Ilelm-
holtz has shown that the curval lire of the posterior surface of the

leu- i- also Increased slightly; but the change is so slight that the
increased refractive power is referred chiefly to the change in the
anterior Burface. The means by which the change is effected

DIOPTRICS OF THE EYE. 307

was first explained satisfactorily by Helmholtz.* He attributed
it to the contraction of the ciliary muscle. This small muscle,
composed of plain muscle fibers, is found within the eyeball, lying
between the choroid and the sclerotic coat at the point at which the
sclerotic passes into the cornea and the choroid falls into the ciliary
processes. Some of its fibers take a more or less circular direction
around the eyeball, resembling thus a sphincter muscle, while others
take a radial direction in the planes of the meridians of the eye and
have their insertion in the choroid coat (Fig. 130). When this
muscle contracts the radial fibers especially will pull forward the
choroid coat. The effect of this change in the choroid is to loosen
the pull of the suspensory ligament (zonula Zinnii) on the lens and
this organ then bulges forward by its own elasticity. The theory
assumes that in a condition of rest the suspensory ligament, which
runs from the ciliary processes to the capsule of the lens, exerts a

Ciliary Border

process, of iris. Ciliary muscle.

l>ens

Pigment
y epithelium,

Ora serrata.

Fig. 130. — Meridional section of eyeball after removal of sclerotic coat, cornea, and iris,
to show the position of the ciliary muscle. — (Schultze.)

tension upon the lens which keeps it flattened, particularly along
its anterior surface, since the ligament is attached more to this side.
When this tension is relieved indirectly by the contraction of the
ciliary muscle the elasticity of the lens, or rather of the capsule of
the lens, causes it to assume a more spherical shape along its anterior
surface, and the amount of this change is proportional to the
extent of contraction of the muscle. Other theories have been
proposed to explain the way in which the contraction of the ciliary

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

30S THE SPECIAL SENSES.

muscle effects a change in the curvature of the lens,* but none is
so simple and, on the whole, so satisfactory as the one suggested
bv Helmholtz.

It is interesting to note that in fishes accommodation is effected in a
different way, namely, by movements of the lens forward and backward.
In these animals the eye when at rest is accommodated for near vision, and
in sec objects at a distance the refractive power of the eye is diminished by
the contraction of a special muscle, retractor lentis, which pulls the lens toward
the retina. t

Limit of the Power of Accommodation — Near Point of
Distinct Vision. — When an object is brought closer and closer to
the eye a point will be reached at which it is impossible by the
strongest contraction of the ciliary muscle to obtain a clear image
of the object. The rays from it are so divergent that the refractive
surfaces are unable to bring them to a focus on the retina. Each
luminous point makes a diffusion circle on the retina, and the
whole image is indistinct. The distance at which the eye is just
able to accommodate and within which distinct vision is impos-
sible is called the near point. Observation shows that this near
point varies steadily with age and becomes rapidly greater in dis-
tance between the fortieth and the fiftieth year. In the case of the
normal eye the recession of the near point varies so regularly with
age that its determination may be used to estimate the age of the
individual. Figures of this kind are given :

Age. Near Point.

10 7 cm. or 2.76 in.

20 " 10 " " 3.94 "

30 14 " " 5.61 "

Ki 22 " " 8.66 "

50 40 " " 15.75 "

60. '.'.'. 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
Blighl as bO escape notice, but after it reaches a distance of about
25 cm. (aboul 10 inches) the fact obtrudes itself upon us in the use
of our eves for near objects, reading, for example. The condition
i then designated as old-sightedness or presbyopia. Most normal
eves become so distinctly presbyopic between the fortieth and the
fiftieth year ae to require the use of glasses in reading. If no other
defed exist in the eye, this deficiency of the lens is readily over-

* Bee Tscherning, "Optique phyeiologique," Paris, L898; and Schoen,
" Archiv f. die gei ammte Physiologic." 59, 427, ix!).r>.

ee \\i<r, "Wiener klinische Wochenschrif t, " 1898, No. 12.

DIOPTRICS OF THE EYE. 309

come by using suitable convex glasses to aid the eye in focusing
the rays. It is obvious that in such cases the glasses need not be
used except for near work.

Far Point of Distinct Vision. — The normal eye is so adjusted
that parallel rays are brought to a focus on the retina. The far
point is therefore theoretically at infinity. Objects at a great
distance are seen distinctly, as far as their size permits, without
accommodation, — that is, with the eye at rest. Practically it is
found that objects at a distance of 6 to 10 meters (20 to 30 feet) send
rays that are sufficiently parallel to focus on the retina without
muscular effort on the part of the eyes, and this distance, therefore,
measures the practical far point, panctum 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 p. (0.085
mm.), and since the displacement of the focus of an object moved
from an infinite distance (parallel rays) to 6 or 10 meters from the
eye is less than this amount, the focused image would continue to
fall on some part of the cones without the aid of the mechanism of
accommodation.

The Refractive Power of the Eye and the Range of Accom-
modation.— -The refractive power of lenses is expressed usually
in terms of their principal focal distance. A lens with a distance
of one meter is taken as the unit and is designated as having a
refractive power of one diopter, 1 D. Compared with this unit,
the refractive power of lenses is expressed in terms of the recipro-
cal of their principal focal distance measured in meters; thus,
a lens with a principal focal distance of y^- meter is a lens of 10
diopters, 10 D., and one with a focal distance of 10 meters is
^ diopter (0.1 D.). The anterior principal focal distance of
the combination of refractive surfaces in the eye is 15.5 mms. or
j^ meters. The reciprocal of this length of focus, ^ or 64.5 D.,
expresses the refractive power of the eye under the normal con-
ditions in which the rays are refracted into the dense vitreous
humor. The anterior focal length of the cornea alone is given as
23.3 mm., which would correspond to a power of 42.9 D.. while the
anterior focal length of the lens alone is equal to 50.6 mm. or about
20 D. In the combined system, therefore, the action of the cornea
is more important than that of the lens. Removal of the lens, as
in cataract operations, does not lessen the refractive power of the

310 THE SPECIAL SENSES.

eye so much as when the action of the cornea is destroyed, as
happens for the most part when the head is immersed in water.
The total refractive power of the eye is increased by the act of
accommodation, on account of the greater curvature of the lens.
As stated in a preceding paragraph the extent of accommodation
varies with age. At 10 years the range is from infinity, when the
eye is at rest, to 7 ctm. when the maximum accommodation is
used. In this case, therefore, the refractive power is increased
from 64. o D. to 78.5 D., since a distance of 7 ctm., y^- meter, is
equivalent to -M-fi or 14 -J- D. The decreasing range of accom-
modation as age increases is expressed conveniently in the number
of diopters which may be added to the refractive power of the
eye by the action of the ciliary muscle.

The following table illustrates the usual range of accom-
modation for different ages :

Range of accommodation
Years. in diopters.

10 14

15 12

20 10

25 8.5

30 7

35 5.5

40 4.5

45 3.5

oi) 2.5

55 1.75

60 1

65 0.75

70 0.25

Optical Defects of the Normal Eye. — The refractive surfaces
of the eye exhibit some of the optical defects commonly noticed
in lenses, particularly those defects known as chromatic and spherical
aberration. White light is composed of ether waves of different
lengths and different rapidities of vibration, the shortest waves being
i hose at 1 he violet end of the spectrum and the longest those at the
I'd end. in passing through a prism or lens these waves are re-
fracted unequally and arc therefore more or less dispersed accord-
ing to the character of the refracting medium. The short, rapid
waves ;tt 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 locus when, viewed

DIOPTRICS OF THE EYE. 311

by red light it can be shown that the focus must be changed if the
same object is illuminated by violet light. Helmholtz estimates
that if the media of the eye possess the same dispersive power as
water the rays of violet light must be brought to a focus at about
0.434 mm. in front of that of the red rays.

Spherical aberration depends upon the fact that the rays near the
circumference of a lens are refracted more and therefore are brought
to a focus sooner than those entering nearest the center. This
defect may be noticed in an uncorrected lens by the fact that
when the center of the image is in exact focus its margins are
slightly out of focus and vice versa. The defect is usually cor-
rected, as in photography, by use of a diaphragm to cut off
the rays from the periphery of the lens. In the eye both spher-
ical and chromatic aberrations are remedied to a large extent by
a similar device. The iris constitutes an adjustable diaphragm,
which is reflexly narrowed as the light increases in intensity and
thus cuts off the rays that would go through the periphery of
the lens. The interesting physiological control of the movements
of the iris is described below. In the eye the defect of spherical
aberration is counteracted also by the peculiar structure of the
crystalline lens. This organ is composed of concentric layers
whose density increases toward the center. The result of this
arrangement is that the center of the lens is more refractive than the
periphery, and the tendency of the latter portion to refract more
strongly is more or less neutralized. A third optical defect of the
eye consists in the fact that its refractive surfaces are not absolutely
centered, — that is, the centers of curvature of the cornea and of the
anterior and the posterior surfaces of the lens do not lie in the same
straight line. Moreover, the optical axis of the system does not
coincide exactly with the line of sight. By the latter term we mean the
line from the point looked at to the fovea centralis or the part of the
fovea on which the image of the point falls. This line of sight or
visual axis makes an angle of about five degrees with the optical
axis. The system would be more perfect as an optical apparatus
if the two axes coincided.

Abnormalities in the Refraction of the Eye — Ametropia. —
The eye that is normal and in which parallel rays focus on the
retina when the eye is at rest is designated as 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 refractive troubles of the eye
are due to short-sightedness or myopia, far-sightedness or hyper-
metropia, astigmatism, and old-sightedness or presbyopia. Some
description of these conditions is useful to emphasize by contrast

312 THE SPECIAL SENSES.

the mode of action of the dioptric mechanism in the normal eye,
but for a full description of the extent and complexity of these
defects reference must be made to special treatises upon the
errors of refraction in the eye.

In myopia or near-sightedness parallel rays of light are brought
to a focus before reaching the retina. Consequently when the rays
fall upon the retina each point forms a diffusion circle and the image
is indistinct. This defect may be due to an abnormally great cur-
vature of the refractive surfaces, the cornea or the lens, or to an ab-
normal length of the eyeball in its anteroposterior diameter. The
latter cause is the more common. The defect may be congenital,
but usually it is acquired, and in the latter case its cause is generally
attributed to a weakness in the coats of the eyeball. The interior
of the eye is under some pressure, intra-ocular tension, which is
estimated to be equal to the pressure of a column of mercury 25 to 30
mms. in height. This tension is increased by strong convergence of
the eyeballs in looking at near objects. If the coats of the eye are
weak or become so from disease or malnutrition they may yield
somewhat to this pressure and the eyeball become lengthened in the
anteroposterior diameter. The condition as regards refraction of
parallel rays is represented then by the diagram B, in Fig. 131.
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 1 he extent of the myopia. On the contrary, the near point
of distinct vision — that is, the nearest point at which distinct vision
can be obtained with the aid of the muscles of accommodation — is
closer than in the normal eye. Much of the prevalent myopia in the
young is attributed by oculists to bad methods in reading, such as
insufficient lighting, small print, and a faulty position of the book.
Such conditions lead to an excessive muscular effort and thus
aggravate any tendency that exists toward the development of a
near-sighted condition.

in hypermetropia the conditions are the opposite of those in
myopia. Parallel rays of light, afler refraction in the eye cut the
retina before they come to a locus. The principal focal distance, in
older words, is behind the retina. In this case, also, each poinl

DIOPTRICS OF THE EYE.

313

of a distant object will make upon the retina, when the eye is not
accommodated, a diffusion circle, and the image consequently is
blurred. This defect may be caused by a lessened curvature or
refractive power in the cornea or lens, but in the majority of cases
it is referable to a diminution in the anteroposterior diameter of
the eyeball. This condi-
tion is usually congenital:
the eyeball from birth is
smaller than the normal.
The path of the parallel
rays in this case is repre-
sented in- the diagram C,
Fig. 131. When such an
eye looks at a distant ob-
ject a clear image may be
obtained only by using the
ciliary muscle, and to pre-
vent this constant strain
upon the muscle of accom-
modation convex glasses
must be worn. Glasses of
this kind converge the
rays and if properly chosen
will bring parallel rays to
a focus without the con-
stant aid of accommoda-
tion. It is obvious that
in the hypermetropic eye
there is no far point of
distinct vision when the
eye is at rest, since some
accommodation must be
used to bring even parallel rays to a focus. The near point of
distinct vision will be farther away than in the normal eye, since
accommodation begins when the rays are parallel and its limits
are reached with a less degree of divergence; hence the name of
far-sightedness.

Presbyopia or old-sightedness has been referred to above. It
is due to a gradual failure in the effectiveness of accommodation
with increasing age, and is attributed usually to a progressive in-
crease of rigidity in the lens. The near point of distinct vision
recedes farther and farther from the eye, and consequently in close
work convex glasses must be worn to aid the accommodation. It
is obvious that this effect of old ae:e will be less noticeable in the

Fig. 131. — Diagram showing the difference be-
tween normal (/I), myopic (£), and hypermetropic
(C) eyes. In B and C the dotted lines represent the
path of the rays after correction by glasses. — (Bow-
ditch.)

314 THE SPECIAL SENSES.

myopic than in the emmetropic eye, since in the former the greater
length of the eyeball requires less accommodation in near vision and
the failure of the lens to refract is therefore not felt so soon What
is known as second-sight in the old may be brought about by
the late development of a myopic condition. — that is, by a change
in the length of the eyeball or by a swelling of the crystalline
lens. — and in such a case convex glasses for near work may be
dispensed with.

Astigmatism. — In a perfectly normal or ideal eye the refractive
surfaces, cornea, anterior and posterior surfaces of the lens, are
sections of true spheres, and, all the meridians being of equal
curvature, the refraction along these different meridians is equal.
Such an eye will bring the cone of rays proceeding from a luminous
point to a focal point on the retina, barring the disturbing influence
of chromatic and spherical aberration. If, however, one or all of the
refractive surfaces have unequal curvatures along different merid-
ians, then it is obvious that the rays from a luminous point can not
be brought to a focal point, since the rays along the meridian of
greater curvature will be brought to a focus first and begin to diverge
before the rays along the lesser curvature are focused. Such a
condition is designated as astigmatism (from a, not, and art^a,
point). The effect may be illustrated by the diagram in Fig. 132,
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 (7, but those from the horizontal meridian are still converging;
so that a screen placed at this point will give the image of a horizontal
line (a-a'). The rays along the horizontal meridian are brought to a
focus at B, but those from focus G have by this time spread out
in a vertical plane, so that a screen placed at this point will give
the image of a vertical line (fe-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
,-i way thai the meridians of greatest and least curvature are at
ii'_rlit angles to each other or approximately so. Ordinary astig-
matism is of the regular variety, and is usually attributed to a
detect in the curvature of the cornea. If the astigmatism is such
that the vertical meridian has the greatest curvature it is termed
"with the rule,'' since, usually this meridian is slightly more

DIOPTRICS OF THE EYE.

315

curved than the horizontal one. If, on the contrary, the cur-
vature along the horizontal meridian is greater, the astigmatism
is "against the rule." The meridians of greatest and least curva-
ture may not lie in the vertical and horizontal planes, but in some
of the oblique planes; but so long as they are at right angles the
astigmatism is regular. It is evident that such a condition may
be corrected by the use of cylindrical lenses, so chosen as to in-
crease the refraction along the meridian in which the cornea
has the least curvature, in which case a convex or plus cylinder is
used, or, on the other hand, to diminish appropriately the refraction
along the meridian of greatest curvature, in which case a concave
or minus cylinder is used. An eye that suffers from a marked

Fig. 132. — 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.

degree of astigmatism cannot focus distinctly at the same time
lines that are at right angles to each other; hence the use of a
series of lines whose images are formed along the different meridians
of the eye, as shown in Fig. 133, will reveal this defect if it exists.
If the eye is directed to the center of intersection of the lines some
of the lines appear distinct while those at right angles to them
are blurred. A normal eye can be thrown into an astigmatic con-
dition by approximating the eyelids closely. In this position the
tears make a concave cylindrical lens, which alters the curvature
along the vertical meridian. What is known as irregular astig-
matism is due to the fact that the meridians of greatest and least
curvature are not at approximately right angles, or, as is more

316

THE SPECIAL SENSES.

commonly the case, it is due to an irregularity in the curvature
along some one meridian, such as ma}' 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 pupillsR 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 ins. The histological differentiation
of the dilator pupilke is much less distinct. For a Ions time its
i nee was the subject of controversy, but it. is now conceded
thai such a muscle is presenl in the form of a layer of elongated
spindle-like cells which lie close to the pigment layer of the iris and

Fig. 133.— Astigmatic chart.

DIOPTRICS OF THE EYE.

317

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. 134. The entire
course of the motor
paths, preganglionic and
postganglionic fibers, is
represented diagrammat-
ically in Fig. 135. The
motor fibers to the ciliary
muscle and sphincter
pupillse 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
muscle have a very different path.

Course of constrictor nerve fibers, .
Course of dilator nerve fibers,- - ■

Fig. 134. — Diagrammatic representation of the
nerves governing the pupil (after Foster) : II, Optic
nerve; e.g, ciliary ganglion; r.b, its short root from
77/, 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.

The fibers to the dilator
They arise also in the brain,
most probably in the midbrain, although their exact origin has
not been determined satisfactorily, and pass down the spinal

* For a physiological proof and the literature of the controversy see
Langley and Anderson, "Journal of Physiology," 13, 554, 1892. For the
histological proof, Grunert, "Archives of Ophthalmology," 30, 377, 1901.

3 IS

THE SPECIAL SENSES.

cord to terminate in the lower cervical region. From this point
the path is continued by spinal neurons which leave the cord in the
eighth cervical and the first and second thoracic spinal nerves and
pass by way of the corresponding rami communicantes into the
sympathetic chain at the level of the first thoracic ganglion. From
this point the fibers pass upward in the cervical sympathetic with-
out terminating until they reach the superior cervical ganglion near
the base of the skull. From this ganglion the path is continued
by sympathetic (postganglionic) fibers which pass to the Gasserian
ganglion and unite with its ophthalmic branch. Subsequently
they leave the ophthalmic nerve in the long ciliary branches. These
fibers under normal conditions are in constant (tonic) activity, so
that if the path is interrupted at any point by section of the cervical

Gasserian. v — N Ojbhttalmie branJiof£t^ Zona ciliary nerves.

6anSlior,.\ > V Motor

jiupillae.

Superior Ceruieal/
Ganglion/ ~?

/

Q/ju/ial
Cord

A

/ 3° 'Cranial W
/ nerve.

CuwryGanjlvoru Short Ciliary heroes

Ceruieal
SjmpaVietic

Fig. 135. — Schema showing the path of the preganglionic and postganglionic fibers
to the ciliary mu.scle and to the sphincter and dilator muscles of the iris. — (Modified from
Schultz.) The course of the long ciliary nerves is represented very diagrammatically.

sympathetic, for instance — the pupil is seen to contract. This
constant activity may be referred directly to the activity of the
spinal neurons whose cells lie in the spinal cord in the lower cervical
and upper thoracic region. The cells in question constitute what
is sometimes called the lower ciliospinal center of Budge.

The Accommodation Reflex and the Light Reflex of the
Sphincter Muscle.- When the eye is accommodated for a near
object by the contraction of the ciliary muscle there is always a
simultaneous contraction of the sphincter pupillse whereby the
pupil is narrowed. The net is one of obvious value in vision, since
by diaphragming down the lens the focus is improved and more
exacl vision, such ae is needed in close work, is obtained. The act

uallv spoken of as the accommodation reflex, hut in reality it

DIOPTRICS OF THE EYE. 319

is rather what is known as an associated movement. The voluntary
effort inaugurated in the brain affects the cranial centers for both
muscles, and under normal conditions they always act together, —
a fact which implies a close connection of their centers. An example
of a similar associated action is seen in the effect of the respiratory
movements on the rate of heart beat, the inspirator}' 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

320 THE SPECIAL SENSES.

is stimulated.* We may conclude, therefore, that the bilaterality
of the reflex in the higher animals is dependent upon the partial
decussation of the optic fibers in the chiasma, a sensor}' stimulus
upon one retina giving rise to impulses which are conveyed to the
two sides of the brain. It is possible, however, that in addition
commissural connections may exist between the central connections,
— the motor centers in the midbrain. It is usually stated that
the effect of the light upon the sphincter muscle is greatest when
the retina is stimulated at or near the fovea and that it varies
directly with the intensity of the light and the area illuminated.t
The Action of Drugs upon the Iris. — The condition of con-
striction of the pupil is frequently designated as miosis (mi-o'-sis)
and the condition of dilatation as mydriasis (myd-ri'-as-is). Many
drugs are known which, when applied directly to the absorptive
surfaces of the eye or when injected into the circulation, affect
the muscles of the iris and therefore vary the size of the pupil.
Those drugs that cause miosis are spoken of as miotics, and those
that produce mydriasis as mydriatics. Atropin, the active prin-
ciple of belladonna, homatropin, and cocain are well-known myd-
riatics, while physostigmin (eserin) and muscarin or pilocarpin are
examples of the miotics. There has been much question as to the
precise action of these drugs. For an adequate discussion of this
question the student is referred to works on pharmacology; but
it may be said that the evidence from the physiological sidej indi-
cates that atropin causes mydriasis by paralyzing the endings of
the constrictor nerve fibers in the sphincter muscle, while phy-
sostigmin and muscarin cause miosis by -stimulation of the endings
of these same fibers. In the case of cocain it is probable that the
drug first stimulates mainly the endings of the dilator fibers in the
dilator muscles, and in stronger doses causes additional mydriasis
by paralyzing the constrictor fibers. The stronger mydriatics
paralyze not only the sphincter pupillaj, 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 cycloplcgics.
On the contrary, the stronger miotics stimulate the ciliary muscle,
and therefore during their period of action throw the eye into a
condition of forced accommodation.

• Steinach, "Archiv f. d. gesammte Physiologic," 47, 313, 1800.
f Sec Abelsdorfi and Feilchenfell, "Zeitschnit f. Psychologic unci Phys-
iologic dee Sinnesorgane," 34, 111, L904.

JSchultz, "Archiv f. Physiologic," 1898, 47.

DIOPTRICS OF THE EYE. 321

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, particularly in regard to the dilator mechan-
ism. P"or example, adrenalin applied to the eye causes dilatation of the pupil,
but with varying degrees of rapidity for different eyes, the least rapidly
for the eyes of those animals which are most sensitive to light (Schultz).
When the superior cervical ganglion is removed, on the contrary, the dilating
action of the adrenalin is much more rapid. (Meltzer and Auer.)

The Balanced Action of the Sphincter and Dilator Muscles
of the Iris. — It would seem that under normal conditions both the
sphincter and the dilator muscle are kept more or less in tonic
activity by impulses received through their respective motor fibers.
They thus balance each other, to speak figuratively, and a mechan-
ism of this kind in which two opposing actions are in play is in a
condition to respond promptly and smoothly to an excess of stimu-
lation from either side. The two muscles, in fact, act as antago-
nists in the same manner as the flexor and extensor muscles around
a joint. At the same time this relation adds some difficulties to
the explanation of specific reactions, since it is evident that a dila-
tation of the pupil may be caused either by a contraction of the
dilator muscle or a loss of tone (inhibition) in the sphincter, while
in constriction of the pupil the effect may result either from a con-
traction of the sphincter or an inhibition of the dilator; or, last,
the contraction of one muscle may always be accompanied by an
inhibition of its antagonist, as is supposed to be the case with the
flexor and extensor muscles of the limbs * (law of reciprocal in-
nervation). Anderson 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 contracting first and subsequently
the tone of the constrictors suffering 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 cir-
cumstances, 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 character-
istic of these conditions. Writers speak of the eyes dilating with
terror or darkening with emotions of deep pleasure. This pupil-

* " Journal of Physiology," 30, 15, 1903.
21

322 THE SPECIAL SENSES.

lary accompaniment of the emotional states may occur even when
it is a matter of memory rather than immediate experience. The
explanation of this mydriasis can hardly be obtained by experi-
ment, but reasoning from analogy we know that strong emotional
states are usually accompanied by more or less distinct inhibitory
effects on motor centers, and perhaps in tins case the reaction is
most satisfactorily explained by attributing it to an inhibition of
the constrictor center in the midbrain.

Intraocular Pressure.— The liquids in the interior of the
eye are normally under a pressure, the average value of which
may be estimated at 25 mms. of mercury. In consequence of
this internal pressure the eyeball is tense and its external surface,
including the cornea, shows a regular curvature. It is obvious
that folds or creases in the cornea would entirely destroy its use-
fulness, so far as the formation of an image is concerned. The
amount of the intraocular pressure may be measured by thrusting
a tubular needle, properly connected with a manometer, into the
anterior chamber of the eye. The liquid in the interior of the
eyeball may be considered as tissue lymph, and like the lymph-
elsewhere it is derived from the blood-plasma. Investigation
has shown that the lymph is formed in the ciliary processes, but
in this as in other cases there is a difference of opinion as to whether
the production is due to so-called secretory or to mechanical
causes, such as filtration. The facts that are known seem to
be explicable from the mechanical point of view.* We may
suppose that the liquid niters into the eye through the vessels
in the ciliary processes, and, on the other hand, drains off at the
angle of the anterior chamber through the canal of Schlemm.
The intraocular pressure rises until, under its influence, the out-
flow just balances the inflow. It is evident from this point of
view that intraocular pressure' will be increased by any change
that will augment the production of the liquid at the ciliary
processes, such as a rise of blood-pressure, or by any interference
with the outflow, such as might arise from a blocking of the canal
of Schlemm. Certain pathological conditions (glaucoma) are
characterized by an abnormally high intraocular tension, the
difference from the normal being such that it is easily recognized
by pressure with the fingers.

Methods of Determining the Refraction of the Eye. The condition

of the eye a regards its refraction may be determined by the use of

suitable charts and a Beries of spherical and cylindrical lenses. The results

n a method depend largely upon the statements of the patient, that

bey are Largely subjective. A uumber of instruments have been

I, however, by means of which the refraction of the eye may be studied

For di cu ion and Literature, see Henderson and Starling, 'Proceed-
ing Royal Society," L906, B. Lxxvii.

DIOPTRICS OF THE EYE.

323

in a purely objective way, so far as the patient is concerned. The most
important of these instruments are the ophthalmoscope, the retinoscope or
skiascope, and the ophthalmometer. A brief description is given of each
of these instruments, but for the numerous practical details necessary to
their successful use reference must be made to special manuals.

The Ophthalmoscope. — The light that falls into the eye is partly ab-
sorbed by the black pigment of the choroid coat and is partly reflected back
to the exterior. This latter portion is reflected back in the direction in which
it entered. Merely holding a light near
the eye does not, therefore, 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 ar-
range the light to enter the observed eye
as though it proceeded from our own eye,
then the returning rays would be per-
ceived, and with sufficient illumination
the bottom or fundus of the observed eye
might be seen. Arguing in this way,
Helmholtz constructed his first form of
the ophthalmoscope in 1851. The value
of the ophthalmoscope is twofold: It en-
ables the observer to examine the interior
of the eye and thus recognize diseased
conditions of the retina; it is also useful
in detecting abnormalities in the refrac-
tive surfaces of the eye. The principle of
the instrument is well represented in the
original form devised by Helmholtz, as
shown schematically in Fig. 137, A. I
represents the observed eye and II the
eye of the observer. Between the two
eyes is placed a piece of glass inclined at
an angle. Light from the candle falling
upon this glass is in part reflected from
the surface to enter eye /, and these rays
on emerging from the eye along the same
line pass through the glass in part and
enter eye //. In place of the plane un-
silvered glass it is now customary to use
a concave mirror with a small hole through
the center, the observer's eye being placed
directly behind this hole. Such an in-
strument is shown in Fig. 136, The in-
strument is used in two ways, known as

the direct and the indirect method. In the direct method the mirror is held
very close to the observed eye and the paths of the rays of light into and out
of the eye are represented schematically in Fig. 137, B. The light from a
lamp caught upon the mirror is thrown into the eye, the rays coming to a
focus and then spreading out so as to give a diffuse illumination of the fundus.
This latter surface may now be considered as a luminous object sending out
rays of light. Taking any three objects on the retina, A, B, C, it is apparent
that if eye I is an emmetropic eye these points are at the principal focal dis-
tance and the rays sent from each after emerging from the eye are in parallel
bundles. These rays penetrate the hole in the mirror and fall into the ob-
server s eye as though they came from distant objects. If the observer's eye
is also emmetropic, or is made so by suitable glasses, these bundles of rays
will be focused on his retina without an act of accommodation. He must, in
fact, in looking through the mirror, gaze, not at the eye before him, but, re-

Fig. 136. — Loring's ophthalmoscope.

324

THE SPECIAL SENSES.

taxing his accommodation, gaze through the eye. as it were, into the distance.

]n this way he will see the portion of the retina illuminated, the image of the
objects seen being inverted on liis own retina and therefore projected or seen
erect. If the observed eye is myopic its retina is farther back than the prin-
cipal focus of its refracting surfaces; consequently the rays sent out from the
illuminated retina emerge in converging bundles and cannot be focused on
the retina of the observer's eye. By inserting a concave lens of proper power
between his eye and the mirror the observer can render the rays parallel and
thus bring out the image. From the power of the lens used the degree of my-
opia may be estimated. Just the reverse happens if the observed eye is
hypermetropic. In such an eye the retina is nearer than the principal focal

.1

137. Diagrams to represent the principle of the ophthalmoscope: A, The orig-
inal form of ophthalmoscope, consisting of a piece of glass, .i/, inclined at a suitable angle.
j from the source of light are reflected into the observed e\r, /, and i hence return
along the same lines passing through .1/ to reach the observer"* eye, //. li, 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
e //. C, the indirect method with ophthalmoscopic mirror ami intercalated
i be rays of light-red lines are brought to a locus within the anterior chamber of the
I thence diverge to give a general illumination of the interior of the eyeball. The
returning rays of light are indicated foi a ingle point, b. At a', f, i '. a real inverted image
of a portion of the retina it formed in the air, which in turn is focused on the retina of the
observer1 eye.

distance of the refractive Burface; consequently the lij,rht emitted from the
retina emerges in bundles of diverging rays which cannot be broughl to a
focus on the retina of the observer unless he exerts his own power of accom-
modation or interposes a convex lens between his eye and the mirror.

The indirect method of using the ophthalmoscope is represented in Fig.
The mirror is held al some distance, a1 arm's length, from bhe ob-
served eye, /. while just before this eye a biconvex lens of shoii focus is
placed, fit 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.
Tbii leni brings tin- rays to a focus at or near the eye, whence they again
diverge and light up the retina with a diffuse illumination. The lighl from

DIOPTRICS OF THE EYE. 325

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 represented in the diagram at a", b" ', c" , and is projected outward or seen
inverted as regards the original position of the points in the retina of eye /.
The indirect method is the one usually employed in ophthalmoscopic exam-
inations of the retina. It gives a larger field than the direct method, although
the objects seen are of smaller size.

The Retinoscope or Skiascope. — When one reflects a spot of light
upon a wall, any movement of the reflecting (plane) mirror is followed by a
movement of the reflected spot in the same direction. So if the fundus of the
eye is illuminated by a plane mirror provided with a peep-hole, the observer
looking through this hole may see a spot of light reflected from the retina
and can determine whether the spot moves in the same direction as the
mirror or against it. If the eye under observation is normal (emmetropic),
then the rays of light starting from the retina will emerge in parallel bundles,
since the retina lies at the principal focal distance, and as the mirror is tilted
from side to side the illuminated spot moves in the same direction. By placing
a convex lens of suitable focus in front of the observed eye we can cause the
emerging parallel rays to come to a focus and cross before reaching the ob-
server's eye. In such a case the movements of the spot of light upon the retina
will be against those of the mirror. For example, let us suppose that the
observing eye is placed just 1 meter away from the eye observed, then if
we put in front of the latter a convex lens of 1.25 D. the emerging rays will be
focused at a point 25 ctm. in front of the observer's eye and the movements
of the spot of light will be against the mirror. A lens of less than 1 D. placed
in front of the observed eye would not bring the rays to a focus in front of
the observer's retina, consequently the movements of the spot would be with
the mirror. Assuming that we are dealing with an emmetropic eye, it can
be shown that at the distance mentioned (1 meter) any lens of less than
1 D. placed in front of the eye leaves the movements with the mirror,
while any lens of more than 1 D. gives movements against the mirror.
Consequently a lens of just 1 D. would mark the exact "point of rever-
sal. " With a lens of tins power the focus would fall theoretically just on the
observer's retina. In such a case any movement of the mirror would be
followed by the appearance or disappearance of the spot, but no direction of
movement would be perceived. The movements of the spot of light formed
upon the retina by the retinoscopic mirror may be used to determine all the
various abnormalities of refraction of the eye according to the following
general schema : The observer sits at a fixed distance, say 1 meter, from
the patient, and determines whether the reflected spot from the illuminated
fundus moves with or against the mirror. If the movement is with the mirror,
then the eye under observation is either normal or hyperopic (or if myopic
the myopia is less than 1 D.). By placing convex lenses in front of the eye
the observer seeks for the point of reversal. If this point is given by a lens
of + 1 D., then the eye under examination is emmetropic ; if»a stronger lens
is required the eye is hyperopic, that is, the emerging rays are divergent and
require a stronger lens to bring them to a focus before reaching the observer's
eye. In the latter case the amount of hyperopia is obtained by ascertaining
the strength in diopters of the lens required to just reverse the movement
and subtracting 1 D. from it, since the latter amount is required, at a distance
of 1 meter,' to get reversal with the normal eye. If the reversal is given by
a convex lens of less than 1 D., then the eye is myopic to an extent less than
1 D. When the movements of the spot of light are against the mirror
from the beginning, then the observer is dealing with a myopic eye (the myopia
being greater than 1 D.). To reverse the movement it is now necessary to
place concave lenses in front of the observed eye until the point of reversal
is obtained, that is, until the focus of the emerging rays falls behind the

326 THE SPECIAL SENSES.

retina of the observer. The concave lens necessary to give this result, plus 1 D.
for distance, gives the extent of the myopia in diopters. With astigmatic
eyes tae point of reversal may be determined for the different meridians
of the eye, tne movements of the mirror being in the same meridian. By
the character of tiie reflected spot and the points of reversal it is possible
with tae retinoscope to determine the principal meridians, and the difference
in refraction between them, that is, the degree and the axis of the astigmatism.
The Ophthalmometer. — The ophthalmometer is an instrument for
measuring tae curvature of the refracting surfaces of the eye. As actually
applied in practise it is arranged especially for measuring the curvatures
of the cornea along its different meridians. The point for which the instru-
ment is designed is to obtain the size of the image reflected from the convex
surface of the cornea. Any luminous object placed in front of the eye will give
a reflected image from the cornea as from the surface of a convex mirror.
If the size of the object and its distance from the cornea are known and the
size of the corneal image is determined, then the radius of curvature of the

cornea is given by the equation r — _ Pl, in which p represents the distance of

o

Fig. V.ifi. — Schema to indicate the general principle of ll phthahuoineter : T,

Telescope to observe the reflected images from the cornea; .1 and />', the targets or mires
in the shield at a known distance apart whose images are reflected from the Cornea; a
and b, the rellected images of A and B on the cornea. The distance a b has to be determined.

the object from the cornea, i, the rfze of the corneal image, and o, the size
of the object. For example, let A and B in Fig. 138 be two luminous areas
arranged on the arc of a circle. If placed in front of the cornea C each
will give a reflected image a and l>, which may be observed by means of
the telescope T. The distance between A and />' represents the size of
the object and the distance between n and l> the size of the image. This
latter factor i.» determined by means of the telescope. A scale, for in-

stance, mighl I"- placed in the eye-piece of the telescope and the distance
o-4 be determined in terms of its graduation. This valuation might then be
K>nverted into milHmeters by substituting a scale for the cornea and measuring
off upon ii the observed distance in the eye-piece scale. If the .arc carrying
.1/; i arranged so thai it may be rotated it is obvious thai the size of the
corneal images may be measured for the differenl meridians and thus enable
one i" compare their curvatures, in modern instruments, such as is repre-
sented in I h'. L39, the luminou areas, known as targets or mires, are placed in a

Spherical shield which may be rotated around the axis of the t elescope. The
shield ha a 1:1 < I i 1 1 of curva t ure of 0.35 meters ami its center of rotation is

approximately coincidenl with thai of the cornea when the eye is in its

proper position. The rellected images of the mires from the surface of the

DIOPTRICS OF THE EYE.

327

cornea are each doubled, when viewed through the telescope, by means of
a double vision prism of Iceland spar and the displacement produced in
this way is a definite amount for the distance chosen. Four images of the
mires are thus seen, and when the mires are properly adjusted for a cornea of
average curvature the two inner images are in contact with each other.
A variation from this average is indicated by an overlapping of the images,

Fig. 139.— Ophthalmometer (Hardy).

the value of which in diopters or in radii of curvature is read off upon the
instrument. The instrument, therefore, when once calibrated enables one
to read off at once the radii of curvature for the different meridians and thus
determine the axis and degree of astigmatism. It should be added that
the instrument gives only the curvatures and degree of astigmatism, if any
exists, of the cornea, and is therefore of no immediate service in determining
the total astigmatism, that is, the astigmatism of cornea and lens acting
together.

CHAPTER XVIII.

THE PROPERTIES OF THE RETINA— VISUAL STIMULI
AND VISUAL SENSATIONS.

The Portion of the Retina Stimulated by Light. — The normal
stimulus to the sensory cells in the retina is found in the vibrations
of the ether, the waves of light. When sunlight is passed through a
prism the waves of different lengths are dispersed, and those capable
of stimulating the retina form the visible spectrum extending from
red to violet. The limits of the spectrum are, on the one hand, the
extreme red rays with a wave length of TTmrWff 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 TFtHrlnny mm- aQd
a rate of vibration of 770,000,000,000,000 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. 140. — To demonstrate the blind spot. Fix the center of the cross with the right
eve, then move the book slowly to or from the fare. 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 optii di e.

through the oilier layers of the retina. That the rods and cones arc
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, fn the fovea centralis, in which vision is

most perfect , the layers of the retina are thinned out until practically
only the rod- and cone remain to be acted upon. That, the optic
fibers themselves are no1 acted upon by li^hi waves is proved
by the existence of the blind spot. The termination of the optic
nerve within the eyeball, the optic disc, lies about L5 degrees to the

Qfl $al side of the fovea and has a diameter of about 1.5 inms. From
t his point t he nerve-libers spread out over 1 he rest of I he optic cup

to form the internal layer of t he pel in a. But the optic disc itself has

328

PROPERTIES OF THE RETINA. 329

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. 140.
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
Ktihne, the electrical response to light is a negative variation similar
to that described for stimulation of nerves in general (p. 103). 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-
sponse," when the light is suddenly withdrawn. This last-
interesting fact would seem to indicate a stimulation process of
some kind in the retina due to darkness — that is, withdrawal

* Dewar and McKendrick, " Transactions, Royal Society, Edinburgh," 27,
1873; Got«h, "Journal of Physiology," 29, 388, 1903, and 31, 1, 1904.

330 THE SPECIAL SENSES.

of the objective stimulus. Einthoven and Jolly* have applied
the sensitive string galvanometer to the study of this phenome-
non. They find that the electrical response of the illuminated
eye. when photographed, presents a curve of much complexity.
and they conclude that its complexity is due to the fact that
several different processes occur together in the stimulated
retina. They offer some evidence to indicate that three different
processes depending on the reaction of three different substances
may be distinguished. These substances react with different-
velocities ami with different changes in electric potential to
Mashes of light and "flashes of darkness." What physiological
effects may be connected with these three processes cannot
yet be stated. The electrical 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 sensitiveness. 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, f 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 arc 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, J and the facts were afterward carefully

investigated by Kiihne.§ The red pigment, known usually as

visual purple or rhodopsin, is t mind only in the external segments

* Einthoven and .Jolly, "Quarterly Journal of experimental Physiology,"
I, 373, L908.

| /■ a] < i. ■■ Aidiiv f. mil.. \ 1 1 : 1 1 < . 1 1 1 i < ■ , " :;, 248, is(>7.

J Boll, "Archiv t Physiologie," 1877, 4.

§ Kuhne, "Untersucn. a. of. physiol. Inst. d. Qniv. Heidelberg," vol. i,
IS7S. Also "The Photochemistry of the Retina," etc., translated by Foster,
London, 1878.

PROPERTIES OF THE RETINA. 331

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
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. 141). 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- 0

preSSlOn; and there Fig. 141.— 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

332 THE SPECIAL SENSES.

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,
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 ;i flat surface would have the form of a
circle the center of wliicli would Correspond to the fovea centralis.
As ;i matter of fact, the configuration of the face is such as to cut
off a considerable pari 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 hones serve to thus limit the field.
To obtain the exact outline and extent of the visual field in any given
h i- only necessary to keep the eye fixed and then to move a

PROPERTIES OF THE RETINA.

333

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 142. The shape
of the visual fields in the normal eye is represented in Fig. 143.
The determination of the visual fields is of especial importance in
cases of brain lesions involving the visual area in the occipital lobe.

Fig. 142. — 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.

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

334

THE SPECIAL SENSES.

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

Fig. 14.'?. — Perimeter chart to show the field of vision for a right eye when kept in a fixed

position.

retinal image from the fovea. In using our eyes, therefore, we keep
them continually in motion so as to bring each object, as we pay
especial attention to it, in the field of central vision. The line
from the fovea to the point looked at is designated as the line of
sight. The area of the fovea is quite small. The measurements
given by different observers vary somewhat, especially as in some
the measurements are estimated for the bottom of the de-
ion, the fundus, and in others for the diameter from edge to

edge. The average diameter is usually given as lying between ().)!
and o.l mm. bines drawn from the ends of this diameter to the

nodal point of the eye subtend an angle of I 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, i are comprised in the

central field of vision, and their retina] images fall upon the fovea,.

Unilateral lesions of one occipital lobe cause half-blindness (herni-
Opia) in the retinae OI] thesame side, that, is, lesions in the right

PROPERTIES OF THE RETINA. 335

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. 204) ; 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
its special functions in vision the fovea centralis possesses a peculiar
structure. It forms a shallow depression in the center of the retina
described by some authors as elliptical, by others as circular in out-
line. In the center of the fovea lies a smaller, very shallow depres-
sion spoken of as the foveola. The diameter of the fovea, as stated
above, is estimated differently by different authors. While meas-
urements on preserved specimens give the diameter as 0.2 to
0.4 mm., ophthalmoscopic examination seems to indicate that in
the fresh state it may be larger. According to Fritsch,* the fundus,
reckoned from the point at which the depression begins, has a diam-
eter of 0.5 to 0.75 mm. Within the fovea cones only are present,
and these cones are longer and more slender (diameter, 0.002 mm.)
than in the rest of the retina. Moreover, the thickness of the retina
is much reduced in the fovea, whence arises the depression. At
this point the cones are practically exposed directly to the light,
whereas in other parts the light must penetrate the other layers
before reaching the rods and cones. Lying around the fovea is an
area about 6 mm. in diameter, of a yellowish color, and hence
known as the macula lutea. According to recent observers f
the yellow color of the macula is due to post-mortem changes.
In a normal retina this area does not show a yellow color and there
is, therefore, no reason why it should be given a special designation.
Visual Acuity. — The distinctness of vision varies greatly in
different parts of the retina. It is usually measured by bringing
two fine lines closer and closer together until the eye is unable
to see them as two distinct objects. Measured in this way it is
usually stated that when the distance between the lines subtends an
angle of 1 minute (60 seconds) at the eye the limit of visibility is
reached. This angle on the retina comprises an area of about 0.004
mm. in diameter, sufficient to cover two cones in the fovea. A
simpler method to ascertain the size of a just perceptible image
on the retina is to use a black spot upon a white background. At a
sufficient distance this object will be invisible, but if brought closer
to the eye it will be just seen at a certain distance. The diameter
of the spot being known, and its distance from the eye, the size of the
retinal image may be calculated. Using this method, Guillery J
estimated the size of the just perceptible retinal image, or, as it
has been appropriately called, the physiological point, at 0.0035 mm.

* Fritsch, "Pitzungsberichte d. konig. Akad. d. Wiss.,'' Berlin. 1900.
fSiven, "Skandinaviscb.es Archiv f. Physiol.." 1905, 17, 306.
t Guillery, "Zeitschrift f. Psychologie u. Physiol, d. Sinnesorgane, " 12,
243, 1896.

136

THE SPECIAL SENSES.

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-
logical point is smaller — less than half the size given above. We
may believe, therefore, that under the most favorable conditions

It

ir

A'

a

\

\

\

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.—

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s

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60° J0° W JO £0" iQ° 6° 0° <5° iO' Z0°

JO

40° tffO' 60'

lit'. 111. — Curve to show the relative acuity of vision in the mitral and peripheral
field and in the light-adapted and 'In- dark-adapted eye. (Koeater.) Tho full line repre-
i.- relative acutene of vision in the eye expo e<l in usual illumination. From the
center of the fovea, o°, the acuity of vision falls rapidly at first and then more slowly as one
(I into the peripheral field. The dolled line represents the acuity of vision in
dim lights. The fovea, it will be noticed, i le en itive than the parts of the retina at an
angular distance of 10° or even 60°.

we '•;tii perceive an object whose image on the fovea is less than the
diameter (0.002 mm. I of a single cone. The acuity of vision does
not vary greatly throughout the fovea; any object whose retinal
image falls well wit hin I he fovea can he seen quite disl inctly in nil

Of it - parts when I he eye is fixed \'<>v I lie center of t he object. This

is the case, for instance, with the moon. Nevertheless, in looking

ich an object as the moon the eye, to make out details, will

fixate one point after another, showing thai lor most distinct

PROPERTIES OF THE RETINA. 337

vision we use probably only the center of the fovea. As we pass
out from the fovea into the peripheral field of vision the acuity of
vision diminishes 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
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. 144. 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 -nrV

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
22

338 THE SPECIAL SENSES.

perceptible difference in the conscious reaction. Proceeding upon
this method, it is found in the case of the visual sensations and the
optic nerve, a^ 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
acting. If, for instance, the retina is being stimulated by a light of
1 candle power an increase of illumination to 1.1 candle power may
make a perceptible difference in sensation. But if the retina is
being illuminated by a light of 10 candle power an increase to 10.1
candle power would probably make no perceptible difference. For
a certain range of stimulation, in fact, it has been stated that the
increase in stimulus must be a constant fractional part of the stimu-
lus already acting. That is, in the hypothetical case given, if, with
1 candle power, an increase to 1.1 candle power makes a just per-
ceptible difference in consciousness, then with 10 candle power an
increase of -^ 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, tins 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. When one passes from daylight into a dark room vision
at first is very imperfect, but after some minutes it rapidly im-
proves, "as the eye becomes accustomed to the dark." The
change is known as an adaptation, and in this respect the retina
differs from the sensitive photographic plate. Comparison of the
threshold stimulus for different parts of the retina, in an eye
exposed alternately to darkness and to light, lias shown that.
in the dark the sensitiveness in the peripheral field increases
greatly during an hour or BO, while that of the foveal held is appar-
ently unchanged. With such a dark-adapted eye. therefore,
there will he a certain dim lighl which will he seen by the per-
ipheral parts of the retina, hut perhaps will cause no reaction

upon the fovea. For such a degree of light, therefore, the fovea

would he blind. This general fact has, indeed, long been known.

Anyone may notice in late twilight, when the stars are beginning
to appear, thai a very faint star may disappear when looked at,— that

18, When it - image U brought upon t he fovea ;tO see it one must direct,

little to 1 be side, so as to bring its image into the periph-

PROPERTIES OF THE RETINA. 339

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. 144 shows that in the dark-adapted eye
the acuity of vision in the peripheral field is greater than in the
fovea. In accordance with these facts von Kries* has suggested that
the rods, the peripheral field of the retina, are especially adapted
for vision in dim lights, 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

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

340

THE SPECIAL SENSES.

of the different spectral colors is found to vary with the amount of
illumination, as shown in the curves given in Fig. 145. With a
brilliant spectrum the maximum brightness is in the yellow, but
with a feeble illumination it shifts to the green. This fact accords
with what is known as the " Purkinje phenomenon," — namely, the
changing luminosity and color value of colors in dim lights. As the
light becomes more feeble the colore toward the red end of the
spectrum lose their quality, the blue colors being perceived last of
all, just as in late twilight it may be noticed that the sky remains
distinctly blue after the colors of the landscape become indistin-
guishable. It should be added that the " Purkinje phenomenon "
is true only for the parts of the retina lying outside the fovea,
that is, for the peripheral field. As the light grows dimmer the
perception of blue is lost first in the fovea, so that with a certain

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di tnbunpp of relative bnghtnei i with changes in degree <>f illumination. With the
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feebleness of illumination the central field becomes blue-blind.
With a very feeble illumination the dark-adapted eye becomes
practically totally color blind.

Qualities of Visual Sensations. -The different qualities of our
color sensations may be arranged in two scries: an achromatic

PROPERTIES OF THE RETINA. 341

series, consisting of white and black and the intermediate grays,
and a chromatic series, comprising the various spectral colors,
together with the purples made by combination of the two ends
of 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 Series. — Our standard white sensation is that
caused by sunlight. Objects reflecting to our eye all the visible
rays of the sunlight give us a white sensation. This sensation,
therefore, is due primarily to the combined action of all the visible
rays of the spectrum, each of which, taken separately, would give
us a color sensation. White or gray may be produced also by the
combined action of certain pairs of colors, — complementary colors, —
as is described below. Black, on the contrary, is the sensation
caused by withdrawal of light. It must be emphasized that in
order to see black a retina must be present. It is probable that
a person with both eyes enucleated has no sensation of darkness.
That black is a sensation referable to a condition of the retina is
made probable also by the interesting observations recorded by
Gotch,* — namely, that when an eye that has been exposed to light
is suddenly cut off from the light there is an electrical change in the
retina, a dark response, similar to that caused by throwing light on
a retina previously kept in the dark. Blackness, therefore, is a
sensation produced by withdrawing light from the retina, and a
black object is one that reflects no light to the eye. Black may be
combined with white to produce the series of grays, and when com-
bined with the spectral colors it gives a series of modified color tones,
thus the olives of different shades may be considered as combina-
tions of green and black in varying proportions.

The chromatic series consists of those qualities to which we give
the name of colors, and, as stated above, they comprse the spectral
colors, and the extraspectral color, purple, together with the light-
weak and light-strong hues obtained by combining the colors with
white or black. In the spectrum many different colors may be
detected, — some observers record as many as one hundred and
sixty, — but in general we give specific names only to those that
stand sufficiently far apart to represent quite distinct sensations, —
namely, the red, orange, yellow, green, blue, and violet. When
light is taken from a definite limited portion of the spectrum we
have a monochromatic light that gives us a distinct color sensation
varying with the wave length of the portion chosen.

Color Saturation and Color Fusion. — The term saturation as
applied to colors is meant to define their freedom from accompany-
ing white sensation. A perfectly saturated color would be one
entirely free from mixture with white. On the objective side it is
* Gotch, " Journal of Physiology," 29, 388, 1903.

342 THE SPECIAL SENSES.

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 sensat ion 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 Fusion. — By color fusion we mean the combination of two
or more color processes in the retina, this end being obtained by
superposing upon the same portion of the retina the rays giving
rise to these color processes. It must be borne in mind that color
fusion upon the retina is quite a different thing -from color mixture
as practised by the artist. A blue pigment, such as Prussian blue,
for instance, owes its blue color to the fact that when sunlight falls
upon it the red-yellow rays are absorbed and only the blue, with
some of the green, rays are reflected to the eye. So a yellow pig-
ment, chrome yellow, absorbs the blue, violet, and red rays and
reflects to the eye only the yellow with some of the green rays. A
mixture of the two upon the palette will absorb all the rays except
the green and will therefore appear green to the eye. If, however,
by means of a suitable device, we throw simultaneously upon the
retina a blue and a yellow light, the result of the retinal fusion is
a sensation of white. Many different methods have been employed
to throw colors simultaneously upon the retina, the most perfect
being a system of lenses or mirrors by which different portions of
a spectrum can be superposed. The usual device employed in
laboratory experiments is that of rotation of discs of colored paper.
Each disc has a slit in it from center to periphery so that two discs
can be fitted together to expose more or less of each color. If a
combination of this kind is attached to a small electrical motor it
can be rotated so rapidly that the impressions of the two colors
upon I he ict ina follow at such a short, interval of time as to be prac-
tically simultaneous.

The Fundamental Colors. -By the methods of color fusion
il ran be shown that three colors may he selected from the spec-
trum whose combinations in different proportions will give white,
or any of the intermediate color shades, or purple Considered

purely objectively, a Bel of three such colors may be designated
as the fundamental color and red, yellow, and blue, or red,

green, and violet have been the three colors selected. On the

LOlogical 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-

PROPERTIES OF THE RETINA. 343

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-
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

344 THE SPECIAL SENSES.

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 inten-
sity of illumination may give positive after-images, especialy
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. 146). 'White becomes black,
red, a bluish green, and vice versa. Negative after-images
are produced very easily by fixing the eyes steadily upon a
given object for an interval of twenty seconds or more and
then closing them. In the case of colored objects the after-
image is shown better, perhaps, by turning the eyes upon a
white surface after the period of fixation is over. After-images
produced in this way often appear and disappear a number of
times before ceasing entirely, and, although the color at first is the
complementary' of that of the object looked at, it may change before
it- 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 showr 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 diown in Fig. 146 one moves the white paper used
to catch t he 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 :iLr.-iin-i :i yellow background. The influences of contrasl

may tie shown in a greal variety of ways.* for instance, if a disc;

like thai in the illustration, Fig. I ix.i, b rotated rapidly, it should

, the darke I ;it the middle; but each circle should

he uniform ;i ■ it i- made by the fusion of a definite amount of white

and black. ' >B t tie conl rary, t he appearance obtained is that repre

■ Rood, " Modem Chromatics," " International Scientific Series."

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PROPERTIES OF THE RETINA.

345

sented in Fig. 1485. 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
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. 147. The gray square on the green background suffers no
apparent change from contrast, but if the figure is covered by a
sheet of white tissue paper the gray square at once takes on a red-
dish hue. It is evident that in all artistic and ornamental employ-
ment of colors this influence must be considered, and empirical
rules are established which indicate for the normal eye the bene-

Fig. 148A — Black and white disc for ex-
periment on contrast. — {Rood.)

Fig. 148B. — Showing the result when the
disc A. is set into rapid rotation. — (Rood.)

ficial or the killing effect of different colors when brought into
juxtaposition.

Color Blindness. — The fact that some eyes do not possess
normal color vision does not seem to have attracted the attention
of scientific observers until it was studied with some care by Dalton,
the distinguished English chemist, at the end of the eighteenth
century. Dalton himself suffered from color blindness, and the
particular variety exhibited by him was for some time described
as Daltonism, but is now usually designated as red blindness. The
subject was given practical importance by later observers, espe-
cially by the Swedish physiologist Holmgren,* who emphasized its
relations to possible accidents by rail or at sea in connection with

* Holmgren, "Color Blindness in its Relations to Accidents by Rail and
Sea," " Smithsonian Institution Reports," Washington, 1878. See also Jeffries,
"Color Blindness, its Dangers and its Detection," Boston.

3-46 THE SPECIAL SENSES.

colored signals. It is now the practice in all civilized countries to
require tests for color blindness in the case of those who in railways
or upon vessels may be responsible for the interpretation of signals.
The numerous statistics that have been gathered show that the
defect is fairly prevalent, especially among men. It is said that
on the average from 2 to 4 per cent, are color blind among males,
while among women the proportion is much smaller, — 0.01 to 1 per
cent. Among the poorly educated classes the defect is said to be
more common than among educated persons. Color blindness
may exist in different degrees of completeness, from a total loss to
a simple imperfection or feebleness of the color sense, and it is
usually congenital. Those who are completely color blind as re-
gards some or all of the fundamental colors fall into two groups:
the dichromatic, whose color vision may be represented by two
fundamental colors and their combinations with white or black,
and the monochromatic or totally color blind, who see only the
white-gray-black series.

Dichromatic Vision. — The color-blind who belong to this class
fall into two or three groups, which have been designated, under
the influence of the Young-He lmholtz theory of color vision, the
red-blind, the green-blind, and the violet-blind. As the terms
red-blind and green-blind imply a more specific condition of
vision than is found to be the case on careful examination, von
Kries has suggested as a substitute the names protanopia and
deuteranopia, as indicating a defect in a first or second constit-
uent necessary for color vision. According to the same nomen-
clature so-called violet-blindness would be designated as tritanopia.
The most common by far of these groups is that of so-called red-
blindness (protanopia); it constitutes the usual form of color
blindness. As a matter of fact, persons so affected are in reality
red-green blind. In what may be called the most typical cases
they distinguish in the spectrum only yellows and blues. The
red, orange, yellow, and green appear as yellow of different shades,
the green-blue as gray, and the blue-violet and purple as blue.
The red end of the spectrum is distinctly shortened, especially
if the illumination is poor, and the maximum luminosity, instead
of being in the yellow, as in normal eyes, is in the green. When
the spectrum is examined by such persons a neutral gray band is

geen a1 the junction of the blue and green. In some cases, how-
ever, this neutral band is not seen, the yellow passing with but
little change into the blue. As a matter of fact, in red-blindness
the most Characteristic defect is a failure to see or to appreciate
the green. This color is confused with the grays arid with dull
Shades Of red Wnen SUCh persons are examined for their negative

after-images for different colors, it will be noted thai they de-

PROPERTIES OF THE RETINA. 347

scribe some of their after-images as red, the after-image of indigo-
blue, for example, but that they describe none as green. The
after-image of purple, for instance, which to the normal eye is
bright green, is described by them as gray blue or pale blue.
From the descriptions given it is probable that the color vision
of the so-called red-blind is not by any means the same in all cases,
but exhibits many individual differences. The green-blind are
also, according to recent descriptions, red-green blind; they also
confuse reds and greens and in the spectrum are conscious of only
two color qualities, namely, yellow and blue. They differ from
the red-blind in that the red end of the spectrum is not shortened,
and the maximum luminosity, as with the normal eye, is placed
in the yellow. In the matching and combination of colors they
show distinct differences from the red-blind, so that though re-
sembling the latter in general features, they differ obviously in
some details. Violet blindness (tritanopia) seems to be so rare
as a congenital and permanent condition that no very exact study
of it has been made. In cases of acquired tritanopia resulting
from pathological changes it is reported that the violet end of
the spectrum is colorless (neutral) and that a neutral band appears
also in the yellow-green region of the spectrum.* By the ingestion
of santonin it is said that a condition of this kind may be produced
temporarily. The violet end of the spectrum is shortened and
white objects take on a yellowish hue. The conditions produced
by santonin are evidently more complex than can be explained
by simply assuming that the violet color sense is lost. Recent
observers f state that the drug produces a condition of yellow
vision, outside the fovea, in the daylight, and a condition of
violet vision with yellow-blindness, but no red- or green-blindness,
in dim lights.

Tests for Color Blindness. — Although the vision of the red and
the green blind is deficient as regards green and red colors, it will
be found in many cases that they recognize these colors and name
them correctly, having adopted the usual nomenclature and adapted
it to their own standards. In order to detect the deficiency they
must be examined by some test which will compel them to match
certain colors. Under these circumstances it will be found that
along with correct matches they will make others which to the nor-
mal eye are entirely erroneous. A great number of methods have
been proposed and used to detect color blindness. The simplest
perhaps is that of Holmgren. J A number of skeins of wool are used

* Collins and Nagel, " Zeitschrift f. Psychol, u. Physiol, d. Sinnesorgane,"
1906, xli., 74.

fSiven and Wendt, " Skandinavisches Archiv f. Physiologie," 14, 196,
1903, and 1905, 17, 306.

% For details see the works of Holmgren and of Jeffries, already quoted.

348 THE SPECIAL SENSES.

and three test colors are chosen, — namely, (1) a pale pure green
skein, which must not incline toward yellow green; (II) a medium
purple (magenta) skein; and (III) a vivid red skein. The person
under investigation is given skein I and is asked to select from the
pile of assorted colored skeins those that have a similar color value.
He is not to make an exact match, but to select those that appear
to have the same color. Those who are red or green blind will see
the test skein as a gray with some yellow or blue shade and will
select, therefore, not only the green skeins, but the grays or grayish
yellow and blue skeins. To ascertain whether the individual is red
or green blind tests II and III may then be employed.

With test II, medium purple, the red blind will select, in addition
to other purples, only blues or violets; the green blind will select as
"confusion colors" only greens and grays.

With test III, red, the red blind will select as confusion colors
greens, grays, or browns less luminous than the test color, while the
green blind will select greens, grays, or browns of a greater brightness
than the test.

Monochromatic Vision. — A number of cases of total color
blindness have been carefully examined.* It would seem that in
such individuals there is an entire loss of color sense,- — they possess
only achromatic vision. The external world appears to them only
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 (ield is frequently blind or amblyopic, it has been assumeu
that this condition is one of loss of function in the cones.

Distribution of the Color Sense in the Retina. — What has
been said above in regard to color blindness refers especially to the
central field of vision. When we examine the peripheral field in
the normal eye it is found that on the extreme periphery (lie retina
i- totally color blind, perceiving only light and darkness, — that is,
the h.nli - of gray. As we pass in toward the center the color
Bense develops gradually, the blue colors being perceived first and
the greens last,- that is, nearest to the center, — so that in a cer-
tain /one the normal eye is red-green blind. The distribution of
the color sen <■ may be studied conveniently by means of the pe-
limeter (see \>. 332). It will l>e found to vary with each individual,
so much so thai it is possible that a test of this character might he
used for the identification of individuals. Exceptionally if is found
that the entire retina possesses ;i nearly normal color sense. Usu-
•"Gninert, "Archiv flir Ophthalmologic," 56, 132, L903.

PROPERTIES OF THE RETINA.

349

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. 149. 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

061 081 O^-1

Fig. 149. — Perimeter chart indicating the average fields of vision for blir;, red, and
green compared with white (gray). Right eye: The outlines of the color fields are repre-
sented as smooth since the chart is an average from many determinations. As a matter of
fact, in each individual the outline is highly irregular. Normally green (bright green) is the
smallest field, green objects outside the limit appearing yellow and farther out colorless
(gray).

the different fields usually show many irregularities, and in some
cases it will be found that bright green is perceived over a larger area
than the red. The fields are not identical in the two eyes, and in
each eye it is, as a rule, more extensive upon the nasal than
upon the temporal side of the retina. In the red-green blind the
peripheral fields of color vision, judged by the individual's own
standards, may be markedly constricted as compared with the nor-
mal retina (see Fig. 150).

Functions of the Rods and Cones. — Many facts unite in mak-
ing it probable that the rods and cones are different in function.

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

350 THE SPECIAL SENSES.

They differ in structure ami especially in their connections. As is
shown in the diagram given in Fig. 151, the cones terminate in the
external nuclear layer in arborizations which connect with the
bipolar ganglion cells, and in the fovea at least this connection is such
that each cone connects with a single nerve cell and eventually per-
haps with a single optic nerve fiber. The rods, on the contrary,
end in a single knob-like swelling, and a number of them make con-
nections with the same nerve cell. Histologically, therefore, the

06i 081 oLX

09V

Fig. 150. — Perimeter chart showing the highly restricted color fields in the left eyo
of a typical ca e •■! o-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
snort distance outside the fovea. It is interesting that the ability to distinguish blue was
in this case limited as compared with a normal eye.

conduction paths lor the cones seem to be more direct than in
the case of the rods. These latter elements, moreover, possessthe

visual purple, which is lacking in the cones. Lastly, in the eye of

i lie 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

mot distinctly night-seeing animals, such as the mole and the owl,

vision eemi to be effected solely by the rods. These facts find
their Bimplesl explanation perhaps in the view advocated by J'ari-
naud, I ranklin, von Kries,* and others, according to which the

perception of color IS a function of the cones alone, while the rods
+ Von Kries, "Zeil chrifl i. Psychologic u, Physiol, d. Sinnesorgane," it,

SI, IS'.).',.

PROPERTIES OF THE RETINA.

351

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

B

Fig. 151. — 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 amacrmal cells
(without axons); VIII, inner plexiform layer; IX, ganglion cell layer; X, nerve fiber
layer; 6, fiber of Mtiller.

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, probabby from lack of formation of
visual purple.

352 THE SPECIAL SENSES.

Theories of Color Vision. — A number of theories have been
proposed to explain the facts of color vision. None of them has
been entirely successful in the sense that the explanations it affords
have been submitted to satisfactory experimental verification. The
immediate stimuli that give rise to the visual impulses are assumed
to be of a chemical nature, and it seems probable that in this
case as in that of many other problems of physiology, we must
await the development of a more complete knowledge of the
chemical processes involved. The theories proposed at present,
while all tested by experimental inquiries, are in a large measure
hypotheses constructed to fit more or less completely the facts that
are known. Three of these theories may be described briefly as
examples of the modes of reasoning employed:

I. The Yomig- Helmholtz Theory. — This theory, proposed essen-
tially by Thomas Young (1807) and afterward modified and ex-
panded by Helmholtz* rests upon the assumption that there are
three fundamental color sensations, — red, green, and violet — and
corresponding with these there are three photochemical substances
in the retina. By the decomposition of each of these substances cor-
responding nerve fibers are stimulated and impulses are conducted
to a special system of nerve cells in the visual center of the cerebrum.
The theory, therefore, assumes special nerve fibers and nerve centers
corresponding respectively to the red, green, and violet photo-
chemical substances, and the peculiar quality of the resulting sensa-
tions are referred, in the original theory, to the different reactions
in consciousness in the three corresponding centers in the brain.
When these three substances are equally excited a sensation of
white results, of greater or less intensity according to the extent of
the excitation. White, therefore, on this theory, is a compound
sensation produced by the combination or fusion in consciousness
of the three equal fundamental color sensations. The sensation of
black, on the other hand, results from the absence of stimulation,
from the condition of rest in the retina and in the corresponding
aerve fibers and nerve centers. All other color sensations — yellow,
for instance — are compound sensations produced by the combined
stimulation of the three photochemical substances in different propor-
tions. It is assumed, furthermore, that each of the photochemical
substances is acted upon more or less by all of the visible rays of the
spectrum, but that the rays of long wave lengths at the red end
of the spectrum affect chiefly the red substance, those corresponding
to the green of the spectrum chiefly the green substance, and the

hortesl wavelength chiefly the violet substance. These rela-
tionships are expressed in the diagram given in Fig. 152. The figure
also indicates that it is impossible to stimulate any one of these sub-

* Helmholtz, "Handbuch der pliysiolotfischen Optik," second edition,
JS9G, [,344.

PROPERTIES OF THE RETINA.

353

stances entirely alone, — that is, we cannot obtain a perfectly satu-
rated color sensation. Even the extreme red or the extreme violet
rays act more or less on all of the substances, and the resulting red
or violet sensation, is, therefore, mixed to some extent with white, —
that is, is not entirely saturated. The theory, as stated by Helm-
holtz, held strictly to the doctrine of specific nerve energy, in assuming
that each photochemical substance serves simply as a means for the
excitation of a nerve fiber, and that the quality of the sensation
aroused depends on the ending of this fiber in the brain. The phe-
nomenon of negative after-images finds a simple explanation in terms
of this theory. If we look fixedly at a green object, for example,
the corresponding photochemical substance is chiefly acted upon, and
if subsequently the same part of the retina is exposed to white light,
the red and violet substances, having been previously less acted
upon, now respond in greater proportions to the white light, and

Fig. 152. — Schema to illustrate the Young-Helmholtz theory of color vision. — (Helm-
holtz.) The spectral colors are arranged in their natural order, — red to violet. The curves
represent the intensity of stimulation of the three color substances: 1, The red perceiving
substance; 2, the green perceiving; 3, the. violet perceiving. Verticals drawn at any
point of the spectrum indicate the relative amount of stimulation of the three substances
for that wave length of the spectrum.

the after-image takes a red- violet — that is, purple — color. Many
objections have been raised to the Young-Helmholtz theory. It
has been urged, for instance, that we are not conscious that white
or yellow sensations are blends or compounded color sensations;
we perceive in them none of the supposed component elements as
we do in such undoubted mixtures as the blue-greens or the purples.
The theory explains poorly or not at all the fact that on the periphery
of the retina we are color blind and yet can perceive white or gray,
and it breaks down also in the face of the facts of partial and com-
plete color blindness. The explanation given for black is also
unsatisfactory in that it assumes an active state of consciousness
associated with a condition of rest in the visual mechanism.

II. Hering's Theory of Color Vision. — This theory also assumes
the existence in the retina of three photochemical substances, but
23

354

THE SPECIAL SENSES.

of such a nature as to give us six different qualities of sensation.
There is a white-black substance which when acted upon by the
visible rays of light undergoes disassimilation and sets up nerve
impulses that arouse in the brain the sensation of white. On the
other hand, when not acted upon by light this same substance under-
goes assdmilatory processes that in turn set up nerve impulses which
in the brain give us a sensation of black. There are in the retina also
a red-green and a yellow-blue substance. The former when acted
upon by the longer rays undergoes disassimilation and gives a
sensation of red, while the shorter waves cause assimilation and
produce a sensation of green. A similar assumption is made for
the yellow-blue substance. The essence of the theory may be stated,
therefore, in tabular form, as follows *:

Photochemical Substance.
Red-green

Retin'al Process.
Disassimilation =

1 Assimilation

Tr „ , , f Disassimilation

Yellow-blue \ Assimilation

White-black.

f Disassimilation
\ Assimilation

Sensation.
red
green
yellow
blue
white
black

It will be observed that the theory gives an independent ob-
jective cause for the sensations of white, black, and yellow, and in

i L63. Schema to illu trate the Hcrinc theory of color vision. — (Foster.) The
curves indicate the relative inten itie "i timulation ol the three color i ubstanoes by dif«
ferenl part "I the pectrum. Ordinates above the axis, X—X, indicate oatabolic chances
imilation), those below anabolic changes (assimilation). Curve a represents the
conditioni for ih<- black-white substance. Ii is stimulated by all the rays <>l the visible
spectrum with maximum inten ity in the yellow. Curve c representi the red-green sub-
stance, the longer wave lengths causing disassimilation (red), the horter ones assimilation
(greei mditions for the yellow-blue substance.

this respect satisfies the objections made on this score to the Young-
Helmholtz theory. It fits better, also, the facts of partial and total
color blindness. In the latter condition one may assume, in terms of
* For discussion of color theories see Calkins, "Archiv f. Physiologic,"
L902, uppl. volume, p, 2 1 1.

PROPERTIES OF THE RETINA.

355

v.„.y

w

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 remains over only
the disassimilatory effect on
the white substance which is
exerted by all the visible
rays. The effect of the vari-
ous visible rays of the spec-
trum on the three photo-
chemical substances is illus-
trated by the chart given in
Fig. 153. Ordinates above
the abscissa representing dis-
assimilatory effects; those
below, assimilatory.

III. The Franklin Theory
of Color Vision (Molecular
Dissociation Theory) . — This
theory, proposed by Mrs. C.
L. Franklin,* takes into ac-
count the fact of a gradual
evolution of the color sense
of the retina from a primitive
condition of colorless vision
such as still exists in the
periphery of the retina and
in the eyes of the totally
color blind. It assumes that
the colorless sensations —
white, gray, black — are occa-
sioned by the reactions of a
photochemical material
which for convenience may
be designated as the gray

substance. This substance in the normal eye exists in both rods
and cones; in the latter, however, in a differentiated condition
capable of giving color sensations. When the molecules of this
substance are completely dissociated by the action of light, gray

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

Ji

Fig. 154. — 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.

356 THE SPECIAL SENSES.

sensations result, and as this is the only reaction possible in the
rods these elements can furnish us only sensations of this quality.
The molecules of gray substance in the cones, on the other
hand, have undergone a development such that certain portions
only of the molecule may become dissociated by the action of light
of certain periods of vibration. This development may be sup-
posed to have taken place in two stages: first, the i'oimation of
two groupings within the molecule, one of which is dissociated by
the slower waves and gives a sensation of yellow, and one of which
is dissociated by the more rapid waves and gives the sensation of
blue. This stage remains still on portions of the periphery of the
retina, and is the condition present in the fovea also in the eyes
of the red-green blind. The second stage consists in the division
of the yellow component into two additional groupings in one
of which the atomic movements are of such a period as to be
affected by the longest visible waves, the red of the spectrum,
while the other is dissociated by rays corresponding to the green
of the spectrum and gives rise to the sensation of green. If
the red and green groupings are dissociated together the resulting
effect is the same as follows from the dissociation of the entire yellow
component, while the complete dissociation of the red, green, and
blue groupings gives the stimulus obtained originally from the disso-
ciation of the whole molecule, and causes gray sensations. The idea
of this subdivision or differentiation in structure of the original gray
substance is indicated diagrammatically in Fig. 154. The theory
accounts admirably for many phenomena in vision, and is perhaps
esp cially adapted to explain the facts of color blindness and the
variations in quality of our visual sensations in the peripheral areas
of the retina. An extension and modification of this theory
has been published by Schenck.* He assumes that each of the
three-color perceiving substances is composed of two parts.
One part which acts as a receiver for the stimulus, a sort of an
optical resonator, in fact, and a second part which is set into
activity by the receiver and gives rise to the corresponding
color sensation. The theory is very elastic in its adaptability
to the various kinds of color blindness.

The two latter theories seem to imply thai a number of different kinds
of impulses may be transmitted along the optic fibers. Bering's theory re-
quiree apparently the possibility <>!' six qualitatively different impulses, —
namely, while, black, red, green, yellow, ana blue, while the Franklin theory
ee impulse com ponding i<> white (gray), red, green, yellow, and blue.
Black i not specifically accounted for except ae a part of the gray series. At
i in physiology there is n<> 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 a tunes thai nerve impulses are, as regards quality, always

♦ Schenck, "Archiv f. d. gesammte Physiologic," 118, L29, L907.

PROPERTIES OF THE RETIXA. 357

the same, and differ from one another only in intensity, the qualitative differ-
ences that exist among sensations being referred to a difference in reaction
in the end-organ in the brain.

Entoptic Phenomena. — Under the term entoptic phenomena
is included a number of visual sensations due to the shadows of
various objects within the eyeball itself. Ordinarily these shadows
are imperceptible, owing to the diffuse illumination of the interior
of the eye through the relatively wide opening of the pupil. By
means of various devices the illumination of the eye may be so
controlled as to make these shadows more distinct and thus bring
the retinal images into consciousness. Some of these entopic ap-
pearances are described briefly, but for a detailed description the
reader is referred to the classical work of Helmholtz.*

The Blood-corpuscles. — The entoptic images that are most easily
recognized perhaps are those of the moving corpuscles in the capil-
laries of the retina. If one looks off into the blue sky he will have
no difficulty in recognizing a number of minute clear and dark specks
that move in front of the eye in definite paths. The character of
the movement leaves no doubt that these sensations are due to the
shadows of the blood-corpuscles. In fact, the shadows often show
a rhythmic acceleration in velocity synchronous with the heart-
beats, a pulse movement. By projecting the moving images upon
a screen at a known distance from the eye the velocity of the capil-
lary circulation has been estimated in man.

The Retinal Blood-vessels. — The blood-vessels of the retina lie
in front of the rods and cones and must necessarily throw their
shadows upon these sensitive end-organs. The shadows may be
made more distinct and a visual picture of the vessels obtained by
a number of methods. For instance, if a card with a pin hole
through it is moved slowly in front of the eye the images of the
blood-vessels stand out in the field of vision with more or less
distinctness. The card should be given a circular movement. If it
is kept in one position the images quickly disappear, since the
retina apparently fatigues very quickly for such faint impressions.
A more impressive picture may be obtained by the method of
Purkinje. In a dark room one holds a candle toward the side of the
head in such a position as to give the sensation of a glare in the
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 magni-
fied in proportion to the distance of projection; the picture makes
the impression of a thicket of interlacing branches. In this ex-
periment the light from the candle strikes the nasal side of the

♦Helmholtz, "Handbuch der physiologischen Optik, " second edition,
I, 184.

358

THE SPECIAL SENSES.

retina at an oblique angle and is reflected toward the other side
of the globe. The blood-vessels are in tins way illuminated from
an unusual direction and their shadows are thrown upon a por-
tion of the rethui not usually affected and for that reason perhaps
more sensitive to the impression.

Imperfections in the V itreous Humor and the Lens. — Small frag-
ments of the cells from which the vitreous humor was constructed
in the embryo and simi-
lar relatively opaque ob- .a
jects in the lens may A
throw shadows on the |J
retinal bottom. These
shadows take different
forms, but usually are de-
scribed as small spheres
or beads, single or in
groups, that move with
the eyes and are desig-
nated, therefore, as the
musca* 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. 155. 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.

Fig. 155. — Helmholtz's method of showing en-
toptic phenomena due to imperfections in the lena
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 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

359

360 BINOCULAR VISION.

eyes, — that is, that position taken by the eyes when we look straight
before us toward the horizon, — a position, therefore, in which the
plane of the horizontal axes is parallel to the ground; all other
positions of the eyes are spoken of as secondary.

With regard to the movements of the eyes about its axes of
rotation the following general statements are made: Starting from
the primary position, rotations of the eyes about the vertical axis —
that is. movements directly to right or left — may be made by the
contraction of the internal or the external rectus as the case may be.
Rotations around the transverse axis — that is, movements directly
up or down — require in each case the co-operation of two muscles.
In movements upward the superior rectus, acting alone, would in

Fig. l.">'i. " Diagram showing for the left eye the paths of the line of eight caused by the
action of i in- different eye-muscles (Hering). The horizontal line indicates movements out or
in to various degrees as caused by the contraction of the internal or external rectus. The

Curved lines -how the amount of torsion Kiven the eyeball by tilt' superior and inferior
Uperior and inferior oblique when contracting separately. The short

line at the end of the paths indicates the position of the horizontal meridian at
the end of the movement." R. <■., the external rectus; R, i., the internal rectus; /,'. S.,
■ nor rectus; /.'. inf., the interior rectus; O. i., the inferior oblique; U. S., the superior
oblique.

rotating the eyeball upward also ^ive it a slight torsion so as to
turn the upper pail of the vertical meridian inward. To obtain a
movement directly upward (rotation around the transverse axis)
tip- superior rectus and inferior oblique must act together. For
a similar reason rotation directly downward requires the com-
bined art ion of tip; inferior rectus and superior oblique. These
facts are expressed dearly in Hering' s diagram, reproduced in
Fig. 156, which indicates the paths traversed by the line of sight
iball is moved by the different muscles acting sepa-
rated. Rotation of the eyeballs around oblique axes require
the co-operation of three of the muscles : movements upward

and outward the Superior rectus, inferior oblique, and external

rectus; movements upward and inward— superior rectus, inferior

BINOCULAR VISION. 361

oblique, and internal rectus; movements downward and outward —
inferior rectus, superior oblique, and external rectus; movements
downward and inward — inferior rectus, superior oblique, and
internal rectus. Most of the movements of the eyes are of the
latter kind, — namely, rotations around an oblique axis, — and
the position of the axis for each definite movement of this character
may be determined by Listing's law, which may be stated as
follows : When the eye passes from a primary to a secondary
position it may be considered as having rotated around an axis
perpendicular to the lines of sight in the two positions. It will
be noted readily from observations upon the movements of one's
own eyes that they ordinarily make only such movements as will
keep the lines of sight of the two eyes parallel or will converge
them upon a common point. In movements of convergence the
internal recti of the two eyes are associated, while in symmetrical
lateral movements the internal rectus of one eye acts with the
external rectus of the other. Under normal conditions it is
impossible for us to diverge the visual axes, — that is, to associate
the action of the external recti. A movement of this kind would
produce useless double vision (diplopia), and it is, therefore, a kind
of movement which all of our experience has trained us to avoid.
The Co-ordination of the Eye Muscles — Muscular Insuf-
ficiency— Strabismus. — In order that the eyeballs may move with
the minute accuracy necessary in binocular vision, a beautifully
balanced or co-ordinated action of the opposing muscles is neces-
sary. The object of these movements is to bring the point looked
at in the fovea of each eye and thus prevent double vision, diplopia
(see following paragraphs). This object is attained when the eye-
balls are so moved that the lines of sight unite upon the object or
point looked at. In viewing an object or in reading we keep
readjusting the eyes continually to bring point after point at the
junction of the lines of sight. When we look before us at a
distant object the muscles in each eye should be so adjusted
that without any contraction the antagonistic muscles will
just balance each other — that is, when the eye muscles are
entirely relaxed, except for their normal tone, the visual axes
should be parallel. If this balance does not exist, we have a
condition designated as heterophoria. In this condition a
constant contraction of one or more muscles is required, even
in far .vision, to prevent diplopia. When the eye at rest shows
a tendency to drift toward the temporal side, owing to the fact
that the pull of the external rectus overbalances that of the
internal rectus, the condition is known as exophoria. If, for the
opposite reason, there is a tendency to drift to the nasal side, the
condition is described as esophoria. A tendency to drift up or
down is called hyperphoria, and this is further specified as right

362 THE SPECIAL SENSES.

or left hyperphoria according to the eye whose axis deviates
upward. A lack of resting balance of this kind will make itself
felt also in near work, particularly in reading, sewing, etc., since
it will require a constantly greater innervation of the muscle
whose antagonist overbalances it. Under some conditions the
resulting muscular strain causes much uneasiness or distress.
The heterophorias are easily detected and measured by the use
of prisms, but they do not show the same constancy as the
refractive errors of the eye, owing probably to the fact that they
involve the variable factor of muscular tonus. The defect
may be remedied by surgical operations upon the muscles or
by the use of proper prisms with their bases so adjusted as to
help the weaker muscle. In exophoria, for example, the greater
pull of the external rectus rotates the front of the eye outward,
while the back of the eye with the fovea is moved inward toward
the nose. A prism of the proper strength placed before the
eye with its base in toward the nose will throw the image of an
external object on the fovea where it is, without necessitating
a contraction of the internal rectus to bring the fovea back into
its normal position. When the lack of balance between the
opposing muscles is so great that the visual axes cannot by
muscular effort 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, lei 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. Hut the two fields overlap for a
portion of their extent, and this overlapping; area constitutes
the field of binocular vision (see big. 157). livery 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 he -een double when
one'.- attention is directed to the fact. Whether any given object
ii 9ingle or double depends upon whet her it- image does or does
not fall upon corresponding points in the two retinas.

Corresponding or Identical Points. — By definition corre-
sponding or identical point- in t he I we retinas are t hose which when
simultaneously stimulated by the same luminous object give us a
single sensation, while non-corresponding points are those which
when so Stimulated give us two visual sensations. It is evident,
from our experience, that the fovea' form corresponding points or
When ue look at any object we so move onr eyes that the

BINOCULAR VISION.

363

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

* 061 081 OU

Fig. 157. — 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.

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 foveas 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
to point correspondence has not been determined experimentally.
Experiments have shown, however, that the corresponding points
in the upper halves of the retinas along the vertical mid-line do
not cover each other, that is, they do not lie in the actual anatom-
ical vertical meridian, but form two meridians which diverse

364 THE SPECIAL SENSES.

symmetrically from the mid-line so as to make an angle of about
2 degrees (physiological incongruence of the retinas). Within the
limits of our powers of observation for ordinary objects we may
adopt Tscherning's rule, — namely, that when the images of
an object on the two retinas are projected to the same side of the
point of fixation they are seen single, their retinal images in this
case falling on the retina to the same side of the lines of sight ; when,
however, the retinal images fall on opposite sides of the lines of
sight and are projected to opposite sides of the point of fixation,
they are seen double. The doubling of objects that do not fall on
corresponding points (physiological diplopia) is most readily
demonstrated for objects that lie between the lines of sight, either
closer or farther away than the object looked at. If, for instance,
one holds the two forefingers in front of the face, in the median
plane, one hand being at about the near point of distinct vision
and the other as far away as possible, it will be noticed that when
the eyes are fixed on the far finger the near one is seen double
and vice versa. In this, as in other experiments in which the eyes
are accommodated for one object while the attention is directed
to another, some difficulty may be experienced at first in disso-
ciating these two acts which normally go together, but a little
practice will soon enable one to distinguish clearly the doubling
of the point upon which the lines of sight are not converged.
If a long stick is held horizontally in front of the eyes the end
near the face will be doubled when the eyes are directed to the
far end and vice versa. Moreover, by a simple experiment it
may be shown that objects nearer the eyes than the point looked at
are doubled heteronymously, — that is, the right-hand image be-
longs to the left eye and the left-hand one to the right eye. This is
easily demonstrated by closing the eyes alternately and noting
which of the images disappears. The reason for the cross-projec-
tion of the images is made apparent by the const miction in Fig. L58,

/. bearing in mind the essential fact that in projecting our retinal

images we always project to the plane of the object upon which the

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
See® double and are projected to the plane Of A, the image on the
right eye being projected to //on the left of .1 and that on thelefteye
to 6 on the right of A. In a similar way it may be shown that ob-

farther away from t he eye than the point looked a1 are doubled

homonymous!)',- that is, the right-hand image belongs to the right
eye, and the left-hand one to the left eye. The fad is explained by
the cob bruction in Fig. L58, II, in which A is the point converged
upon and B the more distanl object. In all binocular vision, there-
fore, the eriee of objects between the eye and thepoini looked at are

BINOCULAR VISION.

365

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 and 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

Fig. 158. — Diagrams to show homonymous and heteronymous diplopia: In 7 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.

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

366 THE SPECIAL SENSES.

points in the two retinas the mind ignores or suppresses one of the
images. This peculiarity is exhibited especially in the case of per-
sons suffering from " squint " (strabismus). In this condition the
individual, for one reason or another, is unable to adjust the contrac-
tions of his eye muscles so as to unite his lines of sight upon the
object looked at. The image of the object falls upon non-corre-
sponding points and should give double vision, diplopia. This
would undoubtedly be the case if the condition came on suddenly ;
just as double vision results when we dislocate one eyeball by
pressing slightly upon it. But in cases of long standing one of the
images, that from the abnormal eye, is usually suppressed. The
act of suppression seems to be a case of a stronger stimulus prevail-
ing over a weaker one in consciousness, just as a painful sensation
from stimulation of one part of the skin may be suppressed by a
stronger pain from some other region.

Struggle of the Visual Fields. — When the images of two dis-
similar objects are thrown, one on each retina, the mind is presented,
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
i- 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 t he 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 i- buill are of several differenl kinds, partly monocular, —
that is, such as are perceived by one eye .alone, partly binocular.
If we close one eye and look a1 a bit of landscape or a solid object,
ue 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 corred visual judgments concerning three dimen-
sional mace. Nevertheless it i true that with binocular vision

BINOCULAR VISION. 367

our judgments of perspective are more perfect, and that under
certain circumstances data are obtained from vision with two eyes
which give us an idea of solidity far more real than can be obtained
with one eye alone. This difference is shown especially in the
combination of stereoscopic pictures, and in ordinary vision when
the light is dim, as in twilight, or in exact judgments of perspective
in the case of objects close at hand. If, for example, we close one
eye and attempt to thread a needle, light a pipe, or make any similar
co-ordinated movement that depends upon an exact judgment of
the distance of the object away from us, it will be found that the
resulting movement is far less perfectly performed than when two
eyes are used. The sensation elements upon which our judgments
of depth or perspective are founded may be classified as follows:*

The Monocular Elements. — That is, those that are experienced
in vision with one eye. (a) Aerial perspective. The air is not en-
tirely transparent, and, therefore, in viewing landscapes the more
distant objects are less distinctly seen, as is illustrated, for instance,
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

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

368 THE SPECIAL SENSES.

the distance in spite of the fact that they continue to increase in size. The
inverted or pseudoseopic vision thus produced is due undoubtedly to the in-
version of the lines of perspective. Parallel lines which, without the lens,
would have on the retina a project ion of t his kind /\ are with the lens projected
inverted \/ , and our visual judgments arc controlled by this factor in spite
of the opposing evidence from the size of the retinal images. In order lor
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 verv
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 ami 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 actualsize alsoof 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. Thifi element, consists in the fact that the retinal images
of externa] objects, particularly near objects, are different in the two
[nasmuch 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 retina- may, in fact, be represented by the drawings given in
Fig. J.'/.i. Whenever this condition prevails, whenever what we

BINOCULAR VISION.

369

Fig. 159. — 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.

may call a right-eyed image of an object is thrown on the right eye
and simultaneously a left-eyed image on the left eye, whether in
nature or by an artifice, we at once perceive depth or solidity in the
object. This fact is made use of in all devices employed to produce
stereoscopic vision.

Stereoscopic Vision. — Stereoscopic pictures may be obtained

by photographing the
same object or collec-
tion of objects from
slightly different
points so as to get a
right-eyed and a left-
eyed picture ; or for
simple outline pic-
tures, such as geo-
metrical figures, they
may be made by draw-
ings of the object as seen by the two eyes, respectively (see Figs.
159 and 161). 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;

the one that is most frequently A ^ >

used is the Brewster stereoscope :\ \ /

represented in principle in Fig.
160. 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

)>'£

Fig. 160. — Diagram to illustrate the
principle of the Brewster stereoscope
{Landois) : P and P', the prisms, a, 6,
and a, 0, the left- and ri^ht-eyed pictures,
respectively, b, P, being a point in the
foreground and a, a, a point in the back-
ground. The eyes are converged and
focused separately for each point as in
viewing naturally an object of three di-
mensions.

object in the two pictures is about 80 mms. — greater, therefore, than
the interocular distance. A simple form of stereoscope that is very
24

170

THE SPECIAL SENSES.

effective and interesting is sold under the name of the anaglyph.
The two pictures in this case are approximately superposed, but the
outlines of one are in blue and the other in red. When looked at,
therefore, the picture gives an ordinary flat view with confused
red-blue outlines. If, however, one holds a piece of red glass in
front of the left eye and apiece 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
spectacles the right-eyed image may be thrown upon the left eye
and vice versa. Under these conditions the picture for most per-
sons may be seen in inverted
relief (pseudoscopic vision),
objects in the foreground re-
ceding into the background.
This inversion of the relief
when the projection upon the
retinas is reversed is a strik-
ing indication of the potency
of the normal projection as a
factor in our judgments of
solid objects. It will be ob-
served, moreover, that those
pictures that show least
mathematical perspective are the most readily inverted, and that
the ability to invert the picture varies in different individuals; in
some, what we have called the binocular perspective, founded upon
tlic dissimilar images, prevails over fhe mathematical perspective
more readily than in others.

Stereoscopic pictures may also be combined very successfully
withoul i he He of :i stereoscope by virtue of the phenomenon of
physiological diplopia. If, for instance, two stereoscopic drawings,
such as are represented in Fig. 161, are held before the eyes and one
relaxee hi accommodation bo as to look through the pictures, us it

Fig. 161. — Stereosropie 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 fool or more and gaze beyond.

BINOCULAR VISION. 371

were, to a point beyond, then, in accordance with what was stated
on p. 364, each picture gives a double image, since it falls on
non-corresponding parts of the two retinas. Four pictures, there-
fore will be seen, all out of focus. With a little practice one can so
converge his eyes as to make the two middle images come together,
and since one of these is an image of the right-eyed picture and is
falling on the right eye, and the other is a left-eyed picture falling
on the left eye, the combination of the two fulfills the necessary
conditions for binocular perspective. The figure stands out in
bold relief.

Explanation of Binocular Perspective. — Our perception of
solidity or relief is a secondary psychical act, and, so far as the binoc-
ular element is concerned, it is based upon the fact that the images
are slightly different on the two retinas; but why this dissimilarity
should produce an inference of this kind is not entirely understood.
Certain facts have been pointed out as having a probable bearing
upon the mental process. In the first place, in stereoscopic pictures,
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. 158). 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. 364). 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

372 THE SPECIAL SENSES.

distances or we suppose that such is the case, our judgment of the
distance controls our judgment of size. This fact is beautifully
shown in the case of after-images (see p. 343). 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,

-A _ B

Fig. 162. — 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,
1 herefore, seem to be much farther away, since under normal condi-
tions such small images of familiar objects are formed only when
they are a1 a great distance from us.

Optical Deceptions. Wrong judgments as regards distance
and size are frequently made and the fad may be illustrated id a
number of interesting ways. Thus, in Fig. L62 the lines .1 and B
are of the same length, but B seems to be distinctly the longer. So
in Fig, 103 the vertical lines, although exactly parallel, seem, on
the c<uii rary, 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 angle and overvalue those

BINOCULAR VISION,

373

that are obtuse. A very remarkable delusion is given by Fig. 164.
If the book is held flat at the level of the chin and six or eight

k

\

i

'/

V

/

\

s

\

// SS //

'/. XX '/.

xtxx

\

/

\

Fig. 163. — Zollner's lines.

inches from the face and the eyes are focused on the point of
intersection of any two of the lines, a third line will be seen per-

Fig. 164. — Optical illusion in projection. — (Franklin.)

pendicular 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

374

THE SPECIAL SENSES.

head from side to side the lines sway in the same direction. It
forms a very striking instance of the fact that we may see most
distinctly a thing that has no real existence, — a case, therefore,
in which we can not trust our senses. The delusion seems to be
due to the fact that the two lines, in the position indicated, form
a projection on the retina such as would be made by an actual
vertical rod placed at the point at which we see one. Fig. 165
give- 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
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. That the act of accommoda-
tion plays a part in the changes is shown by the fact that if one

lir. L65. — Figure ><> illu-t rate binocular deceptions depending upon different inter-
pretation of the mathematical perspective and the lights and shades. On gazing fixedly
tin- image will Change From B single cube with black top resting on two others with black
top , to one ')! two cube with black bottoms resting upon a single cube with black
bottom. .Still other figures may appear from time to time.

focuses for the point a, this point may be held in the foreground
and the second of the above appearances be scon. While if the
are accommodated Btrongly for point &, it will be brought
forward and the firsl of the two appearances described is brought
into view.

PHYSIOLOGY OF THE EAR.

CHAPTER XX.

THE EAR AS AN ORGAN FOR SOUND SENSATIONS.

In discussing the physiology of the ear it is necessary to consider
the functional importance of its various parts, the external ear
consisting of the lobe or pinna, the external auditory meatus, and
the tympanic membrane; the middle ear, with its chain of ossicles,
its muscles and ligaments, and the Eustachian tube; and the internal
ear, with its cochlea, vestibule (utriculus and sacculus), and semi-
circular canals. The eighth cranial or so-called auditory nerve is

Fig. 166. — 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; aS, 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 ampullse of the semicircular canals. We may consider
first the functions of the ear in respect to the sensations of sound.

375

376

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 scheznatic figure
employed by Czermak and reproduced in Fig. 166 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
rnuking 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
mini! 'nine h:is the shape of a shallow funnel with the apex, or
umbo, OS it Is called, somewhat below the center. The fibers of
the fibrous layer ure arranged partly circularly and partly in lines
radiating from the umbo to the peripheral margin (Fig. 167).
The walls of the funnel are slightly convex outwardly; so that

-To show the structure of the
tympanic membrane, looked at from the side
of the meatus (f/ensen): 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.

377

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. 168. — 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, epitympanic 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-

! 78

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
perilvmph 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. 168 and 169. To
understand the manner in winch 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 IS 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 bj^ 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
proff—cs nearly at right angles to each other. The shorter process
extends posteriori;, 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
of the stapes. This latter Lone is extremely light, weighing
about 3 milligrams, its oval base heing attached to the margins
of the fenestra ovalis by s Bhort, stiff membrane.

The Mode of Action of the Ear Bones. — The movements of

Fig. 169.— The bones of the
middle ear in natural connections
(Helmholtz): M, The malleus; Mcp,
the head; Mc, the neck; Ml, the

Erocessus gracilis; Mm, the rnanu-
rium; Ic, body of the incus; lb,
short proces.-); //, long process; <S,
the stapes.

EAR AS AN ORGAN FOR SOUND SENSATIONS.

379

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. 170. 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. 170.1). The chain of bones, therefore, acts
like a bent lever whose fulcrum is at a, the power arm being repre-

Fig. 170. — 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. 170.4. — 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 rams., while r-a
is 6.3 mms. The movement at r, therefore, or the movement
of the stapes, will have only two-thirds of the amplitude of the
movement at p, but will have a correspondingly greater force
(one and one-half times). The mechanisms of the tympanic
membrane and the ear bones combine, therefore, to convert the
vibratory movements of the tympanic membrane into smaller
but more intense movements of the membrane of the fenestra
ovalis. It should be borne in mind, however, that the amplitude

* Helmholtz, "Die Lehre von den Tonempfindungen, etc.," fifth edition,
1896. See also English translation by Ellis.

380 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 nock of the stapes. This muscle is
innervated through a branch of the facial. When it contracts it
tends to pull the stapes laterally, and thus probably places the mem-
brane attached to its base under greater tension. The functions
fulfilled by these muscles have been the subject of much controversy.
According to a view first proposed by Johannes Miiller, l hey act as
a protective mechanism to the membranes of the middle ear. By
increasing I he tension of the membranes they limit the amplitude of
their vibrations and thus protect the membranes from injury or
po ible 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. 381

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 b}^ 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 Physiologie," S7, 355, 1901.

382 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 tins part of the ear by one
path. — namely, the tympanic membrane and its accessor}' 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. 171. They
consist of short more or less cylindrical cells (A', 0, (>', ('/', Fig. 171),
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 Retains,* about twenty — short,
stiff hairs. The hair cells are arranged in four to six rows, one

• The moel complete details of the structure of the ear will be found in
the great work of Etetzius, "Das GehOrorgan der Wirbelthiere," vol. ii, 1884,
Stockholm.

EAR AS AN ORGAN FOR SOUND SENSATIONS.

383

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

Fig. 171. — 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 bod}r,
and may vary greatly in length, in amplitude, and in form. For

3S4 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. 80 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 properly of musical
sounds is tlicir variations in quality or timbre. The same note of
one amplitude when given by different musical instruments
varies in quality, so that we have no difficulty m recognizing the
note of a piano from the same note when given by a violin or the
human voice. The underlying physical cause of variationsin timbre
is found in 1 he form of the sound waves produced, and immediately,
therefore, in the form of vibratory movement communicated to
the perilymph. Examination of 1 he forms of sound waves produced

EAR AS AN ORGAN FOR SOUND SENSATIONS. 385

by different musical instruments shows that they may be divided
into two great groups: (1) The simple or penclular 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. 172. 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. 172. — 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.
173. In this figure A and B represent two simple vibrations such
as would be given by two tuning-forks, the vibrations in B being
double those of A. If these two waves are communicated to the air
at the same time the actual movement of the molecules will be a
resultant of the forces acting upon them at any given instant, and
the actual movement will be indicated, therefore, by the algebraical
sum of the ordinates above and below the lines of rest. If the
movements are so timed that e in curve B is synchronous with d° in
curve A, then the resulting compound wave form is illustrated by C.
If, however, curve B is supposed to be in a different phase, so that e
is synchronous with d' , then a form of wave illustrated by D will be
25

3S6

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, 173.— Schema by Helmholtz to illustrate (lie formation of a compound wave
from two [jcmliihtr waves: A and /.', pendular vibrations, B being die octave of A. If
superpo ed o that e coincides with d" and the ordinates arc added algebraically, the non-
pendular curve C is produced. If .superposed so that e coincides with </' the non-pendular
curve l> i 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
ri'.t Mnl- :i a whole, but also in its aliquot parts, as may be repre-
sented in Fig. 174, illustrating the vibrations of a string. When
I lie string is plucked it vibrates as a whole (a), giving large waves
which produce what is called the fundamental lone, but at the same
time each half (6), third (c), fourth (<1), 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.

387

composition determines the quality of the tone heard. As
many as ten or sixteen of these overtones ma}- be detected from the
vibrating strings of a violin or guitar. When the period of vibra-
tion of these overtones bears a simple ratio to that of the funda-
mental, a ratio that can be expressed by the simple numbers, 1, 2,
3, 4, 5, they harmonize with it and form the harmonic overtones.
It should be borne in mind that, so far as the tympanic membrane
is concerned, it does not respond separately to the single tones
which constitute the compound wave, but swings in unison with
the movement of the compound wave.' Nevertheless the internal

Fig. 174. — To illustrate the mechanism of the formation of overtones. — (Helmholtz.)
In a the string vibrates as a whole, giving its fundamental tone; in b, c, and d, its halves,
thirds, and fourths are vibrating independently. When a string is struck, plucked, or bowed
these movements may happen simultaneously and the fundamental note due to the vibra-
tions of the whole string is combined with the notes due to the vibrations of aliquot parts,
the overtones. The combination gives a compound wave whose form and musical quality
vary with the number and relative strength of the overtones.

ear, according to the law of Ohm, is capable of analyzing the com-
pound wave form into the series of simple or pendular wave forms
of which it is composed and of distinguishing the series of corre-
sponding tones. While this analysis cannot be made consciously
except by the trained musician, it is made unconsciously, as it
were, by even- 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

>n 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 12S 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 fenestr.-i rotunda, between the middle and the inter-
nal car (see Fig. 166). As the membrane of the fenestra ovalis is
pushed in. flint of the fenestra rotunda is pushed out, and vice
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. 389

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.
171). 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 tt in
the basal portion to 220 li in the middle spiral and to 234 tt 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-

390 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 the}' 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 Basse, has suggested
that the tectorial membrane, especially its U-vc 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
md to different periods of vibrations in its different pads,
it- movements being communicated directly to the hair cells upon
which it, rest 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

«

Avers, "Journal <>f Morphology." 6, 1, l.s!>'_'.

* /were, journal <>i worpnoiogy. o, i, iv.u.

t Kollil.i r, " Handbuch a. Gewebelehre," sixth edition, vol. Hi, pt. u,
p. 968, 1902.

EAR AS AN ORGAN FOR SOUND SENSATIONS.

391

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"", e'"".

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. 175, 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 musical harmony —
combinational tones and beats — reference must be made 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, 1SS3.
t Ewald. "Archiv f. d. gesammte Physiologie," 76, 147, 1S99.

Fig. 175.— To il-
lustrate the idea of
a fixed sound wave. —
(.Ewald.) The illus-
tration shows a fun-
damental note and its
first overtone.

392 THE SPECIAL SENSES.

ing to Helmholtz, to the beats produced when two dissonant notes
are sounded together. On the physical side the beat, — that is, a
rhythmical variation in the intensity of the sound, — is due to the
phenomenon of interference. If the rates of vibration of two notes
are such that at certain intervals the crests of the waves fall to-
gether and again the crest of one coincides with the hollow of the
other, the sound sensations will be periodically increased and
decreased. While there is no fundamental explanation for the
fact that a regularly varying intensity of sound is disagreeable, it
is a well-known phenomenon and it finds analogies in the other
sensations,— for instance, in the very disagreeable effect of a flick-
ering light. When two notes are sounded together the number of
beats varies with the difference between the rates of vibration;
thus, two notes, one of 128 vibrations and the other of 136 vibra-
tions, give 8 beats per second. When the number of beats
rises to 33 per second the discord is most disagreeable ; if, however,
the rate of interference is more rapid, the unpleasant sensation
becomes less perceptible, and beyond 132 per second is not notice-
able. When the rates of vibrations of two tones are such that
neither the fundamentals nor any of the overtones give beats, the
effect is that of harmony, the vibrations of one note strengthening
those of the other. The most perfect harmony is that of a note
sounded simultaneously with another of the same rate, ratio 1:1,
or with its octave, ratio 1: 2. The various intervals which in
mi isic 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
;i less perfect consonance. Three or more notes bearing such rela-
tion- to each other constitute a chord, the vibrations in the
major chord being, for instance, in the ratios 4:5:G, — c' (128),
e' (160), </ (192).

The Limits of Hearing.- The rates of vibration that can be
perceived by the ear as musical tones lie between fairly well-
defined limit-', although in this organ, as in the ease of the eye,
then: are individual variations, variations, indeed, which are
more marked in the case of the ear, sinee its range of appreciatioE
is larger. The lowest pate of vibration thai can cause a. musical
tion is usually placed ;it 28 i<> :!<> per second, although some

-•in -till respond to an octave lower, about Hi per second. To

vibrations below ::<» per second are fell , if perceived al nil,

ogle pulses thai stimulate the sensory nerves of the tympanic

membrane itself. The cochlea does not respond. It may happen,

EAR AS AN ORGAN FOR SOUND SENSATIONS. 393

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 contrac-
tions of which the compound contraction is composed, occur at the
rate of only 10 per second; so that what is heard is, on this theory,
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 yf or ff ;
^hus, c"= 256 vibrations and the d" of the same octave corresponds

:'See Helmholtz, Popular Scientific Lectures, "Ueberdie phvsiologischen
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-
lyniph, which communicates through the five openings with the
endolymph in the utriculus. The canals lie in three planes that are,
approximately at least, at right angles to one another (Fig. 170).
The horizontal or external canals lie in a horizontal plane at right

angles to the mesial or sagittal
plane of the body, the vertical
canals on each side make an angle
of about 45 degrees with this
mesial plane. The plane of each
of the anterior canals is parallel to
that of the posterior or inferior
vertical canal of the opposite side,
as represented in the figure. At
one end of each canal near iis
junction with the utriculus is the
swelling known as the ampulla
and within the ampulla lies the
crista acusl tea containing the hair
cells wilh which the nerve fibers
communicate, and which, there-
fore, are considered as the sense
cells of the organ.
cells are cylindrical
gives off a long hair,
perhaps of a bundl
hairs, which projects
interior of the canal for a distance
of ai least 28 ,". The nerve hhers
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 (ramu jacculo-ampullaris) furnishes libers to the sacculus
and the posterior ampulla.

394

Fig, I 76 I "' gram to how I -
tion of the semicircular canals in the head

bird. < >n «■--«.<- 1 1 i'l'- it n ill l"
i ha) the three canal lie in plane at right
angles to one anot hei . I he e ternal 01
mtal canal I E) <>f the i wo ide lie
in the same plane, l he antei ior ca rial ol
one ide A lie in a plane pa rallel tol hat
i,f tli<- posterior canal (P) "I i he ot hei ide

The hair
and each

consisting

of liner
into the

SEMICIRCULAR CANALS AND THE VESTIBULE. 395

Flourens's Experiments upon the Semicircular Canals.—

Modern experiments and theories concerning the functions of the
semicircular canals date from the classical researches of Flourens*
(1824). This investigator laid bare the canals in birds and mam-
mals and studied the effects of sections of one or more of them.
The experiments have since been repeated by numerous observers,
and the results obtained have been described in great detail, for an
account of which reference must be made to original sources.f In
general, it may be said that injuries to the canals are followed by
certain more or less definite movements of the head, eyes, and bod}',
and by a disturbance in the power of the animal to co-ordinate nor-
mally the muscles used in standing, locomotion, or flying. The
character and extent of these results vary with the number of
canals injured, and, indeed, show a more or less definite relationship
to the several canals. When the horizontal canal is cut on one side
in pigeons the animal makes movements of the head in the plane of
that canal, and if the similar canal on the other side is also sec-
tioned these movements are more pronounced. The animal may
also in moving show an inability to walk normally and a tendency,
especially when excited, to make abnormal forced movements of
rotation of the whole body. After such an operation the pigeon will
not fly voluntarily and if thrown into the air is not able to guide
its flight with accuracy and soon descends. Similar operations
on the anterior or the posterior canals cause movements of the head
in the corresponding planes and a tendency in walking or flying
to make forced movements — somersaults — forward or backward.
When all three canals are cut on one or both sides the animal shows
a distressing inability to maintain a normal position. The head is
twisted, it is not able to stand unless supported, and any attempt
at walking or flying results in violent forced and inco-ordinated
movements. The animal makes continual somersaults at each
attempt to stand or walk and the head is kept in spasmodic, forceful
movements, which may produce injury or death. To preserve the
animal from injury after such an extensive operation it is necessary
to keep it wrapped in bandages. It should be added that results
of this character are obtained only when the membranous canals
are injured. If the bony canal alone is cut and even if the peri-
lymph is removed by suction no such effects are obtained. At
most slight and relatively transient movements of the head are
observed. If the exposed membranous canal is pricked with a

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

fThe 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 Funk'tionen der einzelnen Theile des Ohrlaby-
rinths," by von Stein, 1894; Richet's " Dictionnaire de Physioiogie," article
by Cyon, on "Espace," 1900. Ewald, 'Physiolog. Untersuchungen u. &
Endorgan des nervus octavus," 1892.

396 THE SPECIAL SENSES. ,

needle more violent movements result . and if sectioned these move-
ments are maintained for a longer period and are accompanied by
the other results described. Similar effects have been obtained
from operations on mammals and other animals, but the results
are more pronounced in some animals than in others, varying
apparently with the delicacy of the co-ordination necessary to the
movements (Ewald). Thus, the movements of walking or flying
in the pigeon may be assumed to require a nicer adjustment of the
muscles used than is necessary in the swimming movements of the
fish, and in correspondence with this idea it is found that opera-
tions on the canals of fishes are not followed by conspicuous effects
upon the movements of the animals.

Temporary and Permanent Effects of the Operation. — The
general effects of operations on the semicircular canals, so far as
disturbances of equilibrium and occurrence of forced movements
are concerned, resemble those resulting from operations upon the
cerebellum, and, as in the case of the last mentioned organ, it is
found by most observers that if the animal is properly cared
for the severity of the first effects passes off to a greater or less
extent. Flourens states that his pigeons, with two or more canals
cut, continued to show the effects of the operation almost with the
same intensity for nearly a year. Some unpublished experiments
made in the author's laboratory have given different results.*
Pigeons with only one canal cut recover practically completely
within ten or more days. Those with two canals cut recover nearly
completely within a month, so far as walking is concerned, although
they exhibit an unwillingness to fly. Those with three or more
canals cut never recover completely, but their final condition is very
different from that exhibited shortly after the operation. Even
when all six canals have been cut the animal, if well cared for in the
beginning, is able finally to stand and walk and feed itself. It
is not able, however, to fly, and in walking its progress is uncertain;
there is a tendency to walk zigzag or in circles, first to one side, then
to the other. If hurried or excited some return of the violent
movements of the head and inco-ordination of the movements of
locomotion may be seen. If, instead of cutting the canals, the
ampullae are destroyed, the initial effects of the operation seem
to be less violent, owing possibly to the fact thai in the former

the irritative effects of the lesion still have the end organs

in the ampulla? t'» acl upon. Pigeons with all six ampulla?
destroyed may make eventually an excellent recovery. Within
a few month- they walk and perch with little difficulty when
not frightened. In the matter of flying they do qo1 recover
their former skill, but this may be due to lack of practice, since
• i |.m ni lasting over two year made by Dr. E. Rosencrantz,

SEMICIRCULAR CANALS AND THE VESTIBULE. 397

in the experiments quoted (Rosencrantz) no provision was
made for exercise in flying. The very marked degree of recovery
noted, even after loss of all six ampullae, seems to be due to the
fact that the animal learns to use his other sensory data in
co-ordinating his muscles. If after a nearly complete degree of
recovery has taken place a new operation is performed in which
the canals are cut, the resulting disturbance to motion is relatively
small and soon passes off. That there is any effect at all from
the second operation may be due to the emptying of the endo-
lymph and the consequent effect upon the remaining ampullae,
or, if these had all been previously destroyed, to the effect upon
the sense organs of the vestibular sacs.

Effect of Direct Stimulation of the Canals. — The membranous
canals or their ampullary enlargements have been stimulated
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 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 bjr
forced movements, especially by rolling movements around the
long axis of the body. When the nerves are cut on both sides
disturbances in the power to maintain equilibrium perfectly are
more or less distinctly marked. In fishes (dog-fish) the animal may
swim or come to rest in unusual positions, — on the back or side, for
instance.

Is the Effect of Section of the Canals Due to Stimulation?—
The movements that result from section of one or more of the canals
have been attributed by some authors to stimulations set up by the
injur}'- 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
*Lee, "Journal of Physiology," 15, 328, 1903.

398 THE SPECIAL SENSES.

so long lasting as to make it improbable that they are entirely due to
the irritation of the operation. Moreover, Gaglio * 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 man)' 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, f 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
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
I 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 lic.'nl .- 1 1 ) r 1 enable us, therefore, to control its movements
and also those of the body. < »n 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, ei al. I modified this view by the assumption that the
hair cells are stimulated not so much by the hydrostatic pressure of
the endolymph as by I he pressure changes developed during move-

glio, ■ \rrhivi-, ital. de biologie," 31, 377, L899.
i I or :i detailed and complete account of these views to 1892, see Stein,
"Die Leliren von den Funktionen der eizelnen Theile dea Ohrlabyrinths,"
Jena, L894

SEMICIRCULAR CANALS AND THE VESTIBULE. 399

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. 176), 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
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.

* Consult Lee, loc. cit.

400 THE SPECIAL SENSES.

4. Cyon* has advocated the view that the semicircular canals
constitute an organ for the perception of space in its three dimen-
sions. 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 space in three dimensions. On this fun-
damental conception of space are projected the additional space
conceptions derived from our visual, tactile, and muscle senses.
This author is not specific in stating by what means the sensory
cells in the three canals are stimulated. In addition to the
sensations of direction and of space furnished by the canals,
the nerve impulses from them are supposed to co-ordinate the
action of the motor centers concerned in movements 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-
circular canals constitute what might be called a muscle-tone organ,
and the obvious disturbances in motion caused by their injury are
due primarily to a diminution or loss in muscle tone, each canal
possibly being reflexly connected with special muscles.

Summary. — With reference to the kind of sensation mediated
by the nerves of the semicircular canals, it should be borne in mind
that these sensations are not distinctly recognized by consciousness;
hence the difficulty of designating them by a specific name. Of
the many qualities of sensation or consciousness which we can
distinguish some have characteristics so clear that we recognize
them at once and give them distinctive names, such, for instance,
as the sensations of sight, hearing, taste*, etc. Others, however,
produce a psychical reaction of such an indefinite character that
they escape recognition by mere introspection. The change in con-
sciousness is not sufficiently marked to make itself felt to the un-
trained mind. This condition prevails regarding the sensations,
if ;my, aroused through the semicircular canals; they are too
indistinct to be recognized and named by an appeal to conscious-
ness, and it would seem to be wiser to designate them after the
analogy of the muscle sensations simply as semicircular canal
sensations. Our perceptions or ideas of space and direction are

* E. von 'yon, " Das Ohrlabyrinth ale organ der mathematischen Sinne
fiir Raum und Zeit.," L908.

SEMICIRCULAR CANALS AND THE VESTIBULE. 401

possibly founded in part upon these reactions and in part upon
the muscle sense, visual, and tactile sensations. Our reasoning
with regard to the semicircular canal sensations would be more
satisfactory if it could be shown that the vestibular nerve after
ending in the brain was continued forward by sensory paths to
the cortex of the cerebrum. As a matter of fact, such paths have
not been demonstrated, and if we assume that conscious sensations
are mediated only through the cortex of the cerebrum we have
no anatomical proof that the semicircular canals give us any
reaction in consciousness. The vestibular nerve fibers end in the
nucleus of Deiters and the nucleus of Bechterew, through which
reflex connections are established with the motor centers of the
spinal and possibly the cranial nerves. There is a connection
also with the nucleus fastigii of the cerebellum and through
this possibly with the cerebellar cortex, although this latter
connection has not been actually demonstrated. With regard
to the influence of the nerve impulses from the semicircular canals
upon movements, all the facts known seem to indicate that they
play an important part in the regulation or co-ordination of the
movements of equilibrium and locomotion. Inasmuch as this gen-
eral co-ordination or control seems to rest normally in the nervous
mechanisms of the cerebellum and inasmuch as the vestibular
nerves make possible end connections with the cerebellum, to-
gether with the fibers of muscle sense, we may assume that the
cerebellum forms the brain center in which the semicircular canal
impulses exert their influence upon co-ordinated muscular con-
tractions,— the cerebellum forms the nerve center for the semi-
circular canals or the semicircular canals form a peripheral sense
organ to the cerebellum. Some such hypothesis seems to be
necessary to account for the general similarity between the effects
of lesions of the canals and of the cerebellum. Whether the
impulses from the canals are excitatory or inhibitory or both, as
regards their effect upon muscular contractions, is not clearly
apparent from the experimental evidence so far furnished, but
Ewald's suggestion that they serve to maintain reflexly the tonus
of the body musculature is perhaps the most acceptable view.
In regard to the means by which these nerves are normally stim-
ulated there is also much room for conjecture, but provisionally
at least it seems permissible to adopt the view that variations
in the pressure of the endolymph upon the hairs of the hair cells,
especially in movements of rotation, constitute the immediate
cause of their excitation. Granting that changes in position or
movement of the head may cause such variations in pressure the
theory offers a simple and satisfactory explanation of the mode
of excitation and the means by which the excitation may vary
26

402 THE SPECIAL SENSES.

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
i- -"inetimes expressed, the sacs form a static and the canals a dy-
namic organ of equilibrium. According to this view, the otoliths
act as a means of mechanical stimulation of the hairs. Being
heavier than the endolymph, they press upon the hairs with a force
varying with the position of the head and thus give rise to sensations
or reflexes which are adapted to the maintenance of equilibrium.
Since the planes of the two sacs are different, they may be differ-
ently affected by the same position or movement. So also in pro-
gressive movements forward the weight of the otoliths may be im-
agined to exercise a stress of some sort upon the hairs. This theory
has been the subject of much investigation, numerous experiments
having been made chiefly upon fishes and invertebrates.* Accord-

* Consult the following papers: Sewall, "Journal of Physiology," 1, :»;;!),
1884; Lee, ibid., 15, 311, L893, :> n< I "American Journal of Physiology," I,
128, 1898; Lyon,' American Journal of Psychology, " 3, 86, L900.

SEMICIRCULAR CANALS AND THE VESTIBULE. 403

ing to some observers destruction of these sacs or section of their
nerves is accompanied by a distinct interference with the fish's nor-
mal equilibrium: the animal swims at times upon its back or side
and apparently loses its normal means of judging correctly its posi-
tion. In many invertebrates there is present a sac, known as the
otocyst, containing hair cells and otoliths. Its structure resembles
that of the vestibular sacs of the mammalian ear, and it has been
assumed that it has a similar function. Experiments by numerous
observers have indicated that when the otoliths are removed the
animal shows disturbances in equilibrium, particularly in the matter
of the compensatory movements exhibited during rotation. Others,
however, deny these facts and state that invertebrates without oto-
cysts make compensatory movements when rotated and that in
those with otocysts compensatory movements and maintenance of
normal equilibrium persist after destruction of the sacs. A very
ingenious experiment reported by Kreidl seems to show that the oto-
liths may affect the hairs by their weight. When the palsemon, a
crustacean, molts it casts off the inner lining of the otocyst, together
with the otoliths. The otocysts in these animals lie at the base of
the antennules and open freely to the exterior. After molting the
animal by means of its claws places fine grains of sand in the otocyst
to act as otoliths. Taking advantage of this peculiarity, Kreidl
placed the animal, after molting, upon finely powdered iron, with
the result that some of the iron granules were deposited in the oto-
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 b}?" the animal under these conditions was such
as would be expected as a resultant of the forces of magnetism and
gravity, and the experiment, therefore, justifies the hypothesis that
under normal conditions gravity affects the otoliths and through
them the muscular co-ordination of the animal. These experiments
have been confirmed by Prentiss.* This author has shown,
moreover, that if larval lobsters (4th stage) are prevented from
obtaining otoliths after moulting by placing them in filtered sea-
water, their movements, like those of larvae deprived of their
otocysts, show a distinct instability and lack of normal orientation.

* Prentiss, 'Bulletin of Museum of Comparative Zoology," Harvard.
1901, xxxvi., No. 7.

SECTION IV.
BLOOD AND LYMPH.

CHAPTER XXII.

GENERAL PROPERTIES: PHYSIOLOGY OF THE
CORPUSCLES.

The blood of the body is contained in a practically closed system
of tubes, the blood-vessels, within which it is kept circulating by the
force of the heart beat. It is usually spoken of as the nutritive
liquid of the body, but its functions may be stated more explicitly, al-
though still in quite general terms, by saying that it carries to the tis-
sues foodstuffs after they have been properly prepared by the diges-
tive organs ; that it transports to the tissues oxygen absorbed from
the air in the lungs ; that it carries off from the tissues various waste
products formed in the processes of disassimilation ; that it is the
medium for the transmission of the internal secretion of certain
glands; and that it aids in equalizing the temperature and water
contents of the body. It is quite obvious, from these statements,
that a complete consideration of the physiological relations of the
blood would involve substantially a treatment of the whole subject
of physiology. It is proposed, therefore, in this section to treat the
blood in a restricted way, — to consider it, in fact, as a tissue in itself,
and to study its composition and properties without special reference
to its nutritive relationship to other parts of the body.

Histological Structure. — The blood is composed of a liquid part,
the plasma, in which float ;i vast number of microscopical bodies, the
blood corpuscles. There arc ;it least three different kinds of cor-
puscles, known respectively as the red corpuscles or erythrocytes;
the white corpuscles or leucocytes, of which in turn there are a
number of different kinds; and the blood i>l<ti<s. Blood-plasma,
when obtained free from corpuscles, is perfectly colorless in thin
layers, for example, in microscopical preparations; when seen in
quantities it, shows a slightly yellowish tint., the depth of
color varying with differenl animals. The red color of blood is
not due, therefore, to coloration of the blood-plasma, but is caused
by I lie mass of red corpuscles held in suspension in this liquid.

404

GENERAL PROPERTIES: THE CORPUSCLES. 405

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 442. 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. — The reaction of the blood seems to
differ according to the indicator used. With litmus or lakmoid
paper plasma or serum gives a distinct alkaline reaction. With
phenolphthalein, on the contrary, its reaction is neutral. On ac-
count of the more common use of litmus as an indicator, the belief
that blood and lymph are normally alkaline has long existed in
physiology, but the development in physical chemistry of more
precise methods of measuring acidity and alkalinity has resulted in
demonstrating that these body-liquids under normal conditions
are approximately neutral. From the point of view of physical
chemistry a solution is acid or alkaline according as it has an

+ -

excess of hydrogen ions (H) or hydroxy! ions (OH). Acids
are bodies which in aqueous solution dissociate more or less
completely with the production of hydrogen ions, for example,

+ -

HC1 dissociates into H and CI, and the strength of the acid is
proportional to its degree of dissociation, that is, to the number
of hydrogen ions set free. Bodies which act as alkalies, on the
contrary, are those which upon solution set free an excess of

+ -

hydroxyl ions; for example, NaOH dissociates into Na and OH.

406 BLOOD AND LYMPH.

In some cases the hydroxy! ions may l>e set free indirectly by

+ ' +
a secondary reaction. Thus Xa.,C03 dissociates into Na, Na

= + -

and C03, but the acid ion reacts with water, H, OH to form

HC03 and OH. If we wish to know whether the blood or lymph
has a true alkaline reaction, it is necessary to determine in them
the proportion of hydrogen and hydroxyl ions. This has been
done, with the result that they are found to exist in practically
equal amounts, as in the case of pure water, and we must believe,
therefore, that these liquids, which constitute the internal
environment of the living cells, have neither a distinct acid nor
alkaline reaction. When we examine the salts of the blood wc
find that in addition to such neutral salts as sodium or potassium
chloride there is present also a considerable amount of sodium
carbonate, and one may ask why this latter salt does not give
to the blood a real alkaline reaction in accordance with its
behavior in aqueous solutions. The answer to this question
is found in the fact that the liquids of the body are exposed
continually to a certain pressure of carbon dioxid which is
formed steadily in the tissues, on the one hand, and the excess
of which is as steadily eliminated through the lungs, on (he
the other hand. This carbon dioxid keeps the sodium carbonate
in the form of a bicarbonate, which, so far as it is dissociated,

+

yields no hydroxyl ions, NaHC03 = Na, HC03, and therefore
gives to the blood no actual alkalinity. When plasma or serum
is treated with litmus-paper it gives an alkaline reaction, owing
to the fact that the indicator, litmus acid, is ;i sufficiently strong-
acid to combine with the base (Na) and drive it out, as it were,
from its combination with carbonic acid. Phenolphthalein,
being a weaker acid, does not displace 1 lie carbonic acid. If a
relatively strong acid, such as acetic or tartaric, is added to the
blood, it will unite with the base (Na) so far as this latter exists
in combination with weaker acids, that is. in the liquid under
consideration with carbonic or phosphoric acid. When, there-
fore, 1 he blood is titrated with a standard solution of tartaric

acid, it will continue to give a blue reaction with lit mus-pa per

until all the base present in combination as carbonate or phos-
phate has been united with the stronger acid. The amount of

the standard acid used may be employed, therefore, to express
the amount of base presenl in the blood in combination with

such weak acids. For clinical and experimental purposes

determinations of this kind are often made. Formerly the
method was supposed to determine the alkalinity of the blood

GENERAL PROPERTIES: THE CORPUSCLES. 407

on the assumption that the blue reaction of litmus is a true in-
dication of alkalinity. While the process throws no light on the
actual alkalinity of the blood, it does yield a valuable indication
in regard to what may be called its potential alkalinity, that is,
its power to neutralize acids added to it during the processes
of normal or pathological metabolism, or under experimental
conditions. The blood as it exists in the body contains always
a certain amount of C02, NaHC03, Na2HP04, and also some
sodium in combination with protein, which from this stand-
point is to be regarded as a weak acid. It has been shown that
to such a solution a considerable amount of acid or alkali may
be added without altering its approximately neutral reaction.
Since this property is due in large measure to the amount of
base present in combination with weak acids, it is evident that
the determination of this latter factor, that is, the "potential
or titration alkalinity" of the blood, may be a matter of interest
and importance.*

Specific Gravity. — The specific gravity of human blood in the
adult male may vary from 1.041 to 1.067, the average being about
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. f 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. B}r 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 J
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

* See Henderson, "American Journal of Physiology," 1908, 21, 427.
| Hammerschlag, "Zeitschrift f. klin. Med.," 20, 444, 1S92.
% See Jones, "Journal of Physiology," 12, 299, 1891.

408 BLOOD AND LYMPH.

in another. The specific gravity of the corpuscles is slightly greater
than that of the plasma. For this reason the corpuscles in shed
blood, when its coagulation is prevented or retarded, tend to settle
to the bottom of the containing utensil, leaving a more or less clear
layer of supernatant plasma. Among themselves, also, the cor-
puscles differ slightly in specific gravity, the red corpuscles being
heaviest.

Red Corpuscles. — The red corpuscles in man and in all the
mammalia, with the exception of the camel and other members of
the group Camelidae, are biconcave circular discs or, according to
some authors, bell-shaped corpuscles without nuclei; in the Cam-
elidae they have an elliptical form. Their average diameter in
man is given as 7.7 in (1 ,u = 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
blood to purplish red in venous blood, this variation in color being
dependent upon the amount of oxygen contained in the blood in
combination with the hemoglobin. Speaking generally, the func-
tion of the red corpuscles is to carry oxygen from the lungs to the
tissues. This function is entirely dependent upon the presence of
hemoglobin, which has the power of combining easily with oxygen
gas. The physiology of the red corpuscles, therefore, is largely con-
tained in a description of the properties of hemoglobin.

Condition of the Hemoglobin in the Corpuscle. — The finer structure
of the red corpuscle is not completely known. It is usually stated
that the corpuscle is composed of two substances, stroma and hem-
oglobin, together with a certain amount of water and salts and
also a certain amount of lecithin and cholesterin. The stroma is a
delicate, extensible, colorless substance that gives shape to the
corpuscles; it forms a 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. According to another view the
corpuscles are vesicles with an external envelope or pellicle in
which lecithin and cholesterin are found, while the hemoglobin is

contained within.* Whichever view may be correct, great interest

* For recenl discussions upon the histological structure of the corpuscles,
see Weidenreich, "Anatom. Anzeiger," L905, xxvii., .r>s:j; Ruzicka, ibid.,
iii.. 153; Bchafer. ibid., L905, xxvi., 589.

GENERAL PROPERTIES: THE CORPUSCLES. 409

attaches to the presence of the lecithin and cholesterin, whether
these substances are found in an external membrane or in a stroma
permeating the corpuscle. According to Pascucci the lecithin and
cholesterin constitute as much as 30 per cent, of the dry weight of
the stroma, that is, of the portion of the corpuscle left after re-
moval of the hemoglobin. Such a large proportion of these two
substances is not found elsewhere in the body except in the myelin
sheath of the nerve fibers. It is believed that they play an impor-
tant r61e in maintaining the integrity of the corpuscles and
particularly in giving to the peripheral layer or membrane sur-
rounding the corpuscles certain characteristic properties of
permeability. Under normal conditions this external layer
is easily permeable to water and to certain substances in solution,
such as urea, alcohol, and ether, but it is said to be impermeable
to the neutral salts; the concentration of sodium chloride, for
example, is much greater in the plasma than in the red corpuscles.
The condition in which the hemoglobin exists within the cor-
puscle is not fully understood. It is evidently not in solution,
since the amount present is too great to be held in solution in
the corpuscle, and, moreover, even a thin layer of corpuscles
is far from being transparent. Nor is it deposited in the form
of crystals. It is assumed, therefore, that it is present in a
peculiar, amorphous form, and Gamgee has shown that from
its aqueous solutions the hemoglobin can be obtained in an
amorphous state by the action of an electrical current. It
is protected from the action of the water within and without
the corpuscle. In various ways, 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 of the plasma. (2) By add-
ing ether or chloroform. (3) By the addition of soaps or of the
higher fatty acids, especially the unsaturated acids. (4) By

410 BLOOD AXD LYMPH.

adding bile or solutions of the bile-salts. (5) Ity adding amyl-
alcohol. (6) By adding the serum from the blood of certain
animals. (7) By adding saponin or sapotoxin. (S) By the
addition of an excess of alkali. (9) 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 demand especial men-
tion, as they involve the consideration of processes 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 vupture the cor-
puscles and thus discharge 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
thai 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 coni aiiicd iii the plasma in Largest amounts is sodium
chlorid. In mammalian serum it exists to an amount equal
to 0.56 per cent, and is probably responsible for the greater
pari (60 percent.) of the osmotic pressure shown by this liquid.
In making isotonic solutions this salt is, therefore, generaly

employed. A solution containing nine-tenths of I per cent, of

sodium chlorid (NaCl, ').!) per cent.) gives the same osmotic
pressure as plasma as determined by the effect- of each on the
lowering of the freezing-poinl (see Appendix, Diffusion, Osmosis,
and Osmotic I 'res- 1 ire) . Such a solution mixed with blood

* For .'i lull con ideration of osmotic pressure in its relations to physio-
Logical proi Hamburger, "Osmotischer Druck und [onenlenre,"
Wiesbaden, 1902.

GENERAL PROPERTIES: THE CORPUSCLES. 411

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
without causing any noticeable hemolysis, and this strength of
solution is frequently employed in infusions and experimental
work; it constitutes what is known in the laboratories as nor-
mal saline or physiological 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 0.9 per cent, solution of sodium chlorid
suffices in most cases for infusions and for diluting blood,
it does not entirely replace the normal plasma or serum, since
these liquids, in addition to the sodium salts, contain salts of
calcium, potassium, magnesium, etc., each of which has doubtless
a certain specific importance. In diluting blood outside the body,
when the dilution is large, better results are obtained by using what
is known as Ringer's mixture, which consists of the physiological
saline solution plus small amounts of potassium and calcium
chlorid. One formula for Ringer's solution is :

Sodium chlorid 0.9 per cent.

Calcium chlorid 0.026 " "

Potassium chlorid 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 " globulicidal action of serum," and was compared
to the similar destruction, bactericidal action, exhibited bjr 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
* Bordet, "Annales de l'lnst. Pasteur," 1895.

412 BLOOD AND LYMPH.

some rabbits' blood beneath the skin of a guinea pig and, if neces-
sary, repeats the process it will be found that the blood of this
particular guinea pig has now a strong hemolytic action toward the
red corpuscles of rabbits. This method of producing specific
hemolysins by means of subcutaneous or intraperitoneal injections
of foreign red corpuscles is designated as a process of immunizing,
and the serum of the animal in which a specific hemolysin has been
thus produced is frequently called, for convenience, an immune
serum. These terms are employed on account of the essential
similarity of the processes involved to those underlying the devel-
opment of immunity toward special diseases. When the body is in-
vaded by pathogenic bacteria the toxic substances produced by these
organisms stimulate the tissues to form specific antitoxins which
are capable of neutralizing the action of the bacterial toxins. The
body is thus rendered immune toward special bacteria, and that the
blood of the immunized animal actually contains a definite anti-
toxin may be shown in some cases by the fact that when injected
into another individual the latter also acquires the specific immun-
ity. So in regard to the hemolysins. The presence of the foreign
red corpuscles causes the development of a specific antibody
capable of destroying the special form of red corpuscle injected.
This interesting reaction may be obtained with other cells than
the red corpuscles and bacteria. By injecting spermatozoa a
cytotoxin may be produced in the blood which destroys this
particular form of cell, and the same fact holds good for epithelial
cells, etc. Moreover, solutions of foreign proteins injected in
the same way give rise to the formation of definite antibodies
capable of coagulating or precipitating the special proteins
used. In this last case the antisubstance is designated as a
precipitin on account of its precipitating effect on the solution
of protein (see Appendix, p. 967). This wonderful protective
adaptation of the body toward the invasion of foreign cells
or proteins is at bottom doubtless a chemical reaction dependent
upon the properties of the living cells, but the nature of the proc-
esses involved is not at all understood, and the phenomenon is,
therefore, designated provisionally as a biological reaction. The
specific hemolysins produced by immunization have been studied
by Bordet, Ehrlich, and others.* It has been shown that they
are in reality composed of two substances whose combined action
is necessary lor 1 he hemolysis. There is, first, a new and specific
Substance that is produced by the body as a consequence of the

* For :> brief statemenl of the development of the subject, see Wasser-

mann, "Immune Sera, Hemolysins, Cytotoxins, and Precipitins," trans-

lated by Bolduan, New York, L904. For a more extended review, see Ase.liol'f,

/,.,! chrifl f. allgemeine Physiologie, " L, 69, L902, or Ehrlich, "Collected

Studies on Immunity, " translated by Bolduan, New York, L906.

GENERAL PROPERTIES: THE CORPUSCLES. 413

injection of the foreign blood corpuscles. This substance has been
given different names, but is known most frequently (Ehrlich)
as the immune body (or amboceptor) . It is not destroyed by mod-
erate heating. The immune body is enabled to act upon the
corpuscles by the co-operation of certain substances which are
normally present in the serum and are therefore not produced by
the process of immunization. These substances are known usually
as complements, and it is they that are destroyed by heating to
55° C. If the immune serum of a guinea pig is heated to 55° C.
its hemolytic action upon rabbits' corpuscles is destroyed. The
action may be restored, however, by adding a little of the rabbit's
own serum, since in terms of the above hypothesis the complements
are present in normal serum. That is to say, an experiment of
the following kind may be performed. Washed blood corpuscles
of a rabbit plus immune serum from a guinea pig show hemolysis.
Washed blood corpuscles of a rabbit plus immune serum which has
been made inactive by heating show no hemolysis. Addition of
normal rabbits' serum to this latter mixture again activates the
immune serum and causes hemolysis. The rabbits' serum in this
case supplies the needed complement.

These facts, it should be stated, are interpreted somewhat differently
by Bordet. The immune substance he designates as a "substance sensibila-
trice" and the complement as alexin. The latter forms the protective sub-
tance of the blood, but is unable to act upon the foreign cells until these
latter have been changed in some way, that is, sensitized by the specific
immune substance developed during the process of immunizing.

In the case of some of the natural hemolysins referred to
above it has also been shown that the solution of the corpuscles
depends upon the combined action of two substances. This
point has been made clear particularly in regard to the snake-
poisons, such as cobra venom. In these venoms there is present
a substance analogous to the immune body or amboceptor, but
in order for it to affect the red corpuscles it must be activated
by a complement of some sort, present in the plasma or the red
corpuscle itself. Kyes* has given some interesting facts to
prove that lecithin is an effective complement for these venoms,
and that probably it is this definite substance which is furnished
by the blood in activating the venom toxin. The latter seems
to form a definite compound with the lecithin, designated in
the case of the cobra poison as a cobra-lecithid.

Speaking in general terms, the serum of any animal is more or
less hemolytic in relation to the blood corpuscles of an animal of
another species; but great differences are shown in this respect.
The blood-serum of the horse shows but little hemolytic action
upon the red corpuscles of the rabbit when compared with the
*Kyes, "Berl. klin. Wochenschrift," 1902 and 1903.

414 BLOOD AND LYMPH.

effect of the serum of the dog or cat. Eels' serum has a re-
markably 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 appear-
ance of bloody urine (hemoglobinuria). It should be added
that this curious toxic or lytic effect of foreign serums is not
confined to the red corpuscles. They contain cytotoxins that affect
also other tissue elements, especially those of the central nervous
system, and may therefore cause death. As little as 0.04 c.c. of
eels' serum injected into a small rabbit will cause the death of the
animal, the fatal effect being due apparently to an action on the
vasomotor and respiratory centers in the medulla. The hemolytic
and generally toxic effect of foreign sera has been known for a long
time. It was discovered practically in the numerous attempts made
in former years to transfuse the blood of one animal into the veins
of another. It has been found that this process of transfusion as a
means of combatting severe hemorrhage is dangerous unless the
blood is taken from an animal of the same or a nearly related
species.

Nature and Amount of Hemoglobin. — Hemoglobin is a very
complex substance belonging to the group of conjugated proteins.
Under the influence of heat, acids, alkalies, etc., it may be broken
up, with the formation of a simple protein, globin, belonging to the
group of histons (see appendix) and a pigment, 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 protein
body with hematin. It seems, then, that., although the hemochro-
mogen or hematin portion is I he essential constituent, giving to the
molecule of hemoglobin its valuable physiological properties as a
re piratory pigment, yet in the blood corpuscles this substance is
incorporated into the much Larger and more unstable molecule of
hemoglobin, whose behavior toward oxygen is different from that
of the hematin itself, the difference lying mainly in the fact, that
the hemoglobin as it exist,, in the corpuscles forms with oxygen a
* SchuLz, 'Zeitschrift f. physiologische Chemie, " 24; also Lauraw, ibid., 26.

GENERAL PROPERTIES: THE CORPUSCLES. 415

comparatively feeble combination that may be broken up readily
with liberation 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; 0, 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 500 to 700 grams of hem-
oglobin, which is distributed among some 25,000,000,000,000 of
corpuscles, giving a total superficial area of about 3200 square
meters. Practically 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 capil-
laries, 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 circu-
lating through the lungs, therefore, each corpuscle becomes
exposed more or less completely to the action of the air, and
the utilization of the entire quantity of hemoglobin must be
nearly perfect. Instruments known as hemometers or
hemoglobinometers have been devised for clinical use
in determining the amount of hemoglobin in the blood of
* "Die Blutkrystalle," Jena, 1871.

416 BLOOD AND LYMPH.

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 solu-
tions are exposed to air or are otherwise brought into contact with
oxygen. Each molecule of hemoglobin is supposed to combine with
one molecule of oxygen. According to a determination by Hiifner,t
the O capacity of the Hb of ox's blood is 1.34 c.c. 0 to each gram of
Hb. It should be stated that some observers J find that the maxi-
mum oxygen capacity of the blood may show individual variations
within narrow limits, and that, therefore, what we designate as
hemoglobin may not be a single chemical substance, but a mixture
of closely related compounds. Oxyhemoglobin is not a very firm
compound. If placed in an atmosphere containing no oxygen
it is dissociated, giving off free oxygen and leaving behind hemo-
globin or, as it is often called by way of distinction, "reduced
hemoglobin." This power of combining with oxygen to form a
loose chemical compound, which in turn can be dissociated easily
when the oxygen pressure is lowered, makes possible the function
of hemoglobin in the blood as the carrier of oxygen from the lungs
to the tissues. The details of this process arc described in the
section on Respiration. Hemoglobin forms with carbon monoxid
gas (CO) :i compound, similar to oxyhemoglobin, which is known
;,- carbon >n>>n<ui,/ hemoglobin. In this compound also the union
place in the proportion of one molecule of hemoglobin to one
molecule of tin- gas. Tin- compound formed differs, however,
from oxyhemoglobin in being much more stable, and if is for this
n-:, -(,n thai the breathing of carbon monoxid gas is liable to prove
fatal. The co unite,' with the hemoglobin, forming a firm com-

*See Simon, "A Manual of Clinical Diagnosis." Philadelphia, L904.

t 'Archiv f. Physiologic" 1894, \>. L30.

j See Bohr, in Nagel'a "Handbucb der Physiologie, " vol. I. pt. i.. L905.

GENERAL PROPERTIES: THE CORPUSCLES. 417

pound; the tissues of the body are thereby prevented from obtain-
ing their necessary oxygen, and death results from suffocation or
asphyxia. Carbon monoxid forms one of the constituents of
coal-gas. The well-known fatal effect of breathing coal-gas for
some time, as in the case of individuals sleeping in a room in which
gas is escaping, is traceable directly to the carbon monoxid. Nitric
oxid (NO) forms also with hemoglobin a definite compound that
is even more stable than the CO hemoglobin; if, therefore, this
gas were brought into contact with the blood, it would cause death
in the same way as the CO.

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 0 and the C02 must unite with different portions of the
hemoglobin — the oxygen with the pigment portion and the C02 possi-
bly with the protein 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.
27

418

BLOOD AXD LYMPH.

Y;^

• ill H-1 ^c>

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. 177). As usually prepared, these crystals are really

oxyhemoglobin, but it has
, j .-, ^ 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

Crystallized hemoglobin (after

f man;

ry:

Frey): a, b. Crystals from venous Mood

c, from the Mood of a cat; '/, from the

a guinea ijik; e, from the bl
/, Irom the blood of a Sfjuirrcl

}lood of

jf a hamster;

GENERAL PROPERTIES: THE CORPUSCLES. 419

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. 177),
and in the squirrel in hexagonal plates. This difference in crystal-
line form implies some difference in molecular structure, and taken
together with other known variations in property shown by hemo-
globin from different animals lead us to believe that the huge mole-
cule has a labile structure, and that it may differ somewhat in its
molecular composition or atomic arrangement without losing its
physiological property of an oxygen-carrier. In this connection
it is interesting to state that the hemoglobin of horses' blood, which
crystallizes ordinarily in large rhombic prisms, may be made to give
hexagonal crystals by allowing it to undergo putrefaction, and that
the form of the crystals may then be changed from hexagons to
rhombs by varying the temperature of the solutions.* The crystals
are readily soluble in water, and by repeated crystallization the
hemoglobin may be obtained perfectly pure. As in the case of
other soluble protein-like bodies, solutions of hemoglobin are
precipitated by alcohol, by mineral acids, by salts of the heavy
metals, by boiling, etc. Notwithstanding the fact that hemoglobin
crystallizes so readily, it is not easily dialyzable, behaving in this
respect like non-crystallizable colloidal bodies. The compounds
which hemoglobin forms with carbon monoxid (CO) and nitric oxid
(NO) are also crystallizable, the crystals being isomorphous with
those of oxyhemoglobin.

Absorption Spectra. — Solutions of hemoglobin and its deriv-
ative compounds, when examined with a spectroscope, give
distinctive absorption bands.

Light, when made to pass through a glass prism, is broken up into its
constituent rays, giving the play of rainbow colors known as the spectrum.
A spectroscope is an apparatus for producing and observing a spectrum. A
simple form, which illustrates sufficiently well the construction of the appara-
tus, is shown in Fig. 178, 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, 6-4, 1904.

420

BLOOD AND LYMPH.

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
fight 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. 178. — 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
th:m the other, the "/?-band" (Fig. 17!)). The width and distinct-
of the bands vary naturally with the concentration of the solution
used (see Fig. 180) or, if the concentration remains the same,
with the width of the stratum of liquid through which the light
With a certain minima,! percentage of oxyhemoglobin
(let than 0.01 per cent.) the 0-band is bsl and the '/-band is very
fainl in layers 1 centimeter thick. With stronger solutions the
bands become darker and wider and finally fuse, while some of the

extreme red end and a greal deal of the violet end of the sped ruin

GENERAL PROPERTIES: THE CORPUSCLES.

421

are also absorbed. The variations in the absorption spectrum,
with differences in concentration, are clearly shown in the accom-
panying illustration from Rollett * (Fig. 180) ; the thickness of the
layer of liquid is supposed to be one centimeter. The numbers
on the right indicate the percentage strength of the oxyhemoglobin
solutions. It will be noticed that the absorption which takes

r>

E b

660

650 640 630 620 610 600 5^0 580 S70 560 550 540 530

,li,„l.ii.l„.Jiililiillli..ilmllinilililllmliMllili1lmili]lllli»lmilimlllii[i

510 500 MO

Fig. 179. — Table of absorption spectra (Ziemke and Mutter) : 1, Absorption spectrum
of oxyhemoglobin, dilute solution; 2, absorption spectrum of reduced hemoglobin ; 3, ab-
sorption spectrum of methemoglobin, neutral solution; 4, absorption spectrum of met-
hemoglobin, alkaline solution ; 5, absorption spectrum of hematin, acid solution; 6, ab-
sorption spectrum of hematin, alkaline solution.

place as the concentration of the solution increases affects the
red-orange end of the spectrum last of all-
Solutions of reduced hemoglobin examined with the spectroscope
show only one absorption band, known sometimes as the " j'-band."
This band lies also in the portion of the spectrum included between
the lines D and E; its relations to these lines and the bands of
* Hermann's " Handbuch der Physiologie," vol. iv., 1880

422

BLOOD AND LYMPH.

oxyhemoglobin are shown in Fig. 179. The f-band is much more
diffuse than the oxyhemoglobin bands, and its limits, therefore,
especially in weak solutions, are not well defined. The width and
distinctness of this band vary also with the concentration of the
solution. This variation is sufficiently well shown in the accom-
panying illustration (Fig. 181), which is a companion figure to the
one given for oxyhemoglobin (Fig. 180). It will be noticed that

the last light to be ab-
sorbed in this case is
partly in the red end
and partly in the blue,
thus explaining the pur-
plish color of hemoglo-
bin solutions and of
venous blood. Oxy-
hemoglobin soluti o n s
can be converted to
hem oglobin solutions,
with a corresponding
change in the spectrum
bands, by placing the
former in a vacuum or,
more convenient ry, by
adding reducing solu-
tions. The solutions
most commonly used
for this purpose are am-
monium sulphid a n d
Stokes's reagent.* If
a solution of reduced
hemoglobin is shaken
with ;iir, it quickly
changes to oxyhemo-
globin and gives two
bands instead of <>nc
when examined by the
spectroscope. Any given solution may be changed in this way from
oxyhemoglobin t<» hemoglobin, and the reverse, a. great number of
times, thus demonstrating the facility with which hemoglobin takes
\i\> and surrenders oxygen.

Solutions of carbon monoxid hemoglobin also give a spec-

.[ ! an ammoniacal solution of a ferrous salt, [tismade
by dissolving 2 parts (by weight) of ferrous sulphate, adding 3 parts of tar-
taric acid, and then ammonia to distincl alkaline reaction. A permanent
precipitate bould not !><• obtained.

aBC

Fig. 180. — Diagram to show the variations in the
absorption spectrum of oxyhemoglobin with varying
concentration ..I the solution. — (After Rollett.) The
numbers to the right give the strength of the oxy-
jlobin 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 ihi line passes through the shaded pari
of the diagram absorption takes place, and the width
of the absorption band i seen .-it once. The diagram
shows dearly thai the amounl of absorption increases
a the solution: become nunc concentrated, especially
the absorption of the blue end of the spectrum. It
will be noticed thai with concentrations between 0.6
and 0.7 pei cent, the two bands between D and £ f use
into one.

GENERAL PROPERTIES: THE CORPUSCLES.

423

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
a change in color, taking on a brownish tint. This change is due to
the formation of methemoglobin, and it is said that to some extent
the transition occurs very soon after the blood is exposed to the air,
and that, therefore, determinations of the quantity of hemoglobin
by the ordinary colorimetric methods should be made promptly to
avoid a deterioration in color value. Methemoglobin may be
obtained rapidly by the action of various reagents on the blood,

* For more detailed information concerning the chemistry and literature
of these compounds, see Hammarsten, "Physiological Chemistry," translated
by Mandel, fourth edition, 1904; Abderhalden, " Physiologische Chemie," 1906.

Fig. 181. — 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.
180.

424 BLOOD AND LYMPH.

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. 179. 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 hemorrhage in the stomach or small intestine, since
both the pancreatic and the gastric secretion break up hemoglobin,
with the formation of hematin. It is an amorphous substance, of a
dark-brown color, easily soluble in alkalies or in acid alcoholic solu-
tions. These solutions give a characteristic absorption spectrum
which is represented in Fig. 179.

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 oik- that has been much used in medicolegal cases, and may
be carried out as follows: A bit of dried blood is powdered with a
few crystals of Na('l. 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, tal ing 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,

GENERAL PROPERTIES: THE CORPUSCLES. 425

Hemochromogen (C34H3(.N4Fe05 ?) is obtained when hemoglobin
is decomposed by acids or alkalies in the absence of free oxygen. By
oxidation it is converted to hematin. Hemochromogen is crystal-
line, and gives a characteristic absorption spectrum.

Hematoporphyrin (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. — These pigments are
referred to in the description of the composition of bile and urine.
In this connection the fact may be emphasized that each of them is
supposed to be derived from hemoglobin, and each constitutes, so
to speak, a form of excretion of hemoglobin.

Origin and Fate of the Red Corpuscles. — The mammalian red
corpuscle is a cell that has lost its nucleus. It is not probable, there-
fore, that any given corpuscle lives for a great while in the circulation.
This is made more certain by the fact that hemoglobin is the mother
substance from which the bile pigments are made, and, as these
pigments are being excreted continually, it is fair to suppose that
red corpuscles are as steadily undergoing disintegration in the blood-
stream.

426 BLOOD AND LYMPH.

The number of red corpuscles destroyed daily in the body has never
been determined with any accuracy, but it may be quite large, as would appear
from the following approximate calculation based upon our incomplete
knowledge of the amount of bile-pigment secreted daily. From observations
made upon cases of biliary fistulas in man it is estimated that the daily flow
of bile amounts to about 15 gins, per kilogram of body weight. If we assume
in accordance with the figures given by some authors that the bile contains
as much as 0.2 per cent, of pigment, then 1.95 gms. of pigment will be secreted
per <lay (65 X 15 X. 002). This pigment is formed from approximately the
same weight of hematin and for its formation would require the destruction
of 48 gms. of hemoglobin, since hematin forms 4 per cent, of the molecule of
hemoglobin (1.95-^4=48). The total amount of blood in a man weighing
65 kilograms, according to modern estimates, is about .3510 grams (65,000 X
.054), and this gives us about 480 gms. of hemoglobin (3510X0.14). Accord-
ing to this estimate, therefore, one-tenth of the total hemoglobin may be broken
down daily, and the total duration of life of a red corpuscle in the circulation
could not' exceed ten days. A calculation of this kind is, however, only
suggestive; it cannot be accepted as a basis for further estimates, owing to the
uncertainty that prevails as to the amount of bile pigment formed and excreted
daily.

Just when and how the corpuscles go to pieces is not defi-
nitely known. It has been suggested that their destruction
takes place in the spleen and lymph-glands, but the observations
advanced in support of this hypothesis are not very numerous
or conclusive. Among the reasons given for assuming that the
spleen is especially concerned in the destruction of red corpuscles,
the most weighty is the histological fact that one can sometimes
find in teased preparations of spleen-tissue or of lymph-glands
certain large cells (macrophags) 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 arc in a state
of physiological decline. Against tins idea a number of
objections may be raised. Large leucocytes with vod cor-
puscles 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
me reason for believing, indeed, that the whole act of
ingestion may be ;i postmortem phenomenon; that is, after the
lion of flic blood-stream the ameboid movements of the large
leucoc} fces continue, while the red corpuscles lie at rest, — conditions
that M-c 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 thai no considerable dissolution of red corpuscles is
taking place in the spleen. Moreover, complete extirpation of the
spleen does not seem lo lessen materially the normal destruction
of re<l corpuscles, if we may measure the extent of that normal
destruction by the quantity of bile pigment formed in the liver,
remembering thai hemoglobin is the mother-substance from which
the bile pigments are derived. It is more probable that there is no

GENERAL PROPERTIES: THE CORPUSCLES. 427

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?
on continually, the process being much increased after hemorrhages
and in certain pathological conditions. The details of the histo-
logical changes will be found in the text-books of histology. It is
sufficient here to state simply that groups of nucleated, colorless
cells, erythroblasts, are found in the red marrow. These cells
multiply by karyokinesis and the daughter-cells eventually produce
hemoglobin in their cytoplasm, thus forming nucleated red cor-
puscles. The nuclei are subsequently lost, either by disintegration
or by extrusion, and the newly formed non-nucleated red corpuscles
(erythrocytes) are forced into the blood-stream, owing to a gradual
change in their position during development caused by the growing
hematopoietic tissue. When the process is greatly accelerated, as
after severe hemorrhages or in certain pathological conditions,
red corpuscles still retaining their nuclei (normoblasts) may be
found in the circulating blood, having been forced out prematurely.
Such corpuscles may subsequently lose their nuclei while in the
blood-stream. In the embryo, hematopoietic tissue is found in
parts of the body other than the marrow, notably in the liver and
spleen, which at that time serve as organs for the production of
new red corpuscles. In the blood of the young embryo nucleated
red corpuscles are at first abundant, but they become less numerous
as the fetus grows older.* It is interesting to note that in the
adult after severe anemias — e. g., pernicious anemia — and in rabbits
after the injection of saponin the spleen may again take on its
hematopoietic function. The venous sinuses become crowded with
cells of the marrow type.f

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

* Howell, "Life History of the Blood Corpuscles," etc., "Journal of
Morphology," 1890, vol. iv.; Bunting, "Univ. of Pennsylvania Medical
Bulletin," 1903, xvi., 200.

f See Bunting, "The Journal of Experimental Medicine," 1906, viii., 625.

42^ BLOOD AXD LYMPH.

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,* who believed that the diminished supply of oxygen
in high altitudes may be compensated by an increased amount of
hemoglobin, and subsequently Viaultf demonstrated that living for
a short time at very high altitudes (4000 meters) causes a marked in-
crease in the number of red corpuscles, — an increase, for instance,
from 5,000,000 per c.mm. to 7,000,000 or even 8,000,000. This fact
has since been investigated with great care b}^ 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, J the number of blood plates is also greatly
increased by high altitudes, while the leucocytes are not affected.
There has, however, been much difference of opinion as to whether
this increase in number of the red corpuscles is relative or absolute,
— that is, whether the total number of red corpuscles in the blood,
and therefore probably the total amount of hemoglobin, is increased,
or whether it is simply an apparent increase due, for instance, to a
diminution in the water of the blood and a consequent concentration
as regards the number of corpuscles, or to a variation in the distri-
bution of the corpuscles between the vessels of the skin and those
of the internal organs. The results published upon these questions
have been conflicting. One may, however, believe that the in-
ed number or concentration of red corpuscles is an adaptation
by means of which the oxygen-carrying capacity of the blood
us raised to compensate for the diminished amounl of oxygen in the
air. According to one set of observers, this adaptation is brought
about by ;ui absolute increase in the total number of red corpuscles,
and therefore in the total amounl of hemoglobin. There seems
to be little doubt that such a change occurs in cases of long residence;

* Bert, "La pression barometrique, " L878, p. I ins.

i Viault, "Compte rendu de l'academie dei iciences," 1890 and L891.

X Kemp, "American Journal of Physiology," L0, 34, L904.

GENERAL PROPERTIES: THE CORPUSCLES. 429

in high altitudes, and we may assume that the diminished amount
of oxygen in the air or some other condition peculiar to these
altitudes acts as a stimulus to the blood-forming tissues (red mar-
row) and augments the output of corpuscles and hemoglobin.
Zuntz and his co-workers have shown in experiments upon clogs
that there is a visible increase in the red marrow of the bones as
a result of living for some months at a high altitude. According
to another set of observers, the adaptation is brought about by a
concentration of the blood. The blood-plasma is reduced in
quantity, perhaps by transudation of water into the tissues, and
therefore the number of red corpuscles and the amount of hemo-
globin become greater for each cubic millimeter. If we assume
that this smaller bulk of blood, more concentrated in corpuscles
and hemoglobin, circulates more rapidly, then also the oxygen-
carrying capacity of the blood is increased. In favor of this view,
Abderhalden, for instance, has claimed that, if animals of the
same species and same litter are bled to death and the total quan-
tity of hemoglobin is estimated, the average figures obtained for
the animals at low levels are the same as for those at the high
altitudes. Zuntz has, however, called attention to the fact that
when Abderhalden's figures are estimated per kilogram of weight
they show an increase in total hemoglobin in the high altitudes,
and he and other observers have obtained similar results. It
seems certain, therefore, that high altitudes cause eventually a
marked increase in the production of red corpuscles, but that the
very sudden changes of this kind reported by some authors as
happening within a few hours must be considered as apparent
rather than real, and are to be explained by some change in the
water contents or in the distribution of the blood.*

Physiology of the Blood Leucocytes. — The function of the
blood leucocytes has been the subject of numerous investigations,
particularly in connection with the pathology of blood diseases.
Although many hypotheses have been made as the result of this
work, it cannot be said that we possess much positive information as
to the normal function of these cells in the body- It must be borne
in mind, in the first place, that the blood leucocytes are not all the
same histologically, and it may be that their functions are as diverse
as their morphology. Various classifications have been made,
based upon one or another difference in microscopical structure and
reaction, but at present the system most used is that adopted
by Ehrlich-f According to this nomenclature, the white cor-

* For the extensive literature see Van Voornveld. 'Das Blut im Hoch-
gebirge, " "PfliAger's Archiv," 92, 1, 1902; Zuntz et al., "Hohenklima und
Bergwanderungen in ihrer Wirkung auf den Menschen," 1906.

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

430 BLOOD AXD LYMPH.

puscles fall into two main groups, — the lymphocytes and the
leucocytes. — and each of these into two or more subgroups. Thus:

I. Lymphocytes. No granules in the cell substance, and, though capable of

ameboid changes of form, this property is not characteristic and prob-
ably not sufficient to cause locomotion.

(a) Small lymphocytes are about the size of the red corpuscles; the nu-
cleus is large, symmetrically placed, stains homogeneously, and the
cytoplasm is reduced to a very small amount. They form from 20
to 25 per cent, of all the white corpuscles.

(6) Large lymphocytes. Two to three times as large as the preceding.
Nucleus somewhat eccentric; the cytoplasm is relatively more
abundant than in a, but non-granular. These forms exist only in
small numbers, forming 1 per cent, or less of the white corpuscles.

II. Leucocytes. Granules of different sorts found in the cytoplasm. Cells

characteristically ameboid.

(a) Transition forms (uninuclear leucocytes). Single large nucleus, more
or less lobulated; cytoplasm abundant and faintly granulated. The
granules stain with neutral dyes and are therefore designated as
neutrophile granules. The name, transition form, implies that these
leucocytes represent an intermediate stage between the large lympho-
cytes and the following variety, but this belief is vigorously denied
by many competent hematologists. 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
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.

Aceordino; to some authors the small lymphocytes are cells
that have an origin and function different from those of the granular
leucocytes. While the Latter are supposed to originate from cells
(leucoblasts, myeloblasts) in the bone marrow, the lymphocytes
are produced in the nodules of the lymph glands and lymphoid
tissue, and enterthe blood through the lymph circulation. Others,
however, lay stress on the fad thai lymphocytes occur in the Ik tne-
marrow and hold thai it is possible or probable that the lympho-
cytes of \}\<- blood may In- derived from the marrow tissue as well
an the lymphoid tissue. The suWjecl is one that at present is
discussed cbjefly in connection with the pathology of blood dis-

I

. *

♦ See I. mil' .mi, "Clinical Diagnosis," 1906, p. 483, Pappenheim, "Atlas
(I. mensch. Blutzellen, L905, and Ferrata, " Folia Hsematologica," 1908, v., 655.

GENERAL PROPERTIES: THE CORPUSCLES. 431

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, pregnane}7, 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 and other foreign cells or organisms. In
explanation of this action it has been suggested that they may
either ingest bacteria, and thus destroy them directly, or they
may form certain substances, bacteriolysins, that destroy the
bacteria. The wonderful protective adaptation of the body des-
ignated by the term "biological reaction" has already been referred
to (p. 412). The formation of immune substances in the blood is
attributed, in part at least, to the leucocytes. Leucocytes that
act by ingesting the bacteria are spoken of as " phagocytes "((pdyeiv,
to eat; %uto~} cell). This theory of their function is usually
designated as the "phagocytosis theory of Metchnikoff " ; it is
founded upon the fact that the ameboid leucocytes are known to
ingest foreign particles, including bacteria, with which they come
in contact. The leucocytes which seem especially adapted to
attack bacteria are the polymorphonuclear variety, designated
by Metschnikoff as microphags. One of the most interesting
recent developments in pathology in this connection is the dis-
co very (Wright) that this power of the leucocytes to ingest bac-
teria depends upon the presence in the plasma of certain sub-
stances designated as opsonins (from opso'no, I prepare food for),
which sensitize or in some way prepare the bacteria so that they
are attacked by the leucocytes. These opsonins, like the cyto-
toxins, belong to the group of antibodies, and may be called into
existence or increased in amount by the injection into the body
of suitable bacteria or their products. The amount of opsonins

432 BLOOD AND LYMPH.

present at any time may be determined by measuring the phago-
cytic activity of the leucocytes, that is, by determining the
actual number of bacteria ingested by them, in comparison with
normal conditions.* (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 func-
tion must be reserved until the phenomenon of coagulation is
described. (5) They help to maintain the normal composition
of the blood-plasma in proteins. It may be said for this view
that there is considerable evidence to show that the leucocytes
normally undergo disintegration and dissolution in the circulating
blood, to some extent at least. The blood proteins are peculiar,
and they are not formed directly from the digested food. It is
possible that the leucocytes, which are the only typical cells in
the blood, aid in keeping up the normal supply of proteins. From
this standpoint they might be regarded in fact as unicellular glands,
the products of their metabolism serving to maintain the normal
composition of the blood-plasma. The formation of granules
within the substance of the eosinophiles offers a suggestive analogy
to the accumulation of zymogen granules in glandular cells.

Physiology of the Blood Plates. — The blood plates are small,
circular or elliptical bodies, nearly homogeneous in structure and
variable in size (0.5 to 5.5 ;i), 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, f 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
m, 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.

( >i\ account of their small size and somewhat indefinite form the
struct ure of the blood plot os is not sat isfact orily known. DeetjenJ

* For ;i brief general discussion of opsonins, sec Hektoen, "Science,"
I eb i-'. 1909.

fWrighl I'." ton Medical and Surgical Journal," June 7, L906) calls
attention i<> :i relationship between the blood-plates ami the giant cells of
ili.' marrow (megalokaryocytes), and ventures the opinion thai the plates
are detached pieces "I the cytoplasm of Hie jri.-mi cells.

f'Virchow's Archiv f. path. Anat. u. Physiol.," 164, 239, L901.

GENERAL PROPERTIES: THE CORPUSCLES. 433

has demonstrated that they are capable of ameboid movements.
When removed from the blood vessels to a glass slide they usually
agglutinate into larger or smaller masses, swell, and disintegrate,
but if received upon a surface of agar-agar which has been made up
with physiological saline, together with some sodium metaphos-
phate (NaPOs), they flatten out, show a central granular portion
and a peripheral clear layer, and may make quite active ameboid
movements. Deetjen claims also that they possess a distinct
nucleus. This latter statement is perhaps doubtful, as other
observers report that the material which stains like a nucleus is
present as separate granules in the interior of the plate. These
granules, though doubtless of nuclear material, do not have the
morphological appearance of a cell nucleus. It remains, therefore,
uncertain whether the blood plates are to be considered as inde-
pendent cells or as fragments of disintegrated cells. On account
of their tendency to agglutinate and dissolve when the blood is shed
it is difficult to obtain reliable data as to their numbers under
normal and pathological conditions.* The results obtained by
later observers using special methods to prevent known sources of
error indicate that the average number may be 500,000 per cubic
millimeter. The extremes reported vary from 200,000 or 250,000
to 778,000. Under certain pathological conditions, especially in
pernicious anemia and lymphatic leukemia, their number is greatly
reduced,' while in the acute infectious diseases there is said to
be a diminution in number during the period of fever, followed
by a marked increase beyond the normal during the period of
convalescence. Outside the part that they take in the formation
of thrombi and in the initiation of coagulation, nothing definite
is known of their function under normal conditions.

* For a summary of the literature and methods, consult Kemp, "Journal
of the American Medical Association," April 7 and 14, 1906, and Pratt, ibid.,
Dec. 30, 1905. The preservative solution recommended by Pratt consists
of sodium metaphosphate, 2 grams; sodium chlorid, 0.9 gram; water, 100 c.c.
That preferred by Kemp is, formalin (40 per cent, aqueous solution of for-
maldehyd), 10 c.c; sodium chlorid (1 per cent, solution), 150 c.c.
28

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.
f Fibrinogen.

Protein, \ Paraglobulin {

Scrum-albumin

Euglobulin.
Pseudoglobulin.

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

Salts

of

Nucleo-protcin.
f Fats.

Sugar.
I Urea.
j Jecorin.

Glucuronic acid.

Lecithin.

Cholostorin

Lactic acid.

Chi., rids
Carbonates
Sulphates
Phosphates

Internal secretions.

Tii f Lipase.

Enzymes j GryColMe> eto

Immune bodies (Amboceptors).
I Complements.
[ Opsonins.

A number of detailed chemical analyses of the blood of different
animals, so far as its constituents can be determined by analytical
methods, have been reported at different times. The following

444

Enzymes and unknowns.

Sodium.

Potassium.

Calcium.

Magnesium

Iron.

CHEMICAL COMPOSITION OF BLOOD-PLASMA. 435

table, taken from Abderhalden,* and showing the composition of
dogs' blood, may serve as an example:

1000 Parts, by 1000 Parts, by 1000 Parts, by

Weight, of Blood Weight, of Se- Weight, of Corpus-
Contain rum Contain cles Contain

Water 810.05 923.98 644.26

Solids 189.95 76.02 355.75

Hemoglobin 133.4 327.52

Protein 39.68 60.14 9.918

Sugar... 1.09 1.82

Cholesterin 1.298 0.709 2.155

Lecithin 2.052 1.699 2.568

Fat 0.631 1.051

Fatty acids 0.759 1.221 0.088

Phosphoric acid:

as nuclein 0.054 0.016 0.110

Na^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 protein
in the serum is greater in some cases than in others, — in the dog,
for instance, according to Abderhalden's analyses, the protein
amounts to only 6 per cent., while in the horse it may be 7 or 8 per
cent. So also there are small variations in the amount of choles-
terin, sugar, and other constituents, but, on the whole, the composi-
tion of the liquid part of the blood, blood-serum or blood-plasma,
is remarkably uniform so far as chemical analyses go. We know,
however, that the physiological properties of mammalian serum may
be very different indeed; that the serum of a dog, for instance, will
kill a rabbit when injected into its vessel. Such physiological dif-
ferences as this, however, depend upon constituents which can not
be 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, 1S98.

436 BLOOD AND LYMPH.

Proteins of the Blood-plasma. — The general properties and
reactions of proteins and the related compounds, as well as a classi-
fication of those occurring in the animal body, are described briefly
in the Appendix. This description should be read before attempt-
ing to study the proteins of the plasma and the part they take in
coagulation. Three proteins are usually described as existing in the
plasma of circulating blood, — namely, fibrinogen, paraglobulin,
or, as it is sometimes called, "serum-globulin," and serum-albumin.
The first two of these proteins, fibrinogen and paraglobulin, belong
to the group of globulins, and hence have many properties in com-
mon. Serum-albumin belongs to the group of albumins, of
which egg-albumin constitutes another member.

Serum-albumin. — This substance is a typical protein. It can be
obtained readily in crystalline form from the horse's blood. Its
percentage composition, according to Michel, is as follows: 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
the body-liquids together with the globulins, as is the case in blood.
If such a liquid is thoroughly saturated with solid magnesium sul-
phate or half saturated with ammonium sulphate, the globulins
are precipitated completely, while the albumin is not affected.
So far as the blood and similar liquids are concerned, a definition
of serum-albumin might be given by saying that it comprises all
the proteins not precipitated by saturation with magnesium sul-
phate or by half saturation with ammonium sulphate. When its
solutions have a neutral or an acid reaction, serum-albumin is
precipitated in an insoluble form by heating the solution above a
certain degree. Precipitates produced in this way by heating
solutions of proteins are spoken of as coagulations — heat coagula-
tions— and the exact temperature at which coagulation occurs
is to a certain extent characteristic for each protein. The tem-
perature of coagulation of serum-albumin is usually given at from
70° to 75° C, but it varies greatly with the conditions. — for in-
stance, with the reaction of the solution, its concentration in salts,
or with the nature of the; salts present. It has been asserted,
in fact, thai careful heating under proper- conditions gives separate
coagulations at, three different temperatures, namely, 73°, 77°,
and S4° C, — indicating the possibility that whal is called "serum-
albumin" may be a mixture, of three proteins. Serum-albumin
occurs in blood-plasma and blood-serum, in lymph, and in the
different normal and pathological exudations found in the body;
* "Archiv f. exper. Pathol u, Pharmakol.," 39, 1, 1897.

CHEMICAL COMPOSITION OF BLOOD-PLASMA. 437

such as pericardial liquid, hydrocele fluid, etc. The amount of
serum-albumin in the blood varies in different animals, ranging
among the mammalia from 2.67 per cent, in the horse to 4.52 per
cent, in man. In some of the cold-blooded animals it occurs in
surprisingly small quantities, — 0.36 to 0.69 per cent. As to the
source or origin of serum-albumin, it is frequently stated that it
comes from the digested proteins of the food. It is known that
protein material in the food is not changed at once to serum-albumin
during the act of digestion; indeed, it is known that the final products
of digestion are a group of proteins of an entirely different char-
acter,— namely, peptones and proteoses, — or, indeed, a series of
much simpler split products; but during the act of absorption
into the blood these latter bodies have been supposed to undergo
transformation into serum-albumin. From a physiological stand-
point serum-albumin is often considered to be the main source of
protein nourishment for the tissues generally. As will be explained
in the section on Nutrition, one of the most important requisites
in the nutrition of the cells of the body is an adequate supply of
protein material to replace that used up in the chemical changes,
the metabolism, of the tissues. Serum-albumin has been supposed
to furnish a part, at least, of this supply, although, as a matter of
fact, there is no substantial proof that this view is correct. As
long as the serum-albumin is in the blood-vessels it is, of course,
cut off from the tissues. The cells, however, are bathed directly
in lymph, and this in turn is formed from the plasma of the blood
which is transuded or, according to some physiologists, secreted
through the vessel walls.

Paraglobulin, which belongs to the group of globulins, exhibits
the general reactions characteristic of the group. As stated above,
it is completely precipitated from its solutions by saturation with
magnesium sulphate or by half saturation with ammonium sulphate.
It is incompletely precipitated by saturation with common salt
(NaCl). In neutral or feebly acid solutions it coagulates upon
heating to 75° C. Hammarsten gives its percentage composition
as: C, 52.71; H, 7.01; N, 15.85; S, 1.11; 0, 23.32. Schmiedeberg
gives it a molecular composition corresponding to the formula
C117H182N30SO38 + 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 protein is

438 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, or by dialysis, and portions are not so precipitated.
Recently, therefore, it has been assumed that paraglobulin is in
reality a mixture of two or possibly three different, although re-
lated, proteins. The separation usually given is into euglobulin
and pseudoglobulin, euglobulin being the portion precipitated by
ammonium sulphate when added to one-third saturation (28 to 33
per cent.), and pseudoglobulin the portion precipitated only by
one-half saturation (34 to 50 per cent.). The latter portion shows
properties more nearly related to the albumins.* The whole basis
of classification is, however, unsatisfactory and provisional (see
appendix). It is even stated that under certain conditions of
temperature and reaction serum-albumin may be converted to a
globulin body that precipitates upon one-half saturation with
ammonium sulphate.f The origin of paraglobulin remains unde-
termined. It may arise from the digested proteins absorbed from
the alimentary canal, but there is no evidence to support such a
view. Another suggestion is that it comes from the disintegration
of the leucocytes (and other formed elements) of the blood. These
bodies are known to contain a small quantity of a globulin resem-
bling paraglobulin, and it is possible that this globulin may be liber-
ated after the dissolution of the leucocytes in the plasma, and thus go
to make up the normal supply of paraglobulin. Several observers^
have claimed that during starvation the proportion of globulins
in the blood is increased relatively or absolutely. A possible
explanation is that the increase is due to cell globulins received from
the tissues which must undergo destruction and dissolution in pro-
longed fasting. The fact remains, however, that our knowledge is
too incomplete at present to venture any positive statements
regarding the origin and specific functions of the paraglobulin.

Fibrinogen is a protein belonging to the globulin class and exhibit-
ing all the general reactions of this group. It is distinguished from
paraglobulin by a number of special reactions; for example, its
temperature of heat coagulation is much lower (56° to 60° C), and

* Por^es and Spiro, "Beitrage zur chem. Physiol, u. Pathol.," 3, 277,
1903; and Freund and Joachim, "Zeitechrift f. physiolotfische Chemie," 36,
407, 1002.

fMoll, "Beitrage zur chem. Physiol, u. Pathol. " 4, 561, 1003.

I Bee St. <;itlH-.,s, " lii-Wriifrt- zur diem. Physiol, u. Pathol.," 5, 515, 1904;
ftluo Pcwin.ski, "Pfluger'a ArchlV f. d. gesammte Physiol.," 100, 611, 1903.

CHEMICAL COMPOSITION OF BLOOD-PLASMA. 439

it is completely thrown down from its solutions by saturation with
sodium chlorid as well as with magnesium sulphate. Its most
important and distinctive reaction is, however, that under proper
conditions it gives rise to an insoluble protein, fibrin, whose forma-
tion is the essential phenomenon in the coagulation of blood.
Fibrinogen has a percentage composition, according to Hammar-
sten, of: C, 52.93; H, 6.90; N, 16.66; S, 1.25; 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 proteins. There is no good method of determining
quantitatively the amount of fibrinogen, but estimates of the
amount of fibrin, which cannot differ very much from the fibrinogen,
show that in human blood it varies from 0.22 to 0.4 per cent. In
horse's blood it may be more abundant, — 0.65 per cent. As to the
origin and the special physiological value of this protein we are, if
possible, more in the dark than in the case of paraglobulin, with the
exception that fibrinogen is known to be the source of the fibrin of
clotted blood. But clotting is an occasional phenomenon only.
What nutritive function, if any, is possessed by fibrinogen under
normal conditions is unknown. No satisfactory account has been
given of its origin. It has been suggested by different investigators
that it may come from the nuclei of disintegrating leucocytes (and
blood plates) or from the dissolution of the extruded nuclei of newly
made red corpuscles, but here again we have only speculations, that
can not be accepted until some experimental proof is advanced to
support them. It may be added that there is some evidence to
indicate that the fibrinogen is produced in the liver. Thus Doyon
and his co-workers * have shown that when the fibrinogen is re-
moved from blood by defibrinating and the blood is then returned
to the animal, new fibrinogen is produced within a few hours.
In frogs, at least, the new fibrinogen is not manufactured if the
liver is removed, and in dogs it is also stated that after removal
of the liver the blood may become incoagulable owing to a disap-
pearance of fibrinogen.

The following table f gives some recent results of analyses of

blood which indicate the average amounts of the different proteins

in the blood-plasma of several animals. The figures give the weight

of the protein in grams for 100 c.c. of plasma.

* Doyon et al., "C. R. Soc. de Biol.,'; lx., 606, 681, 860. See also Nolf,
''Archives internat. de Physiol.," 1905, hi., 1.
f Lewinski, loc. r.it.

440 BLOOD AND LYMPH.

Serum-
Total Proteins. Albumin. Paraglobulin. Fibrinogen.

Man 7.26 4.01 2.83 0.42

Dog 6.03 3.17 2.26 0.60

Sheep 7.29 3.83 3.00 0.46

Horse .-.8.04 2.S0 4.79 0.45

Pig S.05 4.42 2.98 0.65

Otlier Proteins of the Blood-serimi or Blood-plasma. — From time to time
other protein bodies have been described in the serum or plasma of the blood.
In the serum after coagulation Hammarsten has obtained a globulin body,
Hbrin-globulin. which he supposes may be split off from the fibrinogen during
the act of clotting. Faust, as was mentioned above, describes an albuminoid
substance, glutolin, which is present in the blood and is usually precipitated
together with the paraglobulin. A number of observers have noted the ex-
istence in blood of a protein not coagulated by heat. By some authors this
has been described as a peptone or an albumose (Langstein), by others as an
ovomucoid (Zanetti), and by others still (Chabrie) as a peculiar protein for
which the name albumon has been proposed. By others still this non-coag[U-
lable protein obtained from serum or plasma has been explained as an artificial
product arising from the globulins of the blood during the process of remov-
ing the coagulable proteins by heating. So, too, nucleoprotein substances
have been described in the blood-serum by several observers, most recently by
Freund and Joachim. It is quite possible, however, that the substance de-
scribed as nucleoprotein is in reality a mixture or combination of lecithin and
protein. Most of the protein when precipitated from the blood carries down
with it some lecithin, and will therefore show a reaction for phosphorus. It
can be shown that the phosphorus present is, in most cases at least, remov-
able by boiling with alcohol, and there is at present no entirely satisfactory
proof that nucleoprotein exists in the blood.

Coagulation of Blood. — One of the most striking properties of
blood is its power of clotting or coagulating shortly after it escapes
from the blood-vessels. The general changes in the blood during
this process are easily followed. At first perfectly fluid, in a few
minutes it becomes viscous and then sets into a soft jelly which
quickly becomes firmer, so that the vessel containing it may be
inverted without spilling the blood. The clot continues to grow
more compact and gradually shrinks in volume, pressing out a
smaller or larger quantity of a clear, faintly yellow liquid to which
the name blood-serum is given. The essential part of the clot is the
fibrin, fibrin is an insoluble protein not found in normal blood,
in shed blood, and under certain conditions in blood while still in the
blood-vessels, this fibrin is formed from the soluble fibrinogen.
The deposition of the fibrin is peculiar. It is precipitated, if the
word may be used, in the form of an exceedingly fine network of
delicate I hreada which permeate the whole mass of the blood and
give the elol its jelly-like character. The shrinking of the
threads causes the subsequent contraction of (lie clot. If
the blood has not been disturbed during the act of clotting,
the red corpuscles are caught in the line 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 ii is possible to get specimens of serum containing
few or no red corpuscles. The; leucocytes, on the con-

COAGULATION. 441

trary, although they are also caught at first in the forming
meshwork of fibrin, may readily pass out into the serum in the later
stages of clotting, on account of their power of making ameboid
movements. If the blood has been agitated during the process of
clotting, the delicate network will be broken in places and the serum
will be more or less bloody — that is, it will contain numerous red
corpuscles. If during the time of clotting the blood is vigorously
whipped with a bundle of fine rods, all the fibrin is deposited
as a stringy mass upon the whip, and the remaining liquid part
consists of serum plus the blood corpuscles. Blood that has been
whipped in this way is known as " defibrinated blood." It resembles
normal blood in appearance, but is different in its composition; it
can not clot again. The way in which the fibrin is normally de-
posited may be demonstrated very easily under the microscope by
placing a good-sized drop of blood on a slide, covering it with a
cover-slip, and allowing it to stand for several minutes until coagu-
lation is completed. If the drop is now examined, it is possible by
careful focusing to discover in the spaces between the masses of
corpuscles many examples of the delicate fibrin network. The
physiological value of clotting is that it stops hemorrhages by
closing the openings of the wounded blood-vessels.

Time of Clotting. — The time necessary for the clot to form varies
slightly in different individuals, or in the blood of the same in-
dividual varies with the conditions. It may be said in general that
under normal conditions the blood passes into the jelly stage in
from three to ten minutes at room temperature (20° C). The
separation of clot and serum takes place gradually, but is usually
completed in from ten to forty-eight hours. The time of clotting
shows marked variations in different animals; the process is
especially slow in the blood of the horse, terrapin, and birds, so
that coagulation of shed blood is more easily prevented in these
animals. In the human being also the time of clotting may be
much prolonged under certain conditions — in fevers, for example.
This fact was noticed in the days when blood-letting was a
common practice. The slow clotting of the blood permitted
the red corpuscles to sink somewhat, so that the upper part of
the clot in such cases was of a lighter color, forming what was
called the "buffy coat." The time of clotting may be shortened
or prolonged, or the clotting may be prevented altogether, in
various ways, and much use has been made of this fact in study-
ing the composition and the coagulation of blood as well as in
controlling hemorrhages.*

* For clinical methods of determining the coagulation time with a drop
or two of blood, reference may be made to the manuals of clinical diagnosis.
For a recent paper, see Addis, "Quarterly Journal of Exp. Physiology,"
1908, I, 305.

442 BLOOD AND LYMPH.

Theories of Coagulation. — The clotting of blood is such a prom-
inent phenomenon 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
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 a substance, known as thrombin
or fibrin ferment, 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 we owe mainly
to the investigations of Alexander Schmidt,* whose work
completed the older observations of Hewson, Buchanan, Denis,
and Briicke.

Preparation of Solutions of Fibrinogen.! — Fibrinogen may
be obtained readily in solution free from other proteins by a modi-
fication of the general method first described by Hammarsten.
One may use the plasma of horse's blood which has been kept
from clotting by prompt cooling, and in which the corpuscles
have been thrown down by centrifugalizing or by long standing
at low temperature, but it is more convenient, perhaps, to use
cat's blood which has been kept from clotting by allowing the
blood, as it escapes from the vessels, to run into a solution of
sodium oxalate, using an amount such that the final mixture
contains 0.1 per cent, of the oxalate. This mixture is cen-
trifugalized, the clear plasma is removed, and the fibrinogen
in it is precipitated by adding one part of a saturated solu-
tion of sodium chloride. The precipitate is centrifugalized, the
supernatant Liquid is decanted, and the precipitate further

washed by the addition of a two-thirds saturated solution of

*"Ardiiv f. Anat., Physiologie, u. wiss. Medicin," Eteichert u. du Bois-
Reymond, L861, pp. 545, 675, and L862, pp. 428, 533; "Pfltlger's Archiv. f.
d ge ammte Physiol., " 6, 413, L872; "Zur Blutlehre," Leipzig, L 892 and L895.

f A number of the facts and points of view used in the following presenta
lion of i lie ulijiTt of coii^iilni ion .urc new and are based upon experiments
made in the author's laboratory by Dr. Rettger. "American Journal of
Physiology," L909, 24, 406.

COAGULATION. 443

sodium chloride. The precipitate is then dissolved in a solution
of sodium chloride (2 per cent.), and is again precipitated and
washed as above, and the process is repeated a third time.
The final precipitate is dissolved in a 0.9 per cent, solution of
sodium chloride and is then dialyzed for twelve hours in a
collodium tube against a solution of 0.9 per cent, sodium' chloride
to remove the last traces of the oxalate originally added to the
blood. A solution of fibrinogen prepared as above clots readily
upon the addition of blood-serum or of other solutions containing
thrombin. As a matter of fact, such solutions may also clot,
although much more slowly, when instead of a thrombin solu-
tion one adds a little Ringer's mixture or a solution containing
calcium chloride and sodium bicarbonate in about the proportion
found in this mixture. This latter fact indicates that the fibrin-
ogen solution as prepared contains some material from which
thrombin may be produced in the presence of the calcium and
the carbonate. Presumably this material is a prothrombin,
and to remove it and obtain a solution which will not clot except
upon the addition of ready formed thrombin one may make
use of the fact that the prothrombin, like the thrombin, is readily
carried down by precipitates. The solution of the fibrinogen
may be wiped free of the prothrombin on forming in it a small
precipitate of barium phosphate by the addition of barium
chloride and sodium phosphate, this process being carried out
before the final dialysis.

Preparation of Thrombin. — Thrombin, or so-called fibrin
ferment, is prepared most readily by the method first described
by Schmidt. Blood is allowed to clot and the serum is then
precipitated by the addition of a large excess of alcohol (usually
twenty volumes). After standing some days or weeks the
precipitate is drained off and dried, and is then ground up and
extracted with water. The aqueous extract contains proteins,
salts, and other things in addition to the thrombin. A solution
made in this way causes a prompt coagulation when added to
a solution of pure fibrinogen. That the thrombin thus obtained
is not present as such in normal blood, but is formed after
shedding, is indicated by the fact that if the animal's blood is
allowed to flow directly from the artery into a large bulk of
alcohol, due care being taken in the process, the precipitate
thus obtained when subsequently dried and extracted, with
water yields no thrombin.

The Factors of Coagulation. — A pure solution of fibrinogen
is converted to fibrin upon the addition of thrombin. These
two substances constitute, therefore, the essential factors in
the process of clotting. It has been shown, moreover, that cal-

444 BLOOD AND LYMPH.

cium salts also play an essential part in the process. This fact
was first demonstrated by the work of Arthus and Pages. If
blood as it flows from the vessels is received into a solution
of potassium or sodium oxalate, it may be kept indefinitely
without clotting. The addition, however, at any moment of
a small excess of calcium chloride will cause clotting to take
place. This experiment, which any one may repeat, seems to
show conclusively that calcium plays a specific role in the process
of coagulation. Hammarsten has furnished the proof that the
role of the calcium is connected with the formation of the
thrombin and not apparently with the action of the thrombin
on the fibrinogen. Thus he has shown that an oxalated solution
of fibrinogen clots readily when some oxalated serum, containing
ready formed thrombin, is added to it. In some way, which
is not clearly understood, the calcium assists in the production
of the thrombin from an antecedent substance which we may
designate as a prothrombin or a thrombogen. The calcium salts
may be regarded, therefore, as a necessary factor in coagulation,
and it is possible that other organic or inorganic substances are
concerned in the act of formation of the thrombin. It has long-
been stated, for example, that extracts from various tissues of
the body contain substances which facilitate the clotting of
blood or other fibrinogen-containing solutions. Substances of
this kind were designated by Schmidt as zymoplastic, and sub-
sequent authors have applied different names to describe similar
bodies — such as cytozym (Fuld-Spiro), coagulin (Loeb), throm-
bokinase (Morawitz), etc. The specific action taken by these
bodies has been differently interpreted by the several authors
named, but it may perhaps lie doubted whether any conclusive
proof has been furnished as vet for the existence of definite
organic substances concerned in the preparation or activation
of the thrombin. The theory proposed by Morawitz assumes
that thrombokinase is a substance of the nature of an enzyme,
which under normal conditions does not preexist in the blood,
but is formed after shedding by the breaking down of the plates
and leucocytes. With the assistance of the calcium salts this
kinase converts Hie prosubstance (thrombogen) info the active
thrombin. To repeat, therefore, we may say with some posi-
tiveness thai the immediate factors of coagulation are fibrinogen
and thrombin, and that in the production of the thrombin from
prothrombin other factors are concerned, one of which at least

is calcium in some form.

Properties and Origin of Thrombin. Thrombin exists ready
formed in fresh serum, a drop or so of such serum readily causing
coagulation in solutions of fibrinogen. <)u standing, however,

COAGULATION. 445

this property of the serum quickly diminishes and finally dis-
appears, owing to the fact that the thrombin is either converted
to another form (metathrombin) or, as seems more likely, is
combined and rendered inactive by some substances in the
serum. The serum in this condition can be reactivated readily
by the addition of alkali or acid and subsequent neutralization,
or it may be rendered active again by simply allowing it to stand
until putrefaction has developed (Rettger). That the thrombin,
once it is formed, is a stable body is shown by the fact that its
aqueous solutions, prepared by Schmidt's method, do not lose
their clotting power on boiling or on putrefaction. When
fresh serum containing active thrombin is boiled or is heated
to 65° C. the thrombin is apparently destroyed, but addition of
alkali will again develop the power to cause the coagulation of
fibrinogen solutions. Contrary to the usual statement made
in the literature, it may be asserted, therefore, that heating
serum does not destroy its contained thrombin, it simply causes
its inactivation. It would seem that the processes of inactiva-
tion which occur slowly at ordinary room temperatures are
hastened greatly by the higher temperatures. In the older
literature especially thrombin was spoken of as fibrin ferment,
and it has been assumed usually that it belongs to the group of
enzymes or ferments. Two facts, however, seem to make this
view untenable. First, it is not destroyed when in solution by
boiling, As stated above, aqueous solutions may be prepared by
Schmidt's method, which after boiling still cause the formation of
fibrin from fibrinogen. So also when serum containing thrombin is
heated, the thrombin is not destroyed but inactivated. Second, in
its action upon fibrinogen it does not conduct itself like a catalytic
agent, which accelerates the conversion to fibrin without itself
being used up in the process. On the contrary, it seems to form
a definite combination with the fibrinogen, and the amount of
fibrin formed varies with the amount of thrombin added up to a
maximum limit. The resistance offered by thrombin to putre-
faction would indicate that it may not be a protein body. It is
nevertheless an organic colloidal substance, since it is not readily
dialyzable, and it is destroyed when, in dry form, it is heated to the
point of charring. As to the origin of the thrombin, all the evi-
dence seems to point to the conclusion that it is formed directly
from an antecedent substance which may be designated as pro-
thrombin. It is, moreover, usually assumed by recent authors
that the prothrombin exists preformed in the circulating blood.
Thus it is stated that when oxalated plasma is cooled by ice a
precipitate is obtained which when dissolved has itself no action
upon fibrinogen solutions, but when calcium salts are added

446 BLOOD AND LYMPH.

becomes converted to an effective thrombin. This and similar
experiments, however, do not prove that the prothrombin is
not formed after shedding from the breaking down of some of
the corpuscular elements. Fresh blood caught under alcohol,
with precautions against exposure, yields no thrombin and,
moreover, gives no indication of the existence of prothrombin.
When the aqueous extract of the precipitate is treated with
acids, alkalies, or putrefaction, no thrombin is formed. We may
fairly conclude that no prothrombin is thrown down by the
alcohol and that, therefore, none is present in the circulating
blood. Accepting this conclusion, we must believe that the
prothrombin and thrombin are both formed after the blood is
shed, and we can scarcely imagine any other origin for them
than the corpuscular elements which disintegrate (blood-plates
and leucocytes) after the blood leaves the blood-vessels. Micro-
scopic evidence shows that the leucocytes and the agglutinated
masses of blood-plates serve as points of origin for the formation
of the fibrin threads, and we may suppose that these elements
in the act of disintegrating, or by some process of secretion,
give rise to the prothrombin. This latter substance is then
converted to thrombin by the action of substances present in
the plasma, the calcium salts being one at least of the factors
that enter into this process of activation.

Summary. — For the sake of clearness it may be said that
perhaps the prevalent theory of coagulation at the present time
is that advanced by Morawitz. The peculiarity of his view is
the supposition that a kinase (thrombokinase) is liberated from
cellular elements in the blood after shedding, and it is this
kinase which with the cooperation of the calcium salts converts
the prothrombin (thrombogen) into active thrombin. The
theory may be expressed in diagrammatic form as follows:

Cellular elements ©-► thrombokinase.

Thrombokinase + calcium salts + thrombogen = thrombin.

Thrombin + fibrinogen = fibrin.

All the factors concerned are supposed to be present in the
plasma of the circulating blood, with the exception of the throm-
bokinase. The theory is apparently based upon an analogy
with the action of enterokinase in converting trypainogen to
trypsin, and it assumes, moreover, • that both the thrombin and
the kinase are ferment bodies. As stated above, the facts known
at present in regard to thrombin speak strongly against the view
that it belongs to the group of enzymes, and so far as the exist-
ence of a kinase: is concerned, the experimental work, upon mam-
malian blood at Least, dues no1 furnish any necessary reason for

adding this factor. Moreover, it seems very doubtful whether

COAGULATION. 447

the prothrombin as such exists in the circulating blood. Bearing
these points in mind, a more conservative statement of the steps
taken in the process of coagulation would be the following:

Corpuscular elements (plates, leucocytes) s-» prothrombin.
Prothrombin + calcium salts

(and other possible conditions) = thrombin.
Thrombin + fibrinogen = fibrin.

Other theories have been advanced in recent years, some of which may
be referred to here very briefly, although for an adequate statement of details
the originals must be consulted. Nolf assumes the existence of three or four
fibrin factors — fibrinogen, hepatothrombin, leucothrombin, and calcium
salts. The leucothrombin is a ferment body formed by leucocytes, although
it may be produced also by the endothelial cells (yasothrombin). The
fibrinogen and hepatothrombin are formed by the liver and are present con-
stantly in the blood. In coagulation the hepatothrombin and leucothrombin
unite to form an addition product, which is thrombin. The thrombin then
combines physically with the fibrinogen, as one colloid may act upon
another, with the production of fibrin. Coagulation is not a ferment action,
and its normal ending is the digestion of the fibrin (fibrinolysis) by the
proteolytic action of the leucothrombin. (See Nolf, "Arch, internationales
de physiologie, " 1906, iv., 165 and 1908, vi., 1 and 115.) Loeb describes
the presence of coagulins in the tissues which are different from the thrombin
of blood, but in the presence of calcium salts are capable of acting directly
on the fibrinogen and converting it to fibrin. (See "Bioch. Centralbl.," 1907,
829 and 899, Review of Literature.) Mellanby uses in general the nomen-
clature of Morawitz, but assumes that prothrombin is always found associated
with fibrinogen, so that kinase and solutions of calcium salts added to a fibrin-
ogen solution will always suffice to cause coagulation, since the elements for
the formation of the thrombin are present. (See "Journal of Physiology,"
1908, 38, 28.)

The Conversion of Fibrinogen to Fibrin. — The nature of the
reaction between fibrinogen and thrombin is not at all under-
stood. It was formerly supposed, on the basis of experiments
made by Hammarsten, that the thrombin caused the fibrinogen
molecule to split, the larger fraction forming the insoluble fibrin,
while a smaller portion remained in solution as a globulin, the
fibrin globulin. This view would be in accord with the prevalent
assumption that the thrombin acts as a ferment, causing, prob-
ably, from this standpoint, hydrolytic cleavage of the fibrinogen,
after the manner of the digestive ferments. Later experiments
have failed to confirm this view, and it has been suggested as
another possibility that the thrombin causes in some way a
molecular rearrangement of the fibrinogen, but this also is an
hypothesis for which there is no experimental evidence. One
of the most significent facts in this connection is the old obser-
vation (Buchanan, Gamger) that the washed clot can be made
to yield a thrombin by treatment with a solution of sodium
chloride. Indeed, very carefully washed fibrin made from pure
fibrinogen, which upon extraction with water yields no thrombin,
may subsequently show a large amount if allowed to undergo

448 BLOOD AND LYMPH.

decomposition by putrefaction (Rettger). Evidently then the
thrombin does not undergo an essential chemical change in its
reaction with fibrinogen, and one ma}' suppose, therefore, with
Nolf, that its union with fibrinogen is physical or physicochemical
rather than chemical. This supposition is supported, moreover,
by the fact (Mellanby, Rettger) that the reaction is practically
not affected, as to its velocity, by temperatures varying between
17° and 38° C, whereas, if the process was of the nature of an
ordinary chemical reaction, we should expect, in accordance with
van't Hoff's law, that the velocity would be doubled for an
increase of 10° C. in temperature.

Why Blood Does Not Clot Within the Blood-vessels — An-
tithrombin. — The reason that blood remains fluid within the blood-
vessels and coagulates in a few minutes after being shed would seem
to be contained in the theories of coagulation just described. We
may assume that in the living blood-vessels the formed elements —
leucocytes and blood plates — do not disintegrate in great numbers
at a time, and therefore do not give rise to any noticeable quantity
of the antecedents of thrombin. It seems most probable that little,
if any. thrombin is actually present in the blood under normal
circumstances, and this in itself may be regarded as the main reason
for the fact that the blood remains unclotted. It is quite possible,
however, that other safeguards may exist in a matter of such
prime importance. It has been shown, for instance, that, when
solutions of fibrin ferment (thrombin) are injected into the circu-
lation, clotting is not produced with the "certainty that one might
expect. Delezenne has described experiments which indicate
that the liver exercises a defensive power in this respect.* He
states that when blood-serum — containing, as it normally does,
some active thrombin — is circulated through a living liver it loses
its power of inducing coagulation in solutions containing fibrinogen.
[ts 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 i H.t 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 thai blood remains u'ncoagulatcd for long periods if
kepi m contacl with what may be culled its normal surface, — that
is. the interior of the hearl or blood-vessels. In an excised heart

or blood-vessel the blood, although a1 rest, remains fluid for a long
time. H was thought possible, therefore, that the normal en-
dothelial walls of the vessels exercise a restraining influence of
* "Travaux <lc Physiologie," Qniversitd de Montpellier, 1898.

COAGULATION. 449

some kind upon the coagulation of the blood. In recent times
this view has taken the form, corresponding to the knowledge of
the day, of a suggestion that an antibody — namely, an anti-
thrombin — exists in the blood and actively retards or prevents co-
agulation. While some authors (Morawitz) believe that such an
antithrombin exists normally in circulating blood and is essential
in maintaining its fluidity, others (Schmidt) hold to the view that
substances retarding coagulation are liberated only from the dis-
integration of the cellular elements and are present practically,
therefore, only in the shed blood. Loeb* has not been able to
detect the existence of an antithrombin in extracts of the inner wall
of the blood-vessels. The fact that in serum the thrombin
present is inactivated slowly at room temperatures and more
rapidly at higher temperatures, would suggest that a similar
process may occur in the circulating blood, and that by this
means the blood may free itself in a measure from any thrombin
liberated within the circulation. f

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

* Leo Loeb, " Virchow's Archiv," 176, 10, 1904; also " Hofmeister's Bei-
trage," 5, 534, 1904.

t For discussion and references, see Morawitz, "Handbuch d. Biochemie,"
1908, IP, 63.
29

450 BLOOD AND LYMPH.

retard it (negative phase). Lilienfeld* has made this hypothesis
more specific by showing that lymphocytes (and blood plates)
yield a nucleoprotein which in turn on decomposition furnishes a
second nucleoprotein, leuconuclein, whose presence favors coagula-
tion, and a simple protein, histon, whose action retards clotting.
Delezenne f has still further added to the hypothesis by experiments
which indicate that the element favoring coagulation (leuconuclein)
is removed or destroyed by the liver. When an insufficient quan-
tity of leucocytes is injected into the circulation the histon action
may predominate, and thus retard coagulation, while with larger
quantities and a more extensive decomposition the leuconuclein
•may bring about clotting before it is completely destroyed by the
liver.

Means of Hastening or of Retarding Coagulation. — Blood
coagulates normally within a few minutes, but the process may be
hastened by increasing the extent of foreign surface with which it
comes in contact. Thus, agitating the liquid when in quantity, or
the application of a sponge or a handkerchief to a wound, hastens
the onset of clotting. This is easily understood when it is remem-
bered that the breaking down of leucocytes and blood-plates is
hastened by contact with foreign surfaces. It has been proposed
also to hasten clotting in case of hemorrhage by the use of throm-
bin solutions or of tissue, extracts containing some thromboki-
nase. Hot sponges or cloths applied to a wound hasten clotting,
probably by accelerating the formation of thrombin 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 ( ' Doling. — 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 dotting by keeping the corpuscles intact.

2. By the Ad ion 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 dot. In this case also the corpuscles settle slowly, or they
may !«• centrifugalized, and specimens of plasma be obtained.
For this purpose horses' or cats' blood is to be preferred. Such
plasma is known as "salted plasma"; if is frequently used in
experiments in coagulation for example, in testing the efficacy
of a given thrombin solution. The best salt to use is magnesium

* Lilienfeld, "Zeitschrifl f. physiol. Cliemie," 18, 473. f Loc. cit.

COAGULATION. 451

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 thrombin solutions are
added to it. How the salts prevent coagulation is not definitely
known, possibly by preventing the disintegration of corpuscles,
but more probably by preventing the transformation of pro-
thrombin to thrombin (Bordet and Gengou).

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 does not clot. Addition of thrombin
to this fluorid blood causes clotting, while calcium salts are
usually stated to be without effect. As a matter of fact, calcium
salts cause a precipitate of a portion of the protein, and if added
cautiously in excess they induce clotting, as in the case of the
oxalated blood. The fluorid plasma may be made to clot also
by dialysis. We may believe that the fluorid, like the oxalate,
prevents clotting by removing the calcium. The calcium is not
precipitated, but is held bound as a fluorid in combination with
a portion of the protein (Rettger).

5. By the Injection of Certain Organic Substances. — There are a
number of substances which when injected into the blood retard
or prevent its coagulation. For instance, solutions of ordinary
preparations of pepsin, trypsin, peptone, snake venom, leech
extracts, etc. .Snake venom may be wonderfully potent in this
particular; it is stated that so little as 0.00001 gm. to each kilogram
of animal suffices to destroy the coagulability of the blood. Of
these various bodies solutions of peptone have received the most
attention from investigators. Peptone, as usually obtained by
digestion experiments, is in reality a mixture of prot roses 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

452 BLOOD AND LYMPH.

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. It is a body belonging to the
groups of albumoses and is supposed to antagonize the action
of thrombin. It should be added that hirudin has little effect
on the blood of some animals (dog, cat).

Total Quantity of Blood in the Body. — The total quantity of
blood in the body has been determined approximately for man
and a number of the lower animals. The method (Welcker)
used in such determinations consists essentially in first bleeding
the animal as thoroughly as possible and weighing the quantity
of blood thus obtained, and afterward washing out the blood-
vessels with water and estimating the amount of hemoglobin
in the washings.

Grehant ("Journal de l'Anat. et de Physiol.," 1882, 504) has devised an-
other method which may be used upon the living animal, as follows : A
specimen of blood is taken from the animal and the volume per cent, of
oxygen h determined by extraction with a gas-pump. The animal is then
made to breathe :t, known volume of carbon monoxid for a certain time, and
the total amount of this carbon monoxid that is absorbed is ascertained by
analysis. A second specimen of blood is then taken and its volume per cent.
in oxygen is again determined. The difference between this volume per cent.
of oxygen and that obtained before the administration of the carbon monoxid
gives the volume per cent, of carbon monoxid in the blood, since the latter
gas displaces an equal volume of oxygen. If the total amount of carbon
monoxid absorbed by the blood is indicated by V and the volume per cent.,
thai i , the number of c.c. to each 100 c.c. of blood, is indicated by v, then the

total quantity of the blood will be given by the formula ->' 100.

r

The average results obtained from numerous experiments are
as follows: The ratio of weight of blood to weight of body is, in the

* "Zeitechrift f. physiol. Chemie," 31, 235. 1900.

REGENERATION AFTER HEMORRHAGE. 453

dog, 7.7 per cent.; rabbit and cat, 5 per cent.; birds, 10 per cent.
On man we have upon record two determinations on guillotined
criminals made by Bischoff, which gave 7.7 and 7.2 per cent.
Haldane and Smith,* however, have devised a modification of
Grehant's carbon monoxid method, which they have applied to
living men. The results of some 74 experiments gave them an
average value of only 5 per cent, for man. The distribution of
this blood in the tissues of the body at any time has been esti-
mated by Ranke,f 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 t is re-
covered from easily, while a loss of 4.5 per cent., more than half
the entire blood, will probably prove fatal. In cats a hemorrhage
of from 2 to 3 per cent, of the body-weight is not usually followed
by a fatal result. Just what percentage of loss may be borne by the
human being has not been determined, but it is probable that a
healthy individual may recover without serious difficulty from the
loss of a quantity of blood amounting to as much as 3 per cent, of
the body-weight. It is known that if liquids that are isotonic to
the blood, such as physiological saline (NaCl, 0.7 to 0.9 per cent.)

* Haldane and Smith, "Journal of Physiology," 1900, xxv., 331; also
Zuntz and Pletsch, "Biochemische Zeitschrif t, " 1908, 47.

t Taken from Vierordt's "Anatomische, physiologische, und physikalische
Daten und Tabellen," Jena, 1893.

t Fredericq, "Travaux du Laboratoire" (Universite de Liege), 1, 189,
1885.

454

BLOOD AND LYMPH.

or Ringer's solution, are injected into the veins immediately after
a severe hemorrhage, recovery is more certain; in fact, it is
possible by this means to restore persons after a hemorrhage that
would otherwise have been fatal. By an infusion of this kind,
particularly if at or somewhat above the body temperature, the
heart beat is increased, the volume of the circulating liquid is
brought to an amount sufficient to maintain approximately normal
conditions of pressure and velocity, and the red corpuscles that still
remain are kept in more rapid circulation and are thus utilized more
completely as oxygen carriers. If a hemorrhage has not been fatal,
experiments on lower animals show that the plasma of the blood is
regenerated with some rapidity, the blood regaining its normal vol-

12 3 4

1

•

•— ,=B"

^ \

^7

\ A

"^N^^"

vt -,/ — -

~7

\R -Jt- ■ i

- ^

^%7 -,

"

\ /

— , ^-3"

X zv

hv

i \ 1

/ V""^-^-^ ■""^

I

/

_

100 Erythrocytes.

8,000,000

7,000,000(73%)

6,000,000(06%)

6,000,000 (55 %)

4,000,000(13%)

(35%)

35,000(25%)

26,000(15%)

!".■■■.

Fig. 1*2. — To show the effect of hemorrhage upon the number of red and white cor-
puscles and the amount of hemoglobin.- (Dawson.) The ordinates express tlie numbers
of corpuscles and also the percentages of hemoglobin as stated in the figures to the left.
'I be ab ci a give the 'lavs after hemorrhage. The experiment was made upon a dope of
fc.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.

lime 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 seven- hemorrhage ( L3 per cent, of the body-weight) followed
by transfusion of an equal volume of physiological saline. So far
as the rod corpuscles and (he amount of hemoglobin are concerned,

BLOOD-TRANSFUSION. 455

it will be noticed that the large sudden fall from the hemorrhage,
first day, is followed by a slower drop in both factors during the
second and third days. This latter phenomenon constitutes what
is known as the posthemorrhagic fall.*

Blood-transfusion. — Shortly after the discovery of the circu-
lation of the blood (Harvey, 1628), the operation was introduced
of transfusing blood from one individual to another or from some
of the lower animals to man. Extravagant hopes were held as to
the value of such transfusion not only as a means of replacing the
blood lost by hemorrhage, but also as a cure for various infirmities
and diseases. Then and subsequently fatal as well as successful
results followed the operation. It is now known to be a dangerous
undertaking, mainly for two reasons: first, the strange blood,
whether transfused directly or after defibrination, is liable to contain
a quantity of thrombin sufficient, perhaps, to cause intravas-
cular clotting; second, the serum of one animal may be toxic to
another or cause a destruction of its blood corpuscles. Owing
to this hemolytic and toxic action, which has previously been
referred to (p. 414), 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 prevent 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 extra vascular
lymph is collected into small capillary spaces which in turn open into
definite lymphatic Vessels. It is still a question among the his-
tologists whether the lymph- vessels form a closed system or are in
direct anatomical connection with the tissue spaces. Modern
work* supports the view that the lymph capillaries are closed
vessels similar 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., or
with the spaces between the meningeal membranes surrounding
the central nervous system. From the physiological 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-
els. 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 lclt lymphatic duct,

* See Babin, "American Journal of Anatomy," I, '-'><'>7, L902, and :'>, is:',,
1904; .il o "General and Special Anatomy of the Lymphatics," from Poiriei
and Charpy, fcran lated l>y Leaf, L904.

156

COMPOSITION AND FORMATION OF LYMPH. 457

and a second smaller right lymphatic duct, which open into the
blood-vessels, each on its own side, at the junction of the sub-
clavian and internal jugular veins. While the supply of lymph
in the lymph-vessels may be considered as being derived ulti-
mately entirely from the blood-plasma, it is well to bear in mind
that at any given moment this supply may be altered by direct
interchange with the plasma on one side and the extravascular
lymph permeating the tissue elements on the other. The
intravascular lymph may be augmented, for example, by a
flow of water from the blood-plasma into the lymph-spaces, and
thence into the lymph-vessels, 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 main-
tained chiefly by the difference in pressure between the lymph
at its origin in the tissues and in the large lymphatic vessels.
The continual formation of lymph in the tissues leads to the
development of a relatively high pressure in the lymph capil-
laries, and as a result of this the lymph is forced toward the
point of lowest pressure — namely, the points of junction of the
large lymph-ducts with the venous system. A brief discussion
of the factors concerned in the movement of lymph will be found
in the section on Circulation. As would be inferred from its
origin, the composition of the intravascular lymph is essentially
the same as that of blood-plasma. It contains the three blood
proteins, the extractives (urea, fat, lecithin, cholesterin, sugar),
and inorganic salts. The salts are found in the same proportions
as in the plasma; the proteins are less in amount, especially the
fibrinogen. Lymph coagulates, but does so more slowly and
less firmly than the blood. Histologically, lymph consists of a
colorless liquid containing a number of leucocytes, 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. The composition of
the exudative liquids of the body, such as the pericardial liquid,
the synovial liquid, the aqueous humor, the cerebrospinal liquid,
etc., which are sometimes classed under the general term lymph,
may vary greatly; thus, the cerebrospinal liquid possesses no
morphological elements, contains no fibrinogen, and, therefore,
does not clot, and, indeed, has only minute traces of protein of
any kind.

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

45S BLOOD AND LYMPH.

prevailing in the tissues outside, and it was supposed that this excess
of pressure is sufficient to squeeze the plasma of the blood through
the very thin capillary walls. Various conditions that alter the
pressure of the blood were shown to influence the amount of lymph
formed in accordance with the demands of a theory of filtration.
Moreover, the composition of lymph as usually given seems to sup-
port such a theory, inasmuch as the inorganic salts contained in it
are in the same concentration, approximately, as in blood-plasma,
while the proteins are in less concentration, following the well-
known law that in the filtration of colloids through animal mem-
branes the filtrate is more dilute than the original solution. This
simple and apparently satisfactory theory has been subjected to
critical examination within recent years, and it has been shown that
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 suj3pose 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 showed 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 2o6 liters of
lymph per day to supply the necessary Ca< ) to the mammary glands.
Heidenhain himself suggests that the difficulty in this case may be
met by assuming active diffusion processes in connection with
filtration. If, for instance, in the case cited, we suppose that the
calcium of the lymph is quickly combined by the tissues of the mam-
mary gland, then the tension of calcium salts in the lymph will be
kept nt zero, and an active diffusion of calcium into the lymph will
occur so long as the gland is secreting. En other words, the gland
will receh e its calcium by much the same process as it receives its

* "Archivf. dicgesammte Physiologic," 49, 209, 1891.

COMPOSITION AND FORMATION OF LYMPH. 459

oxygen, and will get its daily supply from a comparatively small
bulk of lymph. Strictly speaking, therefore, the difficulty we are
dealing with here shows only the insufficiency of a pure filtration
theory. It seems possible that filtration and diffusion together
would suffice to supply the organs, so far at least as the diffusible
substances are concerned.

2. Heidenhain found that occlusion of the inferior vena cava
causes not only an increase in the flow of lymph — as might be ex-
pected, on the filtration theory, from the consequent rise of pressure
in the capillary regions — but also an increased concentration in the
percentage of protein in the lymph. This latter fact has been
satisfactorily explained by the experiments of Starling.* Accord-
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 f
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

* "Journal of Physiology," 16, 234, 1S!»4.
t Ibid., 17, 30, 1894.

460 BLOOD AND LYMPH.

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.* 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
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 liquid, 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 f 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:
" ( )n 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 t" I Ik- increase in the volumeof the blood, and

* "Ccntralblatt f. Physiologic," \), No. 2, L895.
f hoc. cit.

COMPOSITION AND FORMATION OF LYMPH. 461

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 otherexperiments have been devised by Heidenhain
and his followers to show that the physical laws of filtration, diffu-
sion, and osmosis do not suffice to explain the production of lymph ;
but in all these 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 endothelial cells of the capillaries. Asher* and his
co-workers have brought forward many facts to show that the lymph
is controlled as to its amount by the activity of the tissue elements
and may be considered as a product of the activity of the tissues, as
a secretion, in fact, of the working cells. When the salivary glands,
the liver, etc., are in greater functional activity the flow of lymph
from them is increased beyond doubt, so that the activity of the
organs does influence most markedly the production of lymph.
Most physiologists, however, prefer to explain this relationship on
the view suggested by Koranyi, Starling, and others, — namely, that
in the metabolic changes of functional activity the large molecules
of protein, fat, etc., are broken down to a number of simpler ones,
the number of particles in solution is increased and therefore the
osmotic pressure is increased. According to most observers
the molecular concentration of the lymph in the thoracic duct,
and, therefore, the osmotic pressure, is greater than that of the
blood. Thus Botazzi,f in one experiment, reports that the
lowering of the freezing-point of the blood-serum was A =0.595°
C, while that of the lymph from the thoracic duct of the same
animal was A =0.615° C. Back in the tissues, where phys-
iological oxidations are going on, this difference is probably
greater, and greater in proportion to the activity of the tissues.
We can understand that in this way functional activity of an
organ may result in attracting more water from the blood-capil-
laries into the tissue spaces and may thus cause an augmented
flow of lymph. The liquid of the tissues may be drained off
not only through the lymph-vessels but also through the blood-
vessels. That liquids injected directly into the tissues or special
substances dissolved in such liquids may be absorbed directly
by the blood has long been known. Magendie, for example,

* "Zeitschrift f. Biologie," vols, xxxvi-xl. 1S97 to 1900.
f Quoted from Magnus, "Handbuch der Biochemie, " 1908, vol. ii.2
(Formation of Lymph) .

462 - BLOOD AND LYMPH.

proved that when a poison was injected into an organ which
was connected with the rest of the body only by its blood-vessels,
the animal quickly showed the symptoms of a corresponding
intoxication. Ordinary hypodermic injections are absorbed
much more quickly into the general circulation than would-be
the case if they were obliged to traverse the lymph-vessels and
enter the blood through the thoracic duct. Meltzer has shown
that this absorption by the blood from the tissue spaces takes
place with especial promptness if the injection is made into a
mass of muscular tissue.

The liquid in the extravascular tissue spaces is, in fact, sub-
ject to a play of influences from several sides, and it is the bal-
ance among these competing influences which determines at any
time the amount and composition of this tissue lymph. Thus,
the supply of this liquid is furnished, on the one hand, by water
and dissolved substances coming to it from the blood in the
capillaries, on the other hand, by water and dissolved substances
derived from the great reservoir contained in the tissue cells.
The amount of the tissue lymph is continually depleted on the
other side by water and dissolved substances passing back into
the capillaries, or into the tissue elements, or, finally, into the
lymph capillaries. The amount that passes by this latter route
varies greatly in the different tissues, and in the same tissue
may be influenced greatly by pathological as well as normal
changes in conditions.

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 capillaries, or, on the other side, between
this latter liquid and the contents of the tissue elements; third,
the force of osmotic pressure, which varies with the molecular
concentration. These three forces acting everywhere control
primarily the amount and composition of the lymph; but still
another factor must be considered; for when we come to examine
the flow of lymph in different parts of the body striking differ-
ences are found. It has been shown, 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

COMPOSITION AND FORMATION OF LYMPH. 463

a greater percentage of proteins. To account for these differences
Starling suggests the plausible explanation of a variation in permea-
bility in the capillary walls. The capillaries seem to have a similar
structure all over the body so far as this is revealed to us by the
microscope, but the fact that the lymph-flow varies so much in
quantity and composition indicates that the similarity is only
superficial, and that in different organs the capillary walls may
have different internal structures, and therefore different permea-
bilities. This factor is evidently one of great importance. The
idea that the permeability of the capillaries may vary under dif-
ferent conditions has long been used in pathology to explain the
production of that excess of lymph which gives rise to the condition
of dropsy or edema. The theories and experiments made in con-
nection with this pathological condition have, in fact, a direct bearing
upon the theories of lymph formation.* Under normal conditions
the lymph is drained off as it is formed, while under pathological
conditions it may accumulate in the tissues owing either to an
excessive formation of lymph or to some interruption in its circu-
lation.

The scanty flow of lymph from the limbs has been referred
by Magnusf to another possible cause, namely, to the great
capacity of the muscular tissue to imbibe water (and salts).
According to this author the tissues, particularly the muscular
tissues, constitute great reservoirs in which excess of water and
salts may be stored. If, for example, a hypotonic solution of
sodium chloride is injected into the circulation, most of the
water added will be removed from the circulation by imbibition
into the muscular tissues. In the limbs, with their large supply
of muscular tissue, it may be that lymph is formed as elsewhere
from the blood plasma, but it is held back from the lymph-vessels
by absorption into the muscular mass.

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

* Consult Meltzer, "Edema" ("Harrington Lectures"), "American
Medicine, " 8, Nos. 1, 2, 4.. and 5, 1904.
f Magnus, Loc cit.

464 BLOOD AND LYMPH.

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.

SECTION V.

PHYSIOLOGY OF THE ORGANS OF CIRCULA-
TION OF THE BLOOD AND LYMPH.

The heart and the blood-vessels form a closed vascular system
containing a certain amount of blood. This blood is kept in endless
circulation mainly by the force of the muscular contractions of the
heart. But the bed through which it flows varies greatly in width
at different parts of the circuit, and the resistance offered to the
moving blood is very much greater in the capillaries than in the
large vessels. It follows from the irregularities in size of the chan-
nels through which it flows that the blood-stream is not uniform in
character throughout the entire circuit; indeed, just the opposite is
true. From point to point in the branching system of vessels the
blood varies in regard to its velocity, its head of pressure, etc.
These variations are connected in part with the fixed structure of the
system and in part are dependent upon the changing properties of
the living matter of which the system is composed. It is con-
venient to consider the subject under three general heads: (1)
The purely physical factors of the circulation, — that is, the me-
chanics and hydrodynamics of the flow of a definite quantity of
blood through a set of fixed tubes of varying caliber under certain
fixed conditions. (2) The general physiology of the heart and the
blood-vessels, — that is, mainly the special properties of the heart
muscle and the plain muscle of the blood-vessels. (3) The innerva-
tion of the heart and the blood-vessels, — that is, the variations in
the circulation produced by the action of the nervous system.

CHAPTER XXV.
THE VELOCITY AND PRESSURE OF THE BLOOD-FLOW.

The Circulation as Seen Under the Microscope. — It is a

comparatively easy matter to arrange a thin membrane in a living
animal so that the flowing blood may be observed with the aid of a
microscope. For such a purpose one generally employs the web
between the toes of a frog, or better still the mesentery, lungs, or
30 465

466 CIRCULATION OF BLOOD AND LYMPH.

bladder of the same animal. With a good preparation many
important peculiarities in the blood-flow may be observed directly.
If the field is properly chosen one may see at the same time the flow
in arteries, capillaries, and veins. It will be noticed that in the
arteries the flow is very rapid and somewhat intermittent, — that is,
there is a slight acceleration of velocity, a pulse, with each heart
beat. In the capillaries, on the contrary, the flow is relatively very
slow; the change from the rushing arterial stream to the deliber-
ate current in the capillaries takes place, indeed, with some
suddenness. The capillary flow, as a rule, shows no pulses corre-
sponding with the heart beats, but it may be more or less irregular,
— that is, the flow may nearly cease at times in some capillaries,
while again it maintains a constant flow. In the veins the flow
increases markedly in rapidity, and indeed it may be observed
that, the larger the vein, the more rapid is the flow. There is not,
however, as a rule, any indication of an intermittence or pulse in
this flow, — the velocity is entirely uniform. In both arteries and
veins it will be noticed that the red corpuscles form a solid column
or core in the middle of the vessel, and that between them and the
inner wall there is a layer of plasma containing only, under normal
conditions, an occasional leucocyte. The accumulation of cor-
puscles in the middle of the stream makes what is known as the
axial stream, while the clear layer of plasma is designated as the
inert layer. The phenomenon is readily explained by physical
causes. As the blood flows rapidly through the small vessels the
layers nearer the wall are slowed by adhesion, so that the greatest
velocity is attained in the middle or axis of the vessel. The cor-
puscles, being heavier than the plasma, are drawn into this rapid
part of the current. It has been shown by physical experiments
that, when particles of different specific gravities are present in a
liquid flowing rapidly through tubes, the heavier particles will be
found in the axis and the lighter ones toward the periphery. In
accordance with this fact, leucocytes, which are lighter than the
red corpuscles, may be found in the inert layer. When the con-
ditions become slightly abnormal (incipient inflammation) the
leucocytes increase in number in the inert layer sometimes to a
very great extent, owing apparently to some alteration in the
endothelial walls whereby the leucocytes are rendered more ad-
hesive. The agglutination of the leucocytes and their migration
through the walls into the surrounding tissues are described in
works on Pathology.

The Velocity of the Blood-flow. — The microscopical observa-
tions described above show that the velocity of the blood-current
varies widely, beinfj; rapid in the arteries and veins and slow in the
capillaries. To ascertain the actual velocity in the larger vessels
and the variations in vessels of different sizes experimental de-

VELOCITY AND PRESSURE OF BLOOD-FLOW.

467

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 usqd 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 ™ Kg. 183.-— Ludwig's stromuhr: a and b,

. . I he glass bulbs; a is filled with oil to the

CrOSS-area Of the artery, we Can mark (5 c.c), while b and the neck are filled
i , • ,i t .-1 » ,, with salt solution or defibrinated blood: p,

determine the length Of the the movable plate by means of which the

bulbs may be turned through 180 degrees,
c, c, for the cannulas inserted into the artery;
s. 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

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 forcing the salt solution m b into the head

end oi the artery through c . When the

cross-area.

V = length X cross-area, or
V

length =

cross-area

blood entering a reaches the mark, the bulbf

are turned through 180 degrees so that b 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

We Cannot, Of COUrse, make turned, say, ten .times, 50 c.c. of blood have

1 . ' .. ... flowed out. Knowing the time and the

the experiment in thlS Simple caliber of the artery, the calculation is made

v • , ., as described in the text. Several modify

Way Upon a living animal ; the cations of the form of this instrument have

loss of so much blood would at been devisecL

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-

*A modification by Tigerstedt is described in the "Skandinavisches
Archiv f. Physiol.," 3, 152, 1891. One by Burton-Opitz in the "Arch. f. d.
ges. Physiologie," 121, 151, 1908.

468

CIRCULATION OF BLOOD AND LYMPH.

merit different from those at the beginning. By means of the
stromuhr, however, this experiment can be made, with this important
variation, that the blood that flows from the central end of the cut
artery is returned to the peripheral end of the same artery, so that
the circulation is not blocked nor deprived of its normal volume of
liquid. The instrument, as is explained in the legend of Fig. 183,
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 tt2 =
3.15 X 1 = 3.15. Since 1 c.c. equals
1000 c.mm., the length of our cyl-
inder of blood would be given by
the quotient of 3 15- = 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 hcmodromograph of Chauveau.
This instrument is represented in
the accompanying figure (Fig. 184).
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-
r-rum. The anfde of defieM.ion 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. 184. — Chauveau's hemodromo-
grapfa (after Lanyendorff). The tube,
■ laced in the course of an ar-
tery, the blood after removal of clamps
flowing in the direction shown by the
arrow. The current strikes the plate,
pi, and forces it to an angle varying
With the velocity. The movement of
pi i transmitted through the stem, «,
which moves in a rubber membrane
a- a fulcrum, >"■ The angular move-
ment of the projecting end of ra may
be measured directly or may be made
to ad upon a tambour, as shown in

the figure, and thus be transmitted to

n recording di urn.

VELOCITY AND PRESSURE OF BLOOD-FLOW. 469

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 uniform or approximately

uniform and increases as one approaches the heart, although the

velocity in the large veins near the heart is somewhat slower

than in the large arteries of the same region, owing to the fact

that the total area of the venous bed is larger than that of the

arterial bed. Burton-Opitzf gives the following average figures

obtained from experiments upon anesthetized dogs. Jugular,

147 mms.; femoral, 61.6 mms.; renal, 63 mms.; mesenteric vein,

84.9 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.

* Von Kries, " Archiv f. Physiologie, " 1887, 279; also Abeles, ibid., 1892, 22.
f Burton-Opitz, "Am. Journal of Physiology," vols. 7 and 9, and "Pfluger's
Archiv," vols. 123 and 124, 1908.

470

CIRCULATION OF BLOOD AND LYMPH.

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 tlirow upon the rods and cones. The visual images
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;
.4.-/2, 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 X an.
An

AB : An, or ab =

According to this method,
Vierordt calculated that the
velocity of the blood in the
human capillaries is equal to
about 0.6 to 0.9 mm. per
second.

In the arteries, more-

, , . Fig. 185. — Diagram of the eve to show the con-

OVer, It may be Observed struction used to determine the' size of the retinal

4-V.^i- 4-U„ _ _ i "j. image when the size of the external object is known:

that the average Velocity n, The nodal point of the eye. See text.

diminishes the farther

one goes from the heart, — that is, the smaller the artery, — and
reaches its minimum when the arteries pass into the capillaries.
Thus, Volkmann reports for the horse the following figures: Ca-
rotid, 300 mms.; maxillary, 232; metatarsal, 56 rams. 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-

lig. 186. — Schematic representation of the relative velocities of the blood-current in

>.i lie .1 « mI m . v torn: «, The arterial side, indicating the changes with

each heart beat and the fall of mean velocity as the arterial bed widens; c, the capillary

ill'- gieat diminution in veloeit y em re, pond- with the groat widening of the bed;
r, the ' :' Showing the gradual increase Inward the heart, and represented as

entirelj uniform, although, as a matter of fact, the velocity in the large veins is affected by
the respirations and to a small extent by the heart beat, owing t<> the phenomenon known
as the venous pulse p. 513).

mum velocity being found in the vena cava. The general rela-
tions of the velocity of the blood in the arteries, capillaries, and
veins may be expressed, therefore, by a curve such as is shown
in Fig. iso.

* "Archiv I', physiologische Heilkunde, " 15, 2~>.r>, ix.r>(j.

VELOCITY AND PRESSURE OF BLOOD-FLOW. 471

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
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. Vierorclt 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-g-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 fluctua-
tions 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 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)

* "La Circulation du Sang," Paris, 1SS1, p. 321.

47'2 CIRCULATION OF BLOOD AND LYMPH.

will cause the velocity and the arterial pressure to vary in an
inverse sense as regards each other. That, is, an increased re-
sistance diminishes the velocity in the arteries while increasing
the pressure, and vice versa.

The Time Necessary for a Complete Circulation of the
Blood. — It is a matter of interest in connection with man}' 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 (1S29) 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-
t ruled than the blood, is injected into the circulation, the con-
ductivity of the blood is increased. If the injection is made at a
given moment and a portion of the vessel to be examined is properly
connected with a galvanometer so as to measure the electrical
conductivity through it, then the instant that the solution of salt
reaches this latter vessel the fact will be indicated by a deflection
of the galvanometer. I rsing this met hod, Stewart was able to show

that in I he lesser circulat ion (I he pulmonary circuit) the velocity
♦ "Journal el' Physiology," 15, L, L894.

VELOCITY AND PRESSURE OF BLOOD-FLOW. 473

is very great compared with that of the systemic circulation —
only about one-fifth of the time required for a complete circuit
is spent in the lesser circulation. Attention may also be called to
the fact that the important part of the circulation, as regards the
nutritive activity of the blood, is the capillary path. It is while
flowing through the capillaries that the chief exchange of gases
and food material takes place. The average length of a capillary
is estimated at 0.5 mm.; so that with a velocity of 0.5 mm. per
second the average duration of the flow of any particle of blood
through the capillary area is only about 1 sec.

The Pressure Relations in the Vascular System. — That the
blood is under different pressures in the several parts of the vascu-
lar system has long been known and is easily demonstrated. When
an artery is cut the blood flows out in a forcible stream and with
spurts corresponding to the heart beats. When a large vein is
wounded, on the contrary, although the blood flows out rapidly,
the stream has little force. Exact measurements of the hydrostatic
pressure under which the blood exists in the large arteries and veins
were first published by Rev. Dr. Stephen Hales, an English clergy-
man, in his famous book entitled " Statical Essays, containing
Hsemostaticks," 1733.* This observer measured the static pressure
of the blood in the arteries and veins by the simplest direct method
possible. After tying the femoral artery in a horse he connected
it to a glass tube 9 feet in length. On opening the vessel the blood
mounted in the tube to a height of 8 feet 3 inches, showing that
normally in the closed artery the blood is under a tension or pressure
sufficient to support the weight of a column of blood of this height.
A similar experiment made upon the vein showed a rise of only 12
inches.

Methods of Recording Blood-pressure. — Since Hales's work
the chief improvements in method which have marked and caused
the development of this part of the subject have been the application
of the mercury manometer by Poiseuillef (1828), the invention of
the recording manometer and kymographion by LudwigJ (1847),
and the later numerous improvements by many physiologists, and
latterly the development of methods for measuring blood-pressures
directly in man. The Hales method of measuring arterial pressure
directly in terms of a column of blood is inconvenient on account
of the great height, large fluctuations, and rapid clotting. The
two former disadvantages are overcome by using a column of mer-
cury. Since this metal is 13.5 times as heavy as blood, the column
which will be supported by the blood will be correspondingly shorter

* 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.
t Ludwig, "Mailer's Archiv f. Anatomie, Physiologie, etc.," 1847, p. 242.

474

CIRCULATION OF BLOOD AND LYMPH.

and all the fluctuations will be similarly reduced. Poiseuille
placed the mercury in a U tube of the general form shown in Fig.
Is7. M. One leg was connected with the interior of an artery by
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 arter}^ is able to support a column

Fig. 187. — 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 Riven by the distance in millimeters between the levels 1 and 2; one-half of
this distance i- recorded on the kymographion by the pen, I'); F, the float resting upon the
surface of the mercury ; (J, 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;
K, the receptacle containing the soJ ition of sodium carbonate; c, the cannula for insertion
into the artery; »■. the wa ooul arrangement shown in detail in />'.

/;, The washout cannula: c, the glass cannula inserted into the artery; r, the stem
connected with the reservoir of carbonate olution; «. tin; stem connected with the manom-
eter. The arrows hoy, the currenl 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 L3.5 the pressure can be obtained, when desirable,
in terms of a column of blood or wider. 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. 1H7

VELOCITY AND PRESSURE OF BLOOD-FLOW. 475

The distal limb of the U tube in which the mercury rises carries a float
of hard rubber, aluminum, or some other substance lighter than the mercury.
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. 187, B. When this
instrument is attached to the cannula inserted into the blood-vessel one can,
after first clamping off the artery, wash out the connections between the artery
and the manometer with fresh carbonate solution as often as desired. By
such means continuous records of arterial pressure may be obtained during
many hours. Determinations of the pressure in the veins may be made with a
similar apparatus, but owing to the low values that prevail on this side of
the circulation it is more convenient to use some form of water manometer
and thus record the venous pressures in terms of the height of the water column
supported. It should be added also that when it is necessary to know the
pressure in any special artery or vein the connections of the manometer are
made usually to a side branch opening more or less at right angles into the
vessel under investigation, or if this is not possible then a T" tube is inserted
and the manometer is connected with the side branch. The reason for this
procedure is that if the artery 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 con-
tinuation of the tube from the manometer and serves as a side connection
to the intact artery from which it arises. Thus, when a manometer is inserted
into the carotid artery the pressure that is measured is the side-pressure in
the innominate or aorta from which it arises, while a cannula in the central
stump of a femoral artery measures the pressure in the iliac. A specimen of
what is known as a blood-pressure record is shown in Fig. 188. The exact
pressure at any instant, in millimeters of mercury, is obtained by measuring
the distance between the base line and the record and multiplying by 2.
The base line represents the position of the recording pen when it is at its
zero position for the conditions of the experiment. It is necessary to mul-
tiply the distance between the base line and the record by 2 because, as
is seen in Fig. 187, 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. 188) shows usually large rhyth-
mical variations corresponding to the respiratory movements and in
addition smaller waves caused by the heart beat. The causes of the
respiratory waves of pressure are discussed in the section on respi-
ration. Regarding the heart waves or pulse waves the usual record
obtained by means of a mercury manometer gives an entirely false
picture of the extent of the variations in pressure caused by the heart
beat. The mass of mercury possesses considerable weight and iner-
tia, which unfits it for following accurately very rapid changes in
pressure. When the pressure changes are slow, as in the case of

476

CIRCULATION OF BLOOD AND LYMPH.

the long respiratory waves seen in the record, the manometer un-
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

AA^vV'/VVYV A.VvVV^'VV,V,A/V'V^y\''1V

] -'in. 188. — Typical blood pressure record with mercury manometer: Bp, The record
showing (Ik- hcari heal and the larger curves due to (he respirations (respiratory waves

nf blooa pre ure) and -t ill 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
I,-, e line I bal i . I be line of zero pressure to I be blood-pressure hoe, multiplied by two.
The ■• value are indicated in the vertical line drawn to the right, winch shows that the
pre ure al the time of the experiment was 100 nous. Hg_. The small size of the
ion in pre ure due to each heart heat, b altogether a false picture due to the inertia
of the mercury, it inability to follow completely the quick change. Kach heart heat,
in lead of being mailer, bould be larger than the respiratory waves.

determined by other means (see below), and, if the knowledge thus
obtained is applied to the con-eel ion of the record of the mercury
manometer, the tracing given in Fig. 188 should have, so far as the
heart beats are concerned, somewhat the appearance shown in big.
is!). This hitter figure gives a more accurate mental picture of
the actual conditions of pressure in the large arteries, as influenced by

VELOCITY AND PRESSURE OF BLOOD-FLOW. 477

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

Fig. 189. — 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 to 116 mms., while the diastolic
pressure is only 65 to 75 mms. The difference between the
systolic and the diastolic pressure has been designated con-
veniently as the pulse pressure. It measures, of course, the
variation in pressure in any given artery caused by the heart beat,
and so far as that artery is concerned it gives the force of the
heart beat except for the small component used to accelerate
the movement of the blood. From the figures given above it
will be seen that the pulse pressure in the brachial artery of
man averages 45 mms. Hg. Each systole of the heart distends
this artery, therefore, by a sudden increase in pressure equal
to the weight of a column of mercury 45 mms. high. As we
go outward in the arterial tree the pulse pressure becomes less
and less, the oscillations in pressure with each heart beat
are less marked, until, finally, in the smallest arteries and

47S

CIRCULATION OF BLOOD AND LYMPH.

capillaries and in the veins there is no pulse wave, and no difference
between systolic and diastolic pressure. In speaking of the pressure
in the blood-vessels we refer usually to what is called the mean
pressure. It is obvious that, so far as the larger arteries are con-
cerned, the mean pressure is only a convenient expression for the
average pressure during a certain period. If, by the methods
described below, we determine the systolic and diastolic pressures
in the artery of a man, and assume that there has been no general
variation between the two observations, we can estimate the mean
pressure with approximate accuracy by taking the arithmetical
mean of the two figures.

The arithmetical mean of systolic and diastolic pressures during any given
heart-beat does not give the true mean pressure, owing to the form of the
pulse wave (see Fig. 211). If the rise from diastolic to systolic pressure and
the succeeding fall took place uniformly, so that the pulse curve constituted

J it;. 190. — Schema to indicate the general relations of systolic, mean, and diastolic-
pressures throughout the arterial system : s. Systolic; m, mean; (/.diastolic; c, pressure
at beginning of the capillaries. The distance from a tod represents the pulse pressure at
different parts of the arterial system.

a true triangle, the true mean pressure would be given by the arithmetical
mean of the two pressures. As a matter of fact, the descending limb
of the pulse curve is not a straight but a curved line, and it is broken,
moreover, by secondary waves. The position of the mean pressure during
any given heart-beat will vary, therefore, with the form of Ihc pulse curve.
Generally speaking, it lies nearer to the diastolic than to the systolic level.*

In physiological observations, as a rule, no attempt is made to
estimate Ihe mean pressure for any given time with mathematical
accuracy. In the ordinary tracing as given by the mercury man-
ometer (Fig. L88) the mean pressure for any given period during
which the variations have been symmetrical and not extreme is
estimated as the arithmetical mean of the highest and lowest
point- ic'ielifd. When desirable, the mean pressure may be
recorded by introducing a resistance (narrowing the tube by means

of :i stopcock) between the artery and the manometer. The latter
* Sec Dawson, " British Medical Journal," 1906, 996.

VELOCITY AND PRESSURE OF BLOOD-FLOW.

479

will then record mean pressure and show no variations with the
heart beat. A general idea of the variations in systolic, diastolic,
and mean pressures, throughout the arterial system, may be ob-
tained from the schema given in Fig. 190.

Method of Measuring Systolic and Diastolic Pressure in
Animals. — In animals a manometer may be connected directly
with the artery and systolic and diastolic pressures may be obtained
in one of two general ways: (1) By using some form of pressure
recorder or manometer sufficiently mobile to follow very quick
changes of pressure. (2) By using a mercury manometer pro-
vided with maximum and minimum valves. Of the manometers
that have been divised to register accurately the quick changes in
pressure due to the heart beat, the two that are most frequently

Fig. 191. — The spring manometer of Fick (after Langendorff) : f, The flat metal
tube filled with liquid; r, the lead tube connecting with the artery; h, h, h, the lever
mechanism of light wood communicating the movements of / to the writing point, s; p, a
small disc immersed in a vessel of oil to still further dampen the inertia swings.

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

The Fick manometer is shown in Fig. 191. 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 Hiirthle manometer is more frequently
used at present. The principle made use of in this instrument is illustrated
by the diagram in Fig. 192. The instrument consists essentially of a small
box or tambour of very limited capacity; the top of the tambour is covered

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

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

4S0

CIRCULATION OF BLOOD AND LYMPH.

Fig. 192. — Diagram showing construction of Htirthle's manometer. — (After Cvrtis.)
The interior of the heart or the artery is connected by rigid tubing to a very small tambour,
2'. 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 arteri/- ^^

Fig. 1&3. — Schema to illustrate the use of valves in determining maximum (systolic)
and minimum (diastolic) blood-pros ill*-. When :;topeock n i:i open the heart beats are
trail milted through the maximum valve ami flic mercury in llie manometer i prevented

from falling bel ween beats. The manometer will record I be highest pressure reached during
the period "i ob i rvation. The reverse oooure when valve 6 alone is open.

VELOCITY AND PRESSURE OF BLOOD-FLOW. 481

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. 194.
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. 188.

Fig. 194. — Blood-pressure record from a dog with a Hiirthle manometer. The size
of the heart beats is relatively much greater than with a mercury manometer. In this case
the systolic pressure is about 150 mms. Hg; the diastolic, 100 mms. ; and the heart beat or
pulse pressure, 50 mms.

The method that depends upon the use of maximum and minimum valves
may be understood by reference to Fig. 193. On the path between the artery
and the manometer one may place a maximum and a minimum valve so ar-
ranged that the blood-pressure and heart beat may be transmitted through
either valve. As is shown by the figure, if the connection is maintained
through the maximum valve for a certain time the highest pressure reached
during that period will be recorded, while, when the minimum valve is used
the lowest pressure reached will be indicated.

Such valves, of course, act slowly and can not be used to determine the
maximum and minimum pressure in the artery during a single heart beat;
they record the highest and lowest point reached during a certain given
interval.

Actual Data as to the Mean Pressure in Arteries, Veins,
and Capillaries. — The mean value of the pressure in the aorta
has been determined for many mammals. It is found that the actual
figures vary with the conditions under which the results have been
obtained. Such values as the following may be quoted:*

Horse 321 mms. to 150 mms. Hg.

Dog 172 " "104 " "

Sheep 206 " "156 " "

Cat 150 "

Rabbit 108 " " 90 " "

Man (probable, Tigerstedt) 150 "

*See Volkmann, "Die Haemodynamik," 1850.
31

482

CIRCULATION OF BLOOD AND LYMPH.

It appears from these figures that there is no proportion between
the size of an animal and the amount of mean arterial pressure. It
is probable that there may be a general relationship between the
size of the animal — that is. the size of the heart — and the amount

Jb

C-

M

R

F

p

5

IBO

\

\

\

IM

\

\

\

S

IfC

■>

\u

tt

it

r

IM .

i

Vf

'O

-n

/

100

-/

a

if

s

no

M

4(>

10

0

Fig. 195 — 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 arid superior mesenteric; R, left renal; F, left femoral (KHenberger
and Bauni), external iliac; P, profunda branch of femoral; 8, saphena. The pressure in
millimeters is given along the ordinate's to the left. It will lie noted that the mean and
the dia tolic pre ures 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 ia much larger than at the arch. (Dawaon.)

of pulse pressure or the oscillation of pressure with each heart beat,
but sufficient data are not, at hand to determine this point. As
we pass from the aorta to the smaller arteries the mean pressure
decreases somewhat, although not very rapidly, while the pulse
pressure decreases also and to a more noticeable extent.

VELOCITY AND PRESSURE OF BLOOD-FLOW. 483

This fact is illustrated in Fig. 195, which gives a graphic
representation of a number of experimental determinations* of
systolic and diastolic pressures in the large arteries of the dog.

If we turn to the other end of the vascular system, the veins,
we find that the lowest pressure is in the venae cavse and that it
increases gradually as we go toward the capillary area. Accord-
ing to one observer, f the fall in pressure from periphery toward
the heart is at the rate of 1 mm. Hg for every 35 mms. of distance.
We" have such figures as the following:

Dog (Opitz). Sheep.

Superior vena cava (near Jugular vein 0.2 mm. Hg.

auricle) = — 2.96 mms. Hg. Facial vein . 3.0 mms. "

Superior vena cava more Branch of brachial ... 9.0 " "

distal = —1.38 " " Crural 11.4 " "

External jugular (left) . . = 0.52 mm.

Right brachial = 3.90 mms

Left facial = 5.12 "

Left femoral .......= 5.39 "

Left saphenous = 7.42 "

Fig. 196. — 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. The pressures in the veins are represented as
uniform at any one point. In the large veins near the heart there are variations of pressure
with each respiration and with each heart beat (Venous Pulse, p. 513).

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 pres-
sure is below that of the atmosphere, the tension of the blood in
them may also be below atmospheric pressure, although doubt-
less at this point (vena cava) the pressure within the vein is
greater, certainly not less than the pressure on its exterior
(intrathoracic pressure). To complete the general conception of
the pressure relations in the vascular system it is necessary
to know the pressure of the blood in the smallest arteries and
veins and in the capillaries. It is not possible — in the cases of
the capillaries, for instance — to connect a manometer directly

* Dawson, "American Journal of Physiology," 15, 244, 1906.
t Burton-Opitz, "American Journal of Physiology," 9, 198, 1903.

4S4 CIRCULATION OF BLOOD AND LYMPH.

with the vessels, and recourse has been had to a less direct
and certain method. The pressure in the capillaries in dif-
ferent 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.
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 —V" 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.

By means of a more adjustable instrument von Reckling-
hausenf estimates that in man the pressure within the capil-
laries of the finger-tips or, to be more accurate, within the small
arteries supplying these capillaries, is equal to 55 mms. Hg.
(See p. 491.)

The general relations of the pressures in arteries, veins, and
capillaries may be expressed in a curve such as is shown in Fig.
196.

It should be added that in this curve and in all the figures
so far quoted in regard to the actual pressure within the different
arteries and veins, it is assumed that the animal is in a recumbent
posture. In an animal standing upon his feet, especially in
.ui upright animal like man, it is obvious that the effect of
gravity will modify greatly the actual figures of pressure. Upon
the arteries and veins of the feet, for example, there will be
exerted a hydrostatic pressure equal to the height of the column
of liquid between the feet and the heart, which adds itself to
the pressure resulting from the circulation as caused by the
heart. When the animal is in a recumbent position the hydro-
static factor practically disappears. (See p. 500.)

* V. Kries, "Beriehte d. Sachs. Geaellflchaft d. Wiss. Math.-phys. Classe,"
1875, p. I is.

f Von Recklinghausen, "Archiv f. exp. Path. u. Pharnak.," 55, :'>7.r>, l(.)07.

VELOCITY AND PRESSURE OF BLOOD-FLOW.

485

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

Fig. 197. — 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, 6, to meas-
sure the amount of pressure.

diagram in Fig. 190. 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

•486 CIRCULATION OF BLOOD AND LYMPH.

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. 197.

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-

c

Fig. 198. — 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: n represents the normal artery distended by diastolic blood-pressure; the dotted
lines indicate the additional expansion caused by the pulse wave; b represents the artery
when compressed by an outside pressure equal to the diastolic pressure within; the artery
then takes the size of an empty artery kept patent by the rigidity of its walls. The pulse
wave, on reaching this section, finds a relaxed wall and causes, therefore, a maximum
extension.

cury manometer. The moment of obliteration of the artery is determined
by feeling for 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-
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 -ecoiding
by some means the pulsations of the artery under different pressures aiid de-
termining under what pressure the maximal pulsations are given. Thie pres-
sure should be equal to the diastolic pressure within the artery. The prin-
ciple involved may be illustrated by the accompanying figure (Fig. 198).

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 he 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-
i ralize I he ol her, and the diameter of the artery will be equal to that assumed
when the vessel contains Mood 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
and the force of the heart wave will consequently cause a greater dis-

* "Archives italiennes de biologic," 23, 177, L895.

VELOCITY AND PRESSURE OF BLOOD-FLOW.

487

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. 199. — Record {Erlanger) to show the maximum size of the recorded pulse
wave when the outside or extra vascular 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

Fig. 200. — Schema showing the construction of the Erlanger apparatus: a. Rubber
bag of the arm piece ; c, bulb for blowing up this bag and putting pressure on the arm ; 6,
the manometer for measuring the pressure ; i, two-way stopcock (when turned so as to
communicate with the capillary opening, A;, 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.

is diminished, the pulse waves become larger up to a certain point and then
decrease again in size (see Fig. 199). 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

4ss

CIRCULATION OF BLOOD AND LYMPH.

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

Fig. 201.- Erlanger apparatus, The collar for the arm is not shown. The parts maybe
understood by reference to the Bchema given in Fig. 200.

in overcoming this resistance. The amount of the resistance offered by the
tissues lias been estimated differently by various authors, but probably lies
between •» and 10 nuns, 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 Erlangerf is probably the most complete

* Howell and Brush, " Proceedings of the Massachusetts Medical Society,"
1901.

■(■"American Journal of Physiology," "Proceedings of the American
Physiological Society," 6, xxii., 1902; and " Johns Hopkins Hospital Reports,"
12,53, 1 «.J04.

VELOCITY AND PRESSURE OF BLOOD-FLOW. 489

and the most convenient for actual use. This instrument is illustrated in
Figs. 200 and 201.

It may be used to determine both systolic and diastolic pressure.

The way in which the apparatus is used may be understood from the sche-
matic Fig. 200. a is the rubber bag which is buckled upon the arm by a leather
strap. This bag communicates with the mercury manometer, b, with a pres-
sure bag, c, through the two-way stopcock, i, and through the stopcock d with
a rubber bag, e, contained in a glass chamber, /. This glass chamber com-
municates above with a sensitive tambour, h, and by means of the stopcock
g can be placed in communication with the outside air. The systolic pressure
may be determined in two ways: By one method only the mercury manom-
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

lalP^

Fig. 202. — To show the method of detecting the systolic pressure upon the tracing
given by the Erlanger sphygmomanometer. The pressure upon the arm is dropping
slowly and at the point just before the mark x the pulse wave shows the spreading of the
limbs that indicates the first pulse wave to get through the occluded artery. The next
pulse wave shows the sudden increase in size of the pulse, which has also been taken to
mark the systolic pressure.

manometer, at which the pulse just gets through. This pressure will measure
approximately the systolic pressure. The second method (method of v.
Recklinghausen) 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 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 tambour writes these pulsations on a kymo-
graphion. 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 communicated 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 (Fig. 202). This point marks the moment when
the pulse wave is first able to break through the brachial artery, and it gives,
therefore, the systolic pressure. In many cases this method of determining
the point of systolic pressure is not satisfactory, since the pulse waves increase

490 CIRCULATION OF BLOOD AND LYMPH.

gradually in amplitude without a sudden break, or perhaps there is more
than one place at which a sudden increase occurs. A more reliable method
according to Erlanger is to note the point at which the ascending and descend-
ing limbs of the pulse wave show a noticeable separation (Fig. 202). "At
the moment the pressure on the artery falls below systolic, blood succeeds in
making its way beneath the cuff. This must be squeezed out before the lever
can return to the base line, whereas at higher pressures the lever is raised
only through the hydraulic-ram action of the pulse wave upon the upper
edge of the cuff." After finding the systolic 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 manipu-
late 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. 199. It should be added, also, that in order to keep the lever of the
tambour horizontal while the pressure in the system is being lowered there
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 Arterial 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 experiments 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. It should be remembered also that in measuring
arterial pressures in man the measurements must always be
made at the level of the heart, as is usually done, the brachial
artery being selected, or if other arteries are employed, an allow-
ance must be made for- differences in level. (See paragraph
on the Eydrostatic Effect, p. 500.) Under normal conditions
Potain* estimated the systolic pressure in the radial of the adult
at about 170 nuns, of mercury and the variations for different
ages he expressed in the following figures:

Age (i III I.") 20 25 30 40 50 60 SO

Pressure (systolic). 89 135 L50 170 ISO 190 200 210 220
* " La prewiou arterielle de L'homme," Paris, 1902.

VELOCITY AND PRESSURE OF BLOOD-FLOW. 491

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. Von Recklinghausen's figures for the same artery are,
systolic pressure 116 mms. Hg, diastolic pressure 73 mms. Hg.

Erlanger and Hooker report observations upon the effect
of meals, of baths, of posture, the diurnal rhythm, etc.*

The effect of meals is particularly instructive in that it illustrates
admirably the play of the compensatory mechanisms of the circu-
lation by means of which the heart and the blood-vessels are ad-
justed to each other's activity. During a meal there is a dilatation
of the blood-vessels in the abdominal area, or, as it is frequently
called in physiology, the splanchnic area, since it receives its
vasomotor fibers through the splanchnic nerve. The natural
effect of this dilatation, if the other factors of the circulation
remained constant, would be a fall of pressure in the aorta and a
diminution in blood-flow to other organs, such as the skin and the
brain. This tendency seems to be compensated, however, by an
increased output of blood from the heart. Observations with the
sphygmomanometer show that after full meals there is a marked
increase in the pulse pressure, indicating a more forcible beat of the
heart. So far as the effect on the heart is concerned, the result of a
meal is similar to that of muscular exercise, and this reaction may
account for the fact, not infrequently observed, that in elderly
people whose arteries are rigid an apoplectic stroke may follow a
heavy meal.

The Method of Determining Venous Pressures and Capillary
Pressures in Man. — A number of methods have been proposed
for determining venous pressures in man, the simplest being
that described by Gaertner.f It consists simply in raising
slowly the arm of the patient until the veins on the back of the
hand just disappear. The height above the heart at which this
occurs gives the venous pressure in the right auricle, since the
vein may be considered as a manometer tube ending in the
auricle. In this and in other methods of measuring venous

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

f'Muench. mediz. Wochenschrift," 1903, 1904.

492

CIRCULATION OF BLOOD AND LYMPH.

pressures, and the same is true, of course, of arterial and capillary
pressures, there must be some agreement as to what constitutes
the heart-level, since the highest and lowest points of the heart
when the individual is standing or sitting may differ by as much
as 15 centimeters, von Recklinghausen proposes the level
made by a dorso ventral line drawn from the bottom of the
sternum (costal angle) to the spinal column. This authorf has
devised a simple apparatus for determining venous and capillary
pressures, the principle of which is shown by the schema repre-
sented in Fig. 203.

A circular bag of thin rubber with a diameter of about 5J cm. is provided
with a central opening of 2 cm. The bag is connected with a pump so that
it can be blown up, and the degree of pressure exerted is measured by an
attached manometer. This bag, moistened with glycerine, is laid upon a
vein, as represented in the diagram. It is covered by a glass plate held firmly

Fig. 203. — To illustrate the method of measuring venous pressure: //, The back of
the hand in which a single vein is represented; B, the circular rubber bag with central
opening, and with a tube, T, which leads to the pump and the manometer; G, glass plate
held over the rubber bag. The bag, B, is blown up by pressure through the tube T until
the vein is collapsed. The pressure at which this occurs, or the pressure at which the
vein reappears as the bag is allowed to empty, gives the pressure within the vein. — (von
Recklinghausen.)

in posil ion and the bag is then blown up until the vein disappears; the pressure
at which this happens is shown by the manometer and marks (lie pressure
within i ho vein. A convenient modification of this apparatus which lias
been described by Eyster and Hookerf is shown in Fig. 20 1. The box, />',
used for compressing the vein is connected by rubber tubing will: a rubber
manometer, Cf, and a pressure-bull), Ii. The structure of the pressure box is
shown in the smaller figure. It. consists of an aluminum frame or box, the

top and one side of which are made of glass. One of the sides is perforated

by a tube which oonneets with the maiiomel er, as shown in I he larger figure.
The frame is cut away on two sides, so thai when il is tied upon the arm the
vein will not be compressed. Over the bottom of this frame is laid a thin
sheet of rubber dam, :!, with a hole cut ii) I he center, and I he aluminum frame

with its rubber bottom is then set into a close fitting brass frame, 2, which

serves to keep the rubber membrane in place. When placed in position Upon
the arm the rubber dam lies upon the vein and presses upon il as the pressure

i rai ed in the box. The vein is observed through the glass top and the hole

in the rubber, and the pressure at which it is just obliterated is read from the

manometer.

W'iib instruments of ibis kind the degree of pressure neces-
sity to obliterate a given vein in the arm, band, or foot can

* Von Recklinghausen, "Archiv f. exper. Pathol, u. Pharmakol, " 55, 470,

l!ll)li.

• rand Hooker, "The Johns Hopkins Hospital Bulletin," 274, L908.

VELOCITY AND PRESSURE OF BLOOD-FLOW.

493

be determined readily in terms of a column of water, but it
is obvious that for any given vein this pressure will vary with
the position of the vein. When the hand hangs pendent at
the side the pressure within its veins will be greater than when
the hand is raised to the heart-level. The pressure actually
measured for any given position of the hand or foot must,

Fig. 204. — Apparatus for determining venous blood-pressure in man: B, The box
with glass top for putting pressure on the vein; the details are shown in the small figure
(Fig. 2), in which 1 show- the alumimum box; 2, the brass collar which fits over 1 and
holds in place the perforated sheet of rubber dam; 3, which forms the bottom of the box
and is forced down on the vein. E, pressure bulb for increasing pressure in the box until
the vein is obliterated. G, water manometer to measure the pressure. (Eyster and
Hooker.)

therefore, be corrected for the heart-level by determining the
vertical distance between the vein and the heart (costal angle),
and subtracting this distance, expressed in centimeters, from
the pressure, also expressed in centimeters, which was found
necessary to obliterate the vein. Measurements made by this
method and corrected for the heart-level show that in the normal

494 CIRCULATION OF BLOOD AND LYMPH.

person the pressure within the small veins of the hand or arm
may vary between 3 and 10 centimeters of water. Unusual
or pathological conditions which cause a congestion in the venous
side of the heart will raise the venous pressure correspondingly
to 20 centimeters or more.*

When the venous pressure is measured in the small veins of the feet in a
person wliile standing we should suppose that after a reduction to the heart
level it would be about the same as that noted for the veins of the hands,
since the vessels are of about the same order with reference to their distance
from the capillary bed. In a series of observations of this kind, reported by
von Recklinghausen, it was found, on the contrary, that after subtracting the
distance between the foot and the heart, the pressure within the veins was
negative by as much as 40 cm. The author explains this unexpected result
by supposing that the flow through the foot got up only enough pressure in
the veins to lift the blood to the level of the pelvis, and that the complete
closure of the venous valves at this level protected the veins from the full
pressure of the column of blood. If the pressure was not sufficient to lift
the blood to the heart, then evidently no flow was taking place in the foot.
Eventually no doubt the pressure in the veins would have risen sufficiently to
lift the blood to the heart-level and thus reestablish the flow, but it seems
probable that under the ordinary condition's of life this result is effected by
the cooperation of the muscles of the legs. The contractions of these muscles,
aided by the venous valves, squeeze the blood upward to the heart. The
fact that in standing quietly the flow through the feet may be suspended or
impeded, for a time at least, throws some light, as von Recklinghausen suggests,
upon the fact that it is so difficult to stand for any length of time without
moving.

The apparatus described above may be used for determining
capillary as well as venous pressures, according to the principle
described on p. 484. For this purpose the pressure box is laid
upon a given skin area and the pressure is raised until the skin
beneath is blanched. The pressure is then lowered slowly
until the skin again reddens, showing the reestablishment of the
capillary flow. The pressure thus obtained is corrected as
described for the level of the heart, f

* For a description of some pathological cases, see Eyster and Hooker,
loc. cit.

t For some technical details, see von Recklinghausen,, loc. cit.

CHAPTER XXVI.

THE PHYSICAL FACTORS CONCERNED IN THE PRO-
DUCTION OF BLOOD-PRESSURE AND BLOOD-
VELOCITY.

In the preceding pages some of the essential facts have been
stated regarding the pressure and the velocity of the blood in the
different parts of the vascular system. We may now consider the
physical factors that are responsible for the production and mainte-
nance of these peculiarities. The problem as it actually exists in the
circulation, with its elastic vessels varying in size from the aorta,
with an internal diameter of nearly 20 mms., to the capil-
laries, with a diameter of 0.009 mm., is extremely complex, but the
general static and dynamic principles inyolved 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. 205, 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

495

496

CIRCULATION OF BLOOD AND LYMPH.

to the reservoir, and this in general is the picture presented by
the circulation. The reservoir, the head of pressure, is represented
by the aorta, the exit for the outflow by the opening of the venae
cavae into the right auricle, and the side pressure or internal tension
of the blood due to friction against the walls of the vessels increases
from the venae cavae back to the aorta. If from aorta to vena cava
the vessels were of the same diameter the increase would be in a
straight line, as in the case of the model. In this model it will be
noticed that the straight line showing the side pressure does not
strike the top of the column of liquid in the reservoir, but corre-
sponds to a certain height, W. This expresses the fact that, of the
total head of pressure in the reservoir, which we may designate as
H, a certain portion only, but a large portion, h' ', is used in over-

Fig. 205. — Schema to illustrate the side pressure due to resistance, and the velocity pres-
sure (Tigerstedt) : 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, (his 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 arc two important differences
between the circulation as it exists in the body and that repre-
sented by the model. In the body, in the first place, we have
the area of capillaries, small arteries, and veins, intercalated be-
tween the large arteries on one side and the veins on the other;
and, in the second place, the vessels, especially the arteries, are
extensible and elastic. The effect caused by the first of these

BLOOD-PRESSURE AND BLOOD-VELOCITY.

497

factors — namely, a great resistance placed in the middle of the
course — may be illustrated by the model shown in Fig. 206, which
differs from that in Fig. 205 in having a stopcock in the outflow
tube, which, when partly turned off „ makes a narrow opening and a
relatively great resistance. When the stopcock is open the pressure
falls equally throughout the tube, provided the bore of the stopcock
is equal to that of the tube. If, however, it is partially turned the
side pressure is much increased between it and the reservoir on what
we may term the arterial 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

1

-- --.

i

i

^_^

Fig. 206. — 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. 205 and 206, 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 cavae, the pressure throughout the system
would rise to a high point during systole and fall to zero during the
32

498 CIRCULATION OF BLOOD AND LYMPH.

diastole. The elasticity of the arteries, in connection with the
peripheral resistance, makes an important difference. As the heart
discharges into the aorta the pressure rises, but the walls of the
arterial system are distended by the increased pressure, and during
the following diastole the recoil of these distended walls maintains
a flow of blood through the capillaries into the veins. With a
certain rapidity of heart beat the distension of the arterial walls is
increased to such a point that the outflow through the capillaries
into the veins is as great during diastole as during systole; the
rhythmical flow in the arteries becomes converted by the elastic
tension of the overfilled arterial system into a continuous flow in
the capillaries and veins. This effect may be illustrated by a simple
schema such as is represented in Fig. 207. A syringe bulb (a), rep-
resenting the heart, is connected by a short piece of rubber tubing to a
glass tube (b), and also by a piece of distensible band tubing (e) with

Fig. 207. — 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 tlie strokes of the pump); c, outflow with resistance and
also extensible and elastic walls represented by the large rubber bag, e ; the outflow is a
steady stream due to the elastic recoil of the distended bag, e.

a similar glass tube drawn to a fine point (c). In the latter case the
distensible, elastic tubing represents the arterial system, and the
fine pointed glass tube the peripheral resistance of the capillary area.
If the syringe bulb is put into rhythmical play and the flow is directed
through tube b the discharges are in rhythmical spurts, but if
directed through tube c the discharge is a continuous stream,
since I he force of the separate beats becomes stored as elastic tension
in the walls of the band tubing, and it is this constant force which
drives a steady stream through the capillary point. In a general
way, this schema gives us a true picture of the conditions in the cir-
culation. The rhythmical force of the heart beat is stored as elastic
iiii ion in the walls of the arteries, and it is the squeeze of these
distended walls which gives the continuous driving force that is
responsible for- the constant flow in the capillaries and veins.

Enumeration of the Factors Concerned in Producing Nor-
mal Pressure and Velocity. — In the normal circulation we may

BLOOD-PRESSURE AND BLOOD-VELOCITY. 499

say that four chief factors co-operate in producing the conditions
of pressure and velocity as we find them. These factors are: (1)
The heart beat. (2) The resistance to the flow of blood through the
vessels, and especially the peripheral resistance in the region of the
small arteries, capillaries, and small veins. (3) The elasticity of
the arteries. (4) The quantity of blood in the system. The
way in which these factors act may be pictured as follows : Suppose
the system at rest with the definite quantity of blood distributed
equally throughout the vascular system. The internal or side
pressure throughout the system will be everywhere the same, —
probably zero (atmospheric) pressure, since the capacity of the
vascular system is sufficient to hold the entire quantity of blood
without distension of its walls. If, now, the heart begins to beat
with a definite rhythm and discharges a definite quantity of blood at
each beat the whole mass will be set into motion. The arteries
receive the blood more rapidly than it can escape through the capil-
laries into the veins, and consequently it accumulates upon the
arterial side until an equilibrium is reached, — that is, a point at
which the elastic recoil of the whole arterial tree suffices to force
through the capillaries in a unit of time as much blood as is received
from the heart during the same time. In this condition of equilib-
rium the flow in capillaries and veins is constant, and the side
pressure in the veins increases from the right auricle back to the
capillaries. In the arteries there is a large side pressure throughout,
owing to the resistance between them and the veins and especially
to the great resistance offered by the narrow capillaries. This
pressure rises and falls with each discharge from the heart, and the
pulse waves, both as regards pressure and velocity, are most marked
in the aorta and diminish farther out in the arterial tree, failing
completely in the last small arterioles, since if taken together these
arterioles constitute a large and distensible tube of much greater
capacity than the aorta.

General Conditions Influencing Blood-pressure and Blood-
velocity. — Alterations in any of the four chief factors mentioned
above must, of course, cause a change in pressure and velocity.

I. An increase in the rate or force of the heart beat will increase
the velocity of the flow throughout the system, although, of course,
that general difference in velocity in the arteries, capillaries, and
veins which depends upon the variations in width of bed will remain.
Such a change will also cause a rise of pressures throughout the
system. The whole energy exhibited in the vascular system as
side pressure, velocity pressure, etc., comes, in the long run, from
the force of contraction of the heart muscle. This force is what is
represented in the model, Fig. 196, as the total head of pressure (H).
An increase in rate or force of heart beat is equivalent, therefore,

500 CIRCULATION OF BLOOD AND LYMPH.

to an increase in this head of pressure, and along with the increase
in velocity thus caused there is an increased friction or resistance.

II. An increase or decrease in the width of the vessels will
influence both the resistance to the flow and the velocity. Under
normal conditions it is the small arteries that are constricted or
dilated (vasoconstriction and vasodilatation). A constriction of
these arteries causes an increase in arterial pressures and a decrease
in venous pressure. The velocity of the blood-flow is decreased.
A dilatation has the opposite effects. Numerous instances of this
relation will be referred to in describing the physiology of the vaso-
motor nerves.

III. A diminution in elasticity of the arteries will tend to
interfere with the constancy of the flow from the arteries into the
capillaries, and in the arteries themselves the swings of pressure
from systolic to diastolic during the heart beat will be more
extensive. This latter fact can be shown upon elderly individuals
whose arteries are becoming rigid, but whether a change of this
character is ever so advanced in human beings as to seriously modify
the capillary circulation does not appear to have been investigated.

IV. A loss of blood, other conditions remaining the same,
will also cause a fall in blood-pressures and velocity. As a matter
of fact, however, a considerable amount of blood may be lost with-
out any marked permanent change in arterial blood-pressure. The
reason for this result is found in the adjustability or adaptability
of the vascular system. It is in such respects that the system differs
greatly from a rigid schema such as we use for our models. When
blood is withdrawn from the vessels the loss may be offset by an
increased action of the heart and by a contraction of the arterioles,
the two effects combining to give a normal or approximately normal
arterial pressure. To carry out the analogy with the model (Fig.
205) if by chance some of the store of water was lost we might sub-
stitute a narrower reservoir, so that with a diminished supply we
could still maintain the same level of pressure. In the body,
moreover, a loss of blood by hemorrhage may be compensated in
p.nt. bo far as Hie bulk of the liquid is concerned, by a flow of
liquid from the tissues into the blood-vessels.

The Hydrostatic Effect. — In the living animal, especially in
those, like ourselves, that walk upright, the actual pressure in the
arteries of the various tissues must vary much also with the position.
For instance, in standing erect the small arteries in the hands or
feet are, in addition to other conditions noted above, exposed to the
weight of the column of arterial blood standing over them. In
the pendent arm the skin of the fingers is congested; if, however,
the arm is raised above the head the skin may become blanched
because now the column of blood from fingers to shoulder exercises

BLOOD-PRESSURE AND BLOOD-VELOCITY. 501

a hydrostatic pressure in the opposite direction. In determinations
of blood-pressure in the brachial artery of man care should be taken
to keep the arm in the same position in a series of observations in
order to equalize the effect of the hydrostatic factor. The impor-
tance of this gravity effect is most evident in the case of the ab-
dominal (splanchnic) circulation. When an animal accustomed
to go on all fours is held in a vertical position the great vascular
area of the abdomen is placed under an increased pressure due to
gravity, and, unless there is a compensatory contraction of the
arterioles or of the abdominal wall, so much blood may accumulate
in this portion of the system that the arterial pressure in the aorta
will fall markedly or the circulation may stop entirely.* In most
cases the compensation takes place and no serious change in the
circulation results. In rabbits, however, which have lax abdominal
walls, it is said that the animal may be killed by simply holding it
in the erect position for some time. For the same reason an erect
posture in man may be dangerous when the compensatory nervous
reflexes controlling the arteries and the tone of the abdominal wall
are thrown out of action, as, for instance, in a faint or in a condition
of anesthesia. In such conditions the recumbent position favors
the maintenance of the normal circulation. Indeed, under ordinary
conditions some individuals are quite sensitive to the effects of a
vertical position, especially if unaccompanied by muscular or mental
activity, and may suffer from giddiness and a sense of faintness
in consequence of a fall in general blood-pressure. It seems prob-
able that in these cases the gravity effect has drafted off an undue
amount of blood into the splanchnic area. Individuals who have
been kept in bed for long periods by sickness, accident, or other
causes suffer from giddiness and unsteadiness when they first
attempt to stand or walk. It seems quite possible that in such
cases the effect is caused by a fall in arterial pressure brought
about by the dilatation in the splanchnic area. The added
weight of blood thrown on these vessels by the effect of gravity
is not compensated by a vasoconstriction of the arterioles or an
increased tone in the abdominal walls. While certain general
deductions of the kind given above may be made from our
knowledge of the hydrodynamics and hydrostatics of the cir-
culation, it is evident that in particular cases, whether affecting
special organs or the organism as a whole, it is necessary to
obtain directly, if possible, the facts, not only for the arterial
pressure and velocity but also for the venous pressure and
velocity, in order to draw safe conclusions as to the changes in
the circulation. In all observations made upon man it is
especially important to standardize the results by reducing
* Hill and Barnard, "Journal of Physiology," 21, 321, 1897.

502 CIRCULATION OF BLOOD AND LYMPH.

them to a common level. The arterial or venous pressure in
the foot or hand of a man standing erect is increased by the
hydrostatic effect of the vertical column of blood between the
point measured and the heart. This hydrostatic effect varies,
of course, for the different parts of the body, and to compare the
pressures in the different arteries or veins with one another the
vertical distance from the heart should be measured and this
pressure in terms of a column of water or mercury should be
subtracted or added, as the case may be, to the pressure actually
observed. The exact level for which these measurements should
be adjusted has varied somewhat in practice; to simply say the
heart-level is too indefinite, since in the upright position there
is a considerable distance between the level of the base and of
the apex of the heart, von Recklinghausen recommends the
middle of the dorsoventral axis drawn from the lower end of the
sternum to the spinal column.

Accessory Factors Aiding the Circulation. — The force of the
heart beat is the main factor concerned in the movement of the
blood, but certain other muscular movements aid more or less in
maintaining the circulation as it actually exists in the living animal.
The most important of these accessory factors are the respiratory
movements and the contractions of the muscles of the limbs and
viscera. At each inspiratory movement the pressure relations are
altered in the thorax and abdomen, and reverse changes occur during
expiration. These effects influence the flow of blood to the heart,
and alter the velocity and pressure of the blood in a way that is
described in the section on Respiration under the title of The
Respiratory Waves of Blood-pressure. Contractions of the skeletal
muscles must also influence the blood-flow. The thickening of the
fibers in contraction squeezes upon the capillaries and small vessels
and tends to empty them. On account of the valves in the veins
the blood is forced mainly toward the venous side of the heart;
.so that rhythmical contractions of the muscles may accelerate the
circulation. This pumping effect of our muscular movements
is probably quite an important factor in returning the blood
from the lower extremities. In this portion of the body the
venous flow to the heart lias to overcome the hydrostatic pres-
sure of the column of blood, and it has been shown that when
one is standing quite still the venous pressure alone may be
insufficient to overcome this resistance, so that the blood-flow
from the feet may be much retarded. Under these circum-
stances movements of the legs, us in walking, aided by the valves
in the veins, probably help to "milk" the blood toward the
heart. The contractions of the smooth muscles, especially in
the stomach and intestines, during digestion have a similar

BLOOD-PRESSURE AND BLOOD-VELOCITY. 503

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. 472), is also greater in
the lung capillaries than in the systemic capillaries. Exact deter-
minations of the pressure in the pulmonary artery are made with
difficulty on account of the position of the vessel.* The results
obtained by various observers give such values as the following:

Mean Pressure. Extreme Variations.
Mms. Hg. Mms. Hg.

Dog 20 10 to 33

Cat 18 7.5 " 24.7

Rabbit 12 6 "35

It will be seen, therefore, that the mean pressure is not more
than one-seventh to one-eighth of that prevailing in the aorta.
The thinner walls and smaller muscular power of the right ventricle
as compared with the left are an indication of the fact that less force
is necessary to keep up the circulation through the pulmonary
circuit.

The Variations in Pressure in the Pulmonary Circuit. —
Experimental results indicate that the pressures in the pulmonary
circuit do not undergo as marked changes as in the systemic circu-
lation; the flow is characterized by a greater steadiness. With a
systemic pressure, as taken in the carotid, varying from 144 to 222
mms., that in the pulmonary artery changes correspondingly only
from 20 to 26 mms., and extreme variations of pressure in the

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

504 CIRCULATION OF BLOOD AND LYMPH.

pulmonary artery probably do not exceed,, as a rule, 15 to 20 mms.
The regulations of the pressure and flow of blood in the small
circulation do not seem to be so direct or complex as in the aortic
system. The part taken by the vasomotor nerves is referred to
in the chapter upon the innervation of the blood-vessels, and
attention may be called here only to the mechanical factors, which,
indeed, for this circulation are probably the most important. The
output from the right ventricle, and therefore the amount of flow
and the pressure in the pulmonary artery, depends mainly on the
amount of blood received through the venoe cavae by the right auricle.
If one of the vense cava? is closed the pulmonary pressure sinks;
pressure upon the abdomen, on the other hand, by squeezing more
blood toward the right heart may raise the pressure in the pulmonary
artery. By such means, therefore, the variations in blood-flow in
the systemic circulation indirectly influence and control the pressure
relations in the pulmonary circuit. But the changes in the systemic
circulation may affect the blood-flow through the lungs in still
another way, — namely, by a back effect through the left auricle.
When for any reason the blood-pressure in the aorta is driven
much above the normal level the left ventricle may not be able to
empty itself sufficiently, and if this happens the pressure in the
left auricle will rise and the flow through the lungs from right
ventricle to left auricle will be more or less impeded. On the whole,
it would seem that the pulmonary circulation is subject to less
changes than in the case of the organs supplied by the aorta. The
mechanical conditions, especially in the capillary region, are such
that the blood is sent through the lungs with a relatively high
velocity, although under small actual pressure. The special effects
of the respiratory movements and of variations in intrathoracic
pressure upon the pulmonary circulation are referred to in con-
nection with respiration.

CHAPTER XXVII.

THE PULSE.

General Statement. — When the ventricular systole discharges
a new quantity of blood into the arteries the pressure within these
vessels is increased temporarily. If the arteries, capillaries, and
veins were perfectly rigid tubes it is evident that this pressure would
be transmitted practically instantaneously throughout the system,
and that a quantity of blood would be displaced from the venae
cavse into the auricles equal to the quantity forced into the aorta by
the ventricle. The flow of blood throughout the vascular system
would take place in a series of spurts or pulses, the pressure rising
suddenly during systole and falling rapidly during diastole. Since
the blood is incompressible and the walls of the vessels if rigid
would be inextensible, the rise of pressure, the pulse, would be
simultaneous in all parts of the system. The fact, however, that
the walls of the vessels are extensible and elastic modifies the trans-
mission of the pulse wave in several important particulars: It
explains why it is that the pulse dies out in or at the beginning of
the capillaries and why it occurs at different times in different
arteries — that is, why the wave of pressure takes a perceptible
time to travel over the arteries. The result that follows from the
elasticity of the arteries may be pictured as follows: Under the
normal conditions of the circulation when the heart contracts and
forces a new quantity of blood into the aorta room must be made
for this blood either by moving the whole mass of the blood forward
— that is, by discharging an equal amount at the other end into the
auricle — or by the enlargement of the arteries. This latter alter-
native is what really happens, as it takes less pressure to distend
the aorta than to move forward the entire mass of blood under the
conditions that exist in the body. So soon, therefore, as the semi-
lunar valves open and the new column of blood begins to enter the
aorta, the walls of that vessel begin to expand and during the time
that the blood is flowing out of the heart — that is, in round numbers,
about 0.3 sec. — the extension of the walls passes from point to point
along the arterial system. At the end of the outflow from the heart
all the arteries are beginning to enlarge, the maximum extension
being in the aorta, and room is thus made for the new quantity of
blood. The new blood that is actually discharged from the heart

505

506 CIRCULATION OF BLOOD AND LYMPH.

lies somewhere in the aorta, but the pressure that has been trans-
mitted along the system and has caused it to expand has made
room for the blood forced out of the aorta by the new blood.
With the cessation of the heart beat and the closure of the semilunar
valves, the sharp recoil of the distended aorta drives forward the
column of blood, and as the aorta sinks back to its normal diastolic
diameter the more distal portions of the arterial system are at first
distended to a certain point and then return to their diastolic size
as the excess of blood streams through the capillaries into the veins.
At the time that the aorta has reached its diastolic size the walls
of the most distant arterioles have passed their maximum extension
and are beginning to collapse. The distension caused by the pulse,
therefore, spreads through the arterial system in the form of a wave.
At any given point the distension of the walls increases to a maxi-
mum and then declines, and when this change in size is recorded
in the large arteries, by methods described below, it is found that
the expansion of the artery is much more sudden than the subse-
quent collapse. This difference is understood when we remember
that the heart throws its load of blood into the arteries with sud-
denness and force, causing a sharp rise of pressure, while the collapse
of the arteries is due to their own elasticity. The disappearance
of the pulse before reaching the capillary area is readily compre-
hended when one remembers that the arterial tree constantly in-
creases in size as one passes out from the aortic trunk. Many facts,
such as those of pressure and velocity already described, indicate
that the increase in capacity of the arterial system is somewhat
gradual until the region of the smallest arterioles and capillaries is
reached and that at this point there is a sudden widening out or
increase in capacity of the whole system, although the individual
vessels diminish in diameter. It is in this region that the pulse,
under ordinary conditions, becomes imperceptible.* When the
arterioles in any organ are dilated the pulse may spread through
the capillary regions and be visible in the veins.

Velocity of the Pulse Wave. — From the above considerations
it is evident that in a system such as is presented by our blood-
vessels the velocity of the pulse wave must vary with the rigidity
of the tubes. If perfectly rigid the pressure would be transmitted
practically instantaneously; if the walls were very extensible the
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

* For ;i satisfactory discussion of the pulse and for literature consult, von
Prey, "Die Untersuchung des Pulses." Berlin, 1892. For ;i description of
the variations in disease consult Mackenzie, " The Study of the Pulse, etc."
New York. 1902.

THE PULSE.

507

a given point in each artery may be recorded by some convenient
apparatus, such as can be devised in any laboratory. If the waves
are recorded on a rapidly revolving kymographion whose rate of
movement can be determined, then the difference in time in the
arrival of the pulse wave at the two points is easily ascertained.
That there is a perceptible difference in time one can easily demon-
strate to himself by feeling simultaneously the pulse of the radial
and the carotid arteries. If this difference in time is determined
for two arteries — for instance, the femoral and the tibialis anterior
— 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. 208.

Fig. 308. — 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.

508

CIRCULATION OF BLOOD AND LYMPH.

from the other. The latter condition would seem to be more nor-
mal, since the blood-flow and normal tension of the walls are
probably less disturbed. An increase in rigidity of the arteries
causes the velocity to rise; in elderly people, therefore, the velocity
is distinctly greater. In arterial sclerosis with hypertrophy of the
heart the velocity may increase to as much as 11 or 13 m. Any
marked dilatation of the arteries — such as occurs, for instance,
in aneurysms, — retards the pulse wave markedly; so that the
existence of an aneurysm may be detected in some cases by this
fact. If we know the velocity of the wave and the time that it takes
to pass any given point the length of the wave is given by the
formula 1= rt. In an adult the duration of the wave (t) at the radial
may be taken as 0.5 to 0.7 sec; so that if the velocity of the wave
were uniform throughout the arteries the length of the wave would
be from 3.25 to 4.5 m. We can conclude, therefore, that before

Fig. 209. — The Dudgeon sphygrnograph 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 sphygrno-
graph, and very numerous forms have been devised. The move-
tnenl 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 thai is perhaps most frequently employed i.s shown in the
accompanying figures. The instrumenl is strapped upon fcne arm so that the

THE PULSE.

509

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. 211. It will be seen from this figure that the artery dilates
rapidly and then falls more slowly, but it must be borne in mind
that the very pointed apex of the wave recorded by this form of
sphygmograph is due to the instrumental error referred to above,
namely, the "fling" of the lever caused by the sudden expansion

Fig. 210.— 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. 211. — Sphygmogram from the radial artery, Dudgeon sphygmograph: D, The dicrotic
wave; P, the predicrotic wave.

of the artery. The ascending portion of the wave is spoken of as
the 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 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

510 CIRCULATION* OF BLOOD AND LYMPH.

approximately at the middle of the descent (D) and is designated
as the dicrotic wave. A less conspicuous wave between it and the
apex of the pulse wave is known usually as the predicrotic wave, P,
while the wave or waves following the dicrotic are designated as
postdicrotic. These catacrotic waves are too small, under normal
conditions, to be felt by the finger. Under certain abnormal
conditions, however, which cause a low blood-pressure without
marked diminution in the heart beat, the dicrotic wave is empha-
sized and may be detected by the finger. A pulse of this kind is
known as a dicrotic pulse. In each pulse wave we may distinguish
a systolic and a diastolic phase; the former, making due allowance
for transmission, corresponds with the time during which the aortic
valves are open, and blood is streaming from the heart to the aorta,
the latter represents the period during which the aortic valves
are closed and the arteries are shut off from the heart. In Fig. 21 1
the systolic phase extends from s to d, the diastolic from d to sf.

Explanation of the Catacrotic Waves. — It has been found
difficult to give an entirely satisfactory explanation of the catacrotic
waves or, to speak more accurately, it is difficult to decide between
the different explanations that have been proposed. Concerning
the dicrotic wave, it may be said that tracings from different ar-
teries show that, like the main pulse wave, it has a centrifugal
course, — that is, it starts in the aorta and runs peripherally with the
same velocity as the main wave upon which it is superposed. More-
over, simultaneous tracings of the pressure changes in the heart and
in the aorta show that the closure of the semilunar valves is synchro-
nous with the small depression or negative wave (d, Fig. 211) which
immediately precedes the dicrotic wave. The general belief, there-
fore, is that the dicrotic wave results from the closure of the semi-
lunar valves. When the distended aorta begins to contract by
virtue of the elasticity of its walls, it drives the column of blood in
both directions. Owing to the position of the semilunar valves
the flow to the ventricle is prevented; but the interposition of this
sudden Mock causes a reflected wave; which passes centrifugally
over the arterial system. The dicrotic; wave is preceded by a
small negative; wave or notch in the curve which marks the time
Of closure or just follows the closure of the semilunar valves. The
sequence of events as pictured by Mackenzie * is as Follows: "As
soon a- the aortic pressure rises above the ventricular the valves
close. At the momenl this happens the valves arc supported by
the hard, contracted ventricular walls. The withdrawal of the

support by the Sudden relaxation of these walls will tend to produce;

a negative pressure wave in the arterial system. But this negative

* Mackenzie, "The Study of the Pulse arid the Movements of the Heart,"
L902.

THE PULSE. 511

wave is stopped by the sudden stretching of the aortic valves,
which, on losing their firm support, have now themselves to bear
the resistance of the arterial pressure. This sudden checking of
the negative wave starts a second positive wave, which is prop-
agated through the arterial system as the dicrotic wave." The
smaller waves, such as the predicrotic, have been explained
simply as reflected waves, or as instrumental errors, due to fling
of the lever. According to some authors,* an important —
perhaps the chief — factor in the production of the secondary
waves is the reflection that occurs from the periphery. Where
each arterial stem breaks up into its smaller vessels the main
pulse wave suffers a reflection, a wave running backward toward
the heart. It is probable that such reflected waves from different
areas — for instance, from the coronary system, the subclavian
system, the mesenteric system, etc. — meet in the aorta and
may in part summate to larger waves, which again pass peripher-
ally. 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

Fig. 212. — Anacrotic pulse from a case of aortic stenosis (Mackenzie): b. The anacrotic

wave.

opposite views it is not possible to decide, but it is perhaps
permissible to believe that while the dicrotic wave is due pri-
marily to the impulse following upon the closure of the semilunar
valves, nevertheless the actual form of this and the other second-
ary waves is variously modified in different parts of the system
by the reflected waves from different peripheral regions. f

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. 212. Such waves are recorded in cases of
stiff arteries or stenosis of the semilunar valves. In the normal
individual an anacrotic pulse in the radial may be obtained,
according to von Kries/J by raising the arm. He believes that
in this position the reflection of the pulse wave from the periph-

* See von Frey, loc. cit.

f For a general discussion, see Tigerstedt, " Ergebnisse d. Phvsiologie, "
vol. viii., 1909.

X Von Kries, "Studien zur Pulslehre," 1892.

512 CIRCULATION OF BLOOD AND LYMPH.

ery is favored, and that the anacrotic wave is simply a quickly
reflected wave. An opposite interpretation, however, is given
by von Recklinghausen, who states that conditions which lead
to a diminution in vascular tone and a dilation of the arteries
produce "weak reflection" and an anacrotic pulse. Constric-
tion of the small arteries in any system favors quick reflection
in the artery supplying the system and produces a pulse with a
sharp-pointed apex.

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

Fig. 213.— SphyKmoRrama illustrating the <fT«-<t of variations m blood-pressure, partic-
ularly upon the position of the dicrotic wave and notch: n. The dicrotic notch; d, the

dicrotic wave. A. Sphygmogram while blood-pressure was relatively low. li, Sphygmo-
L'ram with higher blood-pn tire I Mackenzie.)

whether the pulse is large (pulsus magnus) or small (pulsus parvus),
whet her the wave rises and falls rapidly (pulsus celer) as happens
in the fuse 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 Mood-pressure is high

THE PULSE. 513-

or low by estimating the force with which the wave presses upon
the fingers, or the pressure necessary to occlude the artery. A
similar inference may be drawn from the character of the sphyg-
mogram, and especially from the relative size and position of the
dicrotic wave. When this latter wave falls at or near the base line
of the curve it indicates a low arterial pressure, since under these
circumstances the artery collapses readily after its first systolic
expansion (see Fig. 213). Since the introduction of the sphyg-
momanometer (p. 485), however, it seems evident that this instru-
ment must be appealed to whenever the determination of blood-
pressure is a matter of importance.

Venous Pulse. — Under usual conditions the pulse wave is lost
before entering the capillary regions, but as a result of dilatation in
the arteries of an organ the pulse may carry through and appear in
the veins, in which it may be shown, for instance, by the rhythmical
flow of blood from an opened vein. The term venous pulse, how-
ever, as generally used applies to an entirely different phenomenon,
— namely, to a pulse observed especially in the large veins (jugular)
near the heart. The pulse in this case is not due to a pressure wave
transmitted through the capillaries, but to pressure changes of
both a positive and negative character occurring in the heart and
transmitted backward into the veins. The venous pulse that has
this origin may usually be seen and recorded in the external (or
internal) jugular. Under pathological conditions, especially when
the flow through the right heart is more or less impeded, it may
be plainly apparent at a further distance from the heart and may
cause a noticeable pulsation of the liver, which is designated as a
liver pulse. The venous pulse curve has been much studied in
recent yea^s.* It is somewhat complicated and an explanation
of some of its details has not been agreed upon, but there can be no
doubt that when properly interpreted it will throw much light upon
the pressure changes in the heart, and will afford a valuable means
of diagnosis in cases of valvular lesions and other pathological
conditions of the heart. It is evident also that the venous pulse
gives a ready means of determining the rate of beat of the auricles,
just as the arterial pulse enables us to count the beats of the ven-
tricles, and in this way records of the venous pulse are important
in the interpretation of irregularities in the beat of the heart
(arrhythmia) .

As usually recorded the venous pulse shows three positive
waves, designated commonly as the a, c, and v waves, and three
negative waves. Of the three positive waves, the a wave marks,

* See Mackenzie, "The Study of the Pulse," 1902; also Hirschf elder,
"American Journal of the Medical Sciences," Sept., 1906, and Morrow, "Brit-
ish Med. Journal, " 1906 and 1907.
33

514

CIRCULATION OF BLOOD AND LYMPH.

undoubtedly, the contraction of the auricle, but in order to
locate this wave or, indeed, to interpret at all the complicated
venous pulse, it is necessary to have a simultaneous tracing of
the arterial pulse, preferably the carotid, or of the apex beat of
the heart. Either of these latter tracings enables one to mark
upon the venous pulse the point at which the ventricular systole
begins, and the wave immediately preceding this point must
be due to the auricular contraction, the a wave (Figs. 214 and
215). Following the rise of the a wave there is a fall, the first
negative wave, which is due to the auricular relaxation. The
interpretation of the other two positive and negative waves
has been the subject of much discussion. Mackenzie, one of
whose tracings is reproduced in Fig. 215, believed that the

Fiy. 214. — Simultaneous tracings of the carotid and venous pulses. In the venous
tracing (internal jugular) a indicates the auricular wave due to the contraction of the auri-
cle; r is the carotid wave due (Mackenzie) to an impulse from the neighboring carotid
artery; v is the ventricular wave due to the checking or stagnation of the flow into the
auricle as this chamber fills during the period of closure of the auriculoventricular valves;
x, dilatation due to auricular relaxation; y, the period of ventricular diastole. (Mackenzie.)

c wave is due simply to the pulse in the neighboring carotid
artery, and that, therefore, it has no significance in regard to
changes within the heart itself. Careful records made by other
observers show, however, that this explanation is insufficient.
The c wave begins in the jugular before the arterial pulse wave
reaches the carotid, hence this wave cannot be due wholly to
the carotid pulse. As is shown in the tracing given in Fig. 215,
the c wave begins, in fact, at the very moment of ventricular
systole. The explanation of it which meets with most accept-
ance is that it is due to a sharp protrusion of the auriculo-
ventricular valves into the cavity of the auricle. At the begin-
ning of the ventricular systole these latter valves are in position
for closure, while the semilunar valves at the opening to the
pulmonary artery are tightly closed. Forashort period the ven-
tricular muscle contracts upon a closed cavity, and the pressure
upon the contents rises rapidly. It. is at the beginning of this
brief period that the auriculoventricular valves are protruded

THE PULSE.

515

somewhat into the auricle and thus cause a positive wave in the
venous blood which is propagated back into the large veins.
Immediately upon the opening of the semilunar valves blood
streams out of the ventricle into the pulmonary artery, and the
ventricle diminishes rapidly in size — especially in the diameter
from base to apex. This sudden descent of the base of the
ventricle pulls downward the floor of the auricle and causes a
sudden enlargement of the auricular cavity, which in turn
produces a temporary negative pressure in the auricle and

Fig. 215. — Simultaneous tracings of the jugular pulse, the carotid pulse, and the
apex beat. (Bachmann.) At the bottom of the tracing the time is given in fiftieths of
a second. The vertical lines 0, 1, 2, 3, etc., mark synchronous points on the curves.
A, The auricular wave; s, the so-called c wave caused by the systole of the ventricle; v, the
stagnation wave caused by the filling of the auricle. It will be noticed that the c wave
(marked s in the tracing) occurs at the beginning of the ventricular systole as marked on
the apex beat, and shortly before the pulse in the carotid artery. The height of the v wave
is reached just after the occurrence of the dicrotic notch on the carotid wave, and coin-
cides with the opening of the auriculoventricular valves; Af, the negative wave caused by
the effect of the ventricular systole; Vf, the negative wave following the opening of the
auriculoventricular valves.

attached veins. The second negative wave is, therefore, due to
a forcible dilation of the . auricle caused by the systole of the
ventricle. This negative wave is converted into a positive wave
by the steady inflow of venous blood, which continues to pour
into the auricle during the whole period of the systole of the
ventricle and of the closure of the auriculoventricular valves.
In this way the wave v is produced. It is frequently of irregular
or toothed form and rises somewhat gradually to its maximum..
The end or maximum of the wave falls in with the beginning
of the muscular relaxation of the ventricle, and the return,

516

CIRCULATION OF BLOOD AND LYMPH.

therefore, of the base of the ventricle to its diastolic position-
Immediately afterward the auriculoventricular valves open,
and the blood accumulated in the auricles is discharged into
the ventricle, causing again a sudden fall of pressure in the
auricles and veins, the third negative wave.

The true relations of these different venous waves to the
sequence of events in the ventricle and aorta are clearly shown

Fife. 216. — Schema of the variations of pressure in the ventricle, auricle, aorta, and
superior vena cava during a (•.•inline cycle in the dog : a, b, Systole of tlie auricle; b, c, </, e,
Systole of the v (.•utricle ; //, openiuK of tlie semilunar valves; c, closure of the semilunar
valve- ; b, V, closure of t lie am iculovent i icular valves ; /, opening of the auriculovcnl ricular
valve-. ( >n the curve for the auricle and vein I lie wave from a to b represents t he auricular
contraction, the a wave; that beginning at // is the. wave due to ventricular systole, the
c wave, and the rise of pressure extending from d to e and ending with the opening of the
auriculoventricular valves constitutes the v wave. The time relations are given along the
ab ci a in tenth- of a second, the pressure relations in nuns, of mercury for the ventricle
and aoita are ^iven alonn the ordinal es to the left.. (After [I'rvilcricq.)

in the diagram given by Fredericq, which isreproduced in Fig.

216. Following this author,* the series of positive and negative

waves which may usually be shown in the auricles and great

during a single heart boat may be enumerated as follows:

1. The auricular wave (a wave), auricular systole.

2. The first negative wave, auricular diastole.

3. First systolic wave (positive), c wave. Beginning of
ventricular systole. Due to sudden closure and protrusion of
the auriculoventricular valves.

•Fredericq, "Centralblatl f. Physiol.," 22, No. LO, L908.

THE PULSE. 517

4. Second negative wave. At the time of opening of the semi-
lunar valves. Due to descent of the base of the ventricle, causing
dilatation of auricle.

5. Second systolic wave (positive), v wave. Latter part of
systole. Due to gradual filling of auricle and at the end to the
return of the base of the ventricle to its diastolic position.

6. Postsystolic (third) negative wave begins at moment of
opening of the a-v valves. Due to emptying of auricular blood
into ventricle.

Other waves have been described, especially one in the post-
systolic or early diastolic phase of the ventricular beat, which
is known as the h wave (Hirschf elder) or b wave (Gibson).
This wave occurs between the v and the a wave, it is seen only
occasionally in the tracings, and has been referred to the tri-
cuspid valves, which at this time are thrown suddenly into
position as the ventricle is distended by the inflow of venous
blood in early diastole. For the variations in the form of the
venous pulse under pathological conditions of the heart, reference
must be made to clinical literature.*

* See Hewlett, "Journal of Medical Research," 17, 1907; "Journal of the
Amer. Med. Assoc," 51, 1908, and "International Clinics," 4, 1907.

CHAPTER XXVIII.

THE HEART BEAT.

General Statement. — We divide the heart into four chambers,
— the two auricles and the two ventricles. What we designate as a
heart beat begins with the simultaneous contraction of the two
auricles, immediately followed by the simultaneous contraction of
the two ventricles; then there is a pause, during which the whole
heart is at rest and is filling with blood. As a matter of fact, the
heart beat is initiated, according to usual belief, not by the auricles
proper, but by a contraction of the mouths of the large veins —
venae cava1 — where they open into the auricle. This portion of these
veins corresponds physiologically to a definite chamber, the venous

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SSSI iSSSESS! ISSSsSiEBSaS iSSS

Fig. 217.- — 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.

anus, 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 il 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, .•m<l pause are represented graphically in the accompanying
figure (Fig. 217). It will be noted that the auricular systole is

5 1 8

THE HEART BEAT.

519

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. 218. — 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. /. 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. 1). ///. The scroll fibers in several layers
forming the deeper strata of the heart's muscu-
lature.

520 CIRCULATION OF BLOOD AND LYMPH.

course of the fibers in the ventricles has been difficult to make
out and several more or less different accounts have been pub-
lished. It is clear from even a casual examination that the super-
ficial fibers are common to both ventricles. They may be considered
as arising from the auriculo-ventricular ring in one ventricle to
pass in a spiral course to the papillary muscles and through their
tendons to the auriculo-ventricular ring of the other ventricle.
Those that begin on the outer surface in one ventricle end on the
inner surface in the other. This arrangement is represented in
Fig. 2 IS. / and II. The contractions of these bands of fibers would
tend not only to diminish the cavities of the ventricles from side
to side, but also to bring the apex and base together and to rotate
the apex from the left to right. Beneath these superficial fibers
lie thicker bands, the fibers of which have a more transverse course.
According to MacCallum,* the fibers form three flat bands which
pass in the form of a scroll from one ventricle through the septum
into the other, as shown in Fig. 218, III. 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.

The Auriculoventricular Bundle. — 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 auriculoventricular groove, which was
formerly believed by many to make a complete separation
between auricles and ventricles. It has now been shown, how-
ever, that there is a definite muscular connection between the
auricles and ventricles. f The connection is made by a most
interesting band of fibers, the cells of which differ somewhat, from
those of the musculature of the heart in general. This con-
necting strand is now designated simply as the atrioventricular
bundle. It may be described as beginning in the; auricular
septum and passing down to the ventricular septum, where it
divides, one limb passing into the right ventricle beneath the
endocardium and em; into I he left ventricle. Within the
ventricle- each limb forms a branching system beneath the

i MacCallum, "Contributions to the Science of Medicine," dedicated to
W. II. Welch, p. 307, Baltimore, L900; contains also tin- literature.

f See Retzer, " Archiv f . Anatomie, " 1904, p, L, and "Anatomical Record,"
2 it'), 1908; Braeunig, "Archiv f. Physiologie, " L904, suppl. volume, p. I;
Da Eteizleitungssystem des Saugetnierherzens, " Jena, 1906.

THE HEART BEAT. 521

endocardium, which constitutes the group of cells long known
as the Purkinje cells. On the auricular side the system has
been traced toward the right auricle as far as the great veins
or into the coronary sinus. Retzer has described this system
as originating in the embryonic heart by an ingrowth of the
musculature of the cardiac sinus. According to some authors the
strand as it enters the ventricles gives off branches to the ven-
tricular musculature; according to others this connection is only
made through the branching system of Purkinje cells on the
inside of the ventricles. Whatever may prove to be the exact
connections and properties of this bundle of fibers, there can be
no doubt that it forms the physiological link between the auricles
and ventricles and that it conducts a wave of excitation of of
contraction from one chamber to the other. It should be added
that non-medullated nerve-fibers accompany the muscular fibers
of the bundle.

The Contraction Wave in the Heart. — The muscular contrac-
tion of the heart beat begins, according to the usual description, at
the mouths of the great veins opening into the auricles, and thence
passes to the auricles first and subsequently to the ventricles.

That this sequence is followed in the case of the lower animals may be
demonstrated beautifully in the terrapin. In the slowly beating heart of this
animal the successive contractions of the veins, auricles, and ventricles may
be followed easily with the eye. According to Fredericq * the sequence is differ-
ent in the mammalian heart ; the cardiac beat begins in the right auricle at
a point lying between the mouths of the two cavse, and thence spreads rapidly
over the auricles and may penetrate for some distance over the veins con-
nected with the auricles. Whether or not this explanation of the sequence of
beat in the mammalian heart is correct will have to be determined by experi-
ment. For a further discussion of this point, consult p. 555.

The continuity of the muscular tissue enables us to understand
how the contraction passes quickly from cell to cell in the direction
of the muscular fibers. In the mammalian heart when exposed to
view it is evident that the auricular systole is not sufficient to
empty its cavity, so far at least as the atrium is concerned. The
contraction of the auricular appendages is more forcible. The
contraction may be regarded as a rapid peristalsis which sweeps a
portion of the blood before it into the ventricle. The force of the
contraction has been determined in a number of cases. For the
auricle of the dog's heart it may reach a value of 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). t It is probable that this wave starts at

* Fredericq, "Archives Internationales de Physiologie, " 1906, iv., 57.
t See Tigerstedt, "Die Phvsiologie des Kreislaufes, " 1893, p.' 80, for
literature.

522 CIRCULATION OF BLOOD AND LYMPH.

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 Adami have
demonstrated graphically that the contraction of the papillary
muscles occurs somewhat later than that of the wall of the ventricle.
The slight pause between auricular and ventricular systole may be
referred to the fact that the muscular bridge between the two
chambers is small. We have experimental evidence that the con-
traction wave proceeds more slowly through a narrow bridge of this
sort. In the dog's heart the time interval between the contractions
of the auricle and ventricle is about y^- second. Since the con-
necting auriculo-ventricular bundle has a length of 10 to 15 mms.
the velocity of the conduction through this bundle must be about
10 to 15 cms. per second.

The Electrical Variation. — The contraction of the heart
muscle, like that of skeletal muscle, is accompanied by an electrical
change. That is, where the muscle substance is in contraction its
electrical potential is different from that of the resting muscle.
The advancing wave of contraction causes a corresponding electrical
change. If two points of the heart are connected with an electrom-
eter an electrical current will be shown, since the electrical change
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. 106). 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 or the string-galvanometer
(p. 100), and since the movement of the mercury or of the string
in these instruments may be photographed, the results can be
studied in detail. Owing to the sensitiveness of the instrument,
the beat of the human heart may be registered in this way
( Waller) when the right hand, ji'ivin^; the potential changes of the
of 1 Ik; heart, is connected with one electrode, and the left
hand (apex of heart) is connected with the other. The electro-
cardiograms thus obtained photographically show that, in the
ventricle al least, the electrical variation exhibits several phases,
and t he character of these phases, that is, whether the base or the
apex first shows a negative potential, has been used in discussions
upon the direction of the wave of contraction. Since the

THE HEART BEAT.

523

character of the electrocardiogram depends so much on the
delicacy of the instruments used, arguments based on this
evidence have not so far proved very satisfactory, particularly
as the later records are quite complex and difficult to interpret
(see Fig. 219 and legend).

Change in Form of the Ventricle During Systole. — 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 in certain diameters? The question is one that cannot
be answered definitely for all normal conditions, owing to the

ojSee.

Fig. 219.— Electrocardiogram obtained by photographing the movements of the
thread of a string-galvanometer. The upper figure shows the photographed curve, while
the lower one is a diagram constructed from the photograph to make clearer the electrical
changes in a single cardiac cycle. To obtain this record the electrodes were connected
with the right and left hands. Waves with the apex upward indicate that the base of the
heart (or the right ventricle) is negative to the apex (or left ventricle). Waves with the
apex downward have the opposite significance. Wave P is due to the contraction of the
auricle. Waves Q, R, S, and T occur during the systole of the ventricle, 'ihe curve seems
to show that the contraction in the ventricles begins first toward the apex (or in the left
ventricle), since the negativity first appears toward that side (wave Q). — (Einthoven).

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, what-
ever 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 natu-
rally be different in different positions. With an excised frog's
heart one can show that the ventricle is elongated in passing from

524 CIRCULATION OF BLOOD AND LYMPH.

diastole to systole or one can show* the reverse. If the heart is laid
upon its side it flattens in diastole so as to increase in length,
and systole causes a shortening. If the heart is held or placed
with its apex pointing upward it flattens during diastole so as
to shorten the diameter from base to apex and during systole
this diameter is lengthened. In ourselves the exact change of
shape is probably different in the erect from what it is in the
recumbent posture. Speaking generally, the accounts agree in
stating that the long diameter of the heart is decreased, base and
apex are brought closer together, and the diameter from right to
left is also decreased, while the anteroposterior or ventrodorsal
diameter is increased. That is, the outline of the base of the heart
during diastole is an ellipse with its short diameter in the ventro-
dorsal direction. During systole this outline approaches that of a
circle.* A more interesting change is described for the apex of the
ventricle. Owing to the whorl made by the superficial fibers at
this point as they turn to pass into the interior (see Fig. 218, /),
the systole causes a rotation of the apex, which is thereby
forced more firmly against the chest wall. This rotation and
erection of the apex during systole may be seen upon the exposed
heart of the lower mammals and has been described also for man
in cases in which the heart is covered only by the skin, owing to
malformation in the chest wall (ectopia cordis) or to surgical
operations.

The Apex Beat. — The apex of the heart rests against the chest
wall at the fourth or fifth intercostal space, and here the systole
may be seen and felt in consequence of a slight protrusion of the
wall. Much discussion has ensued as to why this protrusion
occurs < hiring systole, since the apex is drawm toward the base
and the volume of the heart is diminished by the output of
Mood. The fact seems to be explained satisfactorily by two con-
siderations: The heart during diastole rests against the chest wall
a1 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 COntad J BO that, although the heart is short-
ened in its long diameter, the extent of the movement is not

SUfficienl 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 I he shortening in the
long diameter. The apex beat is proof that the apex remains
3ee Haycrafl and Edes, "Journal of Physiology," L2, 426.

THE HEART BEAT.

525

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. 220.
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

Fig. 220. — 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.

the air of the tambour which are transmitted through tubing to a
recording tambour and recorded on a kymographion. A simple
and effective cardiograph may be made by pressing a funnel
against the skin over the apex and connecting the stem of the
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-
ditions of the circulation, and it is often difficult to give it a correct
interpretation. An uncomplicated form of the cardiogram is

526

CIRCULATION OF BLOOD AND LYMPH.

represented in Fig. 221, 7, and a curve more difficult to interpret in
Fig. 221, 8. It should be borne in mind that the cardiograph curve
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. 221. — Two cardiograms from the same individual to show characteristic records: a,
Beginning <>f systole; k-c, systolic plateau. — (After Marey.)

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 Hurthle (p.
180) seems to have met the requirements more satisfactorily than

other of the numerous instruments described. A typical curve
obtained by means of the Hurthle manometer is given in Fig. 222, V.
(Consull also the classical curve obtained byChauveaii .and Marey
from the hear! of the horse [Tig. 217].) [twill be seen that the

ure in the bearl rises suddenly with the beginning of the ven-
tricular contraction and a certain time elapses before this pressure

THE HEART BEAT.

527

is strong enough to open the semilunar valves. The moment that
this occurs (1, on the ventricular curve in Fig. 222) is determined
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

Fig. 222. — Synchronous record of the intraventricular pressure (V), and the aortic
pressure (A) : S, The time record, — each vibration = ifc sec. ; 0-5, corresponding ordi-
nates in the two curves; 1 marks the opening of the semilunar valves; 3 (or shortly after)
marks the closure of these valves and the beginning of diastole. — {Hiirthle.)

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. 222, 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 tho 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 shortly after 3.

* Hurthle, "Archiv f. d. gesammte Physiologie, " 49, 84, 1891.

528

CIRCULATION OF BLOOD AXD LYMPH.

(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 Mary, given in Fig. 217.

The Volume Curve and the Ventricular Output. — In the
lower animals the thorax may be opened with suitable pre-
cautions as regards anesthesia and artificial respiration, and
the heart may be placed within a plethysmograph (see p. 584)
to measure its changes in volume during systole and diastole.
If the whole heart is treated in this way the curve of volume
changes is complicated by the fact that one chamber, the
auricle, is filling, while the other, the ventricle, is emptying.

Fijr. '22'.',.- Diagram to show the arrangement of the Henderson cardiometer. The
recording tambour is inverted, so that the systole will give an up-stroke on the curve.
(After Hirschfelder.)

A more useful disposition of the apparatus is to enclose only
the ventricles. Several different forms of plethysmograph have
been devised for this purpose, and they are usually spoken of as
ctirtiiniiK i< I-.-. The form described by Henderson* is simple and
easily applied to the heart. Its structure and the connections
of the recording apparatus are indicated in the diagram given
in Fi»-. 223. The apparatus consists of a rubber ball with a
circular opening at one point. Over this opening is placed a
membrane of rubber dam with a central opening through which
the heart is introduced as showD in the diagram. The rubber
membrane lie- -miidy in the auriculoventricular groove, making
an air-tigh1 joint. The interior of the ball is connected by
stiff tubing with a recording tambour. By an arrangement
of this kind the ventricles are kept, within an air-chamber closed
everywhere except at the outlet to the recording tambour.
Every change in volume of the ventricles will be recorded accu-

► Henderson, "American Journal of Physiology," L6, 325, L906, and
23, 345, L909, contain also the literature.

THE HEART BEAT.

529

r ately provided there is no leak. Moreover, these volume changes
may be given absolute values in cubic centimeters if the appa-
ratus is calibrated beforehand. The cardiometer furnishes a
convenient method of estimating directly the amount of blood
entering and leaving the ventricles under varying conditions,
as well as the changes in heart-volume that may result from
variations in tonicity. When the heart is beating slowly the
volume curve has the form shown in Fig. 224. During systole
the ventricles shrink in size as the blood is discharged into the
aorta and pulmonary artery — the up-stroke of the curve. At
the end of the systole, after the closure of the semilunar and the
opening of the auriculoventricular valves, the ventricles are

i

Fig. 224. — Diagram of the normal volume curve (plethysniogram) of the dog's heart
when beating at a slow rate (after Hirschf elder). The up-stroke represents the systole,
the down-stroke the diastole; 4 to 5 the period of diastasis (Henderson). At 5 the auricular
contraction causes a slight additional dilatation of the ventricle. 1, 2, and 3 represent the
time of occurrence of the first, second, and third heart-sounds respectively.

dilated rapidly by the inflow of venous blood. Henderson has
emphasized the fact that the filling takes place nearly as rapidly
as the emptying, owing doubtless to the fact that at the end of
ventricular systole the auricles are dilated under some pressure,
so that their contents escape at once into the ventricles as soon
as the intervening valves are opened. The diastolic curve
comes back nearly to the base line and then forms a shoulder
(4) from which it runs parallel to or approaches gradually to
the base line up to the moment of auricular contraction (5).
The period of rest of the filled or nearly filled ventricles, which
on the curve is shown from 4 to 5, is called the period of diastasis
by Henderson. The heart cycle, so far as the ventricles are
concerned, falls, therefore, into three periods: 1, Systole: 2.
diastole; 3, diastasis. Variations in heart rate affect chiefly
the latter period; this becomes shorter and shorter the more
rapid the rate. When the heart rate is so rapid that the period
of diastasis drops out altogether and the systole begins as soon
34

530 CIRCULATION OF BLOOD AND LYMPH.

as the diastole is complete, then we should have the maximum
output of blood per minute. An increase of rate beyond this
point would lead to a curtailment of the period of diastole and
eventually to a diminished output of blood per minute. Accord-
ing to the account just given, the filling of the ventricle is
practically completed before the auricles contract. Henderson
believes that the contraction of the auricles adds very little or
nothing to the change of blood in the ventricles, but other authors,
using the same methods, differ from him in this conclusion.
It is at least certain that the ventricles are for the most part
filled before the auricular contraction comes on — this latter
act may add a greater or less amount to this charge, according
to the conditions prevailing, and in all cases its contraction,
besides initiating the ventricular systole, doubtless serves, by
raising the tension in the ventricular chamber, to bring the
auriculoventricular valves more completely into the position
of closure. When these valves are deficient, as in mitral stenosis,
the contraction of the auricles plays a larger part in completing
the filling of the ventricles (Hirschf elder). For the cases in
which it can be applied, the volume curve enables us to estimate
the ventricular discharge at each beat and the outflow per
minute. The curve as registered gives the outflow for the two
ventricles, one-half of its indicated volume will give the outflow
from the left ventricle, and this figure, multiplied by the pulse
rate, will give the output per minute. It was formerly assumed
that at each systole the ventricles emptied themselves com-
pletely, but work of the kind described in this paragraph in
which the volume curves were obtained have shown, on the
contrary, that at the end of systole a considerable proportion of
the blood may be left in the cavity of the ventricle. The amount
thus left behind will vary with the rate and other conditions.
According to Henderson's figures for the dog, about one-third or
somewhat less of the ventricular charge is left in the heart after
systole, when the heart is beating at the normal rate (90), and
the quantity of blood discharged from the left ventricle at each
Bystole is approximately .002 of the body weight. It is evident
thai when the aortic pressure rises to an abnormal level the
discharge of blood from the left ventricle will be or may be

diminished, with the result that the blood barks up in I he left

auricle, thus raising the venous pressure in the lungs and retard-
ing the pulmonary circulation. On the other hand, as Hender-
son has especially emphasized, the outflow from the ventricle
musl be Influenced very directly by the inflow into the auricle
from the veins. Variations in the size of the blood-vessels, such
ilatation of the small arteries or possibly loss of tone in the

THE HEART BEAT. 531

veins, may bring about a condition of venous stasis and cut
down the supply of blood to the heart on the venous side. Con-
siderations of this kind are helpful or necessary in explaining
the changes in circulation which occur under pathological
conditions.

The Heart Sounds. — An interesting and important feature
of the heart beat is the occurrence of the heart sounds. Two
sounds are usually described, one at the beginning, the other
at the end, of the ventricular 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 musi-
cal 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
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
* "Journal of Physiology," 11, 486, 1890.

532

CIRCULATION OF BLOOD AND LYMPH.

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

Fig. 225 — To show the time relation of the heart sounds to the ventricular beat
(Marey) : Y.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.

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 (lie 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
theear membrane of the auscultator, the shock of the contracting
heart sets the tympanic membrane to vibrating. If 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 cardiography tracing of

THE HEART BEAT.

533

the heart beat with results such as are shown in Fig. 225. 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 b}^ 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. 226. 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

oisee.

Fig. 226. — 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.)

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
(&'), — that is, at the beginning of the period of emptying according
to the classification given on p. 527. 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 Third Heart Sound. — Several observers* have called
attention to the fact that in certain individuals a third heart

* Einthoven and Geluk, "Archiv f. d. gesammte Physiologie," 57, 617,
1894. Einthoven, ibid., 1907, vol. 117.

t Thayer, "Boston Med. and Sure;. Journal," 158, 713, 190S; Einthoven,
"Archiv f. d. ges. Physiol.," 120, 31, 1907; Gibson, "Lancet," 1907, II., 1380.

534 CIRCULATION OF BLOOD AND LYMPH.

sound may be heard very shortly (0.13 sec.) after the beginning
of the second sound. Thayer describes this sound as being
"softer and of lower pitch" than the second sound, and in some
cases as resembling rather a dull thud or hum. In those persons
in whom it can be detected it is heard most distinctly over the
apex of the heart. Einthoven has shown the existence of this
sound by objective methods. By means of a microphone
attachment the heart sounds can be transmitted to the string-
galvanometer, in which they cause deflections of the string that
can be photographed. In this way he has obtained records of
the third sound upon individuals in whom the stethoscope failed
to reveal its existence. The cause of this sound has been
explained differently by the several authors who have inves-
tigated. It occurs early in the diastole, and Einthoven suggests
that it is due to an after-vibration of the semilunar valves.
Thayer and Gibson suggest the more probable explanation that
it is due to a vibration of the auriculoventricular valves which
is set up by the sudden inrush of blood from the auricles
at the beginning of diastole. This inflow of venous blood
distends the ventricle sharply and throws the valves into a
position of closure with some suddenness. The sound occurs
at about the time of the shoulder on the diastolic limb of the
volume curve, as is indicated in the diagram in Fig. 224.

The Events that Occur During a Single Cardiac Cycle. —
By a complete cardiac cycle is meant the time from any given
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 hearl 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 auriculoventricular valves are still
closed (see diagram, Fig. 216), 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 ventricles relax
the pressure of blood in the auricles opens the auriculoven-
tricular valves, and from thai moment until the beginning of
the auricular systole the blood from the large veins is filling

both ventricles and auricles. As staled on |». 529, the venous

blood which has been accumulating in the auricles during the
ventricular aystole flows into the ventricles with some sudden-
ne "ii the opening of the auriculoventricular valves. The
ventricles, therefore, dilate rapidly and the auriculoventricular
valves are floated into a position ready for closure;. This event
occur- at about the time that the third heart sound is heard.

THE HEART BEAT. 535

In a slowly beating heart there may be quite an interval (period
of diastasis) between this point and the auricular contraction.
The auricular systole sends a sudden wave of blood into the
ventricles, dilating them still further and momentarily blocking
or retarding the flow from the large veins, and causing one of
the waves seen in the normal venous pulse as recorded in the
jugular veins. The ventricular systole follows at once upon
the auricular systole, the exact relations in this case depend-
ing somewhat upon the pulse rate. As the ventricle enters
into contraction the auriculo-ventricular 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 the aorta and pulmonary artery as long
as the contraction lasts. During this interval the flow at the
venous end of the heart continues, the blood being received into
the yielding auricles. Indeed, this capacity for receiving the
venous inflow during the comparatively long-lasting ventricular
systole may be considered as one valuable mechanical function'
fulfilled by the auricles. The venous flow is never completely
blocked and at the most suffers only a slight retardation during
the very brief auricular systole. At the end of the ventricular sys-
tole the excess of pressure in the aorta and the pulmonary artery
closes the semilunar valves and completes the cycle.

Time Relations of Systole and Diastole. — The duration of the
separate phases of the heart beat depends natural^ on the rate
of beat. Assuming a low pulse rate of 70 per minute, the average
duration of the different phases may be estimated as follows:

Ventricular systole = 0.379 sec.

Ventricular diastole and pause = 0.483 "

Auricular systole =0.1 to 0.17 "

Auricular diastole and pause = 0.762 to 0.692 "

Einthoven and Geluk, in the investigation referred to above,
measured the time intervals of systole and diastole during fifteen
heart periods of a healthy man, and found that the time for the
ventricular systole varied between 0.312 and 0.346 sec, while that
for the diastole varied from 0.385 to 0.518 sec. Experiments by
a number of observers indicate that in the great changes of rate
which the heart may undergo under normal conditions the diastolic
phase (period of diastasis) 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 in man, but the deter-
mination has encountered many difficulties. Experiments and

536 CIRCULATION OF BLOOD AND LYMPH.

observations made upon the excised heart are of little value, since
the distensible walls of the ventricles yield readily to pressure,
and it is difficult or impossible to imitate exactly the conditions
of pressure that prevail during life. Nor is it certain whether
normally the ventricles empty themselves completely during
systole; in fact, the evidence from experiments on the lower
animals indicates that, contrary to the opinion which for-
merly prevailed, the ventricles throw out only a portion of their
blood at each beat. The older observers (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 general-
ization that at each systole the amount of blood ejected
from the ventricles is equal to about 4-iro 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 (-sibr) °f the body weight; for a rate of 120 beats per minute
it was equal to 0.0014 (-7-5-0). 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. Ilg. (0.150 meter) and on the right
Bide 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-
Bents 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 13.0) = 204.0 grammeters.

Right " 100 " X (0.00 X 13.G) = 81.0

l's.i.Ci grammeters.

* Bowel! and Donaldson, " Philosophical Transactions," Royal ftoc, Lon-
don, 1884.

f Tigerstedt, "Lehrbuch der Physiologic des Kreislaufes," p. 152, LS93.

THE HEART BEAT. 537

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 2 x 9 8' = 1 .28 grammeters,
or for both ventricles 2.56 grammeters, making a total of over 288
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 " for weight of 72 kgms.

Vierordt 180 " " " " " "

Fick 50-73 "

Howell and Donaldson 75-90 " " " "65 "

Hoorweg 47 "

Zuntz 60 "

Tigerstedt 50-100 "

Plumier 70 "

Loewy and v. Schrotter 55 " " " 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

* See Porter, "American Journal of Physiology/' 1, 145, 189S, for dis-
cussion and literature.

53S CIRCULATION OF BLOOD AND LYMPH.

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-
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. 227, the great acceleration (a) in
velocity at the beginning of systole is quickly followed by a drop to
zero (b) or even a negative value, — that is, a flow in the other direc-
tion, toward the aorta. At the end of the first (relaxation) phase
of diastole there is again a sudden increase in velocity (c), corre-
sponding with the injection of the arteries from the aorta, followed
again by a decrease at the end of the diastole at the time when the
ventricular cavity is filled with venous blood under some pressure.
Porter, moreover, has shown in an interesting series of experiments
that when a piece of the ventricle is kept beating, by supplying it
with blood through its nutrient artery from a reservoir at con-
stant pressure, each systole causes a jet of blood from the sev-

Fig. 227. — Simultaneous record of the blood-pressure (A) and the Wood-velocity (li)
in the coronary arterie (Chauveau and Rebatel): a, Murks the beginning of the systole
(there i i ri i • m \>n- un- :unl 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 ui B
iii. falls olT rapidly); c, curve (li) shows an increase in velocity due to the open-
ing of the mall 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 (lowing 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 HEART BEAT. 539

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
a suction-pump, sucking in blood from the venous side "in conse-
quence of an active dilatation. According to this view, the heart
works after the manner of a syringe bulb, which when squeezed
forces out liquid from one end and when relaxed sucks it in from
the other in consequence of its elastic dilatation. While this view
has long been entertained, modern interest in it was aroused chiefly
perhaps by the experiments of Goltz and Gaule, which showed that
at some point in the heart beat there is or may be a strong negative
pressure in the interior of the ventricles.* Their method consisted
in connecting a manometer with the interior of the ventricle and
interposing between the two a valve that opened only toward the
heart. The manometer was thus converted into a minimum
manometer, which registered the lowest pressure reached during
the period of observation. By this method they and others have
shown that in an animal (dog) with an opened thorax the pressure
in the interior of the ventricles may be negative to an extent equal
to 20, 30, or even 50 mms. of mercury. Moreover, by the use of
some form of elastic manometer, such as the Hiirthle instrument
(p. 462), it has been shown that this negative pressure occurs at the
end of the period of relaxation, at the time, therefore, at which it
might be supposed to exert a marked influence upon the inflow of
venous blood. It should be added, however, that a negative
pressure can not be shown for every heart beat. It may be absent
altogether or slight in amount, varying, no doubt, with the force of
contraction and the condition of the heart. Physiologists have
attempted to determine the cause of this negative pressure and the
extent of its influence on the blood-flow. With regard to the first
question, so many answers have been proposed that it is difficult
to arrive at a satisfactory opinion. According to some, the heart
tends to dilate at the end of its systole by virtue of its own elasticity,
— that is, the elasticity of its own musculature or of the connective
tissue contained in its substance, for example, beneath the en-
docardium, in the walls of the arteries, etc. This view, however,
finds little or no support from direct experiments made upon the

* 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.

540 CIRCULATION OF BLOOD AND LYMPH.

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
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 bo of value in accelerating the opening
of the auriculo-venl ricular valves, ils influence does not extend to an

* Martin and Donaldson, "Studies from the Biological Laboratory, Johns
Hopkins University," 1, 37, L887; also Martin's 'TPhysioloKical Papers,"
Baltimore, 1895. Sec also, for confirmatory results, von den Velden, "Zeit-
Bchrifl f. exp. Pathol, u. Therapie, 1906, iii., 432.
Journal of Physiology,'' 13, 513, 1892.

THE HEART BEAT. 541

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
musculature, and although anastomoses may exist they appear
to be too incomplete to allow a collateral circulation to be estab-
lished when one of the main arteries is occluded. The portion of
the heart supplied by it dies, or to use the pathological term, under-
goes necrosis. On account of the pathological interests involved —
the known serious results that may follow occlusion of any of the coro-
nary Vessels or even any interference with the normal structure of the
vessels — a number of investigations have been made upon animals
to determine the effect of occluding one or more of the coronary
vessels.* It would seem from Porter's experiments that the results
of such an operation vary according to the size of the area deprived
of its blood. When the arteria septi alone was occluded the heart
was not affected, when the arteria coronaria dextra was occluded
the ventricular contractions were arrested in 18 per cent, of the
cases observed. Occlusion of the ramus descendens of the left
coronary artery caused arrest of the ventricles in 50 per cent, of the
cases, while occlusion of the circumflex branch of the same artery
caused arrest in 80 per cent, of the cases. Ligation of three of the
arteries caused stoppage of the heart in all cases.

Fibrillar Contractions. — The arrest of the ventricles in the
experiments just described followed immediately or within a short
period, and the ventricles went into fibrillar contractions. In this
curious condition the various fibers of the ventricular muscle, in-
stead of contracting together in a co-ordinated fashion, contract
separately and irregularly; so that the surface of the ventricle has
the appearance of a vibrating, twitching mass. Such a condition
in the ventricle is usually fatal, — that is, the musculature is not able
to recover its co-ordinated movement. This condition may come
on with great suddenness as the result of occlusion of the arteries,
of injury to certain parts of the heart, or from strong electrical
stimulation. Fibrillation of the auricles also occurs frequently
under experimental conditions, but the musculature in this part of
the heart seems to be able to return to its normal co-ordinated
contractions with much less difficulty. The cause of the sudden

* For a description of results and the literature see Porter, " Journal of
Physiology," 15, 121, 1S93; also "Journal of Experimental Medicine," 1, 1,
1896.

CIRCULATION OF BLOOD AND LYMPH.

change from co-ortinated-to fibrillar contractions has never been

SSftS : thaettred' hl ^ C°nneCti0n h is interest
recall also that when any injury is done to either ventricle suf

ficient to stop the contractions or to cause fibrillation both ven
nc es stop togeth This ^ .g ^ on both ven-

boSl^r1^ * aftGr al1 °ne SGt °f fib- "^

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 dajr.
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.

543

544 CIRCULATION OF BLOOD AND LYMPH.

The dividing line between the ancient and the modern views of the heart
beat is fonnd in the work of William Harvey (1628). Before his time physi-
cians thought along the lines laid down by the ancient masters, Hippocrates,
Aristotle, and Galen, in that they believed that the diastole of the heart is
the active part of the beat. They believed that the heart dilated at the mo-
ment of the apex beat, the dilatation being due to the implanted heat, the
vital spirits, a special pulsatile force, etc. The arteries dilated at the same
time for a similar reason. For a period of over two thousand years men's
minds were so chained to this belief that they apparently could take no other
view. Harvey, liowever, had the boldness and originality to look at the
matter differently. He saw and proved that the active movement of the heart
is a contraction during systole, which drives blood out of the ventricles into the
arteries, and consequently that the pulse of the arteries is not clue to their
active dilatation, but to a distension by the blood forced into them. Harvey
may be considered also as the founder of the myogenic theory of the heart
beat. For although he did not speculate concerning the cause of the beat,
he taught that the" systole is an active contraction of the heart's own muscu-
lature not dependent upon any external influence. In the same century the
first neurogenic hypothesis was formulated. AYillis conceived that the cere-
bellum controls the activity of the involuntary organs, including the heart.
The animal spirits engendered in the cerebellum were conveyed to the heart
by the vagus nerve and catised its beat. Borelli formulated a somewhat
different view. According to him the nerve juice, succus spirituosus, elabo-
rated in the central nervous system was transmitted to the heart through the
cardiac nerves and, distilling slowly into the musculature, set up an ebullition
which caused an active expansion'of the fibers. This expansion constituted
the systole and drove the blood out of the heart. Both of these views were
disproved or rendered improbable largely by the work of Haller, who in 1757
published the second myogenic theory in a form which, somewhat modified,
prevails to-day. Haller believed that 'the contraction of the heart is due to the
inherent irritability of its musculature, ami that the venous blood as it enters
the heart stimulates it to contraction. Haller's views were generally accepted
for some years, but some physiologists continued to believe that the heart beat
i- controlled directly by the central nervous system. This theory found its
most definite expression in the work of Legallois, 1812, who advanced what
may be called the second neurogenic hypothesis. From experiments made
upon animals he concluded that the principle or force that causes the heart
beat is formed in the spinal cord, in all <>!' its parts, and reaches the heart-
through the branches of the sympathetic nerve supplying this organ. Legallois's
conclusions were soon shown to be erroneous, but the general view advocated
by him was entertained by some as late as the middle of the H»th century,
in fact until experimental physiology had demonstrated the true functions
of the vagus and accelerator nerves with reference to the heart. Toward the

middle of the I'.ith century a third form of neurogenic hypothesis arose, which
in the beginning seems to have been due to the work or the system of Bichat.

According to this author the ganglionic or sympathetic system supplies the
of the organic life, meaning thereby the visceral organs which are not
under the direel influence of the will. In' IMI Etemak discovered thai the
heart possesses intrinsic nerve ganglia, and this fact seems to have induced most
physiologists to believe thai these ganglia constitute a motor center for the

heart, initiating and CO ordinating its heat. for a period of forty years this

form of the neurogenic hypothesis enjoyed almost universal acceptance. In
issi 83Gaskell published experiments upon the heart of the frog and tortoise
in which he gave strong reasons for believing thai the beat ismyogenicin
origin, and thai the intrinsic ganglia are simply .-i pari of the inhibitory ap-
paratus of the heart. Since thai time many physiologists have adopted the
myogenic view, and the currenl arguments tending to support this rather than
the neurogenic hypothesis are presented in the text. The most significant
addition to our knowledge <>i the cause of the- heart heat made during the
L-, t quarter of a century is the discovery thai the inorganic salts of the blood
and lymph play a special and essential r61e. The facts hearing upon this
interesting cuscoa ery are sufficiently described in I he text.

PROPERTIES OF THE HEART MUSCLE. 545

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 their
effect is summated. Under abnormal conditions the fibers may
contract irregularly, giving the so-called fibrillar contractions of the
heart, which are inco-ordinatecl. It may be said that this con-
ception of the connections of the intrinsic nervous system rests
mainly upon deductions from physiological experiments. The
histological details regarding the connections of the nerve cells in the
heart are not yet sufficiently known, but it can not be said at present
that they give any positive support to such a view. In regard to
the neurogenic theory the following general statements may be made :

1. Most of the very numerous facts known regarding the heart

* For recent general presentations from different standpoints see Gaskell,
article on "The Contraction of Cardiac Muscle," in Schafer's "Text-book of
Physiology," vol. ii. 1900; Langendorff, " Herzmuskel und intrakardiale In-
nervation" in "Ergebnisse der Physiologie," vol. i, part n, 1902; and Cyon,
"L'innervation du cceur," Richet's " Dictionnaire du Phvsiologie," vol. iv,
1900.

35

546 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. Carlson *
has described experiments upon the heart of the horseshoe crab
(Limulus) which seem to show conclusively that in this animal
the rhythmical contractions are dependent upon the intrinsic nerve
cells. These latter are placed superficially, forming a cord that
runs the length of the tubular heart. When this cord is removed
the heart ceases to beat. There are reasons, however, which at
present make it doubtful whether we can apply the results of this
experiment to the vertebrate heart. The crustacean heart differs
from the vertebrate heart in its fundamental properties; unlike the
latter, it lias no refractory period (see p. 552), can be tetanized, and
gives submaximal contract ions. f It is a tissue, therefore, that
resembles in its properties ordinary skeletal muscle in the verte-
brate, and, like this muscle, it, seems to be lacking in automaticity.

Carlson's experiments liive, however, another instance of automatic

rhythmicity in nerve tissue, and to that extent support the neuro-
genic theory.

The Myogenic Theory of the Heart Beat. — The myogenic

♦ Carlson, "American Journal <>f Physiology," 12, 67, and 471, L905,
| Hunt, Bookman, and Tierney, "Centralblutt f. Physiologic," 11, 275,
1897.

PROPERTIES OF THE HEART MUSCLE. 547

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. 520) .

2. The fact that a contraction started at one part of the heart
may travel to other portions through the intervening musculature
may be said to be demonstrated. Thus, Engelmann has shown
that if the ventricle in the frog's heart is cut in a zigzag fashion,
so that strips are obtained which are connected only by narrow
bridges, a stimulation applied at one end starts a wave of con-
traction which propagates itself over all of the pieces. This and
similar experiments scarcely permit of explanation on the supposi-
tion that conduction from piece to piece is effected by a definite
nervous mechanism. So too it has been shown that under certain
conditions the normal auriculo-ventricular rhythm can be changed
at will to a ventriculo-auricular rhythm. If, for instance, a ligature
be tied around the frog's heart between the sinus venosus and the
auricle (first ligature of Stannius) the auricle and ventricle cease
to beat. In this quiescent condition a slight mechanical stimulus
to the ventricle causes it to beat and its contraction is immediately
followed by that of the auricle. A similar reversed rhythm may be
obtained from the mammalian heart under suitable conditions.
Such an experiment makes it most probable that the contraction
is propagated from one chamber to the other directly through
the muscular connections. It is not possible at present to conceive
that a definite mechanism of neurons should work thus in either
direction.

3. There is much probable proof that the heart muscle tissue
possesses the property of automatic rhythmical contractions. Ex-

5-AS CIRCULATION OF BLOOD AND LYMPH.

periments, initiated by Gaskell and since extended by numerous
observers, show that in the cold-blooded animals strips of heart
muscle taken from various parts of the heart will under proper
conditions develop rhythmical contractions. It is very improbable
that each of these strips, no matter how made, contains its own
resident nerve evils or nerve tissue which act as a motor center.
These results seem to demonstrate an inherent property of rhythm-
icity in cardiac muscle, whether or not this rhythmicity is directly
responsible for the normal beat.

4. It has been shown that in the embryo chick the heart pul-
sates normally before the nerve cells have grown into it, and it
is stated that in the hearts of a number of invertebrates no nerve
cells can be found. Much weight can not be given, however, to
negative evidence of this kind, since, in the first place, better
technical methods may demonstrate the existence of such cells,
and even if absent from the heart itself it is conceivable that they
may be present in the surrounding tissue and send their fibers
to the heart. It is evident from this brief and imperfect presenta-
tion that it is not possible to claim that either the neurogenic or
the myogenic theory is demonstrated, but most physiologists per-
haps at present believe that the latter view is more in accaii
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
composil ion of the I flood or lymph bathing the heart tissue, or in the
products of metabolism of the tissue itself. Regarding this latter
view there i.s nothing of the nature of direel experimental evidence
in its favor. No product of the metabolism of the heart tissue
capable of exerting this stimulating effect has been isolated. In
I In the former view, that the inner stimulus is connected
with ;i definite composition of the blood or lymph, there has been

con iderable experimental work which is of fundamental signifi-
cance. While the older physiologists paid .-it lent ion mainly to (,1k;

compromise view, partly myogenic and partly neurogenic, sec
J redericq, "ArchiveB internationalea de Physiologie, " 1906, iv., 57.

PROPERTIES OF THE HEART MUSCLE. 549

organic substances in the blood, it has been shown in recent years
that the inorganic salts are the elements whose influence upon
the heart beat is most striking. These salts are in solution in the
liquid of the tissue, and are therefore probably more or less com-
pletely dissociated. Attention has been directed mainly to the
influence of the cations, of which three are especially important,
— namely, the sodium, the calcium, and the potassium.

The Action of the Calcium, Potassium, and Sodium Ions in
the Blood and Lymph. — It has long been known that the heart
of a frog or terrapin may be kept beating normally for hours after
removal from the body, provided it is supplied with an artificial
circulation of blood or lymph, so arranged that this liquid enters
the heart through the veins from a reservoir of some sort and is
pumped out through the arteries leading from the ventricle. It
was first shown by Merunowicz, working under Ludwig's direction,
that an aqueous extract of the ash of the blood possesses a similar
action.

Ringer afterwards proved that the frog's heart can be kept
beating for long periods upon a mixture of sodium chlorid, potassium
chlorid, and calcium phosphate or chlorid, and he laid especial
stress upon the importance of the calcium. This work was after-
wards confirmed and extended by Howell, Loeb, and others, who
attempted to analyze the part played by the several ions.* If
a frog's or terrapin's heart is fed with a solution of physiological
saline (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, "American Journal of Phys-
iology," 2, 47, 1898, and 6, 181, 1901, and "Journal of the American Medical
Association," 1906.

550 CIRCULATION OF BLOOD AND LYMPH.

of oxygen than can be obtained by simple exposure to the air.
For the irrigation of the isolated mammalian heart different
forms of Ringer's solution have been employed, but the mixture
most frequently used is that recommended by Locke, consisting
of NaCl, 0.9 per cent.; CaCl2, 0.024 per cent.; KC1, 0.042 per
cent.; XaHCO.,, 0.01 to 0.03 per cent.; and dextrose, 0.1 per cent.
The solution is fed to the heart under an atmosphere of oxygen,
and with this solution Locke and others have kept the mammalian
heart beating for many hours. The dextrose, while not essential
to the action of the irrigating liquid, is said to increase its effi-
ciency, and Locke* has shown that the sugar is apparently
utilized by the heart, since a considerable amount disappears
from the solution when the heart is beating strongly. The
general fact that comes out of these experiments is that the
heart can beat for very long periods upon what has been called
an inorganic diet. Moreover, the salts that are used cannot be
chosen at random; it is necessary to have salts of the three metals
named, and substitution is possible only to a very limited ex-
tent. Thus, strontium salts may replace those of calcium more
or less perfectly.

It is evident that these salts play some very important part
in the production of the rhythmical beat of the heart; and analysis
has shown that the sodium, calcium, and potassium has each
its special role. We may say that the presence of these salts
in normal proportions is an absolute necessity for heart activity.
A striking experiment which shows the importance of the calcium
is to irrigate a terrapin's heart with blood from which the
calcium has been removed by precipitation with sodium oxalate.
In spite of the fact that all other constituents of the blood are
present the heart ceases to beat, and normal contractions can be
started again promptly by adding calcium chlorid in right amounts
to the oxalated blood. Regarding the specific part taken by each
of the cations in the production of the alternate contractions and
relaxations, much diversity of opinion exists, owing to our ignorance
of the chemical changes going on in the heart during systole and
diastole and to the difficulty of controlling experimental conditions.
Thus, while it is an easy matter to control accurately the corn-
posit ion 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 Ihe 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

* Locke :ui'l Ro enheiin, "Journal <>f Physiology, " 36, 2().r>, |<)()7.

PROPERTIES OF THE HEART MUSCLE. 551

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
per cent., and the normal osmotic pressure of the blood is mainly-
dependent upon it. A solution of sodium chlorid of 0.7 to 0.9 per
cent, forms what is known as physiological saline, and although
not adequate to maintain the normal composition and properties
of the tissues it fulfills this purpose more perfectly than the solution
of any other single substance. The sodium ions have in addition
a specific influence upon the state of the heart tissue. Contractility
and irritability disappear when they are absent ; when present alone,
in physiological concentration, in the medium bathing the heart mus-
cles they produce relaxation of the muscle tissue. (2) The calcium
ions are present in relatively very small quantities in the blood, but
they also are absolutely necessary to contractility and irritability.
When present in quantities above normal or when in a propor-
tional excess over the sodium or potassium ions they cause a con-
dition of tonic contraction that has been designated as calcium
rigor. (3) The potassium ions are present also in very small quan-
tities, and, unlike the calcium and sodium ions, their presence in
the circulating liquid does not seem to be absolutely necessary to
rhythmical activity. Under proper conditions a terrapin's heart
beats well for a time upon a solution containing only sodium and
calcium salts. The potassium seems to promote relaxation of the
muscle and in physiological doses it exercises through this effect
a regulating influence upon the rate of beat. When the proportion
of potassium ions is increased the heart rate is proportionally
slowed, and finally the contractions cease altogether, the heart
coming to rest in a state of extreme relaxation, known sometimes
as potassium inhibition. (4) It appears from these statements
that there is a well-marked antagonism between the effects of the
calcium, on the one hand, and the potassium and sodium, on the
other. The calcium promotes a state of contraction, the sodium
and the potassium a state of relaxation. It is conceivable, there-
fore, that the alternate states of contraction and relaxation which
characterize the rhythmical action of heart muscle are connected
in some way with an interaction of an alternating kind between
these ions and the living contractile substance of the heart. It is
impossible to say positively whether or not the inorganic salts
are directly connected with the cause of the beat, — that is, with
the origination of the inner stimulus. According to one point of
view, they are necessary only to the irritability and contractility
of the heart tissue. The inner stimulus is produced otherwise
by some unknown reaction, but it is not able to cause a contraction
of the heart muscle in the absence of the proper inorganic salts.
According to another view, the reaction of these ions with the

552 CIRCULATION OF BLOOD AND LYMPH.

living substance constitutes or leads to the development of the
inner stimulus.

Physiological Properties of Cardiac Muscle. — Cardiac muscle
exhibits certain properties which distinguish it sharply from skeletal
muscular tissue and which have a direct bearing upon the rhyth-
micity of the contractions and the sequence shown by the different
chambers. The most characteristic of these properties are the
following:

1. The contractions of heart muscle are always maximal. In
skeletal muscle and in plain muscle the extent of contraction is
related to the strength of the stimulus, and we recognize the exis-
tence of a series of submaximal contractions of varying heights.
This is not true of heart muscle. As was first shown by Bow-
ditch, a piece of ventricular muscle when stimulated responds, if
it responds at all, with a maximal contraction. The apex of a
frog's heart does not beat spontaneously, but contracts upon
electrical stimulation. If such an apex is connected with a lever
to register its contractions, and the electrical stimulus applied to
it is gradually increased, the first contraction to appear is maxi-
mal, and it is not further increased by augmenting the stimulus.
This property is sometimes described by saying (Ranvier) that
the contraction of the heart muscle is all or none. This fact
must not, however, be interpreted to mean that the force of
contraction of heart muscle is invariable under all conditions.
Such is not the case. The heart muscle under favorable nutritive
conditions may give a much larger and more forcible contraction
than is possible under conditions of poor nutrition; but the point
is, that, whatever may be the condition of the muscle at any
given moment, its contraction in response to artificial stimulation
is maximal for that condition, — that is, does not vary with the
strength of the stimulus. As was said above, this property is not
exhibited by the crustacean (lobster) heart, but has been shown
to be true for the mammalian heart muscle.*

2. The refractory period of the beat. It was shown by Marey f that
the heart muscle is irritable to artificial (electrical) stimuli only
during the period of diastole. During the period of systole an elec-
trical stimulus lias 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. 228. The period of inexcitability
U designated as the refractory period of (he hearl heat. Marey

* For experiments on mammalian heart and literature, woo Wood worth,
" American Journal of Physiology," 8, 213, 1903.
t Marey, "Travaux 'lu laboratoire," 1876, \>. 73.

PROPERTIES OF THE HEART MUSCLE. 553

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

Pig- 228. — 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 S 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 proceded before the stimulus is applied.

55-1 CIRCULATION OF BLOOD AND LYMPH.

of the stimulus. Later experiments by other investigators make it
probable that the refractory period lasts during practically the entire
systole.* According to this point of view, therefore, the heart muscle
during its period of actual contraction is entirely unirritable, and in
this respect it offers a striking difference to skeletal and plain muscle.
The existence of this refractory period explains why the heart
muscle cannot be thrown into complete tetanic contractions by
rapidly repeated stimuli. Since each contraction is accompanied
by a condition of loss of irritability, it is obvious that those stimuli
that fall into the heart during this period must prove ineffective.
The refractory period and the gradual increase in irritability during
the diastole may throw some light also on the rhythmical character
of the beat. The occurrence of the refractory period and the
subsequent gradual return of irritability are connected no doubt
with the metabolic changes taking place in the heart muscle. It
is in the character of this metabolism that we must seek for the
final explanation of these two phenomena and the cause of the
rhythmicity of the contractions. As was stated above, it has been
shown that the crustacean (lobster) heart muscle does not obey the
all-or-none law, shows no refractory period, and is capable of
giving tetanic contractions when rapidly stimulated. In all these
respects it differs from the typical heart muscle of the vertebrate,
but the difference is perhaps sufficiently explained by the discovery
(p. 546) 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 i«nix(>. It has been shown,t however, that the exact compen-
sation in this case is not referable to a property of heart muscle, but is due to
the dependence of the ventricular upon the auricular beat. When the auricle
or ventricle is isolated and stimulated the phenomenon of exact compensation
IS n"i observed. In an entire heart, on the contrary, the beat originates at
th<- venous em I of the auricle and is propagated to the ventricle. If the latter
chamb< r i- stimulated so as to give an extra beat out of sequence it will remain
in diastole until the next auricular beat stimulates it, and will thus pick up
the regular sequence of the heart beat.

The Normal Sequence of the Heart Beat. -The normal
rhythm of the hearl beal is firsl a contraction of the auricles,
then one of the ventricles. Many efforts have Ween made to
determine the precise spot in which the contraction of the heart

* Bee paper by Woodworth, he. cit. Also Schultz, "American Journal of
Phyriology,'5 16, 483, I906,and22, L33, L908.

f Cushny and Matthews, "Journal of Physiology," 21, 227, L897.

PROPERTIES OF THE HEART MUSCLE. 555

normally starts. Formerly it was supposed that the contraction
began in the great veins just before they pass into the auricle,
and it was implied that this initiation of the beat might occur in
the pulmonary veins as well as in the vense cavse. More recent
experiments* which have been made largely upon the isolated
heart while perfused with a Ringer-Locke solution have shown
pretty conclusively that the most rhythmic part of the heart
and the part from which the beat, in all probability, normally
starts is an area of the wall of the right auricle lying between
the openings of the vense cavse. When this portion of the heart
is warmed or cooled the rate of beat of the whole heart is cor-
respondingly increased or decreased, while, on the contrary,
warming or cooling of the ventricles themselves, the auricular
appendages, the left auricle, etc., has no effect upon the heart-
rate. From the point of confluence of the vense cavse the wave
of contraction spreads over the auricles and thence through the
auriculoventricular bundle to the ventricles. 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

♦Consult especially Adam, "Archiv f. d. ges. Physiol.," Ill, 607, 1906,
and Erlanger and Blackman, "American Journal of Physiology, " 19, 125, 1907.

556 CIRCULATION OF BLOOD AND LYMPH.

this connection, and the application of the myogenic theory to the
explanation of the normal sequence of contractions forms one of its
most attractive features. Gaskell assumes* that the rhythmical
power of the muscle at the venous end is greater than that at the
ventricular end, — that is, if pieces from the two ends are examined
separately it will be found that the spontaneous rhythm of the
tissue from the venous end is more rapid. This portion of the
heart, therefore, beating more rapidly, sets the rhythm for the
whole organ, since a contraction started at the venous end will
propagate itself from chamber to chamber. The pause between the
contractions of the successive chambers — between auricle and
ventricle, for instance — is due, in the heart of the tortoise, to the
fact that the muscular tissue at the junction of auricle and ventricle
has a relatively low rate of conduction. At this point, indeed,
the muscular fibers form a ring around the orifice, preserving,
therefore, the arrangement found in the embryo at the time that
the heart has the form of a tube. Gaskell has given reasons for
believing that the conduction of the wave of contraction is slower
through this ring. In the mammalian heart the direct conduc-
tion of the wave of contraction from auricle to ventricle through
intervening muscular tissue is made quite possible, since the
discovery has been made that the auricles and ventricles are
connected by a muscular bundle (p. 520). 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 -mall 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 vaiia! ions in the pressure

♦ Gaskell, " Journal of Physiology," •, 61, L883; also vol. ii., p. 180, of
Schafi l ■ I I«>"1< of Physiology/' L900

Lehrbucb <1<t Physiologic <!<•« Kreislaufes," L893.

PROPERTIES OF THE HEART MUSCLE. 557

upon the bundle intermediate conditions may be obtained in which
the "block" between auricle and ventricle is only partial, and in
which, therefore, the ventricular systole follows regularly every
second or third auricular contraction. When the "block" is com-
plete the ventricular rhythm ceases to have any definite relation-
ship to that of the auricle, it beats entirely independently and its
rate is slower than that of the auricle. It is interesting to remember
that cases of complete or partial heart block occur in man. In
the condition known as the Stokes-Adams syndrome the striking
feature in addition to attacks of syncope is a permanently slowed
pulse, the heart beat falling to 30 or 20 beats per minute or lower.
Erlanger has shown that in such cases there may be complete or
partial heart block. In the former condition the rhythm of the
ventricle is entirely independent of that of the auricle and of course
much slower. The ventricles may be beating at 27 per minute and
the auricles at 90. In partial block the ratio between the ventric-
ular and auricular rate is definite, every second or third auricular
beat being followed by a ventricular systole (see Fig. 229). The
lesion producing this condition has not been determined in many
cases, but it is probable that the trouble will be found in the auriculo-

Fig. 229. — 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.

ventricular bundle, which constitutes the physiological link con-
necting the auricles and ventricles.*

In the hearts of the cold-blooded animals the same general
results are readily obtained when the tissue between the different
chambers is compressed or destroyed. In the frog's heart, for
instance, if one ties a ligature (first ligature of Stannius) between
the sinus venosus and the auricle, the auricle and ventricle cease
beating while the sinus continues pulsating with its normal rhythm.
Later the auricle and ventricle may commence beating again, but
if this happens their rhythm is slower than that of the sinus and
independent of it. So in the terrapin's heart, in which the sequence
of beat is so beautifully exhibited, if one ties a ligature between
auricle and ventricle, or cuts off the ventricle entirely, the sinus

* See Erlanger, ''Journal of Experimental Medicine," 1905. vii., 1906,
viii., and "American Journal of Physiology," 1906, xv. and xvi.

558 CIRCULATION OF BLOOD AND LYMPH.

venosus and auricle continue beating at their normal rhythm, while
the ventricle remains usually entirely quiescent so long as normal
blood flows through it. It would seem from these facts that in the
mammalian heart the ventricle when disconnected from the auricle
is capable of maintaining a fairly rapid rhythm of its own. At the
other extreme, the terrapin's ventricle when similarly treated shows
no spontaneous beats at all. These and many other facts that
might be quoted support well the general view proposed by Gaskell,
that the venous end of the heart possesses the greater rhythmical
power and starts the heart beat, and that the wave of contraction
is propagated from chamber to chamber through the intervening
muscular substance.

There remains a deeper question as to what occasions this greater rhyth-
micity at the venous end, — a question that is, of course, bound up with the
problem of the ultimate causes or conditions of automatic rhvthmicity. In
connection with this latter problem the absolute necessity of the presence of
certain inorganic salts in certain proportions has been emphasized. In this
same general line the author has called attention to the fact that in the ter-
rapin the amount of potassium salts present in the blood explains in itself
why the sinus sets the heart rate. In blood, or in Ringer's solution con-
taining potassium salts in the same amounts as blood, the ventricular muscle
is not automatically contractile; the sinus end of the heart, on the contrary,
beats well in such media, while an increase in the potassium contents will
bring it to rest also. In this animal, therefore, the amount of potassium in
the blood is so adapted that it holds the ventricular end entirely quiescent.
In the mammalian heart it may be assumed that the amount of potassium is
sufficient to keep the spontaneous rhythm of the ventricle slower than that
of the auricles or veins, and therefore subordinates the rhythm of the whole
heart to that of the venous end. In the terrapin's heart, at least, the re-
moval or reduction of the potassium or the increase of the calcium may lead
to an independent ventricular rhythm — the beat of the heart becomes arhyth-
rnical.

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-
flit ion 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 (lie 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

PROPERTIES OF THE HEART MUSCLE. 559

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.

Fig. 230. — To show tone waves in heart muscle. The record shows contractions of a
6trip 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.

As will be described in the next chapter the tone of the heart
muscle is dependent in part upon its extrinsic nerves, but it is
more dependent probably upon the composition of the blood.
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 sus-
pended so that their movements can be recorded, often vary
greatly in length with differences in condition. These varia-
tions are due to changes in tone. Not infrequently these
changes take on a rhythmical character; so that if the ven-
tricle is beating one sees upon the record regular tone waves,
an alternate slow shortening and slow relaxation quite inde-
pendent 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. 230). 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

560 CIRCULATION OF BLOOD AND LYMPH.

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
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, " Beit rage zur Physiologic" 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 some of them, at least,
are stimulated at each beat of the heart (p. 000) and that
possibly some of them help to form the so-called depressor
nerve (p. 594). Under pathological conditions these afferent
fibers may produce painful sensations.

The Course of the Cardiac Fibers. — The vagus nerve gives
off several branches that supply the heart. The superior car-
diac 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
(N. recurrens) and, indeed, some of these branches may spring
directly from the latter nerve. 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. 250) through the vagus nerve. The preganglionic fibers probably
end around ganglion cells in the heart, which in turn send their
axons as postganglionic fibers to the heart muscle.

The Action of the Inhibitory Fibers. — If the vagus nerve

in the neck of an animal is cut and its peripheral end is stimulated

the heart is slowed or stopped altogether according to the strength

of the stimulus. This effect is illustrated in Figs. 231 and 232.

36 561

562

CIRCULATION OF BLOOD AND LYMPH.

This inhibitors* influence upon the heart beat was first described
in 1S45 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,

* See especially Tlianhoffer, " Centralblatt t. d, med. Wiss.," 1875, who
gives an account <>f an experiment in which the vagi were compressed in the
neck, with a resulting Stoppage of the heart and loss of consciousness.

Fig. 231. — To show the inhibit ion
of the terrapin's heart due to stimula-
tion of the vagus nerve. The upper
tracing '/) records t he contractions of
the left auricle; the lower (//) the con-
t ructions of the ventricle. The vagus
was stimulated three times, each
chamber coming to u complete stop.

On removing the stimulus it will be

noted thai the auricular contraction
increase gradually to their normal,
while the ventricular contractions

■tail off at full strength.

THE CARDIAC NERVES. 563

especially in the terrapin, the inhibitory fibers may be found
exclusively or mainly in the right vagus.

Analysis of the Action of the Inhibitory Fibers.— The prom-
inent effect of the action of the inhibitory fibers is the slowing

Fig. 232. — To show the inhibition of the heart from stimulation of the vagus in the
dog. Record B is the blood-pressure tracing. The vagus was stimulated twice. The
marks x, x, indicate the beginning and end of the stimulus. The first stimulation was
weak ; it will be noted that the heart escaped and began beating before the stimulus was
withdrawn. The second stimulus was stronger; the inhibition lasted some time after re-
moval of the stimulus. The upper curve (A") is a plethysmography (oncometer) tracing
of the volume of the kidnev. It will be noted that when the heart stops and blood-pressure
falls the kidney, like the other organs, diminishes in volume. (Dawson.)

of the rate of the heart beat. Numerous observers have called
attention to the fact that the vagus fibers may also cause a weaken-
ing in the force of the beat as well as a slowing in the rate, or,
indeed, the two effects may be obtained separately. This fact has
been shown especially for the auricles.* In the heart of the terrapin
one may, by using weak stimuli, obtain only a weakening of the
*See Bayliss and Starling, "Journal of Physiology," 13, 410, 1892.

564

CIRCULATION OF BLOOD AND LYMPH.

auricular beats without any interference with the rate (Fig. 233),
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 ma}' 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 relative^ 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-
fcracts once to two or three beats of the auricle, vagus stimulation
may be followed a1 once, as :m 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
I,-,- 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,
e i iger fcedt , ' Lehrbuch der Physiologie des Kreislaufes," 1893, p. 247.

Fig. 2:3.*.— To show the effect of
vagus stimulation on the force only of
the auricular beat in the terrapin's
heart: A, Record of the auricular
beats; V, record of the ventricular
beats. The vagus was stimulated be-
tween x and x. It will be noted that
the ventricular beats are not affected,
and that the auricular beats diminish
in extent without any change in rate.

THE CARDIAC NERVES. 565

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. 231). When a block is produced in the
mammalian heart between auricle and ventricle — by clamping the
connecting muscular bundle, for instance — stimulation of the
vagus stops the auricle only (Erlanger), and this result would seem
to indicate that the vagus affects only the auricle, unless it is as-
sumed that the clamp has interrupted the inhibitory paths to the
ventricle. On the other hand, in favor of the view that the vagus
fibers reach the ventricle and influence its beats directly, we have the
fact, emphasized by Tigerstedt, namely, that when the connection
between auricle and ventricle is severed suddenly the ventricle
frequently continues to beat at its own rhythm without any obvious
pause. It would seem from this fact that when the whole heart
is inhibited by stimulation of the vagus the ventricle does not
stop simply because the auricle fails to send on its usual contraction
wave, since, if that were so, cutting off the auricle or clamping the
connection between it and the ventricle should also bring on a
ventricular pause, as happens in the case of the terrapin's heart.
It seems, however, to be the general belief of those who have experi-
mented with the subject that the action of the vagus is exerted
mainly upon the auricles.

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

566 CIRCULATION OF BLOOD AND LYMPH.

Escape from Inhibition.— Strong stimulation of the vagus
may stop the entire heart, but the length of time during which the
heart may be maintained in this condition varies in different species
and indeed to some extent in different individuals.* In some ani-
mals— eats, for example — the strongest stimulation of the nerve
serves frequently only to slow the heart instead of causing complete
standstill. In dogs the heart is stopped by relatively weak stimu-
lation, although if the stimulation is maintained the heart, as a
rule, escapes from the inhibition. In some dogs the heart may
be held inhibited long enough to cause the death of the animal
unless artificial respiration is maintained, but usually the heart
beat soon breaks through the complete inhibition. The "inner
stimulus" in such cases increases in strength sufficiently to overcome
the opposing inhibitory influence, and this circumstance may be
regarded as an argument against those views that trace the origin of
the "inner stimulus" to some of the products formed during the ca-
tabolism of contraction. Moderate stimulation of the vagus, suffi-
cient simply to slow the rate of beat, can be maintained without dimi-
nution in effect for very long periods; indeed, as is explained in the
next paragraph, 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 stimu-
lation of the vagus. Mills reports that he has kept the heart
of the terrapin in this condition for more than four hours. f
Mos1 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
" Eflopfversuch."J In this experiment, made upon frogs, the ob-
server obtained standstill of the heart by light, rapid taps on the
abdomen, and the effect upon the heart failed to appear when the
. agj were cut. In the mammals every laboratory worker has had
numerous opportunities to observe that stimulation of the central
-tump- 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

vague carries afferenl fibers from the thoracic and abdominal

i Hough, 'Journal of Physiology," 18, 161, L895.
t" Journal of Phyi iology," <>, 246.
jGoltz, " Virchow'a Archiv f. pathol. Anatomic, ct,c,"2(i, ll, 1863.

THE CARDIAC NERVES. 567

viscera, and most observers state that the heart may be reflexly
inhibited most readily by stimulation of the sensory surfaces of
the abdominal viscera, by a blow upon the viscera, for example,
or by sudden distension of the stomach. In man similar results
are noticed very frequently. Acute dyspepsia, inflammation of
the peritoneum, painful stimulation of sensory surfaces, — the
testes, for instance, or the middle ear, — may cause a marked slowing
of the heart, — a condition designated as bradycardia. What
takes place in all such cases is that the afferent impulses carried
into the central nervous system reflexly stimulate the nerve cells
in the medulla which give origin to the inhibitory fibers. These
cells form a part of the great motor nucleus (N. ambiguus) from
which arise the motor fibers of the vagus and the glossopharyngeus.
The particular group of cells from which the inhibitory fibers to the
heart originate has not been delimited anatomically. Efforts have
been made to locate them by vivisection experiments, but 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-

568

CIRCULATION OF BLOOD AND LYMPH.

rupting, in some other way — cooling, for example — the connection
between the center and the heart. When the two vagi are cut the
heart rate increases greatly and the blood-pressure rises on account
of the greater output of blood in a unit of time (Fig. 234',. 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

Fitf. 2'M. — To show the '-fleet of sortion of the two vagi in the dog upon the rate of
hear) beat and 1 1 if* blood-pressure: 1 marks the section Ot the vagus on the right side;
2, section of the second VagUS. The numerals on thevertieal mark the blood-pressures;
the numerals on the blood-pressure record give the rate of heart beats. (Dawson.)

severed separately varies undoubtedly with the conditions, — for
instance, with the intensity of tlie 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 Blower; when it is decreased the rate
become- faster. In all probability, this tonic action of the center,
like that of the motor centers generally, is in reality a reflex tonus.

THE CARDIAC NERVES. 569

That is, it is not due to automatic processes generated within the
nerve cells by their own metabolism or by changes in their
liquid environment, but to stimulations received through sensory
nerves. The continuous though varying inflow of impulses into
the central nervous system through different nerve paths keeps
the center in that state of permanent gentle activity which we
designate as "tone." It is possible, of course, that certain
afferent paths may be in specially close functional relationship
to the center, and the fact that at each heart beat its own
sensory fibers are stimulated (p. 668, Fig. 271) would suggest
that these fibers may have this function.

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 Cushnv, " Text-book of Pharmacology and Therapeutics."
Philadelphia, 1903.

570 CIRCULATIOX OF BLOOD AND LYMPH.

existence in the body of definite nerve fibers with apparently the
sole function of inhibition, it seems appropriate in this connection
to refer to the views regarding the nature of this process. Several
general views of the nature of inhibition have been proposed, but
the one that is most definite and has met with most favor is that
suggested by Gaskell.* This author has shown that the after-effects
of stimulation of the inhibitory fibers are beneficial rather than in-
jurious to the heart ; that is, under certain circumstances an improve-
ment may be noticed in the rate or force of the beat or in the con-
ductivity. He has also shown, by an interesting experiment, that
during the state of inhibition the heart tissue is made increasingly
electropositive in comparison with a dead portion of the tissue.
To show this fact the tip of the auricle was killed by heat and this spot
(a) and a point at the base of the auricle (b) were connected with a
galvanometer. Under such conditions a strong demarcation cur-
rent was obtained flowing through the galvanometer from 6 to a.
If the auricle contracted a negative variation resulted, since during
activity b became less positive as regards a. If, on the contrary,
the auricle was inhibited b}' 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

A more specific I heory applicable to the case of the hear! has been proposed
by the author.}: In experiments made upon the isolated hearl of the <l<>^ it
has been shown thai during stimulation of the vagus potassium in diffusible
form is given off from the hearl mu cle (auricles), it is known that potassium
salt* in a certain concentration in the circulating Liquid will bring the heart
to a stand-still, and the state of potassium inhibition thus produced resembles

♦Gaskell, "Philosophical Tran actions of the Royal Society," London;
Croonian Lecture, pari m , L882; also "Beitrage zur Physiologic, " dedicated
to C, Ludwig, L887; and "Journal of Physiology," 7, 46.

f For a general discussion of iliis idea and of the Importance of inhibitory
actions, see Meltzer, "Inhibition, " "New York Medical Journal," May i:;,
20, 27. L899.

% Howell and Duke, "American Journal of Physiology," 21, 51, L908.

THE CARDIAC NERVES.

571

very closely the state of vagus inhibition. Since the vagus when stimulated
liberates potassium in a diffusible form, it is suggested that its action in
stopping the heart is effected through the agency of this substance. The
potassium exists in large percentage in the heart-muscle, but in a combined
form, and the theory assumes that the vagus impulses initiate a dissociation
or cleavage of some sort which sets free some potassium in soluble form. If
it is assumed that this liberation takes place in the part of the heart in which
the beat originates, the theory offers a simple explanation of the stoppage of
the beat, of the quick recovery after stimulation ceases, and of the retention
of irritability to direct stimula-
tion shown by the heart during
vagus inhibition. A heart that
has been stopped by an excess
of potassium chloride added to
the circulating liquid beats very
promptly as soon as the excess
of the potassium is removed, and
as in the case of vagus inhibition
it seems often to show a notice-
able improvement in condition.

That the inhibitory ef-
fect of the vagus im-
pulses upon the heart is
not due to any peculiarity
in properties of these
fibers or of the impulses
themselves, but is depend-
ent rather upon the place
or manner of ending in the
heart, has been demon-
strated by direct experi-
ment. Erlanger* has shown
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.

The Course of the Ac-
celerator 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
* Erlanger, "American Journal of Physiology," 13, 372, 1905.

Fig. 235. — 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 heck
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.

572

CIRCULATION OF BLOOD AND LYMPH.

by the Cyon brothers— M. and E. Cyon* — 1866. These fibers
when stimulated cause an increased rate of beat and are, there-
fore, designated as the accelerator nerve of the heart. Their
course has been worked out physiologically in a number of
animals. Among the mammalia and, indeed, among different
animals of the same species there is some variation, but a general
conception of their origin and course may be obtained from
Figs. 235 and 236, which represent in a schematic way the
anatomical path taken by these fibers. They emerge from the
spinal cord in the anterior roots of the second, third, and fourth

thoracic spinal nerves. Accord-
ing to some authors they may
be found also in the fifth tho-
racic, the first thoracic, or even
the lower cervical spinal nerves.
They pass then by way of the
white rami to the stellate or
first thoracic ganglion (6), and
thence by way of the annulus
of Vieussens (ansa subclavia) (7)
to the inferior cervical ganglion.
A number of branches leave
the sympathetic system and the
vagus in this region to pass to
the cardiac plexus and thence
to the heart. The accelerator
fibers are found in some of these
branches, mixed in some cases
with inhibitory fibers from the
vagus. In the cat Boehm has
described a special branch (ner-
vus accelerans) which runs from
the stellate ganglion directly to
the cardiac plexus (Fig. 236).
The preganglionic portion of some of the accelerator fibers ends
around the ganglion cells in the first thoracic ganglion, while
others apparently make their first termination in the inferior
cervical ganglion. The accelerator fibers may be stimulated in
the -|)iual roots in which they emerge (II, III, IV), in the annulus,
or in some of the branches that arise from the annulus, or from
the inferior cervical ganglion (5, 3, 2). It will be borne in mind
that no accelerator fibers are found in the cervical sympathetic
above the inferior cervical ganglion.

* For the hi tory and literal ure of the accelerator nerves, see ('yon, article
"Cowir," p. L03, initichet's " Dictionnaire de Physiologie," L900; or Tiger-
stedt, " Lehrbuch der Physiologie des Kreislaufes," 260, 1893.

V\k- 236 — Sketch to show the accel-
erator ::ni'i augmentor) branches from the
stellate ganglion (in the cat, lefl side): L,

The ven tr:il branch of the annulus (ansa
subclavia); 2, small branch not constantly

pre.-ent; :',, Bochm's accelerator nerve
(N. canhacus c Kanglio stcllato.).

THE CARDIAC NERVES. 573

At various times investigators have asserted that accelerator 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, stimulation of the
vagus causes an acceleration of the heart. Little attention has been paid to
the physiology of these fibers, since it seems evident that the great outflow of
accelerators is made via the sympathetic system.

The Action of the Accelerator Fibers. — In experimental
work the accelei*ators are usually stimulated in one or more of the
branches represented schematically as 5, 3, 6, in Fig. 235, or 3, in
Fig. 236. The effect is an increase in the rate of beat of the heart,
which may be very evident, amounting to as much as 70 per cent.
or more of the original rate, or may be very slight. When accelera-
tion is obtained the latent period is considerable and the heart
does not return at once to its normal rate upon cessation of the
stimulus (see Fig. 237). In some cases the effect upon the heart
is an acceleration pure and simple, — that is, the rate of beat is
increased without any evidence of an increase in the force of the
beats. The larger number of beats is offset by the smaller amplitude
of each beat; so that the blood-pressure in the arteries is unchanged.
In other cases the effect upon the heart may be an increase not only
in rate but also in the force or amplitude of the beats, or the rate
may remain unaffected and onty the amplitude of the heart
beats be increased. For these reasons most authors favor the
view that the accelerator nerves, so called, contain in reality
two sets of fibers, one, the accelerators proper, whose function
is simply to accelerate the rate, and one, the augmentors, that
cause a more forcible beat. The augmenting action is obtained
especially from the nerves of the left side.

Tonicity of the Accelerators and Reflex Acceleration. —
The results of the most careful work show, without doubt, that the
accelerators to the heart are normally in a state of tonic activity.*
When these nerves are cut upon both sides the heart rate is decreased .
We must believe, therefore, that under normal conditions the heart
muscle is under the constant influence of two antagonistic influ-
ences, one through the inhibitory fibers tending to slow the rate,
one through the accelerator fibers tending to quicken the rate. The
actual rate at any moment is the resultant of these two influences.
While such an arrangement seems at first sight to be unnecessary
from a mechanical standpoint, it is doubtless true that it possesses
some distinct advantage. Possibly it makes the heart more
promptly responsive to reflex regulation. Balanced mechanisms
of this kind are found in other parts of the body where smooth and
prompt reactions to stimulation seem to be especially necessary, — ■
for example, the constrictor and dilator fibers of the iris, the ex-

* For a discussion of this and other points in the physiology of the ac-
celerators see Hunt, "American Journal of Phvsiology," 2, 395, 1S99, and
"Journal of Experimental Medicine," 2, 151, 1897.

574 CIRCULATION OF BLOOD AND LYMPH.

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, therefore, as true antagonists, acting
in opposite ways upon the heart. The existence of the accel-
erator 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, particularly by emotional states.
The natural explanation of such accelerations is that they are

Fig. 237. — To show the acceleration and augmentation produced by a strong stimulus.
Isolated cat's heart, stimulation on left side. The upper curve gives the ventricular
contractions, the lower one the auricular contractions. The lowermost line gives the
time in seconds and the line above indicates the duration of the stimulation of the accel-
erati r nerve.

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
lnoiight 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
indicate; thai an increase in heart rate from reflex action may be
produced by an inhibition of the tonic activity of the cardio-
inhibitory center. He finds, for instance, that when the two
\n</\ are cut stimulation of various sensory nerves fails to give
any increase in the already rapid heart rate, while, on the con-
trary, when the two accelerator paths are cut a reflex increase in
hearl rate may be obtained readily. The negative result after
previous section of the vagi may well be due, however, to the
fad that the; heart is then beating at a very rapid rate, too
rapid for the production of an additional acceleration through
the ordinary physiological mechanism. Acting on this view,

THE CARDIAC NERVES. 575

Hooker* has shown that if the heart is kept slowed by artificial
stimulation of the peripheral end of the vagi, then various
sensory stimuli will provoke a reflex acceleration which can
only occur through the accelerator center. In addition, Hering f
has given experimental evidence to show that the acceleration
of the heart following upon muscular exercise does not occur
when the accelerator nerves are cut, a fact which also seems
to show that these nerves may be reflexly stimulated. We
may conclude, therefore, that the accelerator and the inhibitory
fibers are working constantly on the heart, and that its rate
is the resultant or algebraic sum of their effects, and
that sudden changes in this rate, such as follow from sensoiy
or psychical disturbances of any kind, may be referred to a
reflex effect upon either the cardio-inhibitory or the accelerator
center. While physiology has demonstrated the general properties
of the regulating nerves of the heart, the inhibitory, on the one
hand, and the accelerator and augmentor on the other, it is necessary
for much more work to be done in order to explain satisfactorily
how these nerves participate in the various normal and pathological
changes of rate and force of beat.

The Accelerator Center. — The accelerator fibers arise primarily in
the central nervous system. Since stimulation of the upper cervical region
of the cord causes acceleration, it seems evident that the path must begiu
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.

* Hooker, "American Journal of Physiology," 19, 417, 1907.
t Hering, " Centralblatt f. Physiol.," 1894, viii., 75.

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 SO beats; but the normal rate for some individuals
may be much lower (50) or much higher (90). Among the condi-
tions for which the heart rate shows a certain constant fixed adapta-
tion the following may be mentioned:

Variations with Sex. — The average pulse rate in women is, as
a rule, higher than that in men, and this difference seems to hold
for all periods of life.

Variations with Size. — Tall individuals have a slower pulse
rate than short persons of the same age. Several observers have
thought that they could detect a constant relationship between
size and pulse rate. Thus, Volkmann believed that the pulse
rutc v;uies inversely as the five-ninth power of the height. In
the same direct ion it is found thai small animals, as a rule, have
a higher pulse rate than larger ones. Tims, elephant, 2.r> 28;
horse and ox, 36 50; sheep, 60-80; dog, 100-120; rabbit, 150;
mice, 670 (Buchanan). It would seem, from these facts, that the
f:i i rate in the small animals, with their shorter circulatory path
and smaller volume of blood, is necessary to the mechanical
fulfilment of the functions of the blood, and has been preserved
by natural selection.

676

THE RATE OF THE HEART BEAT 577

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. 573) 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 activit}^ 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 ivith 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
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,

* See Volkmann, "Die Hamodynamik," p. 427, 1850; also Guy, article
"Pulse" in Todd's "Cyclopaedia of Anatomy and Physiology," 1847-49.
37

57S CIRCULATION OF BLOOD AND LYMPH.

effect upon the heart. The experiments of Newell Martin upon
the isolated heart seem to have settled the matter satisfactorily.*
Bv 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 stimulation of the
cardiac nerves. A rise of pressure in the arteries may affect
directly the eardio-inhibitory center or it may affect afferent
fibers in the heart or arteries, and thus reflexly stimulate the
eardio-inhibitory center. This point has been the subject of
a number of investigations, but Eyster and Hookerf appear
to have demonstrated that both methods of stimulation occur.
High arterial pressure affects the medullary center directly
and thus slows the rate, but it affects also certain sensory fibers
in the aorta at or beyond the arch, and through them causes a
reflex slowing.

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. Ho considers this
factor as of relatively subordinate importance. Second, the chief
factor is found in an associated activity of the accelerator nerves.
Thai 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§ supports

the latter pari of this explanation to the extent- of showing that

the increase in heart rate after mUSCUlar exercise is dependent

* Martin, "Studies from the Biological Laboratory, Johns Hopkins Uni-
versity," 2, 213, 1882; also "Collected Phy iologica] Papers," p. '2.',, 1896.
t Eyster and Hooker, "American Journal of Physiology, " 21, 373, l(.)()8.
J Johann on, "Skanoinavisches lArchiv f. Physiologic, " 5, 2Q, L896.
g "Centralblatl f. Phyi iologie," 8, 75, L894.

THE RATE OF THE HEART BEAT.

579

upon the integrity of the accelerator nerves. On the other
hand, after prolonged or excessive muscular exertion the heart
rate remains accelerated for a considerable period after cessation
of the work — in the untrained individual at least — a fact which
would indicate some long-lasting influence, such as is implied
in the first factor given above, namely, 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. 238). 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. 239. The
accelerated heart rate in fevers is therefore due probably to the

* Martin, " Croonian Lecture, Philosophical Transactions, Roval Society,"
London, 174, 663, 1883; also "Collected Physiological Papers," p. 40, 1895.

Fig. 238.— 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.

580

CIRCULATION OF BLOOD AXD LYMPH.

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 artificial circu-
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,

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although a alightly higher temperature may be withstood under
special conditions. At the other extreme the mammalian heart
ceases to beal when the temperature fulls as low as L70tol8°C.
'I he rate of the hearl beal may bo influenced also by many sub-
stances added to I he blood. The influence of atropin and muscarin

• Martin and A-pplegarth, "Studies from the Biological Laboratory,
Johm Hopkins I oiver ity," 4, 275, 1890; also "Collected Physiological
Papers," p. 97, L895.

THE RATE OF THE HEART BEAT. 581

has already been alluded to, but changes also in the normal con-
stituents of the blood may have similar effects. Thus, an increase in
the sodium carbonate of the blood affects the heart beat, particu-
larly in regard to the amplitude or force of the contraction,
while variations in the other inorganic constitutents may have
a marked influence on the rate. The most significant and strik-
ing fact in this connection is the relation of the potassium salts.
As the amount of diffusible potassium is increased the pulse
rate becomes slower and slower, until the heart stops in a con-
dition of potassium inhibition.

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

fcO demonstrate the existence of a second class of nerve; filters, which.

when stimulated, cause a dilatation of the blood-vessels and which

* See "Life of Claude Bernard," bySir Michael Poster, 1899, in the series,
"Masters of Medicine."

582

THE VASOMOTOR NERVES. 583

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. 497).
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

584 CIRCULATION OF BLOOD AND LYMPH.

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 clue to a vasocon-
striction. When the method is applied to a definite organ — the
brain, for instance — it becomes conclusive only when simultaneous
observations are made upon the pressure in the artery and the vein
of the organ, and proof is obtained that the pressures at these points
vary in opposite directions. 4. By observations upon the volume
of the organ. It is obvious that, other conditions remaining un-
changed, a vasoconstriction in an organ will be accompanied by
a diminution in volume, and a vasodilatation by an increase in
volume. This method of studying the blood-supply of an organ is
designated as plethysmography, and any instrument designed to
record the changes in volume of an organ is a plethysmograph*
Plethysmography 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, that for the heart, as a cardiometer.
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
pelthysmograph 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 registered successfully.

The plethysmograph generally employed in laboratories, particularly for in-
vestigations on man, is some modification of the form devised by Mosso (see
Fig. 240). The hand and more or lees of the arm is placed in a glass cylinder
whirl, Lb swung freel) 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 ihe cylinder and connecting tubes
arc filled with warm water and then all openings arc closed except, the
one leading to the recorder. \ny increase in volume of the arm will drive

water from the plethj Olograph to the recorder, :unl any decrease;, on

* for a description of I he development of I his method, see hrancois-Franck-
Marey's " Travaux du Laboratoire, L876, p. I.

THE VASOMOTOR NERVES.

585

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. 241. 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. 240. — 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, 5.

interior of the latter is connected, as shown in Fig. 240, 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 hi 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, clue to a greater or less
amount of blood. Bv using a more sensitive recorder and making the con-

586

CIRCULATION OF BLOOD AND LYMPH

nections entirely rigid the smaller, quicker changes in volume caused by the
heart beat are also recorded. A volume pulse is obtained resembling in its
general form the pressure pulse given by the sphygmograph. When used
for this purpose the instrument is described as a hydrosphygmograph.

Records taken of the volume of the hand, foot, brain, or any
other organ show that in addition to the changes caused by the
heart beat and by the respiratory movements, there are other more
irregular variations that are continually occurring the cause of which
is to be found in the variations in the amount of blood in the organ.
Day and night these changes in volume take place, and they are
referable to the activity of the vasomotor system. Vasoconstriction
or vasodilatation in the organ itself cause what may be called

Fig. "41. — 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 .i, supporting pieces ot stout rubber tub-
ing; D and E, sections of outer and inner rings of hard rubber to fasten the reflected rubber
tubing and reduce the opening for the arm.

an active change in volume. But vasoconstriction or vasodilata-
tion in other organs may cause a perceptible change, of a passive
kind, in the volume of the organ under observation. For, since
the amount of blood remains the same, a change in any one organ
musl 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. 246) 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

THE VASOMOTOR NERVES.

587

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. 242. —Schema to show the path of the preganglionic and postganglionic portions
of a vasoconstrictor nerve fiber: a, Anterior root, showing the course of the preganglionic
fiber as a dotted line ; d, v, dorsal and ventral branches of the spinal nerve ; r, the ramus
communicans; g, the sympathetic ganglion. The postganglionic fibers in each ramus come
from the sympathetic ganglion with which it is connected. The preganglionic fibers enter-
ing at any ganglion may pass up or down to end in the cells of some other ganglion.

outflow that takes place in the thoracic region from the second
thoracic to the second lumbar nerves (p. 248). 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

5SS

CIRCULATION OF BLOOD AND LYMPH.

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. 242). In the general region

Fig. 243. — Vasomotor effect of stimulation of the spl;inelmi<- nerve — peripheral end —
hi the dog (Dawson): I. The line of zero pressure ; 2, the line of the timulating pen ; on
and off mark the beginning and end of the stimulation; •''., the time record in seconds; 4,
the blood-pre ure record ' limnlntioii ran >-.-. a mucked rise of blood-pressure due to stimu-
lation of vb ocon trictoi fibei ); 5, plethysmographic tracing of the volume ol the kidney
(oncometer); timulation of the planchnic causes a diminution in volume of the kidney
owing to the con triction of i' arteriole

under consideration (lower cervical to upper lumbar) each ramus
communicans between a spinal nerve and a sympathetic ganglion
consists, therefore, of two parts, one (white ramus) of preganglionic
fibers passing from the spinal nerve to the ganglion, the older
ramus) of postganglionic fibers coining from the ganglion to

THE VASOMOTOR NERVES. 589

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 sjmipathetic 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-

590

CIRCULATION OF BLOOD AND LYMPH.

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.
244. The exact location of the
group of cells that plays the im-
portant role of a vasoconstrictor
center has not been determined
histologically. The region has,
however, been delimited roughly
by physiological experiments. If
the brain is cut through at the
level of the midbrain there is no
marked loss of vascular tone in
the body sA large. II'. however,
similar sections are made farther
and farther back a point is

reached al 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

tin- vasoconstrictor center must lie. The careful experiments of

this kind made by Dittmar* are now somewhat old. According
* " Berichte d. Sflch . Ikademie, Math.-phys. EClasse," L873, p, 449.

Fin. 244. — Schema to show the path
of tin- vaaocoii-tiictoi IiIm-i- from the vaso-
constrictor center to tin' blood-vessels and
ecbanism for the reflex stimulation
of these fibers: v. <■.. The vasoconstrictor

er-nter; 1, the eent r;il neuron of the vaso-

oonstnetor path; 2, the spinal neuron
(preganglionic fiber); '■'•. the sympathetic
neuron (postganglionic fiber); ", the arte-
riole; i, the sensory fibers of the p., terior
root making connections by collaterals
with thl i rietor renter ; 5, an in-

tercentral lil>er (efferent) acting upon the
.a ocon i rietor center.

THE VASOMOTOR NERVES. 591

to his description, the center is bilateral, — that is, consists of a
group of cells on each side, — and lies about the middle of the fourth
ventricle in the tegmental region, in the neighborhood of the nucleus
of the facial and of the superior olivary. In the rabbit it has a
length of 3 mms., a breadth of 1 to 1.5 mms., and lies about 2
to 2.5 mms. lateral to the mid-line. Assuming the existence of
this group of cells, we must attribute to them functions of the first
importance. Like other motor cells, they are capable of being
stimulated reflexly and by this means the regulation of the blood-
flow is largely controlled. Moreover, they are in constant activity,
— due doubtless also to a constant reflex stimulus from the inflow
of afferent impulses. The complete loss of this tonic influence
would result in a complete vascular paralysis, the small arteries
would be dilated, peripheral resistance would be greatly diminished,
and the arterial pressure in the aorta would fall from a level of
100-150 mms. Hg to about 20 or 30 mms. Hg, — a pressure insuffi-
cient to maintain the life of the organism. There seems to be no
question now that in those conditions known as surgical shock the
loss of control by the vasomotor center, and the consequent vascular
paralysis and fall of blood-pressure, are the chief conditions of a
serious character. We must conceive, also, that in this vasocon-
strictor center the different cells are connected by definite paths
with the vasoconstrictor fibers to the different regions of the body ;
that some of the cells, for instance, control the activity of the
fibers distributed to the intestinal area, and others govern the
vessels of the skin. Under physiological conditions the different
parts of the center may, of course, be acted upon separately.

Vasoconstrictor Reflexes — Pressor and Depressor Nerve
Fibers. — It is obvious that such a mechanism as that described
above is susceptible of reflex stimulation through sensory nerves,
and according to our general knowledge we should suppose that
a tonic center of this kind may have its tonicity increased (excita-
tion) or decreased (inhibition). Numerous experiments in phys-
iology warrant the view that both kinds of effects take place
normally. Those afferent nerve fibers which when stimulated
cause reflexly an excitation of the vasoconstrictor center, and
therefore a peripheral vasoconstriction and rise of arterial pressure,
are frequently designated as pressor fibers, or their effect upon the
circulation is designated as a pressor effect. Those afferent fibers,
on the contrary, which when stimulated cause a diminution in
the tone of the vasoconstrictor center and therefore a periph-
eral vasodilatation and fall of arterial pressure, are designated as
depressor nerve fibers, or their effect upon the circulation is a de-
pressor effect. Pressor effects may be obtained by stimulation of
almost any of the large nerves containing afferent fibers, but espe-

592

CIRCULATION OF BLOOD AND LYMPH.

cially perhaps of the cutaneous nerves. And there is abundance
of evidence to show that similar results can be obtained in man.
The pressor effect manifests itself by a rise in general arterial pres-
sure, if a sufficiently large region is involved, and by a diminution
in size of the organ involved. On the other hand, depressor effects
may also be obtained from stimulation of many of the large nerve
trunks. If one stimulates the central end of the sciatic nerve,
for example, one obtains a pressor effect on the circulation in most
cases, but under certain conditions a marked depressor effect fol-
lows the stimulation.* The simplest explanation of such a result
is that the nerve trunks contain afferent fibers of both kinds.
When we apply our electrodes to a nerve we stimulate every fiber
in it and the actual result will depend upon which group of fibers
exerts the stronger action, and this may vary with the condition

litr. -'•"' i -rapine curve of forearm. The volume of the arm was recorded

by mean 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 arc stimulated under some circumstances, the de-
pressor fibers under others. For instance, when the skin is exposed
bo cold it is blanched not by a direct, but by a reflex, effect. The
low temperature Stimulates (lie sensory (cold) libers in the skin,
and the nerve impulses thus aroused reflexly stimulate the vaso-
constrietor center, or ;i pari of it,, and cause blanching of the skin.
-iirc to high temperatures, on the contrary, Hushes the skin,
and in this case we may suppose thai the sensory impulses carried
by the heal nerves inhibit the tone of the vasoconstrictor center
and cause dilatation or flushing of Hie skin. So far as man is
concerned, experiments made with the plethysmograph show very
e Hunt, "Journal of Physiology," 18,381, 1895.

THE VASOMOTOR NERVES.

593

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. 245) ; and we may find an explanation of the value of the reflex
in the supposition that the rise of arterial pressure thus produced

Fig. 246.— Effect of stimulating the central end of the depressor nerve of the heart in
a rabbit. 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 portion
of the record reproduced. (Daivson.)

forces more blood through the brain (p. 608). 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

594 CIRCULATION OF BLOOD AND LYMPH.

a vasodilator center. Among the many depressor effects that
have been observed on' stimulation of afferent nerve fibers one
has amused especial interest — namely, that caused by certain
afferent fibers from the heart or from the aorta. So far as the
effect in question is concerned the physiological evidence indi-
cates that the fibers arise from the descending aorta ami it
might be more appropriate to speak of them as the depressor
nerve of the aorta.* These fibers in some animals — 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 ami ('yon (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. 246). 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. f Physiological experiments
indicate that the nerve plays an important regulatory role.J
When, for instance, blood-pressure rises above normal limits, it
may be supposed that the endings of this nerve in the aorta or
heart are stimulated by the mechanical effect, and the blood-
pressure is thereby lowered by an inhibition of t he I one of the con-
Btrictor center. Moreover, it has been shown by Einthoven I ha1
every heart beat sends up this nerve a series of nerve impulses,
that is, when the nerve is cut and the ends are connected with
a si ring-galvanometer, electrical variations occur synchronous
with the heartbeat (Fig. 271). To explain this result we can
on];.- assume that each heart beat stimulates sensory endings
in the heart itself or in the aorta, and that- the nerve impulses
thus transmitted to the medulla probably play a role in main-
taining the tonic activity of some of its centers, perhaps, as
Einthoven suggests, the Ionic activity especially of the cardio-

inhibitor) center.

1908

* See Ey fcer and Hooker, "American Journal of Physiology, " 21, '■'>"'■'>,
'us. ,ii o fcfl ter and Tschermak, "Archiv 1'. die gesammte Physiologic, "
!, 24, L902.

f See Porter and Beyer, ''American Journal of Physiology, " 4, 283, 1900;
; : . Bayli , Journal of Phy iology," I I, 303, 1893.

% Sewall and Steiner, "Journal of Physiology," 6, L62, L885.

THE VASOMOTOR NERVES. 595

A most suggestive example of the regulating action of the depressor nerve
is given by Sewall. When the carotids in a rabbit are clamped a variable
and not very large rise of arterial pressure is observed. If, however, the
depressor nerves are first cut, clamping the carotids causes an extraordinary
rise of arterial pressure. When the carotids are closed we may suppose that
the resulting anemia of the medulla stimulates the vasoconstrictor center
and thus tends to raise arterial pressure, but this effect is neutralized because
as the pressure rises the depressor fibers of the heart are stimulated. It
seems evident that during life the depressor fibers must exert a very important
regulating effect upon the circulation.

A similar nerve has been described anatomically in man, while
in animals like the dog, in which it is not present as a separate
anatomical structure, it probably exists within the trunk of the
vagus. If this latter nerve is cut in the dog and the central end
is stimulated a depressor effect is usually obtained.

Vasoconstrictor Centers in the Spinal Cord. — From the description of the
vasoconstrictor mechanism given above the probable inference may be made
that throughout the thoracic region the cells of origin of the preganglionic
fibers may, under special conditions, act as subordinate vasoconstrictor centers
capable of giving reflexes and of exhibiting some tonic activity. Numerous
experiments tend to support this inference. When the spinal cord is cut in
the lower thoracic region there is a paralysis of vascular tone in the posterior
extremities. If, however, the animal is kept alive the vessels gradually re-
cover their tone, although not connected with the medullary center. The re-
sumption of tone in this case may be attributed to the nerve cells in the lower
thoracic and upper lumbar region, since vascular paralysis is again produced
when this portion of the cord is destroyed. Finally, Goltz has shown that
when the entire cord is destroyed, except the cervical region (p. 155), vascular
tone may be restored finally in the blood-vessels affected. In this case the re-
sumption of tonicity must be referred either to the properties of the muscular
coats of the arteries themselves reacting to the stimulus of the internal pres-
sure, or to the activity of the sympathetic nerve cells that give rise to the
postganglionic fibers. Under normal conditions it seems quite clear that the
great vasoconstrictor center in the medulla is the important seat of tonic and
of reflex activity. If the connections of this center with the blood-vessels are
destroyed suddenly — for example, by cutting the cervical cord — blood-pressure
falls at once to such a low level, 20 to 30 mms. Hg., that death usually results
unless artificial means are employed to sustain the animal.

Rhythmical Activity of the Vasoconstrictor Center. —

Throughout life the vasoconstrictor center is in tone the intensity
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. 247), 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.
These latter waves are also due to a rhythmical action of the

596

CIRCULATION OF BLOOD AND LYMPH.

vasomotor center. During sleep, certain much longer, wave-like
variations in the blood-pressure also occur that are again due doubt-
less to a rhvthmical change of tone in the vasoconstrictor center.

/^x y**\ y/vx y*"%<
s \s \^r v/

Fig. 247. — Rhythmical vasomotor waves of blood-pressure in a dog (Traube-Hering
waves). The upper tracing (1) is the blood-pressure record as taken with the mercury
manometer; the lower tracing (2) is taken with a Hiirthle manometer. Seven distinct
respiratory waves of blood-pressure may be recognized on each large wave. {Dawson.)

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 arc 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 (tympanic nerve).
'.',. 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 moutli (lips, gums, and palate), nostrils, and the skin
Of the cheeks. These libers pass up the neck to (lie superior cervi-

ca] ganglion and thence by communicating branches reach the (!as-
serian ganglion and are distributed to the bucco-facial region in flu;
branches of the filth cranial nerve.* From the thoracic portion of

the sympathetic vasodilator fibers pass to (lie abdominal viscera by
way of I Ik: splanchnic nerves and to tin' limbs by way of the
branches of the brachial and lumbar plexuses, hut, the data regarding
I he dilator fibers lor these regions are QOtasyel entirely satisfactory.
Goltz and others have shown that dilator fibers are found in the
nerve: of the limbs, hut, the origin of these fibers from the sympa-
thetic chain has not, been demon: I rated.

* Sec " Recherchee exp6rimentales but le systeme nerveux vasomoteur,"
D&stre and Mforat, 1884.

THE VASOMOTOR NERVES. 597

4. In the nervi ergentes. Eckhard first gave conclusive proof that tha
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
vessel, and it is easy to see that when stimulated to greater con-
traction through the constrictor fibers it must cause a narrowing
of the artery. It is not so evident how the nerve impulses carried
by the dilator fibers bring about a widening of the artery. At
one time peripheral sympathetic ganglia in the neighborhood of
the arteries were used to aid in the explanation, but, since histo-
logical evidence of the existence of such ganglia is lacking, the
view that seems to meet with most favor at present is as follows:
The dilator fibers end presumably in the muscle of the walls of
the arteries, and when stimulated their impulses inhibit the tonic
contraction of this musculature and thus indirectly bring about a
relaxation. Dilatation caused by a vasodilator nerve fiber always
presupposes therefore a previous condition of tonic contraction in
the walls of the artery, this tonic condition being produced either
by the action of vasoconstrictor fibers or possibly by the intrinsic
properties of the muscle itself. In the nerves of the limbs, as
stated above, both vasoconstrictor and vasodilator effects may be
detected by stimulation. It has been shown that the separate
fibers may be differentiated by certain differences in properties.
Thus, if the peripheral end of the cut sciatic nerve is stimulated
by rapidly repeated induction shocks a vasoconstrictor effect is
obtained as shown plethysmographically by a diminution in volume
of the limb. If, however, the same nerve is stimulated by slowly
repeated induction shocks the dilator effect will predominate,*
indicating a greater degree of irritability on the part of these latter
fibers. After section of the sciatic nerve the vasodilators degen-
erate more slowly than the vasoconstrictors, and they retain
their irritability when heated or cooled for a longer time than
the constrictors. t

Vasodilator Center and Vasodilator Reflexes. — Since the

* Bowditch and Warren, "Journal of Phvsiologv, " 7, 439, 1886.

t Howell, Budgett, and Leonard. "Journal of Physiology," 16, 29S, 1894.

598 CIRCULATION OF BLOOD AND LYMPH.

vasodilator fibers from 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 ail normally connected with a single group
of nerve cells located in a definite part of the nervous system. The
dilator fibers in the facial, glossopharyngeal, and cervical sympa-
thetic (distributed through the trigeminal) all arise probably in the
medulla, but not, so far as is known, from a common nucleus.
Intimately connected with the question of the existence of a general
vasodilator center is the possibility of definite reflex stimulation
of the vasodilator fibers. As stated above, reflex dilatation of the
blood-vessels may be produced by stimulating various nerve trunks
containing afferent fibers. The depressor nerve fibers of the heart
give only this effect, and the sensor}- libers from certain other
regions, notably the middle ear and the testis, cause mainly, if not
exclusively, a fall of arterial pressure due presumably to vascular
dilatation. The sensory nerves of the trunk and limbs, when
stimulated by the gross methods of the laboratory, give either
reflex vasoconstriction or reflex vasodilatation, and, as was stated
above, there is reason to believe that these trunks contain two kinds
of afferent fibers, — the pressor and the depressor. The action of the
former predominates usually, but in deep anesthesia, and particu-
larly in those conditions of exposure and exhaustion that precede
the appearance of "shock," the depressor effect is most marked or,
indeed, may be the only one obtained. To explain such depressor
effects we have two possible theories. They may be due to reflex
excitation of the centers giving origin to the vasodilator fibers or to
reflex inhibition of the tonic activity of the vasoconstrictor centers.
The latter explanation is the one usually given, especially for the
typical and perhaps special effect of the depressor nerve of the heart.
This explanation seems justified by the general consideration that

in the two great vascular areas through whose variations in capacity
the blood-flow is chiefly regulated,- namely, the abdominal viscera
and the skin, — the vasoconstrictor fibers arc chiefly in evidence
and are, moreover, in constant tonic activity. On the other hand,
the fact that vasodilator fibers exist is presumptive evidence; that
they are Stimulated reflexly, since it. is by this means only that- they
can normally affect the blood-vessels. Some of the many depressor
effects occurring in the body must be due, therefore, to reflex

THE VASOMOTOR NERVES. 599

stimulation of the dilators and others to reflex inhibition of the
constrictors. It would be convenient to retain the name depressor
for the sensory fibers causing the latter effect, and to designate
those of the former class by a different name, such as reflex vaso-
dilator fibers.* Only experimental work can determine positively
to which effect any given reflex dilatation is due, but provisionally
at least it would seem justifiable to assume that dilatation by reflex
stimulation of the vasodilator fibers occurs in those parts of the
body in which vasodilator fibers are known to exist. Thus, the
erection of the penis from stimulation of the glans may be explained
in this way, also the congestion of the salivary glands during activity,
the blushing of the face from emotions, and possibly the dilatation
in the skeletal muscles during contraction. Gaskell and others
have given reasons for believing that the vessels in the muscles are
supplied with vasodilator nerve fibers, and Kleen f has shown that
mechanical stimulation of the muscles — kneading, massage, etc. —
causes a fall of arterial pressure.

Vasodilatation Due to Antidromic Impulses. — The existence of definite effer-
ent vasodilator fibers in the nerve trunks to the limbs has been made doubt-
ful by the work of Bayliss. This author has discovered certain facts which at
present tend to make the question of vasodilatation more obscure, but which,
when fully understood, will doubtless give us a much deeper insight into the
subject. Briefly stated, he has shownf that stimulation of the posterior roots
of the nerves supplying the lumbo-sacral and the brachial plexus causes vas-
cular dilatation in the corresponding limbs. He has given reasons for believing
that the fibers involved are afferent fibers from the limbs and that, therefore,
when stimulated they must conduct the impulses in a direction opposite to
the normal — antidromic. 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 cen-
tral nervous system. Bayliss gives reasons for believing that the limbs
receive no vasodilator fibers via the sympathetic system, and that either the
blood-vessels in this region are lacking altogether in such fibers or else the
afferent fibers function in the way described (see also p. 83).

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
Efferent vasomotor ) f1 *he m.edulla oblongata, and in constant

nerve fibers \ toni(? actlvlty-

II. 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.

* See Hunt, "Journal of Physiology," 18, 381, 1895.

f Kleen, " Skandinavisches Archiv f. Physiologie," 247, 1887.

t Bayliss, "Journal of Physiology," 26, 173, 1900, and 28, 276, 1902.

Afferent fibers giving
vasomotor reflexes.

600 CIRCULATION OF BLOOD AND LYMPH.

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 fillers. Cause vascular dilatation and
fall of arterial pressure from reflex inhibition
of the tonic activity of the vasoconstrictor
center, — c. g.. depressor nerve of heart.
III. Depressor (or reflex vasodilat or) 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
is diminished, while that through the rest of the body is increased
to a greater or less extent corresponding to the size of the area in-
volved in the constriction. When the blood-vessels of a given
organ are dilated the blood-flow through that organ is increased and
that through the rest of the body diminished more or less. The
adaptability of the vascular system is wonderfully complete, and
is worked out mainly through the reflex activity of the nervous
system exerted partly through the vasomotor fibers and partly
through the regulatory nerves of the heart.

Regulation of the Blood-supply by Chemical and Mechan-
ical Stimuli. — From time to time attention has been called to
the fact that the calibre of the blood-vessels may be influenced
otherwise than through the agency of vasoconstrictor and vaso-
dilator nerve fibers. Gaskell, for example, has shown that acids
in slight concent ration cause a vascular dilatation. Bayliss * has
recently generalized the facts of this kind, and has suggested that
in addition to the nervous regulation described in the preceding
pages there may be formed chemical substances of a definite char-
acter which exert a similar useful regulating action. As examples
of this influence, we have the lactic acid produced in muscles during
activity and probably also the carbon dioxid produced in this as
in other tissues. These substances may act to produce a local
dilatation during functional activity and thus provide the organ

with more blood at the time that it is needed. On the other hand,

the internal secretioo of the adrenal glands (adrenalin) and possi-
bly also of the infundibular portion of the pituitary gland have
the reverse effect, causing a vasoconstriction and thus tending to

maintain normal vascular tone. In a similar way it ifl probable that

the distension of the arteries by internal pres are acts as a me shani-
bimulus which lead- to increased tone and thus aid- in main-
taining a normal arterial ten-ion.

* Baylise in "Ergebnie e der Phy iologie," 1906, v., 319

CHAPTER XXXIII.

THE VASOMOTOR SUPPLY OF THE DIFFERENT
ORGANS.

There are three important organs of the body — namely, the
heart, the lungs, and the brain — in which the existence of a vaso-
motor supply is still a matter of uncertainty. A very great deal
of investigation has been attempted with reference to these organs,
but the technical difficulties in each case are so great that no entirely
satisfactory conclusion has been reached. A brief review of some
of the experimental work on record will suffice to make evident the
present condition of our knowledge.

Vasomotors of the Heart. — The coronary vessels lie in or on
the musculature of the heart. Any variation in the force of con-
traction or tonicity of the heart muscle itself will therefore affect
possibly the caliber of the arterioles and the rate of blood-flow in the
coronary system. At each contraction of the ventricles the coro-
nary circulation is probably interrupted by a compression of the
smaller arteries and veins, and the size of these vessels during dias-
tole will naturally vary with the extent of relaxation of the cardiac
muscle. Since stimulation of either of the efferent nerves supplying
the heart, vagus and sympathetic, affects the condition of the mus-
culature, it is evident at once how difficult it is to distinguish a
simultaneous effect upon the coronary arteries, if any such exists.
Newell Martin* found that stimulation of the vagus causes dilata-
tion of the small arteries on the surface of the heart as seen through
a hand lens. Moreover, when the heart is exposed and artificial
respiration is stopped the arteries may be seen to dilate before
the asphyxia causes any general rise of arterial pressure. Martin
interpreted these observations to mean that the coronary arteries
receive vasodilator fibers through the vagus. Porterf measured
the outflow through the coronary veins in an isolated cat's heart
kept alive by feeding it with blood through the coronary arteries.
He found that this outflow is diminished when the vagus nerve
is stimulated, and hence concluded that the vagus carries vasocon-
strictor fibers to the heart. MaasJ reports similar results also
obtained from cats' hearts kept alive by an artificial circulation
through the coronary arteries. Stimulation of the vagus slowed

* Martin, "Transactions Medical and Chirnrgical Faculty of Maryland,"
1891.

t Porter, "Boston Medical and Surgical Journal," January 9, 1S96.
% Maas, " Arehiv f. die gesammte Physiologie, " 74, 2S1, 1S99.

601

602 CIRCULATION OF BLOOD AND LYMPH.

the stream (vasoconstrictor fibers), while stimulation of the
sympathetic path quickened the flow (vasodilator fibers).
Neither Maas nor Porter gives conclusive proof that the heart
musculature was not affected by the stimulation. Wiggers
reports* that the effect of adrenalin upon a heart perfused
through the coronary arteries, but not beating, is to decrease the
flow, while upon the beating heart this effect is reversed, owing
to the action of the adrenalin upon the heart contractions.
Schaefer,t on the contrary, gets entirely opposite results. 'When
an artificial circulation was maintained through the coronary
system and the amount of outflow was determined, he found
that this quantity was not definitely influenced by stimulation
of either the sympathetic or the vagus branches. Moreover,
injection of adrenalin into the coronary circulation had no
influence upon the outflow, and since this substance causes an
extreme constriction in the vessels of organs provided with
vasoconstrictor fibers, the author concludes that the coronary
arteries have no vasomotor nerve fibers. It is evident from a
consideration of these results that the existence of vasomotor
fibers to the heart vessels is still a matter open to investigation.
Vasomotors of the Pulmonary Arteries. — The pulmonary
circulation is complete in itself and, as was stated on p. 481, it
differs from the systemic circulation chiefly in that the peripheral
resistance in the capillary area is much smaller. Consequently
the arterial pressure in the pulmonary artery is small, while the
velocity of the blood-flow is 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, bj
back pressure from the left auricle when the left ventricle is not
emptying itself as well as usual on account of high aortic presstire.
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, J
by comparing carefully the simultaneous records of the pressures
in flu' aorta and a branch of the pulmonary artery, came to the
conclusion that, the latter may be affected independently by stimu-
lation of the third, fourth, and fifth thoracic Spinal nerves, and
hence concluded that these nerves contain vasoconstrictor fibers

* Wiggers, "American Journal of Physiology," 1909. Proceedings of
the American Physiological Society.

| "Archive de cience biologiques, " LI, suppl. volume, 251, L905.
X Bradford and Dean, " Journal of Physiology, " 16,34, L894.

VASOMOTOR SUPPLY OF THE ORGANS. 603

to the pulmonary vessels, the course of the fibers being, in general,
that taken by the accelerator fibers to the heart, namely, to the
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. Plumiert
finds that the outflow through a perfused lung is diminished in
some cases by stimulation of the sympathetic branches to the lungs,
and also by the use of adrenalin. Under such conditions it is
necessary to defer a decision until more experiments are reported.
Regarding the vasomotors of the lungs, one can only say, as in
the case of the heart, that their existence has not been demonstrated.

The Circulation in the Brain and Its Regulation. — The
question of the existence of vasomotor nerves to the brain brings
up necessarily the larger question of the special characteristics of
the cranial circulation. The brain is contained in a rigid box so
that its free expansion or contraction with variations in the amount
of blood can not take place as in other organs and we have to con-
sider in how far this fact modifies its circulation.

The Arterial Supply of the Brain. — The brain is supplied through
the two internal carotids and the two vertebrals, which together
form the circle of Willis. It will be remembered also that the
vertebral arteries give off the posterior and the anterior spinal
arteries, which supply the spinal cord, and that the last-named
artery makes anastomoses along the cord with the intercostal arteries

* Brodie and Dixon, "Journal of Physiology," 30, 476, 1904.
f Plumier, "Journal de physiologie et de pathologie generate," 6, 665,
1904; see also "Archives internationales de physiologie," 1, 189, 1904.

604 CIRCULATION OF BLOOD AND LYMPH.

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

SKulL

<$ui arachnoid/' f

<5payce. '

Piaftlatir.
CerehruftL

Fig. 248. — 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 Milliliter of small emissary veins. In
some of (he lower animals -the dog, for instance — the main outflow

is into the externa] 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.

VASOMOTOR SUPPLY OF THE ORGANS.

605

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. 248). The capillary space between the arachnoid
and the dura, the so-called subdural space, may be neglected.
Between the arachnoid and the pia mater, however, lies the sub-
arachnoidal space more or
less intersected by septa of
connective tissue, but in free
communication throughout
the brain and cord. This
subarachnoidal space is filled
with a liquid, the cerebro-
spinal liquid, which forms a
pad inclosing the brain and
cord on all sides. The liquid
surrounding the cord is in
free communication with
that in the brain, as is indi-
cated in the accompanying
schematic figure (Fig. 249).
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 cisternal, which
are in communication one
with another by means of the
less conspicuous canals (see
Fig. 250) . 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,

.Break..

Cerebrv-Jfeutal
Liau-ui-

jj/nnai Columrv.
.Dura Mater.

Cerebri) Spinal liautd.

jJhinal Cord,

Fig. 249. — Diagram to show the connec-
tion of the subarachnoidal space in the brain
and the cord.

606

CIRCULATION OF BLOOD AND LYMPH.

pear-shaped protrusion of the arachnoidal membrane into the inte-
rior of a sinus, as represented schematically in Fig. 251. Through

these bodies the cerebrospinal
liquid is brought into close
contact with the venous
blood, the two being sepa-
rated only by a thin layer
of dura and the very thin
arachnoid. The number of
the Pacchionian bodies is
hardly sufficient to lead us
to suppose that they have a
special physiological impor-
tance. The cerebrospinal liq-
uid found in the subarach-
noidal space and the ventri-
cles of the brain is a very
thin, watery liquid having a
specific gravity of only 1.007
to 1.008. It contains only
traces of proteins and other
organic substances, which may vary under pathological condi-
tions. It is thinner and more watery than the lymph, resembling
rather the aqueous humor of the eye. The amount of this fluid

Fig. 2nii — Diagram to show the location
of the cisternse and canals of the subarach-
noidal space. — (Poirier and Charpy.)

I i;-. 251 Schema to haw the relations <>f the Pacchionian bodies to the sinuses:
d, d, I "i'i "i the dura mater, inclosing a sinus between them J ■>>.'<., the blood in the
.■inn ; a, the arachnoidal membrane; i>. the pia mater; I'"-, the Pacchionian body as
a projection "i the arachnoid into the blood sinu ,

present normally is difficult bo determine. Various figures have
been given, but il is usually stated to amount to 60 t<> 80 <•.<•. If

VASOMOTOR SUPPLY OF THE ORGANS. 607

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. 252. A system with an artery, capillary area,

608

CIRCULATION OF BLOOD AND LYMPH.

.

d

V

t/

and a vein is represented as inclosed in a rigid box and surrounded by an
incompressible liquid. According to tbe conditions prevailing in the body,
the pressure in the interior of .4. and its branches is much higher than in V.
If, now, the pressure in A is increased the greater pressure brought to bear
on the walls will tend to expand them; a greater pressure will thereby be
communicated to the outside liquid, which, in turn, will compress the veins
correspondingly. The expansion on the arterial side is made possible by a

corresponding diminution on the
venous side where the internal
pressure is least.

The recorded measure-
ments of the intracranial
pressure show that it may
vary from 50 to 60 mms. of
mercury, obtained during the
great rise of pressure following
strychnin poisoning, to zero or
less, as obtained by Hill * from
a man while in the erect pos-
ture. In this position the
negative influence of gravity
is at its maximum.

The Effect of Variations
in Arterial Pressure upon
the Blood-flow through the
Brain. — Quite a number of
observers f have proved ex-
perimentally that a rise of
general arterial pressure is fol-
lowed, not only by an increase
in the intracranial tension, but
also by an increased blood-flow
through the brain. There has
been much discussion as to
whether a rise of arterial pressure in the basilar arteries can cause
any actual increase in the amount of blood in the brain or whether
it expresses if self solely or mainly as an increased amount of flow.
In the other organs of the body, except perhaps the bones, a general
lie 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, 1 be' increased capacity of the vessels — is of no value; the
important tiling is the increase in the quantity of blood flowing

* Bayliss and Hill, "Journal of Physiology," is, 356, 1895
t See Gartner and Wagner, "Wiener med. Wochenschrift," 1SS7; de
Boeck and Verhorgen, "Journal de M6decine, etc.," Brussels; Roy and Sher-
rington, "Journal of Physiology," ll, 85, 1890; Reiner and Schnitzler,
"Archiv f. exp. Pathol, u. Pharmakol.," 38, 249, 1897.

Fig. 252. — Schema to represent the
transmission of arterial pressure through
the brain substance to the veins: A, The
artery, V, the vein, represented as entering
into and emerging from a box with rigid
walls and filled with incompressible liquid ;
c, c, the intervening area of small arte-
ries, etc. An expansion of the walls of
the arterial system by the pulse wave or by
a rise of arterial pressure increases the pres-
sure on the surrounding liquid and this is
transmitted through the liquid to the walls
of the veins and compresses them, since at
this point of the circuit the intravascular
pre ure is low.

VASOMOTOR SUPPLY OF THE ORGANS. 609

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. 249) 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. 253. — Simultaneous record of puise 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
Hiirthle 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. 253. 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.
39

610 CIRCULATION OF BLOOD AND LYMPH.

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 I here should he 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, Franeois-Franck, and others,! on the other

* Howell, "American Journal of Physiology. " I, 57, L898.

t See Roy and Sherrington, Bayliss and Hill, Hill, Gaertner and Wagner,
inc. rii ., and 1 1 ill and MacLeod, "Journal of Physiology, " 2<>, 394, 1901.

% Httrthle, "Archiv f. diegesammte Physiologie, 4 1, 674, L889; Franeois-
Franck, "Archives de physiol. normale h pathologique, " L890; Cavazanni,
"Archives itah'ennes de biologie," l'.», 214, 1898; M filler and Siebeck, "Zeit-
Bchrifl r. exp. Path. a. Therapie," 4, 57, 1907.

VASOMOTOR SUPPLY OF THE ORGANS. 611

hand, have obtained results, especially from stimulation of the
cervical sympathetic, which indicated local vasoconstriction or vaso-
dilatation in the brain. It would seem, however, that these latter
observers have not excluded the possibility that the variations
in pressure obtained by them were due to reflex effects upon the
blood-vessels of the body, especially as Frangois-Franck has
shown that the sympathetic in the neck contains afferent fibers
which give such reflexes.* In experiments made upon an
isolated brain (in the skull) perfused with an artificial circulation,
Wiggers f states that addition of adrenalin caused a diminution
in the outflow from the organ, thus showing that the adrenalin had
caused a constriction somewhere in the circuit. If, as some authors
believe, adrenalin acts only on plain muscle that is innervated by
sj^mpathetic nerve fibers this result furnishes indirect evidence
for the existence of such fibers in the case of the brain vessels.
Using the same method this author states that electrical stimu-
lation applied directly to the sheath of the internal carotid at
its entrance into the skull also causes a decrease in the outflow,
a fact which would indicate the existence of constrictor fibers
running in the sheath of this artery. As another argument
in favor of the presence of vasomotor fibers, it may be men-
tioned that a number of observers — Gulland, Huber, Hunter J —
have demonstrated that the vessels of the brain are provided
with perivascular nerve plexuses. It must be admitted, how-
ever, that this histological fact is not satisfactory unless it is
supplemented by experimental evidence. Judged from this
latter standpoint, we have no convincing proof at present of
the existence of cerebral vasomotors, although it must be
granted that recent evidence rather tends in that direction.
If vaosmotors are present it is possible that they may serve to
control the distribution of blood within the cerebral area, while
the general supply to the brain as a whole is increased or decreased
by a mechanism of another sort described by Roy and Sherring-
ton. 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

* Frangois-Franck, "Journal de phys. et de path, gen.," 1, 724, 1889.
t Wiggers, '"American Journal of Physiology," 1905, 14, 452; and 21,
454, 1908.

t See Hunter, "Journal of Physiologie, " 26, 465, 1902.

612 CIRCULATION OF BLOOD AND LYMPH.

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 plethysmography 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
providing a greater flow to the central organ at the time that it is
in activity may 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 tho spinal cord in the
upper thoracic nerves, first to the fifth or sixth, emerge by the rami
communicantes to the sympathetic chain, in which they pass upward
and end, for the most part, in the superior cervical ganglion. From
this ganglion they are distributed, by various routes, as postgan-
glionic fibers. In one interesting instance the constrictor fibers
for the head were supposed to take a somewhat different course.
it was shown by Schiff, long ago, thai in the rabbil the ear receives
vasomotor fibers from the auricularis magnus nerve, a branch of the
third cervical nerve. Later investigations indicate (Meltzer) that
the ear, in fact, receives most of its vasoconstrictor fibers by this
route. Fletcher, however, has shown that these fibers do not emerge
from the brain in the roots of the third cervical, but rather in the
general outflow from the thoracic region. After reaching the sym-
pathetic chain these particular U\>rr* 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

VASOMOTOR SUPPLY OF THE ORGANS. 613

vasodilator fibers for the head are supplied in part by way of the
cervical sympathetic, following the same general path as the con-
strictors, and in part by way of the cranial nerves (seventh, ninth)
and the sympathetic ganglia with which they connect. According
to Langley, the outflow of the seventh nerve passes to the spheno-
palatine ganglion, whence as postganglionic fibers they accompany
the branches of the superior maxillary nerve and cause vasodila-
tation in the membrane of the nose, soft palate, tonsils, uvula, roof
of mouth, upper lips, gums, and pharynx. The well-known dilators
of the submaxillary and sublingual glands are contained in the
chorda tympani branch of the seventh nerve; the preganglionic
fibers terminate probably in the small peripheral ganglia connected
with these glands. The fibers that emerge in the ninth pass in
part directly to the tongue and in part terminate first in the otic
ganglion, whence they are distributed with the branches of the
inferior maxillary to the lower lips, cheeks, gums, and parotid and
orbital glands. Dastre and Morat describe the vasodilators in the
cervical sympathetic as reaching the fifth cranial nerve by com-
municating branches from the superior cervical ganglion and state
that they cause dilatation of the bucco-facial region, — that is,
the lips, the gums, cheeks, palate, nasal mucous membrane, and
the corresponding skin areas.

The Trunk and the Limbs. — The vasoconstrictor fibers for
these regions are distributed, so far as is known, chiefly to the skin.
They are all derived immediately from the sympathetic chain and
ultimately from the outflow in the anterior roots of the thoracic
and lumbar spinal nerves. Those for the upper limbs arise from
the midthoracic region chiefly (fourth to ninth thoracic nerves),
those for the lower limbs arise in the nerves of the lower thoracic
and upper lumbar region (eleventh, twelfth, thirteenth thoracic
[dog] and first and second lumbar). The vasodilator fibers in the
nerves of the limbs have been demonstrated frequently, as already
explained. Whether or not these fibers also pass through the
sympathetic system, following the same general course as the
vaso constrictors, has not been shown conclusively. The most
definite work at present (Bayliss) indicates that the vasodilator
effect is directly caused in some unknown way by fibers found
in the posterior roots of the nerves forming the brachial and the
sciatic plexus. The unsatisfactory explanations offered for this
result have been referred to (p. 599).

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

61-4 CIRCULATION OF BLOOD AND LYMPH.

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-
stricter fibers from the same nerve. Most of the vasomotor fibers to
the kidney of the dog emerge from the cord in the roots of the
eleventh, twelfth, and thirteenth thoracic nerves, and those for the
liver (Francois-Franck and Hallion) come from about the same
region. The vasoconstrictors to the spleen are said to leave the
spinal cord chiefly in the anterior roots of the sixth, seventh, and
eighth thoracic nerves.

The Genital Organs. — Both vasoconstrictor and vasodilator
fibers have been discovered for the external genital organs (penis,
scrotum, clitoris, vulva). . The vasoconstrictors arise in the dog
from the thirteenth thoracic to the fourth lumbar nerves, pass over
to the sympathetic chain, and thence reach the organs either by
way of the hypogastric nerve and pelvic plexus or by way of the
sacral sympathetic ganglia and their branches to the pudic nerves.
The vasodilator fibers arise from the sacral spinal nerve, being the
best known of the sacral autonomic system. They enter the ner-
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,
leferens, 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-
peeially has given evidence of the existence of vasomotor libers in
t In- muscles. I [e concludes, as the result of his work, thai I he blood-
vessels of the muscles receive both vasoconstrictor and vasodilator
liber.-, but thai the latter greatly predominate, at least, their
physiological effeel Is much more evident iii experimental work.
As proof of the pr< ence of dilator fibers he gives such results as
these: The mylohyoid muscle of the frog is thin enough to be

• For the bibliography of the vasomotor apply to the various organs see
Langley, "Ergebni e aer Physiologie," vol. ii., pari a., p. 820, 1903.
keil, Journal of Physiology," 1,262, L878 7'.).

VASOMOTOR SUPPLY OF THE ORGANS. 615

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 given evidence to
show (p. 599) that the dilator effect in the limbs is due to the anti-
dromic action of afferent fibers, it is evident that this important
question needs reinvestigation. Various physiologists have shown
that muscular activity is accompanied by an increase in the blood-
flow through the muscle, as we should expect, but it remains uncer-
tain whether this result is brought about solely by an increased
activity of the heart or by the combined effect of vasodilatation and
increase in heart-work. Kaufmann * takes this latter view in con-
sequence of some interesting results obtained upon horses. He
measured the blood-flow through the masseter muscle and the
elevator of the lip in a horse in which the muscles were exercised
normally by the act of eating. The blood-flow was increased as
much as five times over that observed during rest, and that this
increase was due in part at least to a local dilatation seems to be
proved by the fact that the blood-pressure in the artery supplying
the muscle fell, while that in the vein rose. While, therefore, our
experimental knowledge of the vasomotors of the muscles needs
further investigation, we may provisionally accept the view ad-
vocated by Gaskell, — namely, that the vasomotor supply to the
muscles consists essentially of dilator fibers and that these fibers
are brought into action reflexly whenever the muscles contract,
thus providing an increased blood-flow in proportion to the func-
tional activity. It should be added that the local dilatation in
the muscles during activity may be due also to the chemical action
of the (acid) metabolic products on the blood-vessels (p. 600).

The Vasomotor Nerves to the Veins. — It is assumed in physi-
ology that the vasoconstrictors and vasodilators end in the muscula-
ture of the small arteries. The veins also have a muscular coat,
and it is possible that if this musculature were innervated from
the central nervous system we should have another efficient factor
in controlling the blood-flow. Mall has given very clear proof that

* Kaufmann, "Archives de physiologie normale et pathologique," 1892,
pp. 279 and 495.

616 CIRCULATION OF BLOOD AND LYMPH.

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 physiolog-
ically 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 Bancroft, J 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, although it is very evident that if such a system
exists, controlling the tonicity of the veins, it must exert a
very important influence in regulating the supply of blood to the
heart . §

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 jugular veins the pressure is very-
low; in the vein, in fact, it may be zero or even negative as compared with
the atmospheric pressure. 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 pressure in the latter is lower
than that in the lymphatic- duct. At the other extremity 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 nims. Hg,
the pressure in the liquid of the surrounding tissues must also be consider-
able. The tissues are, in fact, in a condition of turgidity owing to the
pressure of the lymph in the tissue-spaces. This difference in pressure
at the two ends of the lymphatic system is the main constant factor in mov-
ing the lymph. It is obvious that in the long run it is dependent, upon the

pressure within the blood-vessels and therefore upon the force of the heart
Deal . The cont ract ion- of t Ik; heart supply t he energy, not only for the move-
men i of the blood, bul also for the much slower movement of t he lymph. The
circulation of the lymph is aided, however, by many accessory factors. In
Some animal- t here are genuine lymph hearts upon t he course of t he vessels, —

that i-. pulsatile expansions of the lymph vessels whose force of heat., con-
trol led by valves, i- aired ly applied to moving the lymph. No such struct ures
an- found in the mammalia, bul 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 How of lymph. The

(low of lymph or chyle in the intestinal area is also, without, doubt, greatly

I d by I he peri -la It ic and especially by I he rhyl Imiic cont ract. ions of the

musculature ol 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

* \l.dl, "Archiv f. Physiologic," p. 109, 1892.

Loy and Sherrington, "Journal of Physiology," II, 85, 1890.
1 Bancroft, " American Journal of Physiology," I, -177, 1898.
3ee I lenderson, " American Journal of Physiology," 23, '■> 15, 1909.

VASOMOTOR SUPPLY OF THE ORGANS. 617

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 b}r 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, for
the development of its energy requirements. On the other
hand, one of the universal end-products of this metabolism
is carbon dioxid. Hence, respiration 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 appara-
tus 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 meanl 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, thai is, the part taken by theoxygen 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 he considered, therefore, more appropriately

in the section on nutrition. In the present section attention will he

directed to the heautiful means that have been adapted to the pur-
of supplying the tissues with oxygen and of removing the
carbon dioxid.

618

HISTORICAL. 619

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
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

620 PHYSIOLOGY OF RESPIRATION.

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 clue 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 Belmont (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 lor life mid for combustion. Be showed, moreover,
thai :ur that had been repeatedly inspired was no longer capable
of maintaining life. Robert Booke (1636-1703) introduced a
method of artificial respiration by means of a bellows, and demon-

HISTORICAL. 621

strated by sending a continuous stream of air through the lungs
that the respiratory movements of these organs are in themselves,
as a mechanical process, in no wise an essential feature of respiration.
John Mayow in 1688-1674 discovered that air is not a simple ele-
ment, but contains a definite substance necessary to life and to
combustion. He designated this substance as the nitro-aerian
vapor or nitrous particles, because he believed that the same
substance is present in condensed form, as it were, in common niter,
having found that combustion is possible even in a vacuum in the
presence of niter.

In the eighteenth century, as is shown in the work of the great
physiologist, Haller, the theories of respiration were in many
respects in a most unsatisfactory state. The new facts that had
been discovered made the old views untenable, but were not in
themselves sufficient to explain clearly what actually takes place.
Such periods of uncertainty and dissatisfaction are frequent enough
in the history of science. In 1757 Joseph Black rediscovered carbon
dioxid, calling it fixed air, and showed that it is present in expired
air. A little later Priestly discovered and isolated oxygen and
nitrogen; but, under the influence of an erroneous view of combus-
tion that had been advanced by Stahl, was unable to give his
discoveries a clear and satisfactory application. The final step
in this progress was made by the wonderful work of Lavoisier
between the years 1771 and 1780. He made correct analyses of
air and of carbon clioxid, 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 physio-
logical oxidations.

After Lavoisier the chief positive advances that have been made
have been in reference to the condition of the gases in the blood.
By means of the gas-pump Magnus (1837) obtained these gases
quantitatively and thus procured data which, as Liebig showed,
demonstrate that the oxygen is held in the blood, not in simple
solution, but in some form of chemical combination, probably
with the red corpuscles. Finally it was shown by Stokes and
Hoppe-Seyler that the oxygen is held in definite chemical com-
bination with the hemoglobin. The nature of the combination of
the carbon dioxid in the blood is not yet entirely understood, while
the actual nature of physiological oxidations — that is, the part
taken by the oxygen in the chemical reactions of living matter—
is one of the great problems of nutrition which may need many years
for solution.

CHAPTER XXXIV.

THE ORGANS OF EXTERNAL RESPIRATION AND THE
RESPIRATORY MOVEMENTS.

Anatomical Considerations. — Some of the anatomical ar-
rangements in the lungs which have an immediate physiological
interest may be recalled briefly. The structures of the trachea and
bronchi are admirably adapted to their functions as air tubes, in that
the walls possess flexibility combined with rigidity. The lining of
ciliated epithelium throughout the air passages is of importance,
primarily it may be assumed, in removing mucus and foreign
material from these passages. The smaller bronchi possess a dis-
tinct muscular layer, and, as we shall see, this musculature is under
the control of a special set of nerve fibers through whose reflex
activity the capacity and resistance of the bronchial system may bo
modified. The smallest bronchioles are expanded into a s}>-stem 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
thifi 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, vena1 cava', azvgos vein,
trachea, esophagus, thoracic duct, various nerves, and lymph
glands. All these organs, therefore, lie outside the lungs. A
schematic view of these relations is represented in Fig. 254.

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

fi'J2

EXTERNAL RESPIRATION AND RESPIRATORY MOVEMENTS. 623

represented in Fig. 254, 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. It is to be remembered, of course, that the
interior surface of the lungs is multiplied greatly by the subr
division into alveoli. It is
estimated that the entire
inner surface of the lungs
amounts to as much as 90
square meters, over one hun-
dred times the skin surface
of the body. The atmos-
pheric pressure on the interior
surfaces of the lungs expands
these structures under normal
conditions until they fill the
entire thoracic cavity not
occupied by other organs.
However 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
occupied. If the wall of the
thorax is opened at any
point so as to make commu-
nication with the outside air, or, if the wall of the lung is pierced
so that the air can communicate with the pleural cavity from
the inside, then at once the lungs shrink in size, since the atmos-
pheric pressure is then equalized on the outside and the inside
of the sacs. We may consider, therefore, that the thoracic cavity
is much larger than the lungs, and that the latter are blown
out to fill this cavity by the atmospheric pressure on the inside.
The Normal Position of the Thorax — Inspiration and Expira-
tion.— During life the size of the thorax is continually changing with
the respiratory movements. But the size and position taken at the
end of a normal expiration may be regarded as the normal position
of the thorax; that is, its position when all of the muscles of respira-
tion are at rest, and substantially, therefore, the position of the
thorax in the cadaver. Starting from this position, any enlarge-
ment of the thorax constitutes an active inspiration, the result of
which will be to draw more air into the lungs ; while starting from
the normal position any diminution in the size of the thorax
constitutes an active expiration, which will drive some air out of the
lungs. It is evident, however, that after an active inspiration the

Fig. 254. — 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.

624 PHYSIOLOGY OF RESPIRATION.

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 ma}'
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 ma3r 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 anatoiii}- of the
diaphragm it is evident that its fixed attachment is found in its
muscular connections with the lumbar vertebrae, the ribs, and the
ensiform cartilage. From these attachments the muscular sheet
extends anteriorly along the walls of the thorax and then bends over
to form the arch which ends in the central tendon. This latter
structure is not entirely free, since it is attached to the pericar-
dium of the heart ; but, relatively, it is the movable portion of
the diaphragm. Speaking generally, a contraction of the dia-
phragmatic muscle draws the central tendon downward toward the
abdominal cavity and therefore enlarges the chest in the vertical
diameter, while an increase in the thoracic cavity around the
periphery of the diaphragm is caused also by the flattening of the
muscular arch. Two results follow this movement: The lungs are
expanded exactly in proportion as the cavity enlarges. There is,
of course, at no time any space between the lungs and the dia-
phragm: as the latter moves downward the lungs follow because of
the excess of pressure on their interior. Although ordinarily we
speak of the new air being sucked into the lungs during this move-
ment, it is, of course, strictly speaking, forced in by the pressure of
i he outside atmosphere. ( )n the oilier 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 -it ron» 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 wonld tend to antagonize the
inspiratory action of the diaphragm, and other muscles are appar-
ently broughl into play to prevent this result. Asstated below, the

EXTERXAL RESPIRATION AND RESPIRATORY MOVEMENTS. 625

Fig. 255. — Sixth dorsal vertebra and
rib. — (Reickert.)

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 saving
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 ah 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. 255).
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 ever)'
movement of the rib up or down would
decrease the size of the thorax and there-
fore cause an expiration. As a matter
of fact, however, the ribs slant downward,
so that if elevated the sternal end is car-
ried farther away from the sternum and
the chest is enlarged in the dorsoventral
direction (see Fig. 256). Moreover, as the rib moves upward there
40

— 1*£

S

Fig. 256. — 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.

626 PHYSIOLOGY OF RESPIRATION.

is an obvious enlargement of the chest in the lateral diameter.
This result may be referred to two causes: In the first place, the
axis of the rotation of the ribs, — that is, the line joining the head
and the tubercle of the rib is inclined downward so that the plane
of rotation, which is, of course, at right angles to this axis, will be
inclined outward. As the rib is moved upward, therefore, it must
also move outward. Secondly the cartilaginous ends of the ribs are
fixed at the sternum so 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 be noted. In
other cases, however, it is necessary to make use of the method
first suggested by Newell Martin, — namely, the determination
whether the contraction of the muscle in respiration occurs simul-
taneously with that of the diaphragm or alternately with it. In the
former case it is inspiratory, in the latter expiratory. The following
muscles may be classed as inspiratory: Levatore costarum. They
arise from the transverse processes of the seventh cervical and first to
eleventh thoracic vertebra? 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
of the cervical vertebrae and arc inserted into the first and
second ril)S. M . slrrno-clcido-mfisloidcus 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. scrratus
posticus superior extends from the spinous processes of the lower

cervical and upper dorsal vertebras to the second to fifth rib.

The Muscles of Expiration. -Expiration — that is, diminution

* Hough, "Studies from the Biological Laboratory. John Hopkins
i'iuvit it.v." r>, oi, 1893, and Bergendal and Bergman, " Skandinavwchea
Archiv f. Phy iobgie," 7, L78, 1896.

EXTERNAL RESPIRATION AND RESPIRATORY MOVEMENTS. 627

iu size of the thorax — may also be produced in two ways: First,
by forcing the diaphragm farther into the thoracic cavity. This
result is obtained, not by any direct action of the diaphragm, but
by contracting the muscular walls of the abdomen, the external and
internal oblique, the rectus, and the transversus. The contraction
of these muscles, which form what has been called the abdominal
press, raises the pressure in the abdomen and this, acting upon the
under surface of the diaphragm, forces it up into the thorax, pro-
vided the glottis is open. If the glottis is kept closed firmly the
increased abdominal pressure is felt mainly upon the pelvic organs,
and this effect is observed in micturition, defecation, and parturition.
Second, by depressing the ribs. The muscles which may be sup-
posed to exert this action are as follows: M. inter xostales 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 them, transversus thoracis is found
on the interior of the thorax on the anterior wall. Its fibers pass
from the sternum, running upward and outward, to be inserted into
the third to sixth rib. The expiratory action of this muscle was
demonstrated by Hough according to the method of Martin. M.
iliocostalis lumborum. The anatomical attachments of this muscle
are such as would enable it to depress the ribs; but its functional
activity in expiration has not been demonstrated. The m. serratus
posticus inferior and m. quadratus lumborum are both placed
anatomically, especially the former, so that their contractions
serve to depress the ribs. It has been suggested, however, that
they may act in forced inspirations so as to antagonize the ten-
dency of the diaphragm to pull the lower ribs inward. Whether
they really act with the diaphragm or alternately with it can only be
determined by actual experiment.

Quiet and Forced Respiratory Movements; Eupnea and
Dyspnea. — Our respiratory movements vary much in amplitude,
and the muscles actually involved differ naturally with the extent
of the movement. In general, we distinguish two different forms of
breathing movements. The ordinary quiet respirations, made
without obvious effort, form a condition of respiration designated
as eupnea. Difficult or labored breathing is known as dyspnea.
It is impossible to draw a sharp line between the two. There are
many degrees of dyspnea, and doubtless in quiet breathing the
amplitude of the movements may vary considerably before they
become distinctly dyspneic. In all conditions of eupnea the chief
point to bear in mind is that the expiration is entirely passive.
* Martin and Hartwell, "Journal of Physiology," 2, 24, 1879.

6*2$ 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 kings, the weight and torsion of
the ribs, etc. As soon as the breathing movements become at all
forced the action of the above-named inspirator}' 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 dvspneic 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 tins 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
facl thai 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 lias been a (|iiesfion whether I his difference is a
genuine gexual distinction or depends simply upon differences
in dress. Hutchinson inclined to the view that if forms what we
should call a secondary sexual characteristic, and that its physio-
Logical value for woman lies in I he fact that provision is thus made,
as it were, against the period of pregnancy, lie states (hat in

twenty-four young girls examined between the ages of eleven and
fourteen the eosfal type was present, although none of them had

* See Hutchinson, article on "Thorax," Todd's "Cyclopaedia of Anat*
omy iui'I Physiology, " L849.

EXTERNAL RESPIRATION AND RESPIRATORY MOVEMENTS. 629

worn tight dress. Later observers, however (Mays, Kellogg, and
others), state that Indian and Chinese women who have not worn
tight dress exhibit the abdominal type, and the same statement is
made regarding civilized white women who habitually wear loose
clothing. It would appear, therefore, that the assumption of the
costal type by women in general is due to the hindrance offered by
the clothing to the movements of the abdomen. From an exami-
nation of four hundred and seven cases Fitz * concludes that when
the restricting effect of dress is removed there is little or no differ-
ence in the type of respiration in the two sexes. The natural type
is one in which " the movement is fairly equally balanced between
chest and abdomen, the abdominal being somewhat in excess."
When the respiration becomes dyspneic it takes on a distinctly
costal type, and Fitz and others have shown that for an equal in-
crease in girth the thoracic movements cause a greater enlargement
of the lungs.

Accessory Respiratory Movements. —In addition to the mus-
cles whose action directly enlarges or diminishes the capacity of the
thorax certain other muscles connected with the air passages con-
tract rhythmically with the inspirations, and may be designated
properly as accessory muscles of inspiration. The muscles es-
pecially concerned are those controlling the size of the glottis and
the opening of the external nares. At each inspiration the elevators
of the wings of the nose come into play. This movement occurs in
normal breathing in many animals, such as the rabbit and horse,
and in some men, while in dyspneic breathing it is invariably
present. The useful result of the movement is to reduce the resis-
tance to the inflow of air. So in many animals the glottis is dilated
at each inspiration by the contraction of the posterior crico-aryte-
noid muscles, and in man also this movement is evident when
the breathing is at all forced. The useful result in this case also is
a reduction in the resistance offered to the inflow of air.

The Registration of the Rate and Amplitude of the Respira-
tory Movements. — Many methods are employed to register the
rate or amplitude of the respiratory movements. Upon man the
amplitude may be measured directly by a tape placed at different
levels to ascertain the increase in girth, or it may be recorded by
some form of lever or tambour applied to the chest or abdomen.
A convenient instrument for this purpose is the pneumograph
described by Marey, which is illustrated and described in Fig. 257.
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.

630 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. 257. — Figure of Marey's pneumograph. — (Verdin.) The instrument consists of
a tambour (/), 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. 268. Curve of QOimal respiratory movements. — (Marc//.) Curve A, full line,
repret«Mii the movements when the re piration is entirely normal. Downstroke, Inspira-
tion; upstroke, expiration. Curved dotted line, represents the increased amplitude "f the

movement , light dy.spn i ..I by l>n-;i I liing 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 18 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 .'it I In- Other end to a tambour may be passed down

EXTERNAL RESPIRATION AND RESPIRATORY MOVEMENTS. 631

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. 258. 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. 259. 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

_ Fig. 259— Wintrieh 's modifi-
cation of Hutchinson's spirometer.
— (Reichert.)

632 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-
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 complemented 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, hut not quite completely. Before
the air cells arc entirely emptied the small bronchi leading to them
collapse and I heir walls adhere with sufficient force to entrap a little
air in I lie alveoli. It is on this account thai the excised lungs float

in water ami arc 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 ha.- constituted, therefore, one of the farts 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 brathea, by an accident or by pathological conditions, the

air caughl in them may be completely absorbed, after a certain

interval, by the circulating blood.

EXTERNAL RESPIRATION AND RESPIRATORY MOVEMENTS. 633

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, sometimes known as the "dead space" of the lungs, since
the air filling this space is not useful in the respiratory processes.
According to observations founded partly on measurements of
casts of the tree and partly upon physiological determinations
made by breathing air poor in oxygen, it would seem that this
volume may be reckoned at 140 c.c* At each inspiration, there-
fore, at least 360 c.c. of air penetrate into the alveoli, and if evenly
disseminated through the lungs add about -fa to the volume of
each alveolus. Once in the alveoli, diffusion must tend to spread
the tidal air rapidly, and that this occurs is shown by an interesting
experiment performed by Grehant. He breathed in 500 c.c of
hydrogen instead of air and then examined the amounts of hy-
drogen breathed out in successive expirations. Only 170 c.c.
were recovered in the first expiration, 180 c.c in the second, 41 in
the third, and 40 in the fourth.

Artificial Respiration. — In laboratory experiments artificial
respiration is employed frequently after the use of curare ; when it is
necessary to open the chest; after cessation of respirations from
overdoses of chloroform or ether, etc The method used in almost
all cases is the reverse of the normal procedure, — that is, the lungs
are expanded by positive pressure (pressure in excess of atmos-
pheric). A bellows or blast worked by hand or machinery is con-
nected with the trachea and the lungs are dilated by rhythmical
strokes. Provision is made for the escape of expired air by the use
of valves or by a side hole in the tracheal cannula. Numerous
forms of respiration pumps have been devised for this purpose.

In cases of suspended respiration in human beings from drown-
ing, electrical shocks, pressure upon the medulla, etc., it is necessary
to use artificial respiration in order to restore normal breathing.
Bellows ordinarily cannot be used in such cases. Some method
must be employed to expand and contract the chest alternately, and
several different ways have been devised. The Marshall Hall
method consists in placing the subject face down and rolling the
body from this to a lateral position, making some pressure upon the
back while in the prone position. The Sylvester method, which is
frequently used, consists in raising the arms above the head and
then bringing them down against the sides of the chest so as to
compress the latter. The Howard method consists in simply com-
* See Loewy, " Archiv f. die gesammte Physiologie, " 58, 416.

634

PHYSIOLOGY OF RESPIRATION.

pressing the lower part of the chest while the subject is in a supine
position. Schaefer. who has recently compared these different
methods, suggests one of his own, which seems to be effective, saves
labor, and is less injurious to the subject.* He describes it as fol-
lows: "It consists in laying the subject in the prone posture,
preferably on the ground, with a thick folded garment underneath
the chest and epigastrium. The operator puts himself athwart or
at the side of the subject, facing his head (see Fig. 260) and places
his hands on each side over the lower part of the back (lowest ribs).
He then slowly throws the weight of his body forward to bear upon

^^^

r

PK' j

_ j

«-~.^r

T^B

Unf

Fig. 260.-

-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. 261.

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
nasal cavities. If the air passages are abnormally constricted at

635

Fig. 261. —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.

636 PHYSIOLOGY OF RESPIRATION.

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 nuns, 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
ie 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,261). Theheart
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 denned as intra-
pulmonic pressure minus the elastic pull of the lungs, and since;

under usual conditions I he int mpiihnnnic pressure is equal to that

PRESSURE CONDITIONS IN LUNGS AND THORAX. 637

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 Donder's method of attaching a manom-
eter to the trachea and then opening the thoracic walls so as to
allow the atmosphere to press upon the exterior face of the lungs.
In this way the elastic force of the lungs is determined, and, as
explained above, this is equivalent to the negative pressure. Second,
by thrusting a trocar through the thoracic wall so that its open end
may lie in the pleural or mediastinal cavity, the other end being
appropriately connected with a manometer. The older observers
(Hutchinson) also made experiments upon freshly excised human
lungs, determining their elastic force when distended by known
amounts of air. The figures obtained by these different methods
have shown some variations, but the following quotations give
an idea of the average extent of this negative pressure. Heynsius,*
making use of the figures obtained by Hutchinson, estimates that
in man the negative pressure in the thorax at the end of expiration
is — 4.5 mms. Hg, while at the end of an inspiration it is equal to
— 7.5 mms. Hg, — a variation during respiration, therefore, of 3 mms.
Hg. That is, assuming that the atmospheric pressure is 760 mms.
Hg, the conditions of pressure in the thorax and lungs at the end of
inspiration and expiration are as follows:

At the End of Inspiration. At the End 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 and at
the end of expiration — 3.02 mms. Hg — results considerably
lower than those estimated by Heynsius. It should be borne
in mind, however, that these values depend upon the condition
of expansion of the chest, — that is, the position of the body and
the depth of inspiration. On dogs Heynsius reports as follows:
At end of inspiration, — 9.4 mms. Hg; end of expiration, — 3.9 mms.
Hg. On rabbits, — 4.5 mms. and — 2.5 mms. Hg.

Variations of Intrathoracic Pressure with Forced and Unusual

Respirations. — After the most forcible expiration, when the air-

* "Archiv f. die gesammte Physiologie, " 29, 265, 1882.
f Aron, quoted from Emerson, "Johns Hopkins Hospital Reports," 11,
194, 1903.

63S 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 'he first and the fourth day, show no measurable negative
pressure in the thorax, and at Hie eighth day the pressure in the
thoracic cavity is less than atmospheric by an amount equal to only
— 0.4 mm. 11%. 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, geeammte Physiologic," 30, 276, L883.

PRESSURE CONDITIONS IN LUNGS AND THORAX. 639

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
lung will collapse completely and eventually will become entirely
solid, since the small amount of entrapped minimal air will be
absorbed by the blood. The other lung, the heart, etc., will also
be displaced somewhat from their normal position by the unusual
pressure. If, however, the opening is closed, then the air in the
pleural cavity may be absorbed completely by the circulating blood
and the lung again expand as this absorption takes place. In
human beings pneumothorax occurs most frequently in conditions
of disease, particularly pulmonary tuberculosis, and the air in the
thorax is associated also with a liquid effusion, this combination
being designated sometimes as hydropneumothorax.*

The Aspiratory Action of the Thorax. — The negative pres-
sure prevailing in the thoracic cavity must affect the organs in the
mediastinal space. The intrathoracic portion of the esophagus,
for instance, is exposed, at times of swallowing at least, to a full
atmosphere of pressure on its interior, while on its exterior it is under
the diminished intrathoracic pressure. This difference tends to
dilate the tube and may aid in the act of swallowing. The main
effect of the difference in pressure is felt, however, upon the flow
of lymph and blood, especially the latter. The large veins in the
neck and axilla are under the pressure of an atmosphere exerted
through the skin, and the same is true for the inferior cava in the
abdomen. But the superior and inferior cavse and the right auricle
are under a pressure less than one atmosphere. This difference in
pressure must act as a constant favoring condition to the flow of
blood to the heart. The difference is markedly increased at each
inspiration; so that at each such act there is an increase in the
velocity and volume of the flow to the heart, — an effect which is

* See Emerson, "Pneumothorax," Johns Hopkins Hospital Reports,
11, 1, 1903.

640 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
n sspi rat ory movements are very shallow, which are synchronous with
the respiratory movements (see Fig. 262). 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 ii is found that the blood-pressure falls slightly at the
beginning of inspiration, but rises during the rest- of the act (Kig.
263). 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 c\'U'c\ 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 he given for these respira-
tory waves: first, that they are due to an activity of the vaso-
constrictor '-enter synchronous with thai 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.

641

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-

%N^^\^^^ ^A^^

Fig. 262. — 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, 1S79, and 27, 152, 1882; also "Journal of Physiology, "
7,130.41

642

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. 263. — Diagram to represent the time relation between the respiratory waves of
blood-preesure and the respiratory movements (dog)! A represents the blood-pressure
record, showing the heart -heats and the larger respiratory waves. H 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 Jagcr
refers these temporary effects to the changes in capacity of the blood-
bed in the lungs. At the cud of inspiration there is a certain ca-
pacity of the bed; when expiration comes on, the lungs shrink, the
capacity oft he blood-vessels is thereby diminished, and con,se<|iient]y
.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 ot her hand, the sudden increase in capillary capacity
in th'e 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 i iger tedt, " Ergebniese der Physiologie, " vol. ii, part h, 560, 1903.

PRESSURE CONDITIONS IN LUNGS AND THORAX. 643

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
Ox 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 its efferent impulses into
the phrenic nerves it also sends impulses by a sort of overflow
into the neighboring cardio-inhibitory center. This latter cen-
ter is, thereby, partially inhibited, its tonic effect on the heart
is diminished, and the rate of the heart is increased.

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 clioxid. 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 clioxid, 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 1<U)2 4.3S

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 food; conse-
quently, while most of it is eliminated in the expired air as carbon
dioxid, some of it is excreted as water. For the sake of complete-
ness it may be stated that traces of hydrogen and methane are also
found in the expired air. They probably originate in the intestines
from fermentation processes and are carried off in solution in the
blood.

Physical Changes in the Expired Air.— The expired air is
warmed nearly or quite to the body temperature and is nearly

saturated wit li wafer vapor. Since, as a rule, the air that we

inspire is much cooler than the body and is far from being saturated
with water vapor, it is evident that the ad of respiration entails
upon the body a Loss of heat and of water. Breathing is, in fact,

fill

CHANGES IN AIR AND BLOOD IN RESPIRATION. 645

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 carried to a certain
point will itself cause death; and in addition the air becomes
heated to a high temperature and saturated with water vapor,
both of these latter conditions preventing loss of heat from
the body and producing a fever temperature. Under the or-
dinary conditions of life poor ventilation produces its ob-
viously 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.*
It seems to be clear that, when the expired air is condensed bypass-
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

* 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, 1900j Weichardt, ibid., 65, 252, 1908.

646 PHYSIOLOGY OF RESPIRATION.

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 ma}' 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-
Sec piard: 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 Formanck 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, affording to work of this character, contains no organic
poison which fan be regarded as a product of respiration.

Borne observers (Hermann, Haldane, and Smith) have made
careful experiments upon men which also seem to throw much
doubl upon the existence of :i toxic substance in expired air. In-
dividuals kepi in :i confined space lor a number of hours show no evil
effects except when the accumulation of the carbon dioxid has
reached ;i concentration of over I per cent. At this concentration
rapid breathing is apparent, and if it rises to LO per cent, great
distress is fell and the face becomes congested and blue. These
author- conclude that expired air is injurious in itself only from

the carbon dioxid it contains, and not because of any special

poi on. As opposed to these negative results, Weichardt reports

CHANGES IN AIR AND BLOOD IN RESPIRATION. 647

a series of experiments upon mice in which the expired air
of a number of animals was passed through acidulated water,
and the latter was then condensed in a vacuum to a small
volume and neutralized. When injected into a fresh animal this
material brought on a soporific condition, fall of body tempera-
ture, and diminution in output of carbon dioxid. The author ex-
plains these results on the assumption that some of the so-called
fatigue-toxin (kenotoxin) is excreted by way of the lungs, and
he believes that the known depressing effects of poor ventilation
are an expression of the action of this substance. This latter
work needs confirmation and, at present, 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 = y> hi which d represents in liters 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

548 PHYSIOLOGY OF RESPIRATION.

latter factor, in accordance with the above statement, to be equal
to 0.02 per cent, and e to be equal to 20 liters per hour (500 X
0.04 X 17 X 60), the value of d is equal to 100,000 liters of air
per hour for each person. The rapidity of renewal of air will
depend naturally upon the cubic space allotted to each individual.
The smaller this space, the more ample must be the ventilation.
The following figures* give an idea of the values adopted for dif-
ferent 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

rectories 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 twice completely renewed by Ventila-
tion 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 port ion of t he carbon dioxid present in the blood is in such stable
combination thai to remove if it may be necessary to add some

dilute acid, such as phosphoric acid. This portion of the emboli

dioxid is designated in this connection as t he fixed carbon dioxid.

The principle of the gas pump may be explained most easily by describing
the simple form devised byGrehant. The essential parts of this pump are
represented in I ilt. 264. The mercury pump consists of two bulbs, one mov-
able (M), the other fixed (F). 1/ may be raised and lowered by the windlass
(]'). Above /•', there i- a three way stopcock (m) by means of which tin;
chamber F may be pul into communical ion with the outi ide air by way of ( ',
or with the bulb B, which L bo contain the blood, or may be shut off com-
pletely, [f M i- raised so as to fill F entirely, and t Ik- stopcock m is shul off,
then on lowering .1/ the mercury will How into it, leaving a, perfect vacuum
in /'', since the di tance between F and .1/ is greater than the barometric
height. If the topcock /» i- turned o a to throw /*' into communication
with /', the chamber of I In- la tier is brought under the influence of the vac-
uum and any ease thai it may contain will he distributed bet, ween /.' and

I li topcock m i again turned off and .1/ is raised the gases in F will be

condensed at it- upper end, and by turning the stopcock m properly these

may be forced to the oul ide bj way of C or may be collected, if de-

♦ Taken from Bergey, "The Principles of Hygiene," 1904.

CHANGES IN AIR AND BLOOD IN RESPIRATION.

649

sired, in a burette filled with mercury and inverted over the opening from
F contained in the bottom of C. In performing an experiment the flask
B, which is to contain the blood, is connected with F, as shown in the figure,
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 Avay 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. 264.— Gas pump for extracting the gases of blood (Grehant) : M and F,
The mercury receivers; P, the windlass for raising and lowering M ; m, a three-way
stopcock protected by a seal of mercury or water; C, a cup with mercury over which
the receiving eudiometer is placed to collect the gases; B, the bulb in which, after a
vacuum is made, the blood is introduced by the graduated syringe, S. By means of the
stopcock m the vacuum in F , caused by the fall of the mercury, can be placed in communi-
cation with B. After the gases have diffused over into F, M is raised, and when the stop-
cock m is properly turned these gases are driven out through C into the receiving tube.
The operation is repeated until no more gas is given off from B.

a measured amount of blood is introduced from a graduated syringe, S, as
represented in the figure. This blood must be taken directly from the vessels
of the animal and be introduced into B at once. B is kept immersed in water
at the temperature of the body, and the bulb M is now raised and lowered a
number of times so that the gases given off from the blood are drawn over

650 PHYSIOLOGY OF RESPIRATION.

into F and then by proper manipulation of the stop-cock are driven into
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
tir.-t" 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 Pfii'iger 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.; C02, 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 1_2 45 L7

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 tin- gases in the venous blood from the brain and the
muscle . respectively. Their average results when both tissues
were al rest were as follows:

OxviiKN. Oaiihon Dioxid.

Venous blood from limbs (femoral) ... . 6.84 percent. 45.75 percent
" brain (torcular) . . . L3.49 " " 41.65 " "

* Hill and Nabarro, "Journal of Physiology," 18, 218, 1895.

CHANGES IN AIR AND BLOOD IN RESPIRATION. 651

It will be seen that under similar conditions there is much less
oxygen used and carbon dioxicl 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 clone in physiology to determine the condition in which
these various gases are held in the blood. The results obtained
show that they are held partly in solution and partly in chemical
combination. To understand the part played by each factor and
the conditions that control the exchange of gases in the lungs and
tissues it is necessary to recall some facts regarding the physical
and chemical properties of gases.

The Pressure of Gases and the Terms Expressing these
Pressures. — The air around us exists under a pressure of one
atmosphere and this pressure is expressed usually in terms of the
height of a column of mercury that it will support, — namely, a
column of 760 mms. Hg, which is known as the normal barometric
pressure at sea-level. Air is a mixture of gases, and according to the
mechanical theory of gas-pressure each constituent exerts a pressure
corresponding to the proportion of that gas present. In atmospheric
air, therefore, the oxygen, being present to the extent of 20 per
cent., exerts a pressure of j* of an atmosphere or £X 760 = 152
mms. Hg. When we speak of one atmosphere of gas pressure,
therefore, we mean a pressure equivalent to 760 mms. Hg, and in
any given mixture the pressure exerted by any constituent may
be expressed in percentages or fractions of an atmosphere, or in the
equivalent height of the mercury column which it will support.

Absorption of Gases in Liquids. — When a gas is brought into
contact with a liquid with which it does not react chemically a
certain number of the moving gaseous molecules penetrate the
liquid and become dissolved. Some of these dissolved molecules
•escape from the water from time to time, again becoming
gaseous. It is evident, however, that if a liquid, water, is brought
into contact with a gas under definite pressure, — that is, containing
a definite number of molecules to a unit volume, — an equilibrium
will be established. As many molecules will penetrate the liquid
in a given time as escape from it, and the liquid will hold a definite
number of the gas molecules in solution; it will be saturated for
that pressure of gas. If the pressure of the gas is increased, how-
ever, an equilibrium will be established at a higher level and more
molecules of gas will be dissolved in the liquid. Experiments have
shown, in accordance with this mechanical conception, that the

652 PHYSIOLOGY OF RESPIRATION.

amount of a given gas dissolved by a given liquid varies, the temper-
ature remaining the same, directly with the pressure, — that is, it in-
creases and decreases proportionally with the rise and fall of the
gas pressure. This is the law of Henry. On the other hand,
the amount of gas dissolved by a liquid varies inversely with the
temperature. It follows, also, from the same mechanical views
that in a mixture of gases each gas is dissolved in proportion
to the pressure that it exerts, and not in proportion to the pressure
of the mixture. Air consists, in round numbers, of 4 parts of N and
1 part of 0. Consequently, when a volume of water is exposed to
the air the oxygen is dissolved according to its "partial pressure,"
— that is, under a pressure of -g- of an atmosphere (152 nuns. 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 nuns.) of pressure and is then exposed to air,
four-fifths of the dissolved oxygen will be given off, since the pressure
of the surrounding oxygen has been diminished that much. Ab-
sorption coefficient. By this term is meant the number that ex-
presses the proportion of gas dissolved in a unit volume of the liquid
under one atmosphere of pressure. The absorption coefficient will
vary, of course, with the temperature. The gases that interest us
in this connection are oxygen, nitrogen, and carbon dioxid. The
absorption coefficients of these gases for the blood at the tempera-
ture of the body are as follows: O, 0.0262: N, 0.0130; C02, 0.5283.*
Thai 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 1 1 1 esc 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 i1 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 100X0.013 X 0.80 l .01 c.c.

■ i gen loo x 0.0202 x 0.15 - 0.393 "

Carbon dioxid LOO X 0.5283 X 0.05 2.64 "

As will be seen from I he analyses given above of I he actual amounts
of Hi- obtained from the blood, the nitrogen alone is present

in quantities corresponding to what would be expected if it is
held in simple physical solution.

* As given by Bohr, the absorption coefficients <>f these three gases at
in C. are a folio 0 jrgen 0.0231; nitrogen, 0.0118; carbon dioxid, 0.530.

CHANGES IN AIR AND BLOOD IN RESPIRATION. 653

The Tension or Pressure of Gases in Solution or Combi-
nation.— When a gas is held in solution the equilibrium is de-
stroyed if the pressure of this gas in the surrounding medium or
atmosphere is changed. If this pressure is increased the liquid
takes up more of the gas, and an equilibrium is established at a
higher level. If the pressure is decreased the liquid gives off
some of the gas. That pressure of the gas in the surrounding
atmosphere at which equilibrium is established measures the tension
of the gas in the liquid at that time. Thus, when a bowl of water is
exposed to the air the tension of the oxygen in solution is 152 mms.
Hg; that of the nitrogen is 608 mms. Hg. If the same water is
exposed to pure oxygen the tension of the oxygen in solution is
equal to 760 mms. Hg, while that of the nitrogen sinks to zero
if the gas that is given off from the water is removed. With
compounds such as oxyhemoglobin the tension under which the
oxygen is held is measured by the pressure of the gas in the sur-
rounding atmosphere at which the compound neither takes up nor
gives off oxygen. If, therefore, it is necessary to determine the
tension of any gas held in solution or in dissociable combination it is
sufficient to determine the percentage of that gas in the surrounding
atmosphere and thus ascertain the partial pressure that it exerts.
If the atmosphere contains 5 per cent, of a given gas the partial
pressure exerted by it is equal to 38 mms. Hg (760 X 0.05), and
this figure expresses the tension under which the gas is held in
solution or combination in a liquid exposed to such an atmosphere.
As regards the tension of the gases in arterial and venous blood,
this procedure is, of course, not possible, since the blood is sur-
rounded, not by an atmosphere whose composition can be analyzed,
but by the liquids of the body, the lymph and cell juices. To
determine the tension of the gases in the blood it is necessary to
remove the blood from the vessels and bring it into contact with an
atmosphere containing a known quantity of O, 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. 265. It is known as an aero-
tonometer (Pfliiger). It consists of a tube (A) which can be con-
nected through b directly with the blood-vessels. This tube A is
surrounded by a jacket (O) containing warm water, so that the blood
may be kept at the body temperature during the experiment. A
is first completely filled with mercury from the bulb M to drive out
the air. An atmosphere of known composition is then sucked into
A by dropping the bulb. Blood is allowed to flow into A through

654

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 13 per cent, of an atmos-
phere or 100 mms. Hg. (760 X 0. 1 3) .
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 willi this view, and,
moreover, it is found thai the
quantity varies directly with the
pressure in accordance with the
law given above. If an animal
I permitted to breathe an atmosphere of oxygen and hydrogen
the nitrogen di appears from the blood, and when ordinary air is
breathed the nitrogen contents of the arterial and venous bloods
exhibit no constant difference in quantity. Ii seems certain, there
fore, thai i lie nitrogen plays no direct role in the physiological pro-
h i absorbed by the blood in proportion to its partial

1'iK- 200. — Diagram to show the
principle of the aerotonometer: A, The
tube containing a known mixture of
eases, O, CO3, N; C, the outside jacket
for maintaining a con tan! hoily tem-
perature. When topcook 6 1 open
the blood trickles down the side 01 I
and enters into 'lilTu ion relations with
the contained gs e , Aitei equilibrium
is reached "lie topcock u i closed and
a i opened. By meane of the mer-
cury liulli the ga e can then l"- forced

out of .1 into a uiiaUe receiver lor
anal'. 1

CHANGES IN AIR AND BLOOD IN RESPIRATION.

655

pressure in the alveoli of the lungs and circulates in the blood in
small amounts without exerting any immediate influence upon the
tissues.

Condition of Oxygen in the Blood. — That the oxygen is not
held in the blood merely in solution is indicated, in the first place,
by the large quantity present and, in the second place, by the fact
that this quantity does not vary directly with the pressure in the
surrounding medium. It is definitely known that by far the largest
portion of the oxygen is held in chemical combination with the
hemoglobin of the red corpuscles, while a much smaller portion,
varying with the pressure, is held in solution in the plasma. The
compound oxyhemoglobin possesses the important property that
when the pressure of oxygen in the surrounding medium falls suffi-
ciently it begins to dissociate and free oxygen is given off. The proc-

0 10 ^b 30 40 SO 60 70 80 90 100 110 110 130 140 150 160

Fig. 266. — Curves of dissociation of the oxyhemoglobin at different pressures of
oxygen. Five curves are shown to indicate that the dissociation of the oxyhemoglobin
is greatly influenced by the presence of COo. The figures along the ordinates (10 to 100)
indicate percentages of saturation of the hemoglobin with oxygen, while the figures along
the abscissa (0 to 160) indicate different pressures of oxygen. The curve marked 5 mm.
CO2 shows the amount of combination of oxygen and hemoglobin when the CO* is absent
or present only in traces. In this curve at a pressure of 30 mms. of oxygen it will be seen
that the hemoglobin is 80 per cent, saturated with oxygen, while with a pressure of 40 mms.
of COo, which approximates that in the body, the hemoglobin at the same pressure of
oxygen is only 50 per cent, saturated. (After Bohr.)

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
- * Hiifner, " Archiv f. Physiologie," suppl. volume, 1901, p. 213.
t Loewy, "Archiv f. Physiologie," 1904, p. 245.

656 PHYSIOLOGY OF RESPIRATIOX.

has been crystallized out and obtained in pure solutions. The re-
sults that have been obtained from experiments upon defibrinated
blood probably represent, therefore, more nearly the conditions
of dissociation in the body. The results obtained by Bohr are
indicated in the curve of dissociation shown in Fig. 266, obtained
from experiments on dog's blood. At a pressure of oxygen of
152 mms. — that is. when exposed to ordinary air — the hemoglobin
is nearly or completely saturated with oxygen. If the oxygen
pressure is increased, — if, for instance, the blood is exposed to pure
oxygen (pressure, 760 mms.), — no more oxygen is combined
chemically by the hemoglobin. Additional oxygen will be taken
up by the blood, but only in so far as it can pass into solution in the
blood-plasma. Oxygen thus dissolved in the blood-plasma obeys
the physical law of solution, and will be at once given off when the
oxygen pressure of the surrounding medium is lowered. If the
pressure of oxygen falls below that of the air (152 mms.) the chemi-
cally combined oxyhemoglobin begins to dissociate slowly at first,
but as the pressure falls below 70 mms. the dissociation becomes
much more rapid, and the oxygen thus liberated from chemical
combination is from a quantitative standpoint much more impor-
tant than that freed from solution in the plasma. This, in fact,
is the process that takes place as the blood circulates through the
tissues. The arterial blood enters the capillaries with its hemo-
globin nearly saturated with oxygen, — about 19 c.c. to each 100 c.c.
of blood. After it leaves the capillaries the venous blood contains
only about 12 volumes of oxygen to each 100 c.c. of blood. In the
passage of the capillaries, which takes only about one second, the
blood loses, therefore, about 'A5 per cent, or more of its oxygen.
The physical theory of respiration furnishes data to show that this
In-- is due to a dissociation of the oxyhemoglobin, owing to the lad
that in passing through the capillaries the blood is brought into
exchange with a Burrounding medium lymph, cell liquid — in
which the oxygen pressure is very low. A fact of subsidiary
importance in this connection is shown in the curves reproduced
in Fig. 266. It will be noted in this figure that the dissociation
of the oxyhemoglobin is facilitated by an increase in the pressure
of the carbon dioxid. In the tissues where the oxyhemoglobin
is broken up there is always a certain tension of carbon dioxid,
a pressure which lies somewhere between 40 and SO nuns, of
mercury, and the presence of t his gas in this proportion probably
helps the dissociation of the oxyhemoglobin to the extent
.shown by the curve- in this figure.

Condition of the Carbon Dioxid in the Blood.— The condition
in which the carbon dioxid is held in the blood is not entirely

understood. It has long been recognized that a certain small

CHANGES IN AIR AND BLOOD IN RESPIRATION. 657

percentage is held in simple physical solution in the plasma and
in the corpuscles, and that a certain additional amount, much
larger than the preceding, is chemically combined with the
alkali of the blood as a carbonate, most probably as a bicarbonate
(HNaC03). It has been suggested, in fact, that the carbon dioxid
of the venous blood is carried chiefly as a bicarbonate and that
in passing through the lungs this compound gives off some of
its carbon dioxid and is converted into a carbonate, according
to the equation 2HNaC03 = Na2C03 + C02 + H20. It is known,
however, that an aqueous solution of bicarbonate of soda does
not give off carbon dioxid when exposed to low pressures of
the gas with anything like the facility shown by blood. Con-
sequently it was further assumed that the proteins of blood,
acting like weak acids, tend to combine with the alkali and that
this additional factor suffices to explain the relative ease with
which the bicarbonate as it exists in blood breaks up into carbon
dioxid and carbonate. This theory has not proved to be com-
pletely satisfactory. Other facts tend to show that the available
alkali of the blood exists as bicarbonate in the arterial as well as
in the venous blood, and, indeed, the total amount of the alkali
in the blood in combination as carbonate or phosphate is not
sufficient to account for the quantity of carbon dioxid normally
present. In recent years an additional possibility has been
suggested by the discovery (Bohr) that carbon dioxid forms
a dissociable compound with hemoglobin (p. 417), and the
probability that a similar compound may be formed with the
proteins of the plasma. Accepting this suggestion it would
seem that the carbon dioxid exists in the blood in three forms.
The amounts present in each form is estimated by Loewy*
as follows: In each 100 c.c. of arterial blood, containing normally
40 volume per cent, of carbon dioxid, there is

Physically absorbed in plasma and corpuscles 1.9 per cent.

Held as sodium bicarbonate { g Jgg^; ] ] ™ } ■ . 18.8 << «

Held in organic combination { £ ^ck ; ; ™ } . . 19.3 " «

When serum or plasma is exposed to a vacuum at body tem-
perature only a portion of the carbon dioxid is given off; to
obtain the balance it is necessary to add acid to the liquid. This
latter portion, liberated only by a stronger acid, is spoken of as
the "fixed carbon dioxid." If instead of exposing serum or
plasma to a vacuum one uses full blood, that is. plasma or serum
plus corpuscles, all the carbon dioxid may be obtained without
the necessity of adding acid. This fact has been explained on

* Loewy, " Handbuch d. Biochemie," 1908, IV1.
42

658 PHYSIOLOGY OF RESPIRATION.

the supposition that the hemoglobin under these conditions
plays the part of an acid in breaking up the compound in which
the carbon dioxid is firmly held. Presumably this fixed carbon
dioxid is the portion which in the above classification is repre-
sented as bicarbonate. Since the portion that is held in organic
combination is apparently more easily dissociated, it seems
likely that it furnishes the main compound which is physio-
logically useful in providing a means for the transportation of
carbon dioxid from the tissues, where it is formed, to the lungs,
where it is eliminated.

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 ran, 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, that is, the
inspired air. A normal expiration contains 500 c.c.j hence the
alveolar air constitutes only 360 c.c. or !* of the entire amount. If
the expired air contains 1.38 per cent, of C02, then the alveolar
air musl contain 4.36h-^-£ or 0 per cent, of carbon dioxid.

CHANGES IN AIR AND BLOOD IN RESPIRATION. 659

Or, to put the mode of calculation in a more general form, the amount
of oxygen in the expired air is equal to the amount of oxygen in the true
alveolar portion of the expired air plus the amount of oxygen in the "dead
space, " namely, the trachea and bronchi. Let A equal the volume of expired
air, e the percentage of oxygen in the expired air, a the volume of air in the
dead space, and i the percentage of oxygen in this air or what is the same
thing in the inspired air. According to the above statement we have the fol-
lowing equation, Ae = ai -f- (A — a) ,x, in which x represents the unknown

percentage of oxygen in the alveolar air. We have, therefore, x = . - .

In ordinary breathing these values are as follows: A — 500 c.c, a = 140 c.c,
e = 16.02 per cent., and i = 20.96 per cent. Substituting these values, x will be
found equal to 14.1 per cent. Reckoned in millimeters of mercury this would
be equal to (760 X 0.141) 107.2 mm. In order, however, to ascertain the'
true pressure exerted by the oxygen allowance must be made for the baro-
metric pressure and for the tension of the aqueous vapor. In the depths of
the lungs the air is saturated with water vapor and the tension of this vapor
at the body temperature may be valued at 46.6 mms. Hg. If we suppose
further that the observation was made at a barometric pressure of 750 mms.,
then the pressure of the oxygen in the alveoli would be (750 — 46.6X0.141)
99+ mms. Hg.

Actual observations made by these authors upon human beings
in whom the expired air was analyzed indicate that the composition
of the alveolar air may vary between the following limits: Oxygen
between 11 and 17 per cent, of an atmosphere; carbon dioxid be-
tween 3.7 and 5.5 per cent, of an atmosphere.

Loewy and von Schrotter have determined also the average ten-
sion of these gases in the blood of man. Their method * consisted
in blocking off one lung or one lobe of a lung by a metal catheter
inserted through the trachea. After the lapse of half an hour or
so the gases in this occluded portion had reached an equilibrium
by interchange with the venous blood which represented the tension
actually existing in the circulating venous blood. A portion of this
air was then withdrawn by means of a suitable device and was
analyzed. Their average result was that in the venous blood the
oxygen exists under a tension of 5.3 per cent, of an atmosphere
(710 X .053 — 37.6 mms. Hg), and the C02 under a tension of 6
per cent. (42.6 mms. Hg). The physical relations of pressure
between the alveolar air and the gases in the venous blood may be
represented as follows :

Oxygen. Carbon Dioxid.

Alveolar air 100 mms. 35 to 40 mms.

Membrane +

Y I

Venous blood . . . 37.6 mms. 42.6 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 awa}^ from the lungs is nearly saturated with

* Loewy and von Schrotter, "Zeitschrift fur experimentelle Pathologie
und Therapie," 1, 197, 1905. See also Loewy, "Handbuch der Biochemie,"
IV1, 1908.

660 PHYSIOLOGY OF RESPIRATION.

oxygen, lacking perhaps only 1 volume per cent, of being completely
saturated (Pfliiger). That is, if the normal arterial blood contains
19 c.c. of oxygen for each 100 c.c. of blood, it is probable that one
more cubic centimeter might be combined by the hemoglobin if
exposed fully to the air or oxygen. The difference in tension
between the carbon dioxid on the two sides of the membrane is not
so great as in the case of the oxygen, but owing to the more rapid
diffusion of this gas it is probable that this difference suffices to
explain the exchange. In this matter one must bear in mind also
the very large expanse of surface offered by the lungs and the very
complete subdivision of the mass of blood in the capillaries. Thus,
following a calculation made by Zuntz, the surface of the human
lungs may be estimated at 90 sq.ms. or 900,000 sq.cms. If we
assume that 300 c.c. of carbon dioxid (500 X 0.04 X 15) are given
off from the blood in a minute this would indicate a diffusion
through each square centimeter of only 0.0003 c.c. (to3o°oVo)-

This same idea is expanded by Loewy as follows: The surface of the
lungs exposed to the air may be reckoned at 90 square meters, and the thick-
ness hi membrane mtervening between this air and the blood in the capillaries
may be estimated at 0.004 of a millimeter. Under these conditions as much
as 6083 c.c. of oxygen might diffuse into the blood in a minute. As a matter
of fact only about 250 to 300 c.c. of oxygen are really absorbed per minute is
quiet breathing, and not more than ten times this amount in the violent
respiration following excessive muscular exercise. It would seem, therefore,
that diffusion should suffice to supply the oxygen actually needed. This
reasoning applies a fortiori to the carbon dioxid, since the velocity of diffusion
of this gas through a moist membrane is much (25 times) greater. If the
tension of the ('<). in the blood were only 0.03 mm. higher than that in the
alveoli, the known exchange might be explained by diffusion.

Exchange of Gases in the Tissues.— The arterial blood passes
to the tissues nearly saturated with oxygen so far as the hemo-
globin is concerned, and this oxygen is held under a tension
equivalent probably to at least 100 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,
5 per cent, of an atmosphere (35 mms.). In the systemic capil-
laries the blood comes into diffusion relations with the tissues,
and direct examination of the latter shows thai the oxygen in
them exists under a very small pressure, practically zero pres-
sure, while the ( ,( )2 is present under a tension (Strassburg) of
7 to 9 per cent. The high tension of the C02 is explained by
the fad that it is being formed in the tissues constantly as a
resull of their metabolism, while the low tension of the oxygen
is <lue bo the fad thai on entering the tissue this substance is
combined in some way in a chemical compound too firm to
dissociate. The physical conditions are, therefore, such as
would cause a stream of C02 from tissue to blood and a stream

of oxygen in the reverse direction.

CHANGES IN AIR AND BLOOD IN RESPIRATION. 661

■ Oxygen. Carbon Dioxid.

Arterial blood 100 mms. 35 mms.

Wall of capillary . T.

Tissues 0 mm. 50 to 70 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 (Fig. 266).
Since these conditions prevail in the capillaries of the body, it
is probable that the mere presence of the C02 in increased
amounts facilitates the liberation of the oxygen.

Suggested Secretory Activity in the Respiratory Exchange. — The

view that the exchange of gases in the lungs and tissues is entirely explained
by the diffusion of the gases from points of high tension to points of low ten-
sion, and that the membranes interposed are entirely passive in the process
has not passed unchallenged. Certain observers (Bohr, Haldane and Smith)f
claim that the tension of the oxygen in the arterial blood may be higher than
the pressure of oxygen in the alveolar air. Bohr, moreover, in a series of
experiments made upon dogs J determined by calculation the tension of oxygen
within the surface layer of the lungs. This tension was found to vary from
35 to 105 mms. The tension of the arterial blood, determined at the same
time, varied from 101 to 144 mms., being in every case distinctly higher than
the tension of the oxygen in the surface layer of the lungs. If these facts
were fully demonstrated they would show that the physical theory outlined
above is insufficient, and would indicate that the membranes concerned take
an active part in the passage of the gases, exerting possibly a secretory activity.
That the cells of these membranes might secrete the gases is not at all impos-
sible, but at present it seems to be unnecessary to make such a supposition.
The results obtained by the observers mentioned in this paragraph have not
been corroborated by the numerous other observers who have worked in the
same field, and it seems possible that they may be due to experimental errors.
A well-known set of experiments that strengthen this conclusion has been
reported by Wolffberg and by Nussbaum§ and has since been repeated upon
man. In these experiments one bronchus in a dog was completely blocked
by a specially designed lung catheter, so arranged as to occlude the bronchus
and yet allow the observer to draw off a specimen of the air at any time. In
such an occluded lung the captured air is in diffusion relations with the venous
blood of the pulmonary artery, and if these relations are maintained for a
sufficient time an equilibrium should be established on the physical theory,
the tension of the gases in the occluded lungs becoming the same as in the
venous blood. Such was found to be the case. When at the end of the
experiment air was drawn off and analyzed it was found to contain 3.6 per
cent, of CO.,, while the tension of the CO., 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.

* " Skandinavisches Archiv f. Physiologie," 16, 402. 1904.
t See Haldane and Smith, "Journal of Physiology," 20, 497, 1896.
J Bohr, in Nagel's "Handbuchder Physiologie des Menschen, 1905, vol. i,
part i, p. 146.

§ "Archiv f. die gesammte Physiologie," 4, 465, 1871, and 7, 296, 1873.

CHAPTER XXXVII.
INNERVATION OF THE RESPIRATORY MOVEMENTS,

The nervous supply to the respiratory muscles is received from
a number of nerves, the nervous machinery being widely dis-
tributed in the brain and cord. The most important of the motor
nerves of respiration is the phrenic, which supplies the diaphragm
and originates from the fourth and fifth cervical spinal nerves.
The N. accessorius 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 (nozud 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. Bach half occupies an area that lies some
distance lateral to the mid-line and beneath the floor of the medulla
.it t he general level of the calamus. According to ( lierke,* the area
extends in rabbits from a point .'; or 4 nuns, in Front of, to a point
2 or :\ mms. posterior to the calamus. No especial group of cells

can be found in this region sufficiently separated anatomically to
make it probable thai I hey constitute the center in question. The
* Gierke, "Archiv f. die geaammte Physiologie," 7, 683, 1873; and "Cen-
tralblatl t. d. tned. Wiasenschaften," No. 34, L885.

662

INNERVATION OP THE RESPIRATORY MOVEMENTS. 663

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. It is probable that these descending fibers decus-
sate in part, so that "each half of the respiratory center is con-
nected with the musculature of both sides of the chest and
the diaphragm. A connection of this kind is indicated by the
fact that section of one-half of the medulla at the lower' end
of the fourth ventricle is followed not by a paralysis, but only
by a weakening of the action of the respiratory muscles on that
side. 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 respira-
tory 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-S6quard, Langendorff, et al.) have insisted that there exist one or

* Mislawsky, Centralblatt f. die med. Wissenschaf ten, " No. 27, 1885.

t Gad, " Archiv f. Physiologie," 1893, p. 75.

% See Kehrer, "Monatshefte f. prakt. Dermatol.," 28, 450, 1892.

664 PHYSIOLOGY OF RESPIRATION.

more spinal respiratory centers, and that the medullary center has not the
commanding importance indicated in the above description. The fact that,
when tin 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
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, ma)' 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 Muhlberg have shown* that, if half of the
cord alone is cut , the movements of the diaphragm on that side are permanently
paralvzed. 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 stim-
ulated from the medullary center; but the evidence at present is altogether
against any distinct physiological independence on the part of those neurons.

The Automatic Activity of the Respiratory Center. — The

constant activity of the respiratory center throughout life suggests
the question as to its automaticity. Is it automatic like the heart?
That is, are the stimuli discharged from it produced within its own
cells as a result of its own metabolism under the normal conditions
of circulation? Or, on the other hand, is it, like most of the motor
nuclei of the central nervous system, only a reflex center, its motor
discharges being dependent upon impulses received from other
neurons by way of the sensory paths? Obviously the only way to
answer such a question directly is to isolate the center from all
afferent paths and leave it connected with the respiratory muscles
only by motor nerves. If under such conditions the respiratory
rhythm continues the center may be regarded as essentially auto-
matic, however susceptible it may be to reflex influences. A close
approximation at least has been made to such an experiment.
Rosenthal finds that rhythmical respiratory movements continue
after the following operations: first, section of the brain at the cor-
pora quadrigemina to cut off influences from the cerebrum, thala-
mus, and midbrain; second, section of the vagi, to shut off afferent
impulses from the viscera, especially from the lungs; third, section
of the cord at the seventh cervical vertebra to exclude sensory
influences through all the underlying posterior roots; and, fourth,
section of the posterior roots of the cervical spinal nerves. The
medulla with its respiratory center was thus isolated from all
afferent impulses except such :is might enter through the fifth,
seventh, eighth, and ninth cranial nerves. Since under these con-
ditions I he center continued to act rhythmically we may draw
the probable conclusion that it is essentially automatic, and that
it probably possesses tin intrinsic rhythmical activity resembling

that of the he.i r! .

Reflex Stimulation of the Center. — According to the results
of numerous observers, Stimulation of any of the sensory nerves
of fli': body may affect the rate or the amplitude of the respiratory
• "American .Journal of Physiology," 4, 334, 1900.

INNERVATION OF THE RESPIRATORY MOVEMENTS.

665

movements. This experimental result is confirmed, by our own
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. 267. — To show the augmenta-
tion of the respiratory movements caused
by stimulation of the sciatic nerve. Ex-
periment upon a rabbit.

Fig. 268. — To show the inhibition of the respiratory movements in a rabbit due to
stimulation of the central end of the vagus. The respiratory movements in this case,
before and after stimulation, were forced, owing to the fact that both vagi were cut.

be changed together with an increased or decreased amplitude, the
inspirations and expirations may each be increased, or one phase

666 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. 267 and 268).
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 sensor}^ 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. 269).
The inspirations especially are deeper and longer, with something
of a pause at the end. When only one vagus is cut an intermediate
effect may be obtained, the respiratory movements may be slowed
somewhat and slightly deepened; but the striking effect is observed
only after section of both nerves. This result is not a temporary
one 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 lias shown that this influence consists in the
tonic action of sensory fibers contained in the vagus and distributed
to the lungs. It is flu; 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.

667

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. 269. — 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. 268), or, second,
the rate of the inspiratory movements may be increased and this
may end finally in an inspiratory standstill, — that is, the respiratory
movements cease with the chest in an inspiratory position (Fig. 270),

Fig. 270. — 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

66S PHYSIOLOGY OF RESPIRATION.

stimuli, and has led to much difference of opinion among investi-
gators.* The two main effects described above are usually inter-
preted to mean that the vagus contains two kinds of sensory fibers
which are distributed to the lungs and act normally on the respira-
tory center. These are: (I) The inspiratory fibers, whose effect
is to increase the rate of inspiratory discharge from the respiratory
center: therefore to quicken the rate. (II) The expiratory (or
inspiratory inhibiting) fibers, whose effect is to inhibit the inspira-
tory discharges, partially or completely. Some authors find it
simpler to assume only one kind of sensory fiber and to explain the
different results by a difference in the nature of the stimulus or
in the condition of the center; but it seems advisable at present,
in accordance with the doctrine of specific nerve energies, to hold
to the view of two varieties.

Influence of the Inspiratory and the Inhibitory Fibers of
the Vagus on the Normal Respirations. — It is assumed that
these two sets of fibers are in constant activity and keep the re-
spirator}' 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. This hypothesis has been much discussed
and many efforts have been made to prove or disprove it by
means of experiments. The result of this work on the whole
tends to show that the hypothesis is essentially correct. Two
kinds of afferent fibers exist in the vagus, one of which is stimu-
lated by expansion of the lungs, the other by collapse. This
I'.u-t is shown most clearly by Einthoven'sf experiments with
his string-galvanometer. When the vagus nerve is cut high in
the neck and is then connected in the usual way with the string-
galvanometer, t Ik lal ter shows a marked ad ion currenl t hrough-
out each inspiration, indicating, therefore, the passage of a series
of nerve impulses during inspiral ion ( Fig. 27 1 ). When by sud ion
the lungs were collapsed, anol her elect rical varial i<>n of ;i different

♦ For discussion and literature, sec Meltzer, "Archiv I'. Physiologic, "
1892, p. 340; also "New York Medical Journal," January 18, 1890. Lewan-
dowsky, "Archiv f. Physiologic, " 1896, pp. 195 and 183.

t Einthoven, "Quarterly Journal of Exp. Physiology," 1908, L, 243:
i:. earche of the Physiological Laboratory of the I University of Leyden/
VII., 1908.

INNERVATION OF THE RESPIRATORY MOVEMENTS. 669

character was produced, indicating the existence of a separate
set of fibers brought into action by the diminution in volume of
the lungs. In quiet respirations the expiration consists in
merely a passive return to what may be called the neutral or
normal volume of the lungs, and in this movement it is probable
that the inspiratory fibers are not affected, being stimulated
only by an active expiration. We may assume, therefore,
with Gad that the normal rate of respirations is maintained

+

1 1 1 1-j.l

1 (+ -f+t

-i*

-

';

Fig. 271. — To show the electrical changes in the different fibers of the vagus nerve
caused by the respirations and the heart beats: V, The electrovagogram, the large waves
are electrical oscillations synchronous with the respiratory movements. The smaller ones
are electrical changes synchronous with the heart beats; P, Mechanical record of the
respiratory movements, ascent of curve, inspiration; C, Mechanical record of pulse beats.
(From Einthoven.)

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 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

* "Archiv f. die gesammte Physiologie," 42, 273

670 PHYSIOLOGY OF RESPIRATION.

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 respirator}- center breaks through the inhibition. In
special cases the inhibition may last for an unusually long time.
Thus, Fredericq states that in aquatic birds water allowed to flow
over the beak so as to penetrate slightly into -the nostrils brings
about an inhibition of respirations for many minutes. There
would seem in this case to be a special adaptation of the reflex to
the needs of diving. We know also that irritating gases or foreign
bodies of any sort that enter the larynx may lead to a coughing
reflex, — that is, to a series of expiratory blasts which have a pur-
poseful end in the expulsion of the stimulating object. In this case
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

INNERVATION OF THE RESPIRATORY MOVEMENTS. 671

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, thej^ 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.
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.

672

PHYSIOLOGY OF RESPIRATION.

(2) By voluntary control from the cerebrum, as in straining. (3)
By stimulation through afferent fibers from the skin, especially the
pain fibers. (4) By the action of an increased venosity of the blood.
Under the latter two conditions it is possible that the irritability
of the center is so increased that it becomes responsive to the in-
fluence of the inspiratory center. The relations of the inspiratory
and expiratory centers under the various conditions of artificial
stimulation are very complex, and although it is possible to rep-
resent these relations more or less completely by schemata of some
sort it does not seem advisable at present to seriously consider
such hypotheses.

The Accessory Respiratory Centers of the Midbrain. — Several observers
have called attention to the existence of a possible accessory respiratory center
in the midbrain at the level of the posterior colliculus. Martin and Booker
found that stimulations in this region caused a marked increase in the rate
of inspiratory movements and finally a standstill in inspiration, — that is,
a complete tetanic contraction of the inspiratory muscles lasting during the
stimulation.* Lewandowsky f 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
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. < )n the other hand, if the blood supplying the center
is more arterialized than normal, by active ventilation of the lungs,
for instance, the center nets more feebly or may fail to act altogether,
giving the condition known as apnea. These facts may be accepted
■ completely demonstrated, but they do not go far enough. When
peak of the arterial Mood being more venous than normal we
mean thai it contains less oxygen and more carbon dioxid than
normal arterial blood. Which of these conditions serves to stimulate

♦Martin and Booker, "Journal of Physiology," 1, 370, 1878.
f'Archiv f. Physiologic," 1890,489.

INNERVATION OF THE RESPIRATORY MOVEMENTS. 673

the center, and which may be regarded as the constant stimulus
throughout life ? The three possible views have been defended:
(1) That the normal stimulus is a lack of sufficient oxygen (Rosen-
thal). When sufficient 0 is supplied the center ceases to act,
becomes apneic. (2) That the normal stimulus is the presence of
an excess of CO., (Traube). When this excretion is quickly re-
moved the center ceases to act, — becomes apneic. (3) It is possible
that the two factors may co-operate. The blood that flows through
the center may stimulate the cells by virtue of the fact that it does
not remove the C02 fast enough and does not supply sufficient
oxygen. Much evidence has been collected to show that the
action of the respiratory center is increased when the tension of the
C02 in the blood is raised without altering that of the oxygen and
that a similar result is obtained if the tension of oxygen is greatly
diminished without any change in that of the carbon dioxid, so
that it must be admitted that a change in either factor, if suffi-
ciently great, acts as a stimulus. Experiments, however, have
indicated that the accumulation of the 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 b}^ 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:

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 bjr 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 $ 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-

* See Zuntz, "Archiv f. Physiol ogie," 1897, 379. See also Friedlander
and Herter, " Zeit. f. physiol. Chemie," 2, 99, and 3, 19.
t Bert, " La pression barometrique," 1878, 691.
% Haldane, "Journal of Physiology," 18, 442, 1895.
43

674 PHYSIOLOGY OF RESPIRATIOX.

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. CO, " " " " 9.060 "

Air of IS. 06 per cent. O, 2.97 per

cent. C02 " " " " 11,326 "

Air of 18.42 per cent. O, 11.5 per

cent. CO,... ■ " " " " 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 trend of recent work favors rather the view that
the normal stimulus to the respiratory center is the carbon dioxid.
When this substance is present above a certain amount or tension
it acts as a stimulus and gives rise to the moderate movements of
normal inspiration. If the tension of the carbon dioxid is increased
its stimulating action becomes stronger and leads to the production
of a condition of hyperpnea and dyspnea. On the other hand,
if for any reason, such as active ventilation of the lungs, the tension
of the carbon dioxid in the blood falls below a certain value,
estimated by Zuntz as lying between 19 and 24 rams., no stimu-
lation occurs, the center is in a condition of apnea and respiratory
movements cease. In reference to the effect of carbon dioxid
in augmenting the respiratory movements an interesting dis-
tinction has been made by Scott* between the rate and the depth
of the respirations. From experiments made upon rabbits he
finds that an increase of carbon dioxid in the air breathed causes
an increase in both the rate and the depth of the respiratory
movements, but if the vagi are first cut then raising the per-
centage of carbon dioxid has an effect only upon the depth of
the respirations. It would appear, therefore, that so far as an
increase of carbon dioxid in the lungs affects the rapidity of
breathing, it does so by .'in ad ion of some sort upon the sensory
fibers of the vagus which end in the lungs. Under special
circumstances other substances may occur in the blood which
act as chemical stimuli to the center, for example, the acid
products formed during muscular contractions (see p. 680).

* Scott, "Journal of Physiology," 37, 301, 1908.

INNERVATION OF THE RESPIRATORY MOVEMENTS. 675

The Cause of the First Respiratory Movement. — The mam-
malian fetus under normal conditions makes no respiratory move-
ments while in utero. After birth and the interruption of the pla-
cental circulation the first breath is taken. The cause of this
sudden awakening to activity on the part of the respiratory center
must be closely connected, if not identical with, the cause of the
automatic activity of the center throughout life. Two or perhaps
three views have been held regarding its immediate cause: (1)
That it is due to the increased venosity of the blood brought about
by the interruption of the placental circulation; (2) that it is due to
stimulation of the skin by handling, drying, etc.; (3) that it is due
to a combination of these causes. Preyer has shown that stimula-
tion of the skin of the fetus while in utero and with the placental
circulation intact sumcies to cause respiratory movements. Cohn-
stein and Zuntz* have shown that interruption of the placental
circulation while the fetus is kept bathed in the amniotic liquid also
brings about respirations. Since both of these events occur normally
at birth, we may believe that each aids in causing the first respira-
tion, and indeed it may be necessary at times deliberately to in-
crease the stimulation of the skin in order to bring on respiratory
movements. If the two causes, stimulation through the nerves and
stimulation through the blood, normally co-operate, it may, how-
ever, be said that the essential cause, according to the theory
adopted in the preceding paragraphs, lies in the greater venosity of
the blood, that is, the increased tension of the carbon dioxid follow-
ing interruption of the placental circulation. During the intra-
uterine period it is evident that the fetal blood is aerated so well
by exchange with the maternal blood that it does not act as a
stimulus to the fetal respiratory center. The fetus is, physiolog-
ically speaking, in a condition of apnea. Since the maternal blood
acts upon the respiratory center of the mother, while the fetal
blood which exchanges gases with it does not act on its own respira-
tory center, it follows that the fetal respiratory center possesses a
lower degree of irritability than that of the mother.

Dyspnea, Hyperpnea, Apnea. — By the term dyspnea in its
widest sense we mean any noticeable increase in the force or rate of
the respiratory movements. As said above, such a condition may
be caused either by stimulation of sensory nerves, particularly
the pain nerves or the sensory fibers of the vagus distributed
to the lungs themselves, 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 com-
position of the blood, some of which are considered in the next
chapter, may also stimulate the respiratory center and cause

* Cohnstein and Zuntz, "Arch. f. die gesarnmte Physiol.," 42, 342, 1S88.

676

PHYSIOLOGY OF RESPIRATION.

dyspnea. The dyspneic movements naturally show many
degrees of intensity corresponding with the strength of the
stimulus, and sometimes the initial stages are designated as
hyperpnea, while the term dyspnea is reserved for the more
labored breathing in which the expirations are active and forced.
When dyspnea is produced by withholding air (suffocation) the
respiratory movements become more and more violent until they
take on a convulsive character. This stage is succeeded by one
of apparent calm, indicative of exhaustion of the centers. Deep,

Fig. 272. — To show the recovery from apnea. The animal (rabbit) had been venti-
lated with a bellows and thrown into a condition of apnea shown at the beginning
of the record. The respirations returned first as feeble movements which gradually in-
creased to the normal. — (Dawson.)

long-drawn inspirations follow at intervals and finally cease. The
animal lies quietly, with feeble heart beat and dilated pupils, in
a condition designated as asphyxia or complete asphyxia.

The term apnea means literally a condition of no breathing, and
since this condition may occur from several causes some confusion in
nomenclature has resulted. In medical literature the term is some-
times employed as a synonym for asphyxia or suffocation. In
physiological literature it is restricted to a very interesting con-
dition which is of great importance with reference to the theories
of respiration. This condition is one of cessation of breathing
movements due to lack of stimulation of the respiratory center.
Jt is brought about by rapid and prolonged ventilation of the
lungs. If, for instance, in a rabbit or oilier 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

INNERVATION OF THE RESPIRATORY MOVEMENTS. 677

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. 272). One may produce a similar condition upon
himself, approximately at least, by a series of rapid, forced inspira-
tions. The question of importance is: Why does the respiratory
center cease to act? Rosenthal explained the phenomenon in terms
of his theory that the normal stimulus to the center results from a
lack of oxygen. With vigorous artificial respiration he imagined
that the blood takes up more oxygen and thus fails to act upon
the center. The apnea is clue 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 ordinary method used to produce it two
factors co-operate, namely a change in the condition of the
gases of the blood and a stimulation of sensory fibers in the
lungs. Since either one of these factors alone may cause a
cessation of breathing, some authors have distinguished two
kinds of apnea, apnea vera or chemical apnea, and apnea vagi
or inhibitory apnea. Whether or not it is proper to speak of
this latter condition as apnea depends altogether upon the
definition one gives to the term. If we adhere to the definition
suggested above, namely, that apnea is a cessation of breathing,
due to lack of stimulation of the respiratory center, then the
inhibition of respirations produced by stimulation of the vagi,
the so-called apnea vagi, ought not to be included under the
term. It is generally statedf that after section of the vagi it
is more difficult than in the normal animal to produce apnea
by vigorous artificial respiration, so doubtless in this last proce-
dure, as usually carried out with a bellows, the rapid stimulation
of the inhibitory fibers of the vagus by the expansion of the
lungs facilitates the production of a true or chemical apnea de-
pendent upon a change in the gases of the blood. That chemical
apnea in Rosenthal'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 sec-
tion of both vagi and of the medulla above the respiratory 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 the apnea is due to an
overoxygenation of the blood, but since the vigorous respirations

* See Rosenthal, in vol. iv., p. 264, of Hermann's "Handbuch der Physi-
ologie."

t See Head, "Journal of Physiology," 10, 1, and 279, 1889.

% Loewy, "Archiv f. die gesammte Physiologic, " 42, 245, 1888; and
Langendorff, "Archiv f. Physiologie, " 1888, p. 286.

678 PHYSIOLOGY OF RESPIRATION.

lower especially the contents of the blood in C02 it is probable,
as insisted upon by Traube, that this latter factor is the more
important. In the preceding paragraphs evidence has been
given to show that the normal stimulus to the center is due to
the presence of C02, and it follows logically that the more com-
plete 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 effect. This observation
is further supported by recent experiments by Mosso* upon
men, in which he shows that apnea cannot be produced by
inflation with carbon dioxid. This author designates the
condition of diminished C02 in the blood as acapnia. According
to this terminology, true apnea is due to a condition of acapnia.
Much other work has tended to strengthen the general view
that a certain tension or pressure of C02 in the blood is neces-
sary to stimulate the respiratory center, and that if the C02 is
washed out to a certain point by unusual ventilation of the
lungs (condition of acapnia), then the respiratory center ceases to
give off its rhythmic discharges. There is no desire to breathe
and the animal lies quiet in a condition of apnea. Voluntary
forced respirations in man maintained for some minutes will
produce a similar condition. According to the interesting
account given by Haldane and Poultonf an apnea may be
produced in this way which will last for 100 to 150 seconds, and
before the individual begins to breathe again he may become
very blue in the face, owing to the loss of oxygen from the
blood. HendersonJ has given experimental evidence to show
that a marked diminution in the pressure of the C02 in the
blood, brought about by forced respiration, may cause not only
a condition of apnea but also a feeble rapid heart-beat, with
fall of blood-pressure and the symptoms of surgical shock. It is
known that a cessation of respirations maybe brought about in
still a third way, namely, by a condition of more or less complete
anemia produced by shutting off the blood-supply to the respira-
tory center. The lack of activity in this case is probably not a
true apnea in the sense of the form given above, since we may
suppose t hat under these conditions the tension of the carbon in-
creases rat her than decreases. In other words, there is no removal
of stimulus, but the cells have lost their irritability, probably

* Mohho, "Archives italiennes de biologie," 40, I, L903.

t Baldane and Poulton, "Journal of Physiology," :V7, :*«.)<), 1(.>(>8.

t Henderson, "American Journal of Physiology," 21, 128, 1908.

INNERVATION OF THE RESPIRATORY MOVEMENTS. 679

in consequence of a lack of oxygen, and hence fail to respond
to stimulation.

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.* 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 nor-
mally 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
p. 669, 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.

* For references to literature, see Dixon and Brodie, "Journal of Physi-
ology," 29, 97, 1903.

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. <lie gesammte Physiologic, " 42, 189,
1888.

(isn

INFLUENCE OF VARIOUS CONDITIONS ON RESPIRATION. 681

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
oxj^gen 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.

682 PHYSIOLOGY OF RESPIRATION.

oxygen show dyspneic respirations, which increase in violence
and finally become convulsive. The ordinary symptoms
described for death from asphyxia are due, therefore, to the
anoxemia — that is, lack of oxygen — not to the accumulation
of CO,.

Owing to this fact, most physiologists have assumed that
mere lack of oxygen may act as a stimulus to the respiratory
center. Some of those who believe, however, that the carbon
dioxid in the blood constitutes the normal stimulus to this
center explain the dyspnea due to sudden anoxemia as an indi-
rect effect. That is to say, it is assumed that the withdrawal
of oxygen leads to an accumulation of acid products (lactic
acid) in the nerve center, just as happens in the case of muscle
when deprived of an adequate supply of oxygen. The acid
products heighten the irritability of the nerve cells so that
they respond more readily to the stimulating action of the
carbon dioxid — whence the dyspnea.*

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
Dieters (33 feet), it will be seen that very high pressures of air
are not usually required. Caisson workers are at times attacked

* Bee Haldane and Poulton, "Journal of Physiology, " 37, 390, 1908.
f Friedlander and Herter, "Zeitschrift f. phyeiol. Chemie," 2, 99, L878,
and 3, 19, 1879.

INFLUENCE OF VARIOUS CONDITIONS ON RESPIRATION. 683

3)y 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 subject* 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,
^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, f 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 mms., — a pressure high enough,
one would suppose, not to endanger the oxygen supply. Mosso

* See Bert, loc. cit., p. 939; also Hill and MacLeod, "Journal of Physi-
ology, " 29, 382, and "Journal of Hygiene," 3, 407.

t See " Zuntz et al. Hohenklima u. Bergwanderungen in ihrer Wirkung
auf d. Menschen," Berlin, 1906. Mosso and Morro, "Archives italiennes de
biologie," 39, 387, also vols. 40 and 41. Cohnheim, article on " Alpinismus,"
'" Ergebnisse der Physiologie," vol. ii., part 1, 1903.

684 PHYSIOLOGY OF RESPIRATION.

states, also, from experiments upon monkeys, that lowering the
barometric pressure sufficiently (to about 250 nuns.) 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,
Crocc'-Spinelli, and Tissandier, April 15, 1875, are described in detail by the
last named in "La Nature," 1875, p. 337, also in Bert's "La pression baro-
metrique, " p. 1061. Only Tissandier survived. The balloonists were pro-
vided with bags containing oxygen (72 percent.), but they were unable to
make satisfactory use of them since shortly after passing 7500 meters they be-
came so weak that the effort to raise the arm to seize the oxygen tube was
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 usually 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 (hiring which the respira-
tory movements are not altered the determination of this ratio
throws lighl 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 and0.95 (Loewy) or between 0.75 and 0.89 (Magnus
Levy). Jf, however, the material oxidized in the body is entirely
carbohydrate the R. Q. should be equal to unify: r(\j = 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

INFLUENCE OF VARIOUS CONDITIONS ON RESPIRATION. 685

for that used in oxidizing the H to H20. Or, as expressed in a
reaction,

C6H1206tr+e602 = 6C02 + 6H20. R. Q. = $ = 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, C3HS(C16H3102)3 = C51Ha806.
2(C51H9806) + 14502 = 102CO2 + 98H20.
R. Q. = iff = 0.703.

In estimating the respiratory quotient for proteins one must
bear in mind the fact that these substances vary somewhat in
composition and, moreover, that the}r are not completely
oxidized in the body. Calculations based upon the amount of
unoxidized carbon and hydrogen escaping in the urine and
feces give the average figure of 0.801 for the R. Q. of proteins.
It is evident from these statements that an increase in the
proportion of carbohydrate food will cause the R. Q. to approach
unity, while an increase in protein and especially in fat will
lower its value. In this way we can understand the actual
variation observed in the average respiratory quotient of different
classes of animals, as shown in the following brief table (Loewy):

Horse, herbivorous — R.Q. =0.960
Sheep, " " =0.900

Man, omnivorous " =0.800
Dog, carnivorous " =0.750.

In starvation, when the body is living only on its own protein
and fat, the R. Q. is much lower than under a normal diet with
its large proportion of carbohydrate. By a determination of
the respiratory quotient before and after varying certain con-
ditions one may ascertain whether the given condition causes
a change in the character of the body metabolism. For example,
this method has been used to ascertain whether muscular work
effects any change in the nature of the material consumed in
the body. Experiments made upon this point indicate that
the R. Q. is not changed by muscular work when it is not
excessive or prolonged. Consequently we may infer that the
same kind of material, sugar, for example, is oxidized by the
contracting muscle as by the muscle at rest. In prolonged
or fatiguing muscular work the R. Q. may be lowered, due

686 PHYSIOLOGY OF RESPIRATION.

probably to the body using more of its fat; or in some conditions
it may be raised, owing to some insufficiency in the respiratory
and circulatory apparatus in furnishing an adequate supply of
oxygen. 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

Pig. 273.— Record showing typical Cheyne-Stokes respiration (from a case of aortic and
mitral insufficiency with arteriosclerosis). The time record gives seconds.

has in itself no nutritional significance, but it is 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.

Modified Respiratory Movements. Laughing, coughing, yawn-
ing, sneezing, sobbing, and even vomiting may be considered
a.- mollified respiratory movements, since the same group of muscles
come into play. These are all movements, with the exception of
yawning, which may be regarded as reflexes that have nothing to
do directly with the processes of respiration. A most interesting
variation of the normal type of respiration is known as the Cheyne-
Stokes respiration. It occurs in certain pathological conditions,
such as arteriosclerosis, uremic states, fatty degeneration of the
heart, and especially under conditions of increased intracranial.

INFLUENCE OF VARIOUS CONDITIONS ON RESPIRATION. 687

pressure. It is characterized by the fact that the respiratory
movements occur in groups (10 to 30) separated by apneic pauses,
which may last for a number (30 to 40) of seconds. After each pause
the respirations begin with a small movement, gradually increase
to a maximum, and then fall off gradually to the point of complete
cessation (see Fig. 273). Great variations, however, are shown in
the character and number of the respirations during the so-called
dyspneic phase. From observations made by means of the
sphygmomanometer Eyster * has shown that in this condition
there are also rhythmic waves of blood-pressure (Traube-Hering
waves), and according to the relation of these pressure waves to
the groups of respirations the Cheyne-Stokes cases fall into two
groups. In one group the dyspneic phase coincides with a fall
of blood-pressure and a slowing of the pulse-rate. In the other
group the reverse relations hold, the blood-pressure and pulse-rate
both rising during the dyspneic phase and falling during the apnea.
This latter group consists of cases in which there is evidence of
increased intracranial tension. Under experimental conditions
the author was able to show on dogs that an artificial increase in
intracranial tension calls forth Cheyne-Stokes respirations, whenever
it happens that rhythmic changes in blood-pressure are produced
of such a character that the blood-pressure rises and falls alternately
above and below the line of intracranial pressure. It is probable,
therefore, that in the clinical cases associated with a rise of intra-
cranial pressure the blood-pressure likewise rises and falls above
and below intracranial tension, and that the alternating periods
of apnea and dyspnea are due to this fact in this class of cases.
When the blood-pressure falls below intracranial pressure there
is a condition of deep anemia of the medulla sufficient to suspend
the activity of the respiratory center. The following rise of blood-
pressure by forcing more blood through the medulla calls forth a
group of respiratory movements.

By examination of the expired air Pembreyf has shown
that during the dyspneic phase the percentage of C02 in the
alveolar air is markedly diminished (2 per cent.), and he believes,
therefore, that the following phase of apnea is due entirely to
this washing out of the C02, that is, to the removal of the normal
stimulus to the respiratory center. Practically he finds that
the apneic phase can be removed by the administration of
either pure oxygen or carbon dioxid (2.2 to 11.2 per cent.).
Pembrey does not give the clinical histories of his patients, but
apparently he has studied cases belonging chiefly to Eyster's
first group. None of the suggestions made at present seem to

* Eyster, "Journal of Experimental Medicine," 1906.

f Pembrey, "Journal of Pathology and Bacteriology," 12, 258, 190S.

688 PHYSIOLOGY OF RESPIRATION.

account adequately for the very labored breathing at the acme
of the dyspneic phase, and the phenomenon evidently requires
further experimental study.

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,

44 689

690 PHYSIOLOGY OF DIGESTION AND SECRETION.

corresponding to the three anatomical regions — mouth, pharynx,
and esophagus — through which the swallowed morsel passes on its
way to the stomach. The first stage consists in the passage of the
bolus of food through the isthmus of the fauces, — that is, the
opening lying between the ridges formed by the palatoglossi muscles,
the so-called anterior pillars of the fauces. This part of the act is
usually ascribed to the movements of the tongue itself. The bolus
of food lying upon its upper surface is forced backward by the ele-
vation of the tongue against the soft palate from the tip toward
the base. This portion of the movement may be regarded as vol-
untary, to the extent at least of manipulating the food into its proper
position on the dorsum of the tongue, although it is open to doubt
whether the entire movement is usually effected by a voluntary
act. Under normal conditions the presence of moist food upon the
tongue seems essential to the complete execution of the act; and an
attempt to make the movement with very dry material upon the
tongue is either not successful or is performed with difficulty. The
second act comprises the passage of the bolus from the isthmus of
the fauces to the esophagus, — that is, its transit through the pharynx.
The pharynx being a common passage for the air and the food, it is
important that this part of the act should be consummated quickly.
According to the older description, the motor power driving the
bolus downward through the pharynx is derived from the contrac-
tion of the pharyngeal muscles, particularly the constrictors, which
contract from above downward and drive the food into the esopha-
gus. Kronecker and Meltzer,* however, have shown that the con-
traction of the mylohyoid muscle in the floor of the mouth is the
most important factor in this act of shooting the food suddenly
through the pharynx into the esophagus. The contraction of this
muscle marks the beginning of the purely involuntary part of the
act of swallowing. The bolus of food lies upon the dorsum of the
tongue and by (he 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 (ho contraction of the hyoglossi muscles, which by moving the
tongue backward and downward tend to increase the pressure put
noon the food. Simultaneously, a number of other muscles are
broughl 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, " L883, suppl. volume,
p. .''.L'.x; also "Journal <-f Experimental Medicine," 2, 453, 1897. For Inter
work, consult Cannon and Moser, "American Journal of Physiology." 1,
436, L898; Schreiber, "Archiv f. exper. Pathol, u. Pharmacologic, 46,
'til, 1001; ;iikI Eykman, "Archiv f. die gesammte Physiologie," ■»'), 513,
1903,

MOVEMENTS OF THE ALIMENTARY CANAL. 691

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-epiglotti clean 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 Phvsiologv, " 1892.
t "Journal of Physiology," 14, 154, 1893.

692 PHYSIOLOGY OF DIGESTION" AND SECRETION.

than a second elapses between the beginning of the contraction of
the mylohyoids and the entrance of the food into the upper end of
the esophagus.

The passage of the food through the esophagus differs apparently
with its consistency. When the food is liquid or very soft Kronecker
and Meltzer have shown that it is shot through the whole length of
the esophagus by the force of the initial act of swallowing. It
arrives at the lower end of the esophagus in about 0.1 sec, and may
pass immediately into the stomach or may lie some moments in the
esophagus according to the conditions of the sphincter guarding
the cardiac orifice. When, however, the food is solid or semi-
solid, as was shown by Cannon and Moser, it is forced clown 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,
ami 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
thai Le -Mot 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 ctnl of the esophagus until the wave of contraction reaches
it 6 gee.) and forces it through (he opening. According to the
observations made by Hertz,* liquids or liquid food arc hold
up at the cud of the esophagus and pass slowly into the stomach
through the sphincter. He estimates thai an interval of from
4.6 i" 8.6 sec. elapses before the swallowed bolus disappears

into the stomach, about one-half of this time being occupied
by the passage to the bottom of the esophagus and one-half in
the transit through the cardiac orifice of the stomach. At the

cardia or cardiac orifice the circular layer of muscles acts as a

sphincter which is normally in a condition of tone, particularly

* Hertz, "Guy's Hospital Reports," 61, 389, 1907.

MOVEMENTS OF THE ALIMENTARY CANAL. 693

when the stomach contains food. The advancing wave of con-
traction in the esophagus either forces the food through the
resistance offered by this sphincter, or probably the sphincter
suffers an inhibition at this moment as a part of the general
reflex action. Indeed, experiments have shown (von Mikulicz)
that the tonus of the cardiac sphincter is largely controlled
through the extrinsic nerves. Small pressures in the bottom of
the esophagus cause a dilatation of the cardia by inhibition.
Anatomically the cardiac sphincter receives-nerve fibers not
only from the vagus but also from the sympathetic by way of
the celiac ganglion. The precise control exerted through these
nerves has not yet been worked out. 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 down by the
first swallow waits in this case for the arrival of the succeeding
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. A still
more striking proof of the same fact is the interesting case cited
by v. Mikulicz of a man in whom a portion of the esophagus
had been resected on account of a carcinoma. The lower end
of the esophagus was given a fistulous opening in the neck and
and it was found that food introduced into this opening was
not moved toward the stomach until the patient made a swallow-
ing movement, f 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

* Moleschott's " Untersuchungen, " 1876, volume xi.

t Quoted from Cohnheim in Nagel's " Handbuch d. Physiologie."

694 PHYSIOLOGY OF DIGESTION AND SECRETION.

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 lib-
erating the reflex normally start. According to Kahn,* 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
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 some waul of agree-
ineni among different authors regarding the nomenclature of
the parts of the stomach, f For the purposes of a physiological
description we may use the names indicated in the accompany-

ehematic figure. The main interest lies in the separation of
i lie pyloric pari of i he Btomach or an1 rum pylori! from the main
cavity of the stomach. The line of separation is marked by a

re on t he small curvature, incisura angularis (/. A.), and on the

Kahn, "Archiv f. Physiologie, " 1903, suppl. volume, 386.
f See His, ' Vrchn f. Anatomie," L903, p. 345.

(Some recenl writers confine this term antrum pylori to thai portion
of the pyloric region bordering upon the pyloric orifice.

MOVEMENTS OF THE ALIMENTARY CANAL.

695

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-

Pyloric Jaart of 'stemai
or antrum hylon

Position of
transverse oand

Fundus

nlermedia.te or
prepyloric region.

Fig. 274.— Schematic figure to show the different parts of the stomach. — (After Retzius.)

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

696 PHYSIOLOGY OF DIGESTION AND SECRETION.

pylorus itself a special development of this layer functions as a
sphincter pylori, which with the aid of a circular fold of the mucous
membrane makes it possible to shut off the duodenum completely
from the cavity of the stomach. The line of separation between
the antrum pylori and the body of the stomach is made by a
special thickening of the circular fibers which forms a structure
known as the "transverse band" by the older writers,* and de-
scribed more recently t as the "sphincter antri pylorici." Under
certain conditions, such as vomiting, stimulation of the vagus,
etc., this sphincter may be contracted with such force as to sep-
arate the antrum entirely from the fundic end of the stomach.

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-
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 4 In recent years the subject has been studied with great
success by meansof the arrays, § on the excised stomach, || and by
means of tambours or sounds introduced into the stomach to meas-
ure the pressure changes. 1 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 pal her 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

♦ See Beaumont, " Physiology of Digestion, " second edition, IM7, p. in I.

f Hof meister und Schtitz, "Archiv f. exper. Pathologie und Pharmakol-
ogie," 1886, vol. xx.

J See (» ler, Journal of the American Medical Association," Nov. 15,
1902, for life of Beaumonl and account of his work.

J See Cannon, "American Journal of Physiology," I, 359, 1898; and
Rou and Balthazard, "Archives de Physiologie, " 10, .xa, 1898.

|| Hofmeister and Schtitz, loc. cit.

% Moritz, "Zeil chrift f. Biologie," 32, 359, 1896.

MOVEMENTS OF THE ALIMENTARY CANAL. 697

food into the stomach. Small contractions start in the middle
region of the stomach and run toward the pylorus. These moving
waves of contraction appear at regular intervals. The pyloric
portion becomes lengthened and it may be noticed that in this
region the peristaltic waves become more and more forcible as
digestion progresses. These running waves or rings of contraction
serve to press the stomach contents against the pylorus. According
to Cannon, they occur in the cat at intervals of 10 seconds and each
wave requires about 20 seconds to reach the pylorus. While in
human beings, to judge from the sounds which may be heard upon
ausculation when food mixed with air is given, they occur at intervals
of about 20 seconds. The obvious result of these movements is to
mix the food thoroughly, in the intermediate and pyloric portions
of the stomach, with the acid gastric juice and to reduce it to a thin,
liquid mass, — the chyme. At certain intervals the pyloric sphincter
relaxes and the contraction wave squeezes some of the fluid con-
tents into the duodenum with considerable force. The mechanism
controlling the relaxation of this sphincter is obscure. It does not
occur with the approach of each contraction wave, but at irregular
intervals. Cannon connects it in part with the consistency of the
food, but mainly with the effect of the hydrochloric acid in the
gastric secretion. Solid objects forced against the pylorus prevent
relaxation and retard the passage of the chyme into the intestine.
When liquid food alone is taken into the stomach numerous ob-
servations, made by means of intestinal fistulas, prove that the
material may be forced into the duodenum within a few minutes.
Hydrochloric acid in the stomach seems to favor or produce a
relaxation of the pyloric sphincter, while in the duodenum, on the
contrary, it causes a contraction of the sphincter. In this way it
may be imagined that after each ejection of acid chyme the sphinc-
ter is kept closed until the acid material in the duodenum is neutral-
ized, and so, automatically, a mechanism is provided by means of
which the duodenum is charged at intervals and at such times as it
is prepared to receive and neutralize a new quantity of the chyme.
According to this description, the portion of the food toward the
pyloric end of the stomach is the first to be thoroughly mixed with
the gastric juice, and to be broken down partly by digestion and
partly by the mechanical action of the contractions. This portion,
as it is liquefied, is expelled, and its place is taken by new material
forced forward from the fundic end. It would seem that this latter
portion of the stomach is in a condition of tone, and the pressure
thus put upon the contents is sufficient to force them slowly toward
the pyloric end as this becomes emptied. The older view was that the
contents of the stomach are kept in a general rotary movement so as
to become more or less uniformlv mixed ; but Cannon's observations,

698 PHYSIOLOGY OF DIGESTION AND SECRETION.

and also those of Gratzner,* 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. Griitzner 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

*ig. 2,o. — Section of frozen ,, » . , . , , ., ,,

stomach of rat during digestion to Walls 01 the Stomach, While the
show the stratification of food given j- .• i

at different times.— {Grutzner.) The succeeding portions were arranged
Sa:.K;u!£Pb&^ regularly in the interior in a con-

A^tet&fSad(iatedicby centric fashion' as shown in the
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 ujDon the relative duration of gastric
digestion for carbohydrates, proteids, and fats when fed separately
and combined. The foods were mixed with subnitrate of bismuth
and their position in the stomach and passage into the intestine
were watched by means of the Roentgen rays. It was found that
carbohydrate food begins to pass out from the stomach soon after
ingesl ion, and requires only aboul one-half as much time as the pro-
teins for complete gastric digestion. Fats remain long in the
stomach when taken alone, and when combined with the other
foodstuffs markedly delay their exit through the pylorus. This
distinct difference! in the main foodstuffs can hardly be referred to
mere mechanical consistency, since the fats .-ire liquefied by the
heal of the body. Cannon has shown thai this regulation is not
effected through I he agency of the exl rinsic nerves. After section of
the splanchnics and vagi the difference in I ime be1 ween t he ejection

* Grutzner, "Archiv f. die gesammte Physiologie, " L06, 463, L905.
f Cannon, "American Journal of Physiology," 12, 387, L904. Por :i
general review of Cannon's work, Bee "American Journal of the Medical
ace ," April, L906.

MOVEMENTS OF THE ALIMENTARY CANAL. 699

of carbohydrate and protein material still exists, so that the con-
trol in this matter must be exerted through some local mechanism
in the stomach itself. If, in a given diet, the carbohydrate is fed
before the protein, the former, having the position of advantage
toward the pyloric end, will be ejected promptly into the intestine,
while the protein is retained for gastric digestion. If the order is
reversed and the protein is fed first, the passage of the carbohydrate
out of the stomach will be retarded. This author has also reported
numerous interesting experiments, of medical and surgical interest,
which indicate that the motor activity of both stomach and intes-
tines may be greatly depressed by certain conditions, especially
by mechanical handling or by conditions of general asthenia.

Regarding the general mechanism of the stomach, it may be
pointed out that it forms an admirably adapted apparatus for
receiving at once, or within a short period, a large amount of food
which it reduces to a liquid or semiliquid condition, partly by
digestion, partly mechanically, and that it charges the intestine
at intervals with small amounts of this chyme in such a condition
as to admit of rapid digestion. It seems obvious that without the
stomach our mode of eating would have to be changed, as it would
not be possible to load the intestine rapidly with a large supply of
food such as is consumed at an ordinary meal.

The Relation of the Nerves to the Movements of the
Stomach. — The stomach receives nerve fibers from two sources, —
the vagi and the splanchnics, — but its orderly movements are merely
regulated through these extrinsic fibers; it is essentially an auto-
matic organ. Thus, it has been shown that the excised stomach
(Hofmeister and Schutz), when kept warm, continues to execute
regular movements which, if not identical with those observed under
normal conditions, have at least an orderly sequence. So also it
would appear from the results of several observers * that gastric
digestion may proceed normally both as regards secretion and
movements after section of the extrinsic nerves. We may regard
the stomach, considered as a motor mechanism, as an automatic
organ like the heart. Its stimuli to movement arise within itself,
but these movements are regulated by the action of the extrinsic
nerve fibers so as to adapt them to varying conditions. Whether
the automaticity is a property of the plain muscle tissue itself, or
depends upon the rich supply of intrinsic nerve ganglia (plexuses of
Meissner and Auerbach), is a question that cannot be answered
definitely at present. The extrinsic nerves not only supply the
stomach with efferent fibers, motor and secretory, but also carry
afferent fibers from the stomach to the central nervous system.

* See Heidenhain in Hermann's "Handbuch der Physiologie, " vol. v.,
p. 118. Also Cannon, "American Journal of Physiology," 1906.

700 PHYSIOLOGY OF DIGESTION AND SECRETION.

Regarding the purely efferent action of the extrinsic nerves, the
results of numerous experiments seem to show quite conclusively
that in general the fibers received along the vagus path are motor,
artificial stimulation of them causing more or less veil-marked con-
tractions of part or all of the musculature of the stomach. It has
been shown that the sphincter pylori as well as the rest of the muscu-
lature is supplied by motor fibers from these nerves. The fibers
coming through the splanchnics, on the contrary, are mainly inhib-
itory. When stimulated they cause a dilatation of the contracted
stomach and a relaxation of the sphincter pylori. Some observers
have reported experiments which seem to show that this anatomical
separation of the motor and inhibitory fibers is not complete; that
some inhibitory fibers may be found in the vagi and some motor
fibers in the splanchnics. The anatomical courses of these fibers
are insufficiently known, but there seems to be no question as to the
existence of the two physiological varieties. Through their activity,
without doubt, the movements of the stomach may be influenced,
favorably or unfavorably, by conditions directly or indirectly affect-
ing the central nervous system. Wertheimer* has shown experi-
mentally that stimulation of the central end of the sciatic or the
vagus nerve may cause reflex inhibition of the tonus of the stomach,
and Doyon f has confirmed this result in cases in which the move-
ments and tonicity of the stomach 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 tonus of intestinal movement have been distinguished,
— the peristaltic and the pendular or rhythmic.

Peristalsis. —The peristaltic movement consists in a constriction
of the walls of the intestine, which, beginning at a certain point,
downward away from the stomach, from segment to segment,
while the parts behind the advancing zone of constriction gradually
relax. The evident ef'feet of such a, movement is to push onward the
contents of the intestines in the direction of the movement. It is
obvious thai the circular layer of muscles is chiefly involved in

* "Archiv de physiologic normale el pathologique, " L892, p. :57i).
\Ibid., L895, p. 374.

MOVEMENTS OF THE ALIMENTARY CANAL. 701

peristalsis, since constriction can only be produced by contraction
of this layer. To what extent the longitudinal muscles enter into
the movement is not definitely determined. The term "anti-
peristalsis" is used to describe the same form of movement running
in the opposite direction — that is, toward the stomach. Anti-
peristalsis is said not to occur under normal conditions; it has been
observed in isolated pieces of intestine or in the exposed intestine
of living animals when stimulated artificially or after complete
intestinal obstructio n (Cannon) , and Grutzner * reports a number of
curious experiments which seem to show that substances such as
hairs, animal charcoal, etc., introduced into the rectum may travel
upward to the stomach under certain conditions. The peristaltic
wave normally passes downward, and that this direction of move-
ment is dependent upon some definite arrangement in the intestinal
walls is shown by the experiments of Mall f upon reversal of the
intestines. In these experiments a portion of the small intestine
was resected, turned around, and sutured in place again, so that in
this piece what was the lower end became the upper end. In those
animals that made a good recovery the nutritive condition gradually
became very serious, and when the animals were killed and ex-
amined it was found that there was an accumulation of food at the
stomach end of the reversed piece of intestine, and that this region
showed marked dilatation.

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, J 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

* "Deutsche medicinische Wochenschrift, " No. 48, 1894.
t "Johns Hopkins Hospital Reports," 1, 93, 1S96.
t "Journal of Physiology," 24, 99, 1899.

702 PHYSIOLOGY OF DIGESTION AND SECRETION.

law they find that in peristalsis the advancing wave of constriction
is preceded by a wave of relaxation or inhibition. The force of the
contraction as measured by Cash* in the dog's intestine is very small.
A weight of five to eight grams was sufficient to check the onward
movement of the substance in the intestine and to set up violent,
colikv contractions which caused the animal evident uneasiness.
The time required for the passage of food through the small in-
testine must vary with its amount and character. From obser-
vations made upon man with the x-ray Hertz estimates that on
the average it requires about 4| hours. After a meal, therefore,
we may imagine that at about the time the stomach has finished
discharging its contents into the duodenum the first portions
have reached the ileocecal valve. That is to say, a column of
food stretches at one time practically along the whole length of
the small intestine.

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.

Rhythmical Movements. — In addition to the peristaltic wave a
second kind of movement may be observed in the small intestines.
It comi t- c . .-cMti.'illy in a scries of local constrictions of the intes-
tinal wall, the constrictions occurring rhythmically at those points
;it which masses of food lie.

( '.union f h;is studied (hose movements most successfully by
means of the l{oentgen rays, lie finds that as a result- of these
contractions the masses or strings of food lying in the intestine are
suddenly segmented, repeatedly and in a definite manner, into a
number of Small pieces, which move to and fro as the pieces combine

*" Proceedings of the Royal Society," London, 41, L887.
f Cannon, "American Journal of Physiology," <>, 251, 1902.

MOVEMENTS OF THE ALIMENTARY CANAL. 703

and are again separated (see Fig. 276) . These segmentations may
proceed at the rate of thirty per minute for a certain time, and the
apparent result is that the material is well mixed with the digestive
secretions and is brought thoroughly into contact with the absorp-
tive walls. During these rhythmical contractions there is no steady
progression of the food; it remains in the same region, although
subjected to repeated divisions. From time to time the separated

x i^Jt ^ r^ r~> r~< ^ <*

' >0 CD CD CD CD cb k.

Fig. 276. — Diagram to show the effect of the rhythmical constricting movements of
the small intestine upon the contained food. A string of food (1) is divided suddenly into
a series of segments (2) ; each of the latter is again divided and the process is repeated a
number of times (3 and 4). Eventually a peristaltic wave sweeps these segments forward
a certain distance and gathers them again into a long string, as in (1). The process of
segmentation is then repeated as described above. (Cannon.)

pieces are caught by an advancing peristaltic wave, moved
forward a certain distance, and gathered again into a new mass.
In this new location the rhythmical contractions again segment
and churn the mass before a new peristaltic wave moves it on.
According to this description, the rhythmical movements are
local contractions (mainly of the circular muscles) which seem
to be due to the local distension caused by the food. They occur
rhythmically for a certain period and then cease until a new series
is started, and it is obvious that they must play a very important
part hi promoting both the digestion and absorption of the food.
Mall* has suggested that these rhythmical contractions of the
circular coats may also act as a pumping mechanism upon the
venous plexuses in the walls and thus aid in driving the blood into
the portal system. Similar movements have been observed
in the human being. f The curious observation is reported!
that during the period of fasting (dog) the whole gastro-intestinal
canal, although empty, shows at intervals rhythmical con-
tractions of its musculature which may last for twenty to thirty
minutes (see p. 762).

The Nervous Control of the Intestinal Movements. — There
is some evidence to show that the rhythmical contractions of the
intestines are muscular in origin (myogenic), while the more co-

* Mall, "Johns Hopkins Hospital Reports," 1896, i., 37.

f Hertz, loc. cit.

% BoldirefT, "Archives des sciences biologiques, " 11,1, 1905.

704 PHYSIOLOGY OF DIGESTION AND SECRETION.

ordiriated peristaltic movements depend upon the intrinsic nervous
mechanism. The intestine is, however, not dependent for either
movement upon its connections with the central nervous system.
Like the stomach, it is an automatic organ whose activity is simply
regulated through its extrinsic nerves.

The small intestine and the greater part of the large intestine
receive visceromotor nerve fibers from the vagi and the sympathetic
chain. The former, according to most observers, when artifically
stimulated cause movements of the intestine, and are therefore
regarded as the motor fibers. It seems probable, however, that the
vagi carry or may carry in some animals inhibitory fibers as well,
and that the motor effects usually obtained upon stimulation are
due to the fact that in these nerves the motor fibers predominate.
The fibers received from the sympathetic chain, on the other hand,
give mainly an inhibitory effect when stimulated, although some
motor fibers apparently may take this path. Bechterew and
Mislawski * state that the sympathetic fibers for the small intestine
emerge from the spinal cord as medullated fibers in the sixth dorsal
to the first lumbar spinal nerves, (or lower — Bunch) and pass to the
sympathetic chain in the splanchnic nerves and thence to the
semilunar plexus. The paths of these fibers through the central
nervous system are not known, but there are evidently connections
extending to the higher brain centers, since psychical states are
known to influence the movements of the intestine, and according
to some observers stimulation of portions of the cerebral cortex
ma}' 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
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-
ment-;. Organic acids, such as acetic, propionic, formic, and
* "Archiv f. Physiologie, " 1889, Buppl. volume.

MOVEMENTS OF THE ALIMENTARY CANAL. 705

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 opening from the
small intestine into the large is controlled both by the ileocecal
valve and by a sphincter, the ileocecal or ileocolic sphincter.
It is stated that this sphincter is normally in tonus and that
its condition of tonus is regulated through the splanchnic nerve
(Magnus). 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 infre-
quent, so that the material received from the small intestine
is slowly moved along while becoming more and more solid
from the absorption of water, until in the form of feces it reaches
the sigmoid flexure and rectum. Bayliss and Starling state
that their law of intestinal peristalsis holds in this portion of
the intestine, — that is, local excitation causes a constriction above
and a dilatation below the point stimulated. Cannon,* however,
from his studies of the normal movements in cats, as seen by the
Roentgen rays, comes to the conclusion that the movements in the
large intestine show a marked peculiarity previously overlooked.
He divides the large intestine into two parts; in the second, cor-
responding roughly to the descending colon the food is moved
toward the rectum by peristaltic waves. A number of constrictions
may be seen simultaneously within a length of some inches. In
the ascending and transverse colon and cecum, on the contrary, the
most frequent movement is that of antiperistalsis. The food in this
portion of the canal is more or less liquid and its presence sets up
running waves of constriction, which, beginning somewhere in the
colon, pass toward the ileocecal valve. These waves occur in groups
separated by periods of rest. The presence of the ileocecal valve
prevents the material from being forced back into the small in-
testine. The value of this peculiar reversal of the normal move-
ment of the bowels at this particular point would seem to lie in the
fact that it delays the passage of the material toward the rectum
and by thoroughly mixing it gives increased opportunities for the
completion of the processes of digestion and absorption. Hertz
estimates that in man the food requires about 2 hours to pass
from the ileocecal valve to the hepatic flexure and about 4+
hours to reach the splenic flexure. As the colon becomes filled
some of the material penetrates into the descending part, where
the normal peristalsis carries it very slowly toward the rectum.

The large intestine — particularly the descending colon and
rectum — receives its nerve supply from two sources (Fig. 277) :
(1) Fibers which leave the spinal cord in the lumbar nerves

* Cannon, loc. cit,
45

706

PHYSIOLOGY OF DIGESTION AND SECRETION.

(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 fibers. From this point
the path is continued by fibers running in the hypogastric nerves
and plexus. Stimulation of these fibers has given different
results in the hands of various observers, but the most recent
work* indicates that they are inhibitory. (2) Fibers that leave
the cord in the sacral nerves (second to fourth), form part of the
nervi ententes and enter into the hypogastric plexus. When

Sympathetic Trunk

I.L umbar

I. Lumbar ganglion

in,

H.L.gangl.

m.L.

M.L.gangl.
JV.L. '
lV.L.gangl.

V.L

VL (jUHql.

VI. L

Vl.h.gangl.

vn.L.

VH li c/angl-
1. Sacral

U.S.
MS.

Plttus Jfypoyos/r/aJS

Fin. 277. — Schema to show the innervation of (lie rectum ami internal sphincter
of the aim.-, ami the formation of the hypogastric plexus. (After Frankt-Hochwart and
Frdhlich.)

stimulated these fibers cause contractions of the muscular coats;
they may be regarded, therefore, as motor fibers. As in the
case of the small intestine and stomach, we may assume that
these motor and inhibitory fibers serve for the reflex regulation
and adaptation of the movements.

Defecation. — The undigested and indigestible parts of the
food, together with some of the debris and secretions from the
alimentary trad eventually reach the sigmoid flexure and
rectum. Authorities <\\i)'cv as io whether the rectum normally

* Langley and Anderson, "Journal of Physiology," L8, 67, 1895. Bay-
aid Starling, ibid., 26, 107, 1900. Also Wischnewsky, in Hermann's
"Jahresberichl der Pbysiologie, " vol, \ii., L905.

MOVEMENTS OF THE ALIMENTARY CANAL. 707

contains fecal material or not. Skiagraphic observations made
by Hertz* seem, however, to establish the fact that in man,
at least, this material accumulates in the rectum in the intervals
between defecations. 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 is thrown
into a condition of tonic contraction until the act of defecation
begins, when it is relaxed. The external sphincter ani is com-
posed of striated muscle tissue and is under the control of the
will to a certain extent. It is supplied by a motor nerve, the
Nn. hemorrhoidales inferiores, arising from the N. pudendus
and eventually from the sacral spinal nerves. This muscle,
therefore, like striated muscle in general, is innervated directly
from the spinal cord, but it possesses properties which are to
some extent intermediate between those of plain and of striated
muscle. For example, it differs from the latter and resembles
the former in the fact that it does not atrophy after section of
its motor nerve; it is much less sensitive to the paralyzing action
of curare than the typical striated muscle, and it is stated that
its curve of contraction, when it is stimulated through its nerve,
exhibits a long latent period and a slow contraction and relaxa-
tion. Both the internal and the external sphincter are normally
in tonus and unite in protecting the anal opening. The force
of the tonic contraction of the internal is somewhat less (30 to
60 per cent.) than that of the external sphincter. f The innerva-
tion and control of the internal sphincter is better understood
than that of the external. Like the rest of the rectum, it receives
motor fibers from the hypogastric plexus by way of the nervus
erigens, and inhibitory fibers from the same plexus by way of the
hypogastric nerve. It has been possible to show experimentally
that each of these sets of fibers may be acted upon reflexly, for
example, by stimulation of the sensory nerves in the sciatic.
The reflex takes place in this case through the lower portion of
the cord. Both the hypogastric nerve and the N. erigens con-
tain also afferent fibers. Stimulation of the central end of the
severed N. erigens gives a reflex inhibition through the hypo-
gastric nerve, and stimulation of the central stump of the cut
hypogastric causes a reflex contraction through the N. erigens.

* Hertz, "Guy's Hospital Reports," Gl, 389, 1907.

f Consult Frankl-Hochwart and Frohlich, "Archiv f. d. ges. Physiologie, "
81, 420.

708 PHYSIOLOGY OF DIGESTION AND SECRETION.

It is even stated that these latter reflexes may be obtained
when the lumbosacral cord is destroyed, a fact which if correct
would indicate a reflex effected through an outlying ganglion
(inf. mesenteric ganglion). The act of defecation as it occurs
normally is partly a voluntary and partly an involuntary act.
The involuntary act consists in peristaltic contractions of the
rectum or, indeed, of the whole colon, together with an inhibi-
tion of the sphincters. Whether the inhibition of the sphincters
is normally entirely an involuntary reflex cannot be stated
definitely. No doubt the sensory stimuli arising from the accu-
mulation of fecal material would eventually cause in this way
a relaxation of the sphincters, but the act of defecation usually
takes place before such a strong necessity arises. It is initiated
usualh'' hy a voluntary act and it is possible that in such cases
the relaxation of both sphincters may be effected by voluntary
inhibition acting upon the spinal centers.

The voluntary factor in defecation consists mainly in the
contraction of the abdominal muscles. When these latter
muscles are contracted and at the same time the diaphragm is
prevented from moving upward by the closure of the glottis,
the increased abdominal pressure is brought to bear upon the
abdominal and pelvic viscera, and aids strongly in pressing the
contents of the descending colon and sigmoid flexure into the
rectum. The pressure in the abdominal cavity is still further
increased if a deep inspiration is first made and then maintained
during the contraction of the abdominal muscles. Hertz, on
the basis of his skiagraphic observations, insists that simul-
taneously with the contraction of the abdominal muscles and
the closure of the glottis the diaphragm is also contracted and
thus aids in bringing pressure to bear upon the pelvic organs.
Although the act of defecation is normally initiated by voluntary
effort, it may also be carried out ;is a purely involuntary reflex
when the sensory stimulus is sufficiently 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 hud recovered 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.

*"Archiv f. die gesammte Physiologie, " 8, L60, L874; 63, 362, L896.

MOVEMENTS OF THE ALIMENTARY CANAL. 709

It would seem that the whole act of defecation is, at bottom,
an involuntary reflex. The physiological center for the move-
ment probably lies in the lumbar cord, and it has sensory and
motor connections with the rectum and the muscles of defecation.
As stated above, the inhibitory fibers to the internal sphincter
pass by way of the hypogastric nerve, the motor fibers through
the nervus erigens, and both of these nerves contain afferent
fibers which may reflexly excite inhibition or contraction. But
this center is probably provided also with intraspinal con-
nections with the centers of the cerebrum, through which the
act may be controlled by voluntary impulses and by various
psychical states; the effect of emotions upon defecation being
a matter of common knowledge. In infants the essentially in-
voluntary 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 stom-
ach itself or whether it is due mainly to the action of the walls of
the abdomen. A forcible spasmodic contraction of the abdominal
muscles takes place, as may easily be observed by any one upon
himself, and it is now believed that the contraction of these muscles
is the principal factor in vomiting. Magendie found that if the
stomach was extirpated and a bladder containing water was sub-
stituted in its place and connected with the esophagus, injection
of an emetic caused a typical vomiting movement with ejection of
the contents of the bladder. Gianuzzi showed, on the other hand,
that upon a curarized animal vomiting could not be produced by an
emetic — because, apparently, the muscles of the abdomen were
paralyzed by the curare. There are on record a number of ob-
servations which tend to show that the stomach is not passive
during the act. On the contrary, it may exhibit contractions, more
or less violent in character. According to Openchowski,* the
pylorus is closed and the pyloric end of the stomach firmly con-
tracted so as to drive the contents toward the dilated cardiac por-
tion. Cannon states that in cats the normal peristaltic waves pass
over the pyloric portion in the period preceding the vomiting and
that finally a strong contraction at the "transverse band" com-
pletely shuts off the pyloric portion from the body of the stomach,
which at this time is quite relaxed. The act of vomiting is, in fact,
a complex reflex movement into which many muscles enter. The
following events are described : The vomiting is usually preceded by
a sensation of nausea and a reflex flow of saliva into the mouth.
These phenomena are succeeded or accompanied by retching move-
"Arehiv f. Physiologie, " 1889, p. 552.

710 PHYSIOLOGY OF DIGESTION AND SECRETION.

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 b}^ 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, probably by an inhibition of the
sphincter caused by the rise of pressure in the stomach, 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 vomit-
ing, however, the vomited material may break through this
latter barrier and be ejected partially through the nose.

Nervous Mechanism of Vomiting. — That vomiting is a reflex act
is abundantly shown by the frequency with which it is produced in
consequence of the stimulation of sensory nerves or as the result
of injuries to various parts of the central nervous system. After
lesions or injuries of the brain vomiting often results. Disagreeable
emotions and disturbances of the sense of equilibrium may produce
the same result. Irritation of the mucous membrane of various
parts of the alimentary canal (as, for example, tickling the back
of the pharynx with the finger); disturbances of the urogenital
apparatus, the liver, and other visceral organs; artificial stimula-
tion of the trunk of the vagus and of other sensory nerves, may all
cause vomiting. Under ordinary conditions, however, irritation of
the sensory nerves of the gastric mucous membrane is the most
common cause of vomiting. This effect may result from the prod-
ucts of fermentation in the stomach in cases of indigestion, or may
he 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 aerves 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 def>-

MOVEMENTS OF THE ALIMENTARY CANAL. 711

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 ma3^
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
directlv on the nerve centers.

Foodstuffs

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:

f Water.
Inorganic salts.
Proteins.

Albuminoids, a group of bodies belonging to the general group
of proteins, but having in some respects a different nutri-
tive 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 mimed above are all foods in this sense. The water and
certain salts of sodium, potassium, calcium, magnesium, iron, and
perhaps other elements arc absolutely necessary to maintain the
normal composition of the tissue. Complete withdrawal of any
one of these eonstituents would cause the death of the organism.
Proteins, fits, 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

712

COMPOSITION OF FOOD AND ACTION OF ENZYMES.

713

molecules into simpler compounds. The chemical changes of metab-
olism or nutrition are, in the long run, mainly exothermic, — that
is, they are attended by the production of heat* Some of the chem-
ical or internal energy that held the complex molecules together
assumes the form of heat, or perhaps muscular work, after these
molecules are broken down by oxidative changes to simpler, more
stable structures, such as water, carbon dioxid, and urea. Proteins,
fats, and carbohydrates form materials that the tissue cells are
adjusted to act upon after they have undergone certain changes
during digestion. Other complex organic compounds containing
chemical energy are either injurious to the tissues, or they have a
structure such that the tissues cannot act upon them. Such
substances cannot be considered as foods in the scientific sense.
When, therefore, we desire to know the food value of any animal
or vegetable product, we analyze it to determine its composition as
regards water, salts, proteins, fats, and carbohydrates. The
following table compiled by Munk from the analyses given by
Konig * may be taken as an indication of the average composition
of the most commonly used foods:

COMPOSITION OF FOODS.

In 100 Parts.

Water.

Protein.

Fat.

76.7

20.8

1.5

73.7

12.6

12.1

36-60

25-33

7-30

87.7

3.4

3.2

89.7

2.0

3.1

13.3

10.2

0.9

35.6

7.1

0.2

13.7

11.5

2.1

42.3

6.1

0.4

13.1

7.0

0.9

13.1

9.9

4.6

10.1

9.0

0.3

12-15

23-26

li-2

75.5

2.0

0.2

87.1

1.0

0.2

90

2-3

0.5

73-91

4-8

0.5

84

0.5

Carbohydrate

Meat

Eggs

Cheese

Cows' milk

Human milk

Wheat flour

Wheat bread

Rye flour

Rye bread

Rice

Corn

Macaroni

Peas, beans, lentils

Potatoes

Carrots

Cabbages

Mushrooms

Fruit

An examination of this table shows that the animal foods, par-
ticularly the meats, are characterized by their small percentage in
carbohydrate and by a relatively large amount of protein or of
protein and fat. With regard to the last two foodstuffs, meats differ

*See Konig, "Die menschlichen Nahrungs und Genussmittel ": and
Atwater and Bryant, "The Chemical Composition of American Food Mate-
rials," Bulletin 28, United States Department of Agriculture, 1899.

•14

PHYSIOLOGY OF DIGESTION AXD 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.

Protein.

Fat.

Carbohydrate.

Ash.

Beef, moderately fat ....

Veal, fat

Mutton, moderately fat. .

73.03
72.31

75.99
72.57
62.58
10.00
71.6

20.96
18.88
17.11
20.05
22.32
3.00
18.8

5.41
7.41

5.77
6.81
8.68
S0.50
8.2

0.46
0.07

1.14
1.33
1.33
1.10

Pork (bacon), very fat* .
Mackerel *

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
proteins and fats, as seen, for example, in the composition of rice,
corn, wheat, and potatoes. Nevertheless, it will be noticed that the
proportion of protein in some of the vegetables is not at all insignifi-
cant. They are characterized by their excess in carbohydrates
rather than by a deficiency in proteins. The composition of peas
and other leguminous foods is remarkable for the large percentage
of protein, which exceeds that found in meats. Analyses such as
are given here are indispensable in determining the true nutritive
value of foods. Nevertheless, it must be borne in mind that the
chemical composition of a food is not alone sufficient to determine
its precise value in nutrition. It is obviously true that it is not what
we eat, but what we digest and absorb, that is nutritious to the
body; so that, in addition to determining the proportion of food-
stuffs in any given food, it is necessary to determine to what extent
the several constituents are digested. This factor can be obtained
only by actual experiments. It may be said here, however, that
in general the proteins of animal foods are more completely digested
than arc those of. vegetables, owing chiefly to the fact that the
Latter may contain a considerable amounl of indigestible cellulose,
which tends to proted the protein from the action of the diges-
tive secretions. In the animal foods, therefore, chemical analysis
conic- 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 abso-
lutely necessary. These substances, differing in nature and
importance, may be classified under the three heads of:

Flavor : the various oils or esters tliut give odor and taste to foods.
Condimenl : pepper, salt, mustard, etc.
Stimulants: alcohol, tea, coffee, cocoa, etc.

* Atwater: "The Chemistry of Foods and Nutrition," 1887.

COMPOSITION OF FOOD AND ACTION OF ENZYMES. 715

The specific influence of these substances in digestion and nutri-
tion is considered in the section on Nutrition.

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 THEK 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. lor the historical develop-

716 PHYSIOLOGY OF DIGESTION AND SECRETION.

ment and interrelation of these theories references must be made to
special works.* It is sufficient here to say that the brilliant work
of Pasteur established the fact that the fermentations in the old
sense — alcoholic, acid, and putrefactive — are due to the presence
and activity of living organisms. He showed, moreover, that
many diseases are likewise due to the activity of minute living
organisms, and thus justified the view held by some of the older
physicians that there is a close similarity in the processes of fer-
mentation and disease. The clear demonstration of the importance
of living organisms in some fermentations and the equally clear
proof of the existence of another group of ferment actions in which
living material is not directly concerned led to a classification which
is used even at the present day. This classification divided fer-
ments into two great groups : the living or organized ferments, such
as the yeast cell, bacteria, etc.; and the non-living or unorganized
ferments, such as pepsin, trypsin, etc., which later were generally
designated as enzymes (Kuhne). The separation appeared to be
entirely satisfactory until Buchner (1897) showed that an unor-
ganized ferment, an enzyme (zymase) capable of producing alcohol
from sugar, may be extracted from yeast cells. Later the same
observer (1903) succeeded in extracting enzymes from the lactic-
acid-producing bacteria and the acetic-acid-producing bacteria
which are capable of giving the same reactions as the living bacteria.
These discoveries indicate clearly that there is no essential difference
between the activity of living and non-living ferments. The so-
called organized ferments probably produce their effects not by
virtue of their specific life-metabolism, but by the manufacture
within their substance of specific enzymes. If we can accept this
conclusion, then the general explanation of fermentation is to be
sought in the nature of the enzymatic processes. Within recent
years the study of the enzymes has attracted especial attention.
The general point of view regarding their mode of action that is
fcnosl frequently met with to-day is that advocated especially
by Ostwald. He assumes, reviving an older view (Berzelius),
ili.it the ferment actions are similar to those of catalysis. By
catalysis chemists designated a species of reaction which is brought
aboui by the mere contact or presence of certain substances, the
catalyzers. Thus, hydrogen and oxygen ;it ordinary temperatures
do not combine to form water, but if spongy platinum is present
the two gases unite readily. The platinum does not enter into the
reaction, at least it undergoes no change, and it is said, therefore,

* Consult, Clrecri. "The Soluble Ferments and Fermentations, " 1899;
Effront, "Enzymes and their Applications" (translation by Prescott), 1902;
Oppenheimer, "Die Fermente and ihre Wirkungen," second edition, 1903;
Moore, in "Recent Advances in Physiology and Biochemistry, London and
New York," 1906: and " rlandbuch der Biochemie," vol. L L908.

COMPOSITION OF FOOD AND ACTION OF ENZYMES. 717

to act by catalysis. Many similar catalytic reactions are known,
and the chemists have reached the important generalization that
in such reactions the catalyzer, platinum in the above instance,
simply hastens a process which would occur without it, but much
more slowly. A catalyzer is a substance, therefore, that alters
the velocity of a reaction, but does not initiate it. This idea is
illustrated very clearly by the catalysis of hydrogen peroxid. This
substance decomposes spontaneously into water and oxygen accord-
ing to the reaction H202 = H20 + 0, but the decomposition is
greatly hastened by the presence of a catalyzer. Thus, Bredig has
shown that platinum in very fine suspension, so-called colloidal
solution, exerts a marked accelerating influence upon this reaction;
one part of the colloidal platinum to 350 million parts of water
may still exercise a perceptible effect. The blood and aqueous ex-
tracts of various tissues also catalyze the hydrogen peroxid readily,
and this effect has been attributed to the action of an enzyme (cata-
lase). The view has been proposed, therefore, that the enzymes of
the body act like the catalyzers of inorganic origin: they influence
the velocity of certain special reactions. Such a general conception
as this unifies the whole subject of fermentation and holds out the
hope that the more precise investigations that are possible in the case
of the inorganic catalyzers will eventually lead to a better under-
standing of the underlying physical causes of fermentation. It
should be borne in mind, however, that some of the best known of the
ferment actions of the body, such as the peptic or tryptic digestion of
protein, fit into this view only theoretically and by analogy. As a
matter of fact, albumins at ordinary temperatures do not split up
spontaneously into the products formed by the action of pepsin;
if we consider that the pepsin simply accelerates a reaction already
taking place, it must be stated that this reaction at ordinary
temperatures is infinitely slow, — that is, practically does not occur.
At higher temperatures, however, similar decompositions of al-
bumin may be obtained without the presence of an enzyme.

Reversible Reactions. — It has been shown that under proper
conditions many chemical reactions are reversible, — that is, may
take place in opposite directions. For instance, acetic acid and
ethyl-alcohol brought together react with the production of ethyl-
acetate and water:

CH3COOH + 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

718 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 I issues, 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 ami Loevenhart, "American Chemical Journal," 24, 401, 1900.
See also Loevenhart, " American Physiological Journal," 0, 331, 1902.

COMPOSITION OF FOOD AND ACTION OF ENZYMES. 719

A similar reversibility has been shown for some of the other
enzymes of the body (maltase by Hill, 1898), but whether or not all
of them will be shown to possess this power under the conditions of
temperature, etc., that prevail in the body can only be determined
by actual experiments.

The Specificity of Enzymes. — A most interesting feature of
the activity of enzymes is that it is specific. The enzymes that
act upon the carbohydrates are not capable of affecting the pro-
teins or fats, and vice versa. So in the fermentation of closely
related bodies such as the double sugars, the enzyme that acts
upon the maltose is not capable of affecting the lactose; each re-
quires seemingly its own specific enzyme. In fact, there is no clear
proof that any single enzyme can produce more than one kind of
ferment action. If in any extract or secretion two or more kinds
of ferment action can be demonstrated, the tendency at present
is to attribute these different activities to the existence of separate
and specific enzymes. The pancreatic juice, for example, splits
proteins, starches, and fats and curdles milk, and there are assumed
to be four different enzymes present, — namely, trypsin, diastase,
lipase, and rennin. So if an extract containing diastase is also
capable of decomposing hydrogen peroxid it is believed that this
latter effect is due to the existence of a special enzyme, catalase.
It seems quite probable that this specificity of the different enzymes
may be related, as Fischer * has suggested, to the geometrical struc-
ture of the substance acted upon. Each ferment is adapted to act
upon or become attached to a molecule with a certain definite
structure, — fitted to it, in fact, as a key to its lock. In this respect
the action of the so-called hydrolytic enzymes differs markedly from
the dilute acids or alkalies which hydrolyze many different substances
without indication of any specificity. Attention has been called to
the fact that this adaptibility of enzymes to certain specific struc-
tures in the molecules acted upon resembles closely the specific
activity of the toxins, and many useful and suggestive com-
parisons may be drawn between the mode of action of enzymes
and toxins. It has become customary to speak of the substance
upon which an enzyme acts as its substrate, and it has been
assumed that the action of the enzyme, like that of the toxins,
takes place in two stages; first, the combination of the enzyme
and the substrate; second, the breaking down of this compound
to give the final products of the reaction. There is some reason
for believing that these two stages may be separated, and that
enzymes which on account of certain conditions, such as heating,
have lost their power of decomposing the substrate, may still
have the power of combining with it. Toxins showing a similar
* Fischer, "Zeitschrift f. physiolog. Chemie, " 26, 71, 1898.

720 PHYSIOLOGY OF DIGESTION AND SECRETION.

property are designated as toxoids, and for the enzyme in this
condition the term zymoid has been suggested (Bayliss).

Definition and Classification of Enzymes (Ferments). — On the
basis of the considerations presented in the preceding paragraphs
Oppenheimer suggests the following definition: An enzyme is a
substance, produced by living cells, which acts by catalysis. The
enzyme itself remains unchanged in this process, and it acts specifi-
cally.— that is, each enzyme exerts its activity only upon substances
whose molecules have a certain definite structural and stereochemi-
cal arrangement. The enzymes of the body are organic substances
of a colloid structure whose chemical composition is unknown.

With regard to the names and classification of the different
enzymes, much difficulty is experienced. There is no consensus
among workers as to the system to be followed. Duclaux has sug-
gested that an enzyme be designated by the name of the body on
which its action is exerted, and that all of them be given the termina-
tion ase. The enzyme acting on fat on this system would be named
lipase; that on starch, amylase; that on maltose, maltase, etc. The
suggestion has been followed in part only, the older enzymes which
were first discovered being referred to most frequently under their
original names. An entirely satisfactory classification is impossible
at present. Having in mind only the needs of animal physi-
ology, the following classification will be used in the treatment of
the subjects of digestion and nutrition:

1. The proteolytic or protein-splitting enzymes. Examples: pepsin

of gastric juice, trypsin of pancreatic juice. They cause a hydro-
lytic cleavage of the protein molecule.

2. The amylolytic or starch-splitting enzymes. Examples: ptyalin
or salivary diastase, amylase, or pancreatic diastase. Their action
is closely similar to dial of the classical enzyme of this group — dias-
tase— 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 I he double sugars or di-
saccharids into the monosaccharids. Examples: maltase, which
splits maltose to dextrose; invertase, which splits cane-sugar to
dextrose ami Levulose; and lad, ase, which splits milk-sugar (lactose)

to dextrose ami galactose. (/') The enzymes which split the m on o-
i hands. There is evidence of the presence in the tissues of an

enzyme capable of splitting the sugar of the blood and tissues
(dexl rose) into lactic acid.

5. The coagulating enzymes, which convert soluble to insoluble pro-
tein . I . cample: The coagulation of the casein of milk by rennin.

ft. The oxidizing enzymes or oxidases. A group of enzymes which set

up oxidation processes. Some of the details of the activity of these
enzymes an- considered in the discussion of physiological oxidations
(p. 918).
7. The deamidizing enzymes, such as adenase and guanase, which by

hydrolyl IC cleavage split off an N 1 1., group as ammonia.

COMPOSITION OF FOOD AND ACTION OF ENZYMES. 721

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:

C12H22Ou + H20 = C6H]206 + C6H1206.

Maltose. Dextrose. Dextrose.

And the hydrolysis of the neutral fats by lipase may be expressed
so:

C3H5(C18H3502)3 + 3H20 = C,Hs(OH)3 + 3(C18H30O2).
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 destroj^ed in the process
of extraction, and to prove its presence pieces of the tissue or the
juice pressed from the tissue must be employed.

Temperature. — The body enzymes are characterized by the fact
that they are destroyed by high temperatures (60° C. to 80° C.) and
that their effect is retarded in part or entirely by low temperatures.
Most of them show an optimum activity at temperatures approxi-
mating that of the body.

Precipitation. — The enzymes are precipitated from their solutions
in part at least by excess of alcohol. This precipitation is frequently
used in obtaining purified specimens of enzymes. The enzymes,
moreover, show an interesting tendency to be carried down mechani-
cally by flocculent precipitates produced in their solutions. If
protein present in the solution is precipitated, for instance, the
enzymes may be carried down with it in part.

Incompleteness of their Action. — In any given mixture of a sub-
stance and its enzyme the action of the latter is usually not com-
plete,— that is, all of the substance does not disappear. An explana-
tion for this fact has been found in the reversibility of the action of
the enzyme. If the reaction proceeds in both directions, then
evidently under fixed conditions a final equilibrium will be reached
in which no further apparent change takes place, although in reality
the condition is not one of rest, but of balance between opposing
processes proceeding at a definite rate. Within the body itself,
on the contrary, the action of an enzyme may be complete, since the
products are removed by absorption and the possibility of a re-
versed reaction is removed.
46

722

PHYSIOLOGY OF DIGESTION AND SECRETION.

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
or proferment. The zymogen may be stored in the cell in the
form of granules which are converted into 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. In connection
with the process of activation various terms have been emplo)red
to designate the substance responsible for the activation.
According to a recent classification* it has been suggested that
inorganic substances causing activation shall be designated
simply as activators, while organic substances playing a similar
role shall be named kinases. An example of the latter is found
in the case of the enterokinase which activates the trypsin of the
pancreatic secretion.

PARTIAL LIST OF THE ENZYMES CONCERNED IN THE PROC-
ESSES OF DIGESTION AND NUTRITION.

-3

s

Cm

Enzyme.

f Ptyalin (sali-
vary diastase.

Amylase
(pancreatic
diastase).

Liver diastase.

Muscle diastase.

Invertase.

Maltase.

Lactase.

Glycolytic?

Lipase (steap-
sin).

Pepsin.

Trypsin.

Brepsin.

Group of auto-
lytic enzymes.

Where Chiefly
Found.

Salivary secretion.

Pancreatic secre-
tion.

Liver.

Muscles.

Small intestine.

Small intestine,
salivary and

pancreatic se-
cretion.

Small intestine.

Muscles?

Pancreatic secre-
1 ion, fat tissues,
blood, etc.

Gastric juice.

Pancreatic juice.

Small intestine.
Tissues generally.

imuely in '' Elandbucb der Biochemie

Action.

Converts starch to sugar

(maltose).
Converts starch to sugar
(maltose).

Converts glycogen to dex-
trose.

Converts glycogen to dex-
trose.

Converts cane-sugar to
dextrose and levulose.

Converts maltose to dex-
trose.

Converts lactose to dex-
trose and galactose.

Splits and oxidizes dex-
trose.

Splits neutral fats to fatty
acids and glycerin.

Converts proteins to pep-
tones and pro I coses.

Splits proteins into sim-
pler crystalline prod-
ucts.

Splits peptones into sim-
pler products.

Splits proteins into nitrog-
enous bases and amino*
bodies.
1908.

COMPOSITION OF FOOD AND ACTION OF ENZYMES.

723

• -• m
o3 C I

p I

Nuclease.

Guanase.

Adenase.

Oxidases.

Catalase.

Pancreas, spleen,
thymus, etc.

Thymus, adrenals,
pancreas.

Spleen, pancreas,
liver.

Lungs, liver, mus-
cle, etc.

Many tissues.

Splits nucleic acid with for-
mation of purin bases,
etc.

Converts guanin to xan-
thin by splitting off an
NH2 group as ammonia
(NH3).

Converts adenin to hypo-
xanthin by splitting off
an NH, group as am-
monia (NH3).

Cause oxidation of organ-
ic substances, as in the
conversion of hypoxan-
thin to xanthin and of
xanthin to uric acid.

Decomposes hydrogen
peroxid.

Chemical Composition of the Enzymes. — It was formerly
believed that the enzymes belong to the group of proteins. They
are formed from living matter, and their solutions as usually
prepared give protein reactions. Increased study, however, has
made this belief uncertain. The enzymes cling to the proteins
when precipitated, and it seems possible that the protein reac-
tions of their solutions may be due, therefore, to an incomplete
purification. In fact, it is stated that solutions of some of the
enzymes may be prepared which show ferment activity, but
give no protein reactions. In this group may be included the
lipase, diastase, invertase, pepsin, oxidase, and catalase. Appar-
ently, however, all enzymes contain nitrogen and most of them
also sulphur. They probably also contain some ash, especially
calcium. 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. The statement made above that they are organic
substances, derived from proteins and of a colloidal nature, is
perhaps as much as can be said positively in regard to their
chemical structure.

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. 278). The sympathetic
autonomics passto the superior cervical ganglion by way of the
cervical sympathetic (Fig. Ill) and thence as postganglionic fibers
in branches which accompany the arteries distributed to the gland.
The bulbar autonomic supply for the submaxillary and sublingual

724

THE SALIVARY GLANDS.

725

glands arises from the brain in the facial nerve and passes out in the
chorda tympani branch (Fig. 279) . This latter nerve, after emerging
from the tympanic cavity through the Glaserian fissure, joins the

Inferior?ft<ail(aw
£ra.ncAoft>t!}

Tetrous
Sanation.

Fig. 278.— 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,

Tnferioflttaxillarv
JJBranehefj&!

Sub- 7Haxilla.rtf i
Su6 lin-yua-t-

Gaiwlu

■^Branches
to

*Tongu£

Fig. 279. — 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

726 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 tin- mucous cells. In consequence of long-continued activity
the mucous cells may disintegrate and disappear, and the demilunes then
lop into new mucous cells. Another view is that the demilunes represent
distind 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.f The accounts differ somewhat as
to details of the finer anatomy, but if seems to be clearly established
I hat f ho secretory fibers from the chorda tympani end first around the

♦ See Noll, "Archiv f. Physiologic," VMY>, suppl. volume, 166.
fSee Huber, "Journal of Experimental Medicine," 1, 281, 1896.

THE SALIVARY GLANDS. 727

intrinsic nerve ganglion cells of the glands (preganglionic fibers), and
from these latter cells axons (postganglionic fibers) are distributed
to the secreting cells, passing to these cells along the ducts. The
nerve fibers terminate in a plexus upon the membrana propria of the
alveoli, and from this plexus fine fibrils pass inward to end on and
between the secreting cells. It would seem from these observations
that the nerve fibrils do not penetrate or fuse with the gland cells,
as was formerly supposed, but form a terminal network in contact
with the cells, following thus the general schema for the connection
between nerve fibers and peripheral tissues.

Composition of the Secretion. — The saliva as it is found in the
mouth is a colorless or opalescent, turbid, and mucilaginous liquid of
weakly alkaline reaction and a specific gravity of about 1.003. It
may contain numerous flat cells derived from the epithelium of the
mouth, and the peculiar spherical cells known as salivary corpuscles,
which seem to be altered leucocytes. The important constituents
of the secretion are mucin, a diastatic enzyme known as ptyalin,
maltase, traces of protein and of potassium sulphocyanid, and
inorganic salts such as potassium and sodium chlorid, potassium
sulphate, sodium carbonate, and calcium carbonate and phosphate.
The carbonates are particularly abundant in the saliva, and the
secretion in addition contains much carbon dioxid in solution.
Thus, PfKiger 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
carbonates. 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 protein 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 proteins, glyco-
proteins (see Appendix), consisting of a protein combined with a
carbohydrate group. The most interesting constituent of the mixed
saliva is the ptyalin or salivary diastase. This body belongs to the
group of enzymes or unorganized ferments, whose general properties
have been described. In some animals (dog) ptyalin seems to be
normally absent from the fresh saliva.

The secretions of the parotid and the submaxillary glands can be
obtained separately by inserting a cannula into the openings of the
ducts in the mouth, or, according to the method of Pawlow, by trans-
ferring the end of the duct so that it opens upon the skin instead of
in the mouth, making thus a salivary fistula. The secretion of the
sublingual can only be obtained in sufficient quantities for analysis
from the lower animals. Examination of the separate secretions
shows that the main difference lies in the fact that the parotid saliva
contains no mucin, while that of the submaxillary and especially of

728 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-
lar}- gland. He established also several important facts with regard
to the pressure and composition of the secretion which will be referred
to presently. It was afterward shown that the salivary glands receive
a double nerve supply, — in part by way of the cervical sympathetic
and in part through cerebral nerves. It was discovered also that
not only are secretory fibers carried to the glands by these paths,
but that vasomotor fibers are contained in the same nerves,
and the arrangement of these latter fibers is such that the cerebral
nerves contain vasodilator fibers that cause a dilatation of the small
arteries in the glands and an accelerated blood-flow, while the sym-
pathetic carries vasoconstrictor fibers whose stimulation causes a
constriction of the small arteries and a diminished blood-flow. The
effect of stimulating these two sets of fibers is found to vary somewhat
in different animals. For purposes of description we may confine
ourselves to the effects observed on dogs, since much of our funda-
mental knowledge upon the subject is derived from Heidenhain's*
experiments upon this animal. If the chorda tympani nerve is
stimulated by weak induction shocks, the gland begins to secrete
promptly, and the secretion, by proper regulation of the stimulation,
may be kept up for hours. The secretion thus obtained is thin and
watery, flows freely, is abundant in amount, and contains not more
than 1 or 2 per cent, of total solids. At the same time there is an
increased flow of blood through the gland. The whole gland takes
on a redder hue, the veins are distended, and if cut the blood that
flows from them is of a redder color than in the resting gland, and
may show a distinct pulse — all of which points to a dilatation of the
small arteries. If now the sympathetic fibers are stimulated, quite
different results are obtained. The secretion is relatively small in
amount, flows slowly, is thick and turbid, and may contain as much
as 6 per cent, of total solids. At the same time the gland becomes
pale, and if the veins be cut the flow from them is slower than in
the resting gland, thus indicating that a vasoconstriction has
occurred.

The increased vascular supply to the gland accompanying the

♦"Pfluger'e Archiv fur die gesaiiinil.e Physiologic," 17, 1, 1878; also
in Hermann' "Handbuch der Physiologic," is*;',, vol. v, part i.

THE SALIVARY GLANDS. 729

abundant flow of "chorda saliva" and the diminished flow of blood
during the scanty secretion of "sympathetic saliva" suggest naturally
the idea that the whole process of secretion may be, at bottom, a
vasomotor phenomenon, the amount of secretion depending only on
the quantity and pressure of the blood flowing through the gland.
It has been shown conclusively that this idea is erroneous and that
definite secretory fibers exist. The following facts may be quoted
in support of this statement: (1) Ludwig showed that if a mercury
manometer is connected with the duct of the submaxillary gland and
the chorda is then stimulated for a certain time, the pressure in the
duct may become greater than the blood-pressure in the gland.
This fact shows that the secretion is not derived entirely by processes
of filtration from the blood. (2) If the blood-flow be shut off
completely from the gland, stimulation of the chorda still gives a
secretion for a short time. (3) If atropin is injected into the gland,
stimulation of the chorda causes vascular dilatation, but no
secretion. This may be explained by supposing that the atropin
paralyzes the secretory, but not the dilator fibers. (4) Hydro-
chlorate of quinin injected into the gland causes vascular dilatation,
but no secretion. In this case the secretory fibers are still irritable,
since stimulation of the chorda gives the usual secretion.

A still more marked difference between the effect of stimulation
of the cerebral and the sympathetic fibers may be observed in the
case of the parotid gland in the dog. Stimulation of the cerebral
fibers, in any part of their course, gives an abundant, thin, and
watery saliva, poor in solid constituents. Stimulation of the sym-
pathetic fibers alone (provided the cerebral fibers have not been
stimulated shortly before and the tympanic nerve has been cut to
prevent a reflex effect) gives usually no perceptible secretion at all.
But in this last stimulation a marked effect is produced upon the
gland, in spite of the absence of a visible secretion. This is shown by
the fact that subsequent or simultaneous stimulation of the cerebral
fibers causes a secretion very unlike that given by the cerebral fibers
alone, in that it is very rich indeed in organic constituents. The
amount of organic matter in the secretion may be tenfold that of the
saliva obtained by stimulation of the cerebral fibers alone.

Relation of the Composition of the Secretion to the Strength of Stimu-
lation.— If the stimulus to the chorda is gradually increased in
strength, care being taken not to fatigue the gland, the chemical
composition of the secretion is found to change with regard to the
relative amounts of the water, the salts, and the organic material.
The water and the salts increase in amount with the increased
strength of stimulus up to a certain maximal limit, which for the
salts is about 0.77 per cent. It is important to observe that this
effect may be obtained from a perfectly fresh gland as well as from a
gland which had previously been secreting actively. With regard

730 PHYSIOLOGY OF DIGESTION AND SECRETION.

to the organic constituents the precise result obtained depends on
the condition of the gland. If previous to the stimulation the gland
was in a resting condition and unfatigued, then increased strength
of stimulation is followed at first by a rise in the percentage of organic
constituents, and this rise in the beginning is more marked than in
the case of the salts. But with continued stimulation the increase
in organic material soon ceases, and finally the amount begins actually
to diminish, and may fall to a low point in spite of the stronger
stimulation. On the other hand, if the gland at the beginning of the
experiment had been previously worked to a considerable extent,
then an increase in the stimulating current, while it augments the
amount of water and salts, either may have no effect at all upon the
organic constituents or may cause only a temporary increase, quickly
followed by a fall. Similar results may be obtained from stimulation
of the cerebral nerves of the parotid gland. The above facts led
Heidenhain to believe that the conditions determining the secretion
of the organic material are different from those controlling the water
and salts, and he gave a rational explanation of the differences
observed, in his theory of trophic and secretory fibers.

Theory of Trophic and Secretory Nerve Fibers. — This theory
supposes that two physiological varieties of . nerve fibers are distrib-
uted to the salivary glands. One of these varieties controls the
secretion of the water and inorganic salts and its fibers may be called
secretory fibers proper, while the other, to which the name trophic
is given, causes the formation of the organic constituents of the secre-
tion, probably by a direct influence on the metabolism of the cells.
Were the trophic fibers to act alone, the organic products would be
formed within the cell, but there would be no visible secretion, and
this is the hypothesis which Heidenhain uses to explain the results of
the experiment described above upon stimulation of the sympathetic
fibers to the parotid of the dog. In this animal, apparently, the
sympathetic branches to the parotid contain exclusively or almost
exclusively trophic fibers, while in the cerebral branches both trophic
and secretory fibers proper are present. The results of stimulation
of the cerebral and sympathetic branches to the submaxillary gland
of the same animal may be explained in terms of this theory by
supposing that in the latter nerve trophic fibers preponderate, and
in the former the secretory fibers proper.

It is obvious that this anatomical separation of the two sets of
fibers along the cerebral and sympathetic paths may be open to
individual variations, and that dogs may be found in which the sym-
pathetic branches to the parotid glands contain secretory fibers
proper, and therefore give some flow of secretion on stimulation.
These variations might also be expected to be more marked when
animals of different groups are compared. Thus, Langley* finds
♦ "Journal of Physiology," I, 96, L878.

THE SALIVARY GLANDS. 731

that in cats the sympathetic saliva from the submaxillary gland is
less viscid than the chorda saliva, — just the reverse of what occurs
in the dog. To apply Heidenhain's theory to this case it is necessary
to assume that in the cat the trophic fibers run chiefly in the chorda.

The way in which the trophic fibers act has been briefly indicated.
They may be supposed to set up metabolic changes in the proto-
plasm of the cells, leading to the formation of certain definite prod-
ucts, such as mucin or ptyalin. That such changes do occur is
abundantly shown by microscopical examination of the resting and
the active gland, the details of which will be given presently. In
general, these changes may be supposed to be catabolic in nature;
that is, they consist in a disassociation or breaking down of the
complex living material, with the formation of the simpler and
more stable organic constituents of the secretion. That these
changes involve processes of oxidation is shown by the fact that
during activity the gland takes up more oxygen and gives off more
carbon dioxid. There is evidence to show that these gland cells
during activity form fresh material from the nourishment supplied
by the blood; that is, that anabolic or building-up processes occur
along with the catabolic changes. The latter are the more obvious,
and are the changes which are usually associated with the action
of the trophic nerve fibers. It is possible, also, that the anabolic
or growth changes may be under the control of separate fibers,
for which the name anabolic fibers would be appropriate. Satis-
factory proof of the existence of a separate set of anabolic fibers has
not yet been furnished.

The method of action of the secretory fibers proper is difficult to
understand. At present the theories suggested are entirely specula-
tive. Experiments have shown that the amount of water given
off from the blood during secretion is somewhat greater than the
amount contained in the saliva,* and there is reason to believe that
the difference between the two is accounted for by an increase in
the flow of lymph from the gland during activity. A satisfactory
explanation of the causes leading to and controlling the flow of
water cannot yet be given. In a general way it has been assumed
that the effect of the nerve impulses is to cause the production
of substances within the cells whereby their osmotic pressure
is increased, and a stream of water is set up from the blood in
the capillaries toward the gland cells, but it cannot be said that
this assumption has been supported by the experiments so far
made.f We must limit ourselves to the more general statement
that the activity of the cells themselves initiates and controls
the flow of water.

*Barcroft, "Journal of Physiology," 1900, 25, 479.

f Carlson, Greer, and Becht, "American Journal of Physiology,'' 19, 360,
1907.

76Z PHYSIOLOGY OF DIGESTION . AND SECRETION.

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 stimulation of the
tympanic nerve the cells show but little alteration, but stimula-
tion 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

.;:-V.

m>

D

Fir. 280. — Parotid gland of the rabbit in a fresh state, showing portions of the secret-
ing tubules: I, In ■> re ting Condition; li, after secretion caused l>y pilocarpin; C, after
ecretion, pilocarpin and stimulation of sympathetic; D, after lonjr-eontinued
stimulation of sympathetic. — (After Langley.)

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 fche animal is in ;i fasting condition the cells have a granular
appearance throughout their substance, the outlines of the different
cells being faintly marked by light lines (Fig. 280, A). When the
gland i- made t<> 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. 280, B),
♦ "Journal of Physiology, " 2, 2G0, 187!).

THE SALIVARY GLANDS.

733

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. 280, C, D). Evidently the granular material is used
in some way to make the organic material of the secretion. Since the
ptyalin is a conspicuous organic constituent of the secretion, it is
assumed that the granules in the resting gland contain the ptyalin,
or rather the preliminary material from which the ptyalin is con-
structed during the act of secretion. On this latter assumption the
granules are frequently spoken of as zymogen granules. During the
act of secretion two distinct processes seem to be going on in the cell,
leaving out of consideration, for the moment, the secretion of the
water and the salts. In the first place, the zymogen granules undergo
a change such that they are forced or dissolved out of the cell, and,
second, a constructive metabolism or anabolism is set up, leading to
the formation of new pro-
toplasmic material from
the substances contained
in the blood and lymph.
The new material thus
formed is the clear, non-
granular substance,
which appears first
toward the basal sides of
the cells. We may sup-
pose that the clear sub-
stance during the resting
periods undergoes meta-
bolic changes, whether of
a, catabolic or anabolic
character can not be

safely asserted, leading to the formation of new granules, and the
cells are again ready to form a secretion of normal composition.
It should be borne in mind that in these experiments the glands
were stimulated beyond normal limits. Under ordinary conditions
the cells are probably never depleted of their granular material to
the extent represented in the figures.

In the cells of the mucous glands changes equally marked may
be observed after prolonged activity. In stained sections of the
resting gland the cells are large and clear (Fig. 281), with flattened
nuclei placed well toward the base of the cell. When the gland is
made to secrete the nuclei become more spherical and lie more
toward the middle of the cell, and the cells themselves become
distinctly smaller. After prolonged secretion the changes become
more marked (Fig. 282) and, according to Heidenhain, some of the

Fig. 281. — Mucous gland: submaxillary of dog
ing stage.

734

PHYSIOLOGY OF DIGESTION AND SECRETION.

Fig. 282. — Mucous gland: submaxillary of
clog after eight hours' stimulation of the chorda
tympani.

mucous cells may break down completely. According to most of
the later observers, however, the mucous cells do not actually dis-
integrate, but form again new material during the period of rest, as in
the case of the goblet cells of the intestine. In the mucous as in the
albuminous cells observations upon pieces of the fresh gland seem
to give more reliable results than those upon preserved specimens.
Langley* has shown that in the fresh mucous cells of the submax-
illary gland numerous large granules may be discovered, about 125

to 250 to a cell. These
granules are comparable to
those found in the goblet
cells, and may be inter-
preted as consisting of mu-
cin or some preparatory
material from which mucin
is formed. The granules
are sensitive to reagents;
addition of water causes
them to swell tip and dis-
appear. It may be as-
sumed that this happens
during secretion, the gran-
ules becoming converted to a mucin mass which is extruded from
the cell.

Action of Atropin, Pilocarpin, and Nicotin upon the Secre-
tory Nerves. — The action of drugs upon the salivary glands and
their secretions belongs properly to pharmacology, but the effects
of the three drugs mentioned are so decided that they have a
peculiar physiological interest. Atropin in small doses injected
either into the blood or into the gland duct prevents the action of
the cerebral autonomic fibers (tympanic nerve or chorda tympani)
upon the glands. This effect may be explained by assuming that
the atropin paralyzes the endings of the cerebral fibers in the glands.
That it does not act directly upon the gland cells themselves seems
to be assured by the interesting fact that, with doses sufficient to
throw out entirely the secreting action of the cerebral fibers, the
sympathetic fibers are still effective when stimulated, l'ilocarpin
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-
Bequent application of atropin, and vice versa. Nicotin, according
to the experiments of Langley,t prevents the ad ton of the secretory

• "Journal of Physiology," L0, 133, L889.

t "Proceedings of the Royal Society," London, 46,423, J 889.

THE SALIVARY GLANDS. 735

nerves, not by affecting the gland cells or the endings of the nerve
fibers around them, but by paralyzing the connections between the
nerve fibers and the ganglion cells through which the fibers pass On
their way to the gland, — that is, the connection between the pre-
ganglionic and postganglionic fibers. If, for example, the superior
cervical ganglion is painted with a solution of nicotin, stimulation
of the cervical sympathetic below the gland gives no secretion; stim-
ulation, however, of the fibers in the ganglion or between the ganglion
and gland gives the usual effect. By the use of this drug Langley is
led to believe that the cells of the so-called submaxillary ganglion
are really intercalated in the course of the fibers to the sublingual
gland, while the nerve cells with which the submaxillary fibers make
connection are found chiefly in the hilus of the gland itself.

Paralytic Secretion. — A remarkable phenomenon in connection
with the salivary glands is the so-called paralytic secretion. It has
been known for a long time that if the chorda tympani is cut the
submaxillary gland after a certain time, one to three days, begins to
secrete slowly, and the secretion continues uninterruptedly for a long
period — as long, perhaps, as several weeks — and eventually the gland
itself undergoes atrophy. Langley states that section of the chorda
on one side is followed by a continuous secretion from the glands
on both sides; the secretion from the gland of the opposite side he
designates as the antiparalytic or antilytic secretion. After section
of the chorda the nerve fibers peripheral to the section degenerate,
the process being completed within a few days. These fibers, how-
ever, do not run directly to the gland cell; they terminate in end
arborizations around sympathetic nerve cells placed somewhere along
their course, — in the sublingual ganglion, for instance, or within the
gland substance itself. It is the axons from these second nerve units
that end around the secreting cells. Langley has accumulated some
facts to show that within the period of continuance of the paralytic
secretion (five to six weeks) the fibers of the sympathetic cells are
still irritable to stimulation. He is inclined to believe, therefore, that
the continuous secretion is due to a continuous excitation, from some
cause, of the local nervous mechanism in the gland. A natural
extension of this yiew which has been suggested (Parlow) is
that, normally the activity of the sympathetic cells or of the
secreting cells is kept in check by inhibitory fibers. After section
of the chorda the action of these fibers falls out and the secre-
tion continues until the glandular tissue undergoes atrophy. On
the histological 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.

* Gerhardt, "Archiv f. die gesammte Physiologie, " 97, 317, 1903.

736 PHYSIOLOGY OF DIGESTION AND SECRETION.

Normal Mechanism of Salivary Secretion. — Under normal con-
ditions 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 glossopharyn-
geal 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 im-
pulse being carried to a center and thence transmitted through
the efferent nerves to the glands. It is found that section
of the chorda prevents the reflex, in spite of the fact that the
sympathetic fibers are still intact. No satisfactory explanation
of the normal functions of the secretory fibers in the sympathetic
has yet been given. Various authors have suggested that possibly
the three large salivary glands respond normally to different stimuli.
This view has been supported by Pawlow, who reports that in
the dog at least the parotid and the submaxillary may react quite
differently. When fistulas were made of the ducts of these glands it
was found that the submaxillary responded readily to a great num-
ber of stimuli, such as the sight of food, chewing of meats, acids, etc.
The parotid, on the contrary, seemed to react only when dry food,
dry powdered meat, or bread was placed in the mouth. Dryness in
this case appeared to be the efficient stimulus.

Pawlow lays great stress upon the adaptability of the secretion of saliva
to the character of the material chewed. Dry, solid food stimulates a large
flow of saliva, such as is necessary in order to chew it properly and to form it
into a bolus for swallowing. Foods containing much water, on the contrary,
excite but little flow of saliva. If one places a handful of clean stones in
the mouth of a dog he will move them around with his tongue for a while
and then drop them from his mouth; but little or no saliva is secreted.
If the same material is given in the form of fine sand a rich flow of saliva
is produced, and the necessity for the reflex is evident in this case, since
otherwise the material could not be conveniently removed from the mouth.
Such adaptations must be regarded from the physiological point of view
as special reflexes depending upon some difference in the nervous mechanism
set into play.*

Since the flow of saliva is normally a definite reflex, we should

expect a distinct salivary secretion center. This center has been

located by physiological means in the medulla oblongata; its exact

position is no! 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.

•See Pawlow, "The Work of the Digestive Glands," translation by
Thompson, London, 1902; also " Ergebnisse der Physiologie," vol hi., part i,
J '.in I . and " Archive internationaies de physiologie," 1, 119, 1904.

THE SALIVARY GLANDS. 737

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.*

The Digestive Action of Saliva — Ptyalin. — The digestive action
proper of the saliva is limited to the starchy food. In human
beings and most mammals the saliva contains an active enzyme
belonging to the group of diastases and designated usually as ptyalin
or salivary diastase. It may be prepared in purified form from saliva
by precipitation with alcohol, but its chemical nature, like that of the
other enzymes, is still an unsolved problem. Saliva or preparations
of ptyalin act readily upon boiled starch, converting it into sugar
and dextrin. This action may be demonstrated very readily by
holding a little starch paste or starchy food, such as boiled potatoes,
in the mouth for a few moments. If the solution is then examined the
presence of sugar is readily shown by its reducing action on solutions
of copper sulphate (Fehling's solution). There is no doubt that the
action of ptyalin upon the starch is hydrolytic. Under the influence
of the enzyme the starch molecules take up water and undergo
cleavage into simpler molecules. The steps in the process and the
final products have been investigated by a very large number of
workers, but much yet remains in doubt. The following points
seem to be determined: The end-result of the reaction is the
formation of maltose, a disaccharid, having the general formula
C12H22Ou, 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

*See Biedennann, " Electro-physiology," translation by Welby, London,
1896.

47

738 PHYSIOLOGY OF DIGESTION" AND SECRETION.

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
tins 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:

Starch<^Ial*?se- , . . .Maltose.

The products formed in this reaction are probably not absorbed as
such. The absorption takes place mainly no doubt after the food
reaches the small intestine, and we have evidence, as will be stated,
that before absorption the maltose and the dextrin are acted upon by
the inverting enzymes (maltase) and converted into the simple
sugar, dextrose. The ptyalin digestion seems therefore to be pre-
paratory, and the combined action of ptyalin and maltase is necessary
to get the starch into a condition ready for nutrition. By way of
comparison it is interesting to remember that when starch is boiled
with dilute acids it is hydrolyzed at once to dextrose. A question of
practical importance is as to how far salivary digestion affects the
starchy foods under usual circumstances. The chewing process in
the mouth thoroughly mixes the food and saliva, or should do so,
but the bolus is swallowed much too quickly to enable the enzyme to
complete its action. In the stomach the gastric juice is sufficiently
acid to destroy the ptyalin, and it was therefore supposed formerly
that salivary digestion is promptly arrested on the entrance of the
food into the stomach, and is therefore normally of but little value
as a digestive process. < )ur recent increase in knowledge regarding
the conditions in the stomach (p. 698) shows, on the contrary, that
Borne of the food in an ordinary meal may remain in the fundic
end of fh^ stomach for an hour or more untouched by the acid
secretion. There is every reason to believe, therefore, that salivary
digestion may he 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
eh; lilacs of temperature. At 0° C. its activity is said to he suspended
entirely. The intensity of its action increases with increase of

THE SALIVARY GLANDS. 739

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 hydrated condition
is acted upon more rapidly by the ptyalin. The practical value of
cooking vegetable foods is evident from these statements.

Functions of the Saliva. — In addition to the digestive action of
the saliva on starchy foods it fulfills other important functions. By
moistening the food it enables us to reduce the material to a consis-
tency suitable for swallowing and for manipulation by the tongue and
other muscles. Moreover, the presence of mucin serves doubtless
as a kind of lubricator that insures a smooth passage along the
esophageal canal. Finally by dissolving dry and solid food it pro-
vides a necessary step in the process of stimulating the taste nerves,
and, as is described below, the activity of the taste sensations may
play an important part in the secretion of the gastric juice.

CHAPTER XLII.

DIGESTION AND ABSORPTION IN THE STOMACH.

The muscular mechanisms by means of which the stomach is
charged with food and in turn discharged, small portions at a time,
into the duodenum have been described. The present chapter deals
only with the chemical and mechanical changes in the food during
its stay in the stomach and the extent to which the products of
digestion are absorbed.

The Gastric Glands. — The tubular glands that permeate the
mucous membrane of the stomach throughout its entire extent differ
in their histological structure, and therefore doubtless in their secre-
tion, in different parts of the stomach. Two, sometimes three, kinds
of glands are distinguished, — the pyloric, fundic (and cardiac).
Those in the pyloric part of the stomach (antrum pylori) are char-
acterized chiefly by the fact that in the secreting part of the tubule
only one type of gland cell is found, the chief or peptic cell, while in
the remainder of the stomach, but particularly in the middle or
prepyloric region the glands (fundic glands) are distinguished by the
presence of two types of cells, — the chief cells and the so-called cover
or border cells (Fig. 283) . 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. Griitznerf
called especial attention to this relation, and in connection with the
differences in movements of these two parts of the stomach he
suggests that normally the bulk of the food toward the fundus
becomes impregnated first with pepsin; then, as it is slowly moved
into the prepyloric region, the acid constituent is added. The
pyloric glands are said (Heidenhain) to secrete an alkaline liquid
containing pepsin, and, according fco Edkins and Starling they
loin, a substance which is capable of acting as a chemical excitant,

Bee Haane, 'Archiv I". Anatomie," L905, I.
| Grtitzner, "Archiv I', die gesammte Physiologic, " LOB, 463, 1005.

740

DIGESTION AND ABSORPTION IN THE STOMACH.

741

to the glands secreting the gastric juice (gastric secretin or gastric
hormone).*

Histological Changes in the Gastric Glands during Secretion.

— The cells of the gastric glands, especially the so-called chief cells,
show distinct changes as the result of prolonged activity. Upon
preserved specimens, taken from dogs fed at intervals of twenty-four
hours, Heidenhain found that in the fasting condition the chief cells
were large and clear, that during the first six hours of digestion the
chief cells as well as the border cells increased in size, but that in a
second period, extending from the sixth to the fifteenth hour, the
chief cells became gradually smaller, while the border cells remained

\a m

mm %
m

Fig. 283. — 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. 283).

Langley * has succeeded in following the changes in a more satis-
factory way by observations made directly upon the living gland.

* See Starling, "Physiology of Secretion," Chicago, 1906, and Edkins,
"Journal of Physiology," 1906, xxxiv., 133.
t " Journal of Physiology, ' ' 3, 269, 1880.

7-12 PHYSIOLOGY OF DIGESTION AXD SECRETIOX.

He finds that the chief cells in the fasting stage are charged with
granules, and that during digestion the granules are dissolved, dis-
appearing first from the base of the cell, which then becomes filled
with a non-granular material. Observations similar to those made
upon other glands demonstrate that these granules represent in all
probability a preliminary material from which the gastric enzymes
are made during the act of secretion. The granules, therefore, are
sometimes described as zymogen granules.

Means of Obtaining the Gastric Secretion and its Normal
Composition. — The secretion of the gastric membrane is formed in
the minute glands scattered over its surface. As there is no com-
mon duct, the difficulty of obtaining the secretion for analysis or
experiment is considerable. This difficulty has been overcome at
different times by the invention of special methods.

The older methods used for obtaining normal gastric juice were
very unsatisfactory. An animal was made to swallow a clean
sponge to which a string wras 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
Ili.it some of the wooden tubes were made very thin, so that the slightest
pressure would crush them, and yet they were voided uninjured. So also
he found that cherries and grapes when swallowed whole, even if entirely
ripe, were usually passed unbroken.

A better method of obtaining normal juice was suggested by the
famous observations of Beaumont* upon Alexis St. Martin. St.
Martin, by the premature discharge of his gun, was wounded in the
abdomen and stomach. On healing, a fistulous opening remained in
the abdominal wall, leading into the stomach, so that the contents
of the latter could be inspected. Beaumont made numerous inter-
esting and most, valuable observations upon bis patient. Since that
time it has become customary to make fistulous openings into the
stomachs of dogs whenever it is necessary to have the normal juice

* Beaumont, "The Physiology of Digestion," 1833; second edition, 1847.
Por a biographical account of Beaumont, see Osier, "Journal of the American
Medical issociation, " November L5, 1902.

DIGESTION AND ABSORPTION IN THE STOMACH.

7-13

for examination. Formerly a silver cannula was placed in the
fistula, and at any time the plug closing the cannula might be re-
moved and gastric juice be obtained. In some cases the esophagus
has been occluded or excised so as to prevent the mixture of saliva
with the gastric juice. Gastric juice may be obtained from human
beings also in cases of vomiting or by means of the stomach tube,
but in such cases it is necessarily more or less diluted or mixed with
food and cannot be used for exact analyses, although specimens
of gastric juice obtained by these methods are employed in the
diagnosis and treatment of gastric troubles.

From the standpoint of experimental investigation a very im-
portant addition to our methods was made by Heidenhain. This
observer showed that a portion of the stomach — the fundic end, for
instance, or the pyloric end — might be cut away from the rest of the
organ and be given an
artificial opening to the
exterior. By this means
the secretion of an isolated
fundic or pyloric sac may
be obtained and examined
as to its quantity and prop-
erties. The method ' was
subsequently improved by
Pawlow, whose important
contributions are referred
to below. Fig. 284 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
some protein, some mucin, and inorganic salts, but the essential
constituents are an acid (HC1) and two or possibly three enzymes,
pepsin, rennin, and lipase. 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. More complete data are published for the
secretion in dogs. According to Rosemann,* the secretion in
* Rosemann, "Archiv f. d. ges. Physiologie," 118, 467, 1907.

Fig. 284. — 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.)

/44 PHYSIOLOGY OF DIGESTION AND SECRETION.

this animal has a specific gravity of 1002 to 1004 and contains
D.4277 per cent, of dry material, of which 0.1325 per cent, is ash.
Analysis of the ash shows that it contains 24 per cent, of potassium,
19 per cent, of sodium, and 0.18 per cent, of calcium. The HC1
amounts to 0.55 per cent., while the total chlorine contents are
more than twice that of blood. This author states, in fact, that
in one animal during a secretion lasting 3\ hours about 5 gm. of
chlorine were given off in the secretion, an amount about equal
to that contained in the entire blood. The organic portion of the
secretion, in addition to the digestive enz^mies, consists chiefly
of protein. 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 with-
stands putrefaction. It may be kept for a long time, for months
even, without becoming putrid and with very little change, if any,
in its digestive action or in its total acidity. This fact shows that
the juice possesses antiseptic properties, and it is usually sup-
posed 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 clue 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, [ts presence is usually explained as being due to the fer-
mentalion of the carbohydrates, and it is therefore more constantly
pr< 'nt in the stomachs of the herbivora. The amount of free
hydrochloric acid varies according to the duration of digestion;
thai is, the secretion does not possess its full acidity in the beginning
owing to the facl (Heidenhain) thai in the firsl periods of digestion,

* Simon, "A Manual of Clinical Diagnosis," 1904.

DIGESTION AND ABSORPTION IN THE STOMACH. 745

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. It is probable
that the juice as secreted has a more or less constant acidity, but
after it is poured out in the stomach this acidity is not only dimin-
ished by the neutralizing action of any alkalies that may be present,
but, what is far more important, the free acid may be combined
with the protein of the food. If the stomach contents of an animal
fed on meat be examined from time to time, it may not be possible
to prove the existence of free HC1 for an hour or more after the
digestion has been going on, owing to the fact that it has com-
bined with the protein material. In speaking of the acidity of
the stomach contents, therefore, it is necessary to distinguish
between the combined acid and the free acid, the two together
constituting the total acidity. The acidity of the human gastric
juice is usually estimated at 0.3 per cent., but during digestion
it may reach (Hornborg) 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
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 chloricls of the blood. The chief chloric!
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

746 PHYSIOLOGY OF DIGESTION AND SECRETION.

KI to the food may cause the formation of some HBr and HI,
together with HC1 in the gastric juice. Maly has suggested that
acid ohosphates may be produced in the first instance, and then by
reacting with the sodium chlorid may give hydrochloric acid, accord-
ing to the formula XaH,PO, + Nad = Xa,HP04 + 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 HOI, and in all probability
this reaction involves a specific metabolism on the part of these
cells.

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
to the exterior instead of entering the stomach. The animal thus
hud the enjoyment of eating without actually filling the stomach.
Eating in this style forms what the author called a fictitious
Hi- -ham meal (Scheinfuttcrung). It was found that it causes
an abundant (low of gastric juice as long as the vagi are intact,
but has no effect mi 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 desig-
nate- a aecretion produced in this way as a psychical secretion,

a term which implies thai Hie reflex must be attended by
conscious sensations. In favorable cases the fictitious feeding lias
been continued for five or six hours and a large amount of gastric

juice (70(1 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, <>n<-<' started, may continue for a long time after

* Sec Pawlow , "'I'll'- Work <.f i lie I Hgest ive ( Hands," translated by Thomp'

Ol,. ,

DIGESTION AND ABSORPTION IN THE STOMACH. 747

the stimulus (the eating) has ceased. Experiments have been made
upon human beings under similar conditions. Thus, Hornborg*
reports the case of a boy with a stricture of the esophagus and a
fistula in the stomach. Food when chewed and swallowed did not
reach the stomach, but was regurgitated; it caused, nevertheless,
an active psychical secretion in the empty stomach.

Normal Mechanism of the Secretion of the Gastric Juice. —
During a meal the gastric juice is secreted, under normal conditions,
as long as the food remains in the stomach. The modern explana-
tion of the origin, maintenance, and regulation of this flow of secre-
tion is due chiefly to Pawlow. Contrary to a former general belief,
he showed that mechanical stimulation of the gastric mucous mem-
brane has no effect on the secretion of the tubules. This factor may
therefore be eliminated. In an ordinary meal the secretion first
started is due to the sensations of eating — that is, it is a psychical
secretion. The afferent stimuli originate in the mouth and nostrils;
the efferent path, the secretory fibers, is through the vagus nerve.
This reflex insures the beginning at least of gastric digestion, but its
effect is supplemented by a further action arising in the stomach
itself. It seems that some foods contain substances designated as
secretogogues, that are able to cause a secretion of gastric juice
when taken into the stomach. In other foods these ready-formed
secretogogues are lacking. Thus, meat extracts, meat juices,
soups, etc., are particularly effective in this respect; milk and water
cause less secretion. Certain common articles of food, such as
bread and white of eggs, have no effect of this kind at all. If
introduced into the stomach of a dog through a fistula so as not to
arouse a psychical secretion, — for instance, while the dog's attention
is diverted or while he is sleeping, — they cause no flow of gastric
juice and are not digested. If such articles of food are eaten,
however, they cause a psychical secretion, and when this has acted
upon the foods some products of their digestion in turn become
capable of arousing a further flow of gastric juice. The steps in
the mechanism of secretion are, therefore, three: (1) The psychical
secretion; (2) the secretion from secretogogues contained in the
food; (3) the secretion from secretogogues contained in the prod-
ucts of digestion. The manner in which the secretogogues act
cannot be stated positively. Since the gastric glands possess
secretory nerve fibers the first explanation to suggest itself is
that the secretogogues by acting on sensory fibers in the gastric
mucous membrane reflexly stimulate the secretory fibers. This
explanation, however, is rendered untenable by the fact that the
effect of these substances is obtained after complete severance

* Hornborg, " Skandinavisches Archiv f. Physiologie," 15, 209, 1904; see
also Bickel, " Verhandl. Kongr. f. innere Medizin," 23, 491.

"4$

PHYSIOLOGY OF DIGESTION AND SECRETION.

of the nervous connections of the stomach. If, therefore, this
so-called chemical secretion is produced by a nervous reflex the
nerve centers concerned must lie in the stomach itself, the reflex
must take place through the peripheral ganglion cells. Another
more probable explanation has been offered. Edkins* has shown
that decoctions of the pyloric mucous membrane, made by boiling

in water acid or
peptone solutions,
when injected into
the blood cause a
marked secretion of
gastric juice. These
substances when in-
jected alone into the
blood cause no such
effect, and decoc-
tions of the mucous
membrane of the
fundic end of the
stomach are with-
out action on the
gastric secretion.
This author sug-
gests, therefore, that
the secretogogues,
whether preformed
in the food or formed
during digestion, act
upon the pyloric mu-
cous membrane and
form a substance
which lie designates
as gastrin or </astric
secretin, and t his sub-
stance after absorp-
tion into the blood
is carried to 1 he gas-
ion. The effect is,

an instance of the
ormed in another.

g„ 2

— M

— 0)

.2 o

U I-

Quantity in
cubic centi-
meters.

Milk, Meat, Bread,
600 c.c. 100 gnis. 100 gins.

QnQ

0..576 |

0..52S
0.480

\

S

0.432
0.384

18
16

t

i

\

i

\

i

\

0.288 12
0.240 10
0.192 8
0 144 A

\

\

1

10

|

8

\

!

6

\

4

0.096

0.048

0

4
2

0

I

\

-

-

_,

2

*

'

0

r

Hours

/ Z3436Y8? MVJZ

Quant ity of secretion.
Acidity.

Di live power.

Pig, 285.— Diagram showing (he variation in quantity
'.f ga trie secretion in the dog alter a mixed meal; al o
the variations in acidity and indigestive power. — (After
Khiffim .)

trie glands and stimulates them to secret

therefore, no1 a usual nervous reflex, but

stimulation of one organ by chemical producl

Starling f has emphasised the fad thai this mode of control is

frequently employed in the body, us will be described in the

following pages in connection with the pancreatic secretion and

' Edkin . Journal of Physiology," L906', Kxxiv., p, L33.

rling, " Recent Advance m the Physiology of Digestion," 1906.

DIGESTION AND ABSORPTION IN THE STOMACH. 749

the internal secretions. He proposes to designate such sub-
stances by the general term of hormones (from bpfiaco, arouse
or excite). Leaving aside for the moment the way in which
the secretogogues excite the secretion it is important to empha-
size the fact that in the normal secretion of gastric juice, that
is to say, in the secretion which takes place during an ordinary
meal, we must distinguish between a nervous secretion due to
the action of the secretory fibers in the vagus, and a chemical
secretion due to the chemical stimulation of the secretogogues
or of the hormones produced by them.

The researches of Pawlow and his co-workers seem also to in-
dicate that the quantity and properties of the secretion vary with
the character of the food. The quantity of the secretion varies,
also, other conditions being the same, with the amount of food to
be digested. The apparatus is adjusted in this respect to work
economically. Different kinds of food produce secretions varying
not only as regards quantity but also in their acidity and diges-
tive action. The secretion produced by bread, though less in
quantity than that caused by meat, possesses a greater digestive
action. On a given diet the secretion assumes certain characteris-
tics, and Pawlow is convinced that further work will disclose the fact
that the secretion of the stomach is not caused normally by general
stimuli all affecting it alike, but by specific stimuli contained in the
food or produced during digestion, whose action is of such a kind
as to arouse reflexly the secretion best adapted to the food ingested.

One of the curves, showing the effect of a mixed diet (milk, 600
c.c; meat, 100 gms.; bread, 100 gms.) upon the gastric secretion,
as determined by Pawlow's method, is reproduced in Fig. 285. 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

750 PHYSIOLOGY OF DIGESTION AND SECRETION".

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. Pekelharing* has prepared pepsin from gastric juice by
dialysis, the substance precipitating as the acid is dialyzed off.
The precipitate may be purified by repeated resolutions in acid
followed by dialysis. As prepared by this method pepsin is a
substance of a protein nature which contains sulphur and also
some chlorin, bu1 no phosphorus. It does not belong, therefore,
to the group of nucleoproteins. Other authors, on the contrary,
assert that active preparations of pepsin may be obtained which
give no protein reactions, although they contain nitrogen.

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 qo1 changed to the active pepsin until after
-(•net inn. The propepsin may be extracted readily from the mucous
membrane, and, since i1 is known that the zymogen is converted
quickly to active pepsin by 1 he ac1 ion of acids, it is evident I ha1 in
the norma] gastric juice the existence of the hydrochloric acid
Insure* thai 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. Beidenhain isolated this portion of the stomach and
collected its secretion. He found thai it was alkaline and contained
pepsin, hater observers, however, s1 ill conl inue to doubl t hesecre-
- Pekelharing, "Zeitschrift I', physiol. Chemie," 35, 8, 1902.

DIGESTION AND ABSORPTION IN THE STOMACH. 751

tion of a true pepsin in this portion of the stomach. Glaessner*
states that propepsin can not be obtained from extracts of the pyloric
glands, and that the proteolytic enzyme that can be shown in this
portion of the stomach by self-digestion in acid or alkaline media is
not a true gastric pepsin. The possibility that a special secretin
(hormone) is formed in the pyloric mucous membrane has been
referred to above (p. 748). From the description of the events
in the stomach (p. 696) it would seem that the food material which
is churned and stirred by the contractions of the pyloric musculature
has already been charged with pepsin and hydrochloric acid by the
glands of the middle and fundic regions before reaching the
antrum pylori.

Artificial Gastric Juice. — In studying peptic digestion it is not
necessary for all purposes to establish a gastric fistula. The active
agents of the normal juice are pepsin and an acid of a proper strength ;
and, as the pepsin can be extracted and preserved in various ways
and the hydrochloric acid can easily be made of the proper strength,
an artificial juice can be obtained at any time and may be used in
place of the normal secretion for many purposes. In laboratory ex-
periments it is customary to employ a glycerin or commercial prep-
aration of the gastric mucous membrane, and to add a small portion
of this preparation to a large bulk of 0.2 per cent, hydrochloric acid.
The artificial juice thus made, when kept at a temperature of from
37° to 40° C, will digest proteins rapidly if the preparation of pepsin
is a good one. While the strength of the acid employed is generally
from 0.2 to 0.3 per cent., digestion will take place in solutions of
greater or less acidity. Too great or too small an acidity, however,
will retard the process; that is, there is for the action of the pepsin
an optimum acidity which lies somewhere between 0.2 and 0.5
per cent. Other acids may be used in place of the hydrochloric
acid — for example, nitric, phosphoric, or lactic — but they are not
so effective, and the optimum acidity is different for each; for
phosphoric acid it is given as 2 per cent.

The Pepsin-hydrochloric Digestion of Proteins. — It has
long been known that solid proteins, when exposed to the action of a
normal or an artificial gastric juice, swell up and eventually pass into
solution. The soluble protein thus formed was known not to be
coagulated by heat and was remarkable also for being more diffusible
than other forms of soluble proteins. This end-procluct of digestion
was formerlv conceived as a soluble protein 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 protein under digestion
passes through a number of intermediate stages. The intermediate

* Glaessner, " Beitrage zur chem. Physiol, u. Pathol.," 1, 24, 1901.

752 PHYSIOLOGY OF DIGESTION AND SECRETION".

products were partially isolated and were given specific names, such
<l-albumin. parapeptone, and propetone. The present concep-
tion of the process we owe chiefly to Kiihne. This author believed
that the protein passes through three general stages before reaching
the final condition of peptone. This view is indicated briefly by the
following schema :

Native protein.

Acid albumin (syntonin).

Primary proteoses (protalbumoses).
Secondary proteoses (deutero-albunioses).
Peptone.

The first step is the conversion of the protein to an acid albumin.
This change may be considered as being chiefly an effect of the hy-
drochloric acid, although in some way the combined action of the
pepsin-hydrochloric acid compound is more effective than a solution
of the acid alone of the same strength. Like the acid albumins
(metaproteins) in general (see Appendix), the syntonin is readily
precipitated on neutralization. In the beginning of peptic diges-
tion, therefore, if the solution is neutralized with dilute alkali,
an abundant precipitate of syntonin occurs. Later on in the
digestion, neutralization gives no such effect — the syntonin
has all passed to a further stage of digest inn. Under the in-
fluence of the pepsin the syntonin undergoes hydrolysis, with
the production of a number of bodies which, as a group, are
designated as primary proteoses or protalbumoses.* Although
several members of this group have been isolated and given
separate names, so much doubt prevails as to the chemical individ-
uality of these substances that it is best perhaps to regard them as a
group of compounds which under the continued influence of the
pepsin undergo still further hydrolysis with the formation of secon-
dary proteoses or deutero-albumoses. As compared with the primary
proteoses, the secondary ones are distinguished by a greater solu-
bility; they require a stronger saturation with neutral salts to precipi-
tate them. (See Appendix.) The secondary proteoses undergo still
further hydrolysis, with the production of peptone, or perhaps it

would be better to say peptones. The peptones show still greater
solubility, ami, in fact, peptone, in Kuhne's sense, is that compound

Or group of compounds formed in peptic digestion which, while still

showing protein reactions (biuret reaction), is not coagulated by

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 \-c\>\f-

*Tlie products intermediate between the original protein and the pep-
tone are described in general a albumo e or as proteoses, according as <>no
the term protein or albumin a the generic name for the original sub-
tance. The term protein i generally used in English; hence, the intermedi-
ate product* are more appropriately designated as proteoses.

DIGESTION AND ABSORPTION IN THE STOMACH. 753

sented as following in sequence. It should be stated, however,
that many authors consider that even in the beginning of the
digestion the protein molecule may be split into several complexes,
and that some of the end-products may be formed in the very
beginning of the action. All that we can state very positively
is that the protein molecules undergo a series of hydrolytic cleav-
ages, the end-result of which is that in place of the originally very
large molecule with a weight of 5000 to 7000 there is obtained a
number of much smaller and much more soluble molecules whose
molecular weights are perhaps only 250 to 400 or less.

It was formerly believed that pepsin was not able to split the complex
protein molecule into compounds of a simpler structure than the peptone.
But a number of recent authors have stated that if time enough is given
the breaking up of the protein molecule may be as complete as after the action
of trypsin, or after hydrolysis by acids (see Proteins in appendix). That
is, along with the peptone or in place of it are found certain simpler bodies
which no longer give the biuret reaction, but are precipitable by phospho-
tungstic acid and for which Hofmeister proposes the general name of pep-
toids. They would correspond, also, apparently, to the group of compounds
designated by Fischer as peptids or polypeptids. In addition, many of the
amino-acids and nitrogenous bases which constitute the final end-products
of the breaking up of the protein molecule may be found.*

In judging the digestive action of any given specimen of natural
or artificial gastric juice it is customary to measure the rapidity
with which an insoluble protein is converted into a soluble form.
The method most commonly employed is that devised in Pawlow's
laboratory by Mett. The Mett test is made by sucking white of egg
into a thin-walled glass tube having an internal diameter of 1 to 2
mms. The egg-albumin is coagulated in the tube by immersing it for
five minutes in water at 95° C. After some time the tube is cut into
lengths of 10 to 15 mms. and these are used to test the digestive action
or amount of pepsin. One or more of the tubes are placed in the
solution to be measured and kept for ten hours at body temperature.
The digestive power is measured in terms of the length in millimeters
of the column of egg-albumin that is dissolved. The relative amounts
of pepsin in solutions compared in this way are determined by the
law of Schiitz, according to which the digestive power is proportional
to the square root of the amount of pepsin. If in two specimens of
gastric juice the number of millimeters of egg albumin digested
was in one case two and in the other three, the digestive powers of the
two solutions would be as the squares of the numbers, as 4 to 9.

The Rennin Enzyme (Rennet, Chymosin). — The property
possessed by the mucous membrane of the calf's stomach of curdling
milk has been known from remote times, and has been utilized in the
manufacture of cheese and curds. This action takes place with
remarkable rapidity under favorable conditions, a large mass of milk
* See Hofmeister, " Ergebnisse der Physiologie," vol. i., part r., 79(5, 1902.
48

754 PHYSIOLOGY OF DIGESTION AND SECRETION.

setting to a firm coagulum within a very brief time. It has been
shown that this effect is due to an enzyme — remain 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 proehymosin, which after secretion is con-
verted to the active enzyme. This conversion takes place very
readily under the influence of acid. Rennin (or its zymogen) may be
obtained easily from the mucous membrane of the stomach (with
the exception of the pyloric end) by extracting with glycerin or water
or by digesting with dilute acid. Good extracts of rennin cause
the milk to clot with great rapidity at a temperature of 40° C; the
milk (cows' milk), if undisturbed, sets at first into a solid clot, which
afterward shrinks and presses out a clear, yellowish liquid — the
whey. With human milk the curd is much less firm, and takes the
form of loose flocculi. The whole process resembles much the clotting
of blood. The rapidity of clotting is said to vary inversely as the
amount of rennin, or, in other words, the product of the amount of
rennin and the time necessary for clotting is a constant. The
curdling of the milk involves two apparently independent proc-
esses : First, the rennin acts upon the casein of the milk and converts
it into a substance known as paracasein. The paracasein then
reacts with the lime salts of the milk, forming an insoluble calcium
salt, which constitutes the curd or coagulum. According to this
view, the enzyme does not cause clotting directly. What takes place
when the casein is changed to paracasein is not understood. Ham-
marsten originally regarded the change as a cleavage process, but
this view has not been supported. Others have supposed that a
transformation or rearrangement of molecular structure occurs.
Indeed, the differences in properties between casein and paracasein
are not great, the most marked difference being that the calcium
salts of the latter are insoluble. If soluble calcium salts are removed
from milk by the addition of oxalate solutions it does not curdle upon
the addition of rennin. Addition of lime salts restores this property.
Jt 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 sonic 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

■ an.

So far as our positive knowledge goes, t-M(' action of rennin is
confined to milk. Casein is the chief protein constituent of milk,
;in<l has therefore an Lmportanl nutritive value. It is interesting
to find that before its peptic digestion begins the casein is acted
upon by .'111 altogether different enzyme. The value of the curdling

DIGESTION AND ABSORPTION IN THE STOMACH. 755

action is not at once apparent, but we may suppose that casein is
more easily digested under the conditions that exist in the body after
it has been brought into a solid form. This has, however, been
doubted, and it has even been suggested that the process is a hin-
drance rather than an aid to the digestion of the casein. Until the
contrary is definitely demonstrated it is preferable to assume that
the process is of importance in the digestion of milk. The action of
rennin goes no further than the curdling; the digestion of the curd
is carried on by the pepsin, and later, in the intestines, by the
trypsin, with the formation of proteoses and peptones as in the
case of other proteins.*

Rennin is found elsewhere than in the gastric mucosa. It has been
described in the pancreatic juice, in the testis, and in many other organs
as well as in the tissues of many plants. In fact, wherever proteolytic enzymes
are found there also some evidence of a curdling action on milk may be ob-
tained. For this reason some observers t 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. 412). 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
have described other enzymes in the gastric juice or gastric mem-
brane, but the evidence at hand is uncertain regarding these
latter, except in the case of what is known as gastric lipase
(Volhard). As was said above, it is probable that the ptyalin
swallowed with the food continues to exert its action upon the
starchy material 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 then intimate
mixture with other food stuffs by the dissolving action of the gas-
tric juice upon proteins, 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 mechan-
ically 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

* For references to the very abundant literature, consult Oppenheimer.
loc. cit.

t See Pawlow and Parastschuk, "Zeitschrift f. physiol. Chemie," 42, 415.

756 PHYSIOLOGY OF DIGESTION AND SECRETION.

supposed that this action may be important in the digestion of
the milk-fat by infants. Regarding the proteins, the practical
point of interest is as to how far they are digested during their
stay in the stomach. It seems probable that this question does
not admit of a categorical answer — that is, the extent of the
digestion varies under different circumstances; with the consistency
of the food, the duration of its stay in the stomach, etc. In seme
experiments reported by Tobler it is stated that 48 per cent,
of a given amount of protein passed through the pylorus as
peptones or proteoses, about 20 per cent, entered the intestine
undigested, and 20 to 30 per cent, was absorbed from the stomach.
In the liquid material (chyme) forced through the pylorus into
the duodenum one may find unchanged proteins, primary or
secondary proteoses, peptones, or even the final split products
of proteolytic action. The true value of peptic 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 proteins
of the food is accomplished by both enzymes, and normally we are
justified in considering them together as effecting a peptic-tryptic
digestion. The preliminary digestion in the stomach is important
as regards the protein foods from several standpoints: First, in the
matter of mechanical preparation of the food and its discharge in
convenient quantities easily handled by the duodenum. Second,
in the more or less complete hydrolysis to peptones and proteoses
whereby the action of the pancreatic juice must he greatly acceler-
ated. Indeed, in some cases, this preliminary action of the pepsin-
hydrochloric acid may be absolutely necessary. Native proteins.
such as serum-albumin, are not acted upon by trypsin, but if sub-
mitted first to pepsin-hydrochloric acid they are quickly digested by
this enzyme. Third, for some as yet unknown reason proteins sub-
mitted to peptic digestion are splil by the trypsin in a way different
from it- action on proteins without this preliminary treatment.
These and other fads seem to indicate that the peptic digestion is not

BO much an end in itself as a preparation for subsequent intestinal

digestion. The stomach, therefore, may I"' 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 i- possible thai

there ma\ be ab orption of the following substances: Water; salts;

ugart and dextrinsthal may have been formed in salivary digestion

•Ludwigand Ogata. "Archiv f. Physiologic," 1883, p. 89; Carvallo and
Paction " Vrchivee <!<■ physiologie norm, et path.," 1894, p. 106.

DIGESTION AND ABSORPTION IN THE STOMACH. (Oi

from starch, or that may have been eaten as such; the proteoses and
peptones formed in the peptic digestion of proteins or albuminoids.
In addition, absorption of soluble or liquid substances — drugs,
alcohol, etc., that have been swallowed — may occur. It was formerly
assumed, without definite proof, that the stomach absorbs easily
such things as water, salts, sugars, and peptones. Actual experi-
ments, however, made, under conditions as nearly normal as possible,
show, upon the whole, that absorption does not take place readily
in the stomach — certainly nothing like so easily as in the intestine.
The methods made use of in these experiments have varied, but the
most interesting results have been obtained by establishing a fistula
of the duodenum just beyond the pylorus.* After establishing this
fistula food may be given to the animal and the contents of the
stomach as they pass out through the pyloric opening may be
caught and examined.

Water. — Experiments of the character just described show that
water when taken alone is practically not absorbed at all in the
stomach. Yon Mering's experiments especially show that as soon
as water is introduced into the stomach it begins to pass into the
intestine, being forced out in a series of spurts by the contractions of
the stomach. Within a comparative^ 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
solutions reach a concentration of 3 per cent, or more does its absorp-
tion become important. This result, if applicable to all the soluble
inorganic salts, would indicate that under ordinary conditions they
are practically not absorbed in the stomach, since it can not be sup-
posed that they are normally swallowed in solutions so concentrated
as 3 per cent. In the same direction Meltzer reports that solutions
of strychnin are absorbed with difficulty from the stomach as com-
pared with the intestines, rectum, or even the pharynx. It is said
that the absorption of sodium iodid is very much facilitated by
the use of condiments, such as mustard and pepper, or alcohol,
which act either by causing a greater congestion of the mucous
membrane or perhaps by directly stimulating the epithelial cells.

* Compare von Mering, "Verhandl. des Congresses f. innere Med.," 12,
471, 1893; Edkins, "Journal of Physiology," 13, 445, 1892; Brandl, 'Zeit-
schrift f. Biologie " 29, 277, 1892.

7.5S PHYSIOLOGY OF DIGESTION" AND SECRETION".

Sugars and Peptones. — Experiments by the newer methods leave
no doubt that sugars and peptones can be absorbed from the stomach.
In von Mering's work different forms of sugar — dextrose, lactose,
saccharose (cane-sugar), maltose, and also dextrin — were tested.
They were all absorbed, but it was found that absorption was more
marked the more concentrated were the solutions. Brandl reports
that sugar (dextrose) and peptone are not sensibly absorbed until
the concentration has reached 5 per cent. With these substances
also the ingestion of condiments or of alcohol increases distinctly the
absorptive processes in the stomach. Examination of the mucous
membrane of a stomach in full digestion shows that it contains
albumoses (Glaessner), — a fact that indicates some absorption.
Direct examination of the stomach contents* indicates that the
products of peptic action beyond the albumose stage — namely,
the peptones, peptids, and amido-bodies — are absorbed. On the
whole, however, it would seem that sugars and peptones are ab-
sorbed with some difficulty from the stomach.

Fats. — As we have seen, fats probably undergo no digestive
changes in the stomach, except when eaten in emulsified form.
The processes of saponification and emulsification are supposed to
be preliminary steps to absorption, and these processes take place
usually after the fats have reached the small intestine. The fat that
is not acted upon at all in the stomach is, of course, not absorbed,
and even those fats in emulsified form which are partially saponified
in the stomach escape absorption until they reach the small intestine.
* Zunz, 'Beitriige zur chem. Physiol, u. Pathol.," 3, 339, 1903.

CHAPTER XLIIL
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 chief ducts, one opening, together with the bile-duct, about 3 to
5 cm. 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

759

760 PHYSIOLOGY OF DIGESTION AND SECRETION.

of the secretion are formed they are frequently designated as zymo-
gen granules. The pancreas contains also certain peculiar groups of
cells, the islands (or bodies) of Langerhans. These cells probably
have nothing to do with the digestive activity of the pancreas.
Their supposed function is referred to in the sections on Internal
Secretions and Nutrition.

Composition of the Secretion. — The pancreatic secretion is an
alkaline liquid which in some animals is thin and limpid, in others
thick and glairy. The secretion in man belongs to the former
type : it is described as water-clear and as having a specific gravity of
1.0075. The secretion may be collected by opening the abdomen
and inserting a cannula directly into the duct, or a permanent
fistula may be made by the method of Pawlow. This method,
applicable to the dog, consists in cutting out a small portion of
the duodenum where the pancreatic duct opens and then suturing
this piece, the mucous membrane outward, into the abdominal
wall. The secretion in this case pours out upon the exterior and may
be collected. The animal, however, suffers nutritive disturbances
from the loss of the secretion, and requires careful dieting and atten-
tion. The secretion of the human pancreas has been collected in a
single case* in which for a few days it was necessary to drain off the
pancreatic juice to the exterior. From the observations made in this
case it appears that the secretion in man is quite abundant, amount-
ing to 500 to 800 c.c. per day. In the cow (Delezenne) from H to 2
liters may 1 )e collected in the course of a day . The secretion possesses
a strong alkaline reaction, due to the presence of sodium carbonate;
it contains also a small amount of coagulable protein and a number
of organic substances in traces. The important constituents, how-
ever, arc 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 splandi-
nics and the vagi have given negative results in the hands of most

observer8SO far as the pancreatic secretion LS concerned. Pawlow f
and liis coworker- claim to have been more successful. Mechanical

stimulation or electrical stimulation of the vagus or splanchnic gave

• 3ee Glae tier, 'Zeil chrifl f. physiol. Chemie," 10, 465, 1903,

; For recent work upon the pancreas and the literature Bee Pawlow,

"The Work of the Digestive Glands, " translation by Thompson, I902j Bay-
ad Starling, "Journal of Physiology," 30, 61, 1904; Walter, "Archive*

Hi' cience biologiquei , " 7, 1. J899.

DIGESTION AND ABSORPTION IN THE INTESTINES.

761

them a marked flow of pancreatic juice, but when the latter form of
stimulus was used upon the splanchnic, it was necessary to cut
the nerve some days previously in order that the vasoconstrictor
fibers might degenerate. The secretion provoked by stimulation
of the vagus is more easily obtained when the stimulus is applied
to the nerve in the thorax below the origin of the branches to the
Heart. 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 stimu-

1.

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Fig. 286. — 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.

lated contain both secretory and inhibitory fibers and that the
antagonistic action of the latter delays the appearance of the
secretion. These observations have been taken as proof of the
existence of secretory nerve fibers to the pancreas, the fibers
running chiefly in the vagus nerve.

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

762 PHYSIOLOGY OF DIGESTION AND SECRETION.

meal of bread alone than after a meal of meat alone. It seems
possible that the latter point, the time at which the maximum flow
is reached, may depend upon the difference in rate at which these
foods are ejected from the stomach. Cannon (p. 698) has shown that
the carbohydrate foods leave the stomach sooner than the proteins or
fats. It is stated, however, that the composition of the secretion
varies also with the character of the food, and indeed shows an
adaptation to the character of the food. The secretion caused by
protein food is especially rich in trypsin, that caused by fatty food
in lipase, etc. The mechanism by which this adaptation is secured
is not understood. Glaessner* has measured the rate of flow in
man, and his curve for a mixed diet is represented also (in
red) in Fig. 286. 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, winch 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
thestomach pass through the pylorus this action begins. Just as the
chewing and swallowing of the food initiate the gastric secretion, so
the acid of the latter starts the pancreatic secretion. Assuming
that the pancreatic gland possesses secretory libers if was thoughl at
firsrl thai the acid acts reflexly through these fibers thai is, theacid
in the duodenum acting upon sensory endings causes a reflex stimu-
lation of I he efferenl secretory libers. It has been shown, however,
that the same effeel takes place after section of the va^us and

* ( il:ic hit, loc.dt.

t Boldireff, " Archives <lcs sciences biologiques, " 11, 1, 1905.

DIGESTION AND ABSORPTION IN THE INTESTINES. 763

splanchnic nerves (Popielski), and Bayliss and Starling * have called
attention to another more probable explanation. These authors find
that if the mucous membrane of the duodenum (or jejunum) is
scraped off and treated with acid (0.4 per cent. HC1) the extract
thus made when injected into the blood sets up an active secretion of
pancreatic juice. They have shown that this effect is due to a special
substance, secretin, which is formed by the action of the acid upon
some substance (prosecretin) present in the mucous membrane.
Secretin is not an enzyme, since its activity is not destroyed by boil-
ing or by the action of alcohol. The experimental evidence at
present favors the view that the normal sequence of events is as
follows: The acid of the gastric juice upon reaching the duodenum
produces secretin; this in turn is absorbed by the blood, carried to
the pancreas, and stimulates this organ to activity. The pan-
creatic secretion furnishes, therefore, a second example of the group
of substances designated by Starling as hormones (p. 749). Accord-
ing to the evidence at present in our possession we must believe
that the pancreatic secretion, like the gastric secretion, consists
of two parts: 1, A nervous secretion caused by the secretory
fibers in the vagus and splanchnic; 2, a chemical secretion due to
the action of the secretin. These two secretions are said to
present quite different characters, f The former is thick, opales-
cent, rich in ferments and proteins, but poor in alkalies. The
trypsin contained in it may be secreted in active form, and the
secretion is suspended by the action of atropin. Administration
of pilocarpin, on the contrary, excites this secretion. The chemical
secretion, on the contrary, is thin and watery, contains relatively
little ferment or proteins, and is rich in alkali. The trpysin in
it is secreted in inactive form (see next paragraph), and the
secretion is not affected by the administration of atropin. The
normal relation of these two forms of secretion in an ordinary
meal is not so apparent as in the case of the gastric secretion, but
will doubtless be made clear by subsequent work.

Activation of the Trypsin — 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
proteins, but if brought into contact with the duodenal membrane
or an extract of this membrane it shows at once powerful pro-
teolytic properties. This discovery has been confirmed repeatedly.
Evidently the proteolytic enzyme of the juice is secreted in a
zymogen or pro-enzyme form (trypsinogen) , which is activated or
converted to trypsin by something contained in the mucous mem-

* Bayliss and Starling, "Journal of Physiology," 28, 235, 1902.
t Sawitsch, " Zentralblatt f. d. ges. Physiol, u. Pathol, d. Stoffwechsels,"
10, 1, 1909.

764 PHYSIOLOGY OF DIGESTION AND SECRETION'.

brane of the small intestine (duodenum, jejunum). This something
Pawlow supposed 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 is very prompt
and decided and was supposed to be specific, but later observers
(Delezenne-Zunz') state that an inactive pancreatic secretion
may be activated by a number of salts, especially those of calcium
and magnesium. 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 in part, at least, in active
form.

The Digestive Action of Pancreatic Juice. — The digestive
action of the secretion depends upon the three enzymes, trypsin,
diastase (amylase), and lipase. The specific effects of each may
be considered separately.

Action oj Trypsin. — The activated trypsinogen causes hydrolytic
cleavage of the protein molecule in a manner analogous to that
i lescribed for pepsin. Its action differs from that of pepsin, however,
in several respects. It attacks the protein in neutral as well as in
slightly acid or markedly alkaline solutions. Its effect upon the
protein is more rapid and powerful than that of pepsin and the
protein molecule is broken up more completely. As was said in
describing the action of pepsin, it and the trypsin really act to-
gether the change begun by the pepsin is completed by the tryp-
sin. The preliminary action of the pepsin not only hastens that of
the trypsin, bul to some extenl alters it; a protein submitted first
to pep-in and then to trypsin is more completely broken up than if
the trypsin acted alone. The steps in the hydrolysis of the protein
molecule by trypsin have been the subject of a very greal amount of
study, and views as to the details have changed somewhat rapidly

of recenl years. Kilhne supposed that the protein molecule contains
two groups, the hemi and the anti. Under I he inlliienco of t he ! pyp-

sin these are. on his theory, converted into corresponding proteoses,

primary and secondary, and then into peptones hcniipeptone and

antipeptone. As distinguished from the pepsin, the trypsin hy-
drolyzes the hemipeptone still further, splitting it up into a number
of much simple]' 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.
\ftr-r a prolonged pancreatic digestion no peptone or peptone-like

body 'an be found; in fact, no substance which gives a biuret, reac-
tion. Under such conditions the protein molecule is broken up very

DIGESTION AND ABSORPTION IN THE INTESTINES. 765

completely into a surprising number of smaller molecules, man}'
of which have been identified, while some have as yet escaped de-
tection so far as their chemical structure is concerned. The actual
products formed depend on the length of time the trypsin is allowed
to act and the conditions, favorable or unfavorable, under which it
acts. The end-products usually obtained most easily are tyrosin,
leucin, aspartic acid, glutaminic acid, tryptophan, lysin, arginin,
histidin. The first two of these substances have been known for a
long time and may be obtained easily in crystalline form from
pancreatic digestions. If the trypsin is allowed to exert its complete
action upon the protein the end-products are closely similar to those
obtained by boiling protein with acids. The hydro lysis caused
by the acids and by the trypsin seems to be nearly identical, although
that caused by the acids is probably more complete, and perhaps
is attended by secondary reactions, since the split products of a
complete acid hydrolysis when fed to an animal give a different
result from those obtained from a complete trypsin-hydrolysis
(see p. 857). The numerous products obtained by this complete
hydrolysis consist chiefly of amino-acids — that is, organic acids
containing one or more amino-groups (NH2) in direct union with
carbon. The nitrogen of the protein molecule appears in the
split products in this form and also partly as ammonia compounds.
Some of the amino bodies are monamino-acids — that is, contain
one NH2 group, such as leucin, tyrosin, glycin — and include sub-
stances belonging to the fatty acid series (aliphatic series), the
benzene or carbocyclic series, and the heterocyclic series. 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 some of these bodies are as follows. For their
properties and chemical relationships reference must be made to the text-
books on physiological chemistry (see also Appendix, Chemistry of Proteins,
for a more complete list):

I. MONAMINO-BODIES.
FATTY ACID SERIES.

Glycin or amino-acetic acid: CH2NH3COOH. This product is obtained
in especially large quantities by hydrolysis of gelatin. According
to Abderhalden,* it is split off with difficulty by trypsin.

Alanin or n-aminopropionic acid: CH3CHNH2COOH.

Valin or amino valerianic acid: p^3>CHCHNH,COOH.

* Abderhalden, "Zeitschrift f. physiol. Chemie," 44, 17, 1905. Consult
for general description of the digestion of proteins.

'6(3 PHYSIOLOGY OF DIGESTION AND SECRETION".

Leucin or aminocaproic acid: £§3^CHCH,CHNH,COOH. As stated

above, this compound was one of the first end-products of protein
hydrolysis that was recognized. It may be obtained readily in
crystalline form.

CHNH,COOH
Aspartic or aminosuccinic acid :

CH,COOH.

r,, + • • ., nxr /CHNH,COOH
Glutammic acid: t/H3' pu COOH

BENZENE OR AROMATIC SERIES.

Tyrosin (para-oxyphenylaminopropionic acid) : C6H4OH . CH2 . CHNH2-
COOH. This substance was also among the first recognized prod-
ucts of protein hydrolysis It occurs early in the process of pan-
creatic digestion, and is easily obtained in crystalline form from
the digested mixture. It is especially interesting because of the
presence of a benzene nucleus, thus giving proof that the benzene
grouping occurs normally in the protein molecule.

Phenylalanin (phenylaminopropionic acid) : C6H5CH,CHNH,COOH. This
benzene derivative is, according to Abderhalden, split off from the
protein with difficulty by the action of trypsin, although readily
produced by acid hydrolysis.

PYRROL AND INDOL SERIES.

CH, — CH2

I I

Prolin or a-pyrrolidin carboxylic acid: CH2 CHCOOH. This substance,

NH
discovered first by Fischer among the products of acid hydrolysis of
proteins, lias since been shown to occur in tryptic digestion. Like
the glycin 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.
Tryptophan (indolaminopropionic acid) : This substance has long been recog-
nized among the products of tryptic digestion by the reddish-violet
color (Tiedemann and Gmelin, 1X2<>) observed upon the addition of
chlorin or bromin. Its chemical st rucl ure was determined by Hopkins
and Colo (1001). According to Ellinger,* tryptophan is an indol-
amino-propionic acid of the formula (' . ( "1 1( '< )( )1I( 'lLNIl.,.

c,h4<(Vh

NH
When fed to dogs it causes the appearance of kynurenic acid

(C,„H7.\< >,) in t he urine.

It is interesting as showing the existence of an indol grouping
in t lie protein molecule.

II. 'I'm: DlAMINO-BODIES (HEXON BASES).

Lysin fo-#-diaminocaproic acid): C'UI IMN2< >-. or < ' 1 1 :. \ 1 1 2 (( ' II ;,) .,0 J I N J I2-
COOH.

Arginill (guanidin «-aininovalerianic acid): C|,IInN.,()2 or NH(!NII2NH-

CH,(CH3)aCHNH,COOH.

Hi tidin: CgHjNgOj (imidazolaminopropionic acid?).

The Significance of Tryptic Digestion. It was formerly

supposed thai the objeel of peptic and tryptic digestion is to con-

bhe insoluble and non-dialyzable proteins into the simpler,

more soluble, and more diffusible peptones and proteoses, In this

* Ellinger. " Zeitschrifl f. physiol. Chemie," 43, '■'^.',, 1904.

DIGESTION AND ABSORPTION IN THE INTESTINES. 767

way absorption of protein material was explained. This, view,
however, is not sufficient. On the one hand, it has not been possible
to prove conclusively that peptones or proteoses are found in the
blood; on the other hand, a better knowledge of the processes of
tryptic or of peptic-tryptic digestion has shown that the hydrolysis
does not stop at the peptone stage ; the protein molecule is split into
a number of simpler crystalline substances, the various amino-
bodies. At present different views exist as to the extent of this
latter process. Some believe that the protein molecule is entirely
broken down into its so-called end-products, and that in order to
serve its nutritive function these products or some of them must be
synthetically combined again during or after absorption. This view
is supported, moreover, by the discovery of the existence of the
enzyme erepsin (see below) in the intestinal mucosa. The action of
this latter enzyme is exerted especially upon the albumoses and pep-
tones, breaking them down into the amino-acids, so that apparently
whatever peptone or albumose may escape the final action of the
trypsin before absorption is likely to be acted upon by the erepsin
before reaching the blood.* Another interesting view is that sug-
gested by Abderhalden.f According to this author, the hydrolysis
of the protein by pepsin and trypsin (and perhaps by erepsin) is not
complete. Many amino-bodies, such as tyrosin, leucin, arginin, etc.,
are split off from the protein molecule, but there remains behind
what one may call a nucleus of the original molecule, which serves as
the starting point for a synthesis. This nucleus is a substance or a
number of substances intermediate between the peptone and the
simpler end-products, and is spoken of as a peptid or peptoid (see
Appendix) . Since its structure is unknown and it is probably not
a simple body, it is designated as a polypeptid. Abderhalden has
shown that in tryptic digestion such substances are formed — that
is, substances which are not peptones, since they no longer give the
biuret reaction, but which have a certain complexity of structure,
since upon hydrolysis with acids they split into a number of mon-
amino- and diamino-bodies. A schema of peptic-tryptic digestion
from this standpoint may be given as follows:

Native protein.
Peptone.

Polypeptid. Tyrosin, leucin, glutaminic acid, aspartic acid,
a-pyrrolidin carboxylic acid, tryptophan, etc.
Arginin, lysin, histidin.

* Vernon ("Journal of Physiology," 30, 330, 1904) believes that the
pancreatic secretion contains two proteolytic enzymes — trypsin proper,
which converts the proteins to peptones, and pancreatic erepsin, which breaks
up the peptones into the simpler end-products, the amino-bodies.

f Abderhalden, loc. cit.

76S PHYSIOLOGY OF DIGESTION AND SECRETION.

From either of the points of view presented it may be suggested that
the value of this more or less complete splitting of the protein of the
food lies in the possibility that thereby the body is able to construct
its own peculiar type of protein. Many different kinds of proteins
are taken as food ami many of them if introduced directly into the
blood act as foreign material incapable of nourishing the tissues.
If these proteins are broken down more or less completely during
digestion the tissue cells may reconstruct from the pieces a form of
protein adaptable to their needs, and more or less characteristic
fur that particular organism. This general point of view is gaining
ground in recent years and has obtained much support from the
fart that an animal may be nourished properly on a diet in which
the protein of the food is entirely replaced by the split products
of a complete pancreatic digestion (see p. 857).

Action of the Diastatic Enzyme (Amylase) of the Pan-
creatic Secretion. — This enzyme is found in the secretion of the
pancreas or it may be extracted from the gland. Its action upon
starch}' 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 aehroodextrin. 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 tins 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
firsi 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
palmitLn :

I ii C II .COO), -I- 3Ha0 - C,H,(0]l)3 -i- 3(C,8H8,COOH)

j'.iliiiiiin. ' ilj rii in. I'.-ilmii io acid.

When lipase from any source is added to neutral oils its splitting
action is readily recognized by (lie development of an acid reaction
flue to the formation of the fatty acid. 11* a, bit of fresh pancreas
• \<A to butter, for example, and the mixture is kept nt the body
temperature the hydrolysis of the hits is soon made evident by the

DIGESTION AND ABSORPTION IN THE INTESTINES. 769

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
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. It is very probable, moreover, that during this
synthesis the fatty acids are combined with the glycerine in such
proportions as to make for the most part the fat characteristic
of the animal, fat of a high melting-point in the case of the
sheep, for example, and of a lower melting-point for the dog.
In connection with this fact of a synthesis of the split products
to form neutral fat, the discovery by Kastle and Loevenhart
(see p. 718) 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 man}- tissues, — muscle, liver, mammary
gland, f etc. — and during its nutritive history in the body the fat may

* See Ratchford, "Journal of Physiology," 12, 27. 1891.

f See Loevenhart, "Arner. Journal of Physiology," 6, 331, 190^

49

770 PHYSIOLOGY OF DICES LION AND SECRETION.

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.*

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. This
effect is now explained on the hypothesis that the bile-acids or
the bile-acids and the lecithin activate a portion of the lipase
which is in the state of a proferment.

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
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
rd them as secretory products and consider them as the impor-

i;int and characteristic feature of the intestinal secretion. These
enzymes and their actions are as follows:

1. Enterokinaae (see p. 763), an enzyme which in Borne way activates Uie
proteolytic enzynie of the pancreatic juice, by converting the tryp-
inogen to i rypsin.

, nil Herzog, "Zeitschrifl f. physiol. Chemie," 37, 383, L903.

DIGESTION AND ABSORPTION IN THE INTESTINES.' 771

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. 767), 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 + C6H1206

Maltose. Dextrose. Dextrose.

In the same way invertase converts cane-sugar to dextrose and levu-
lose, and lactase changes milk-sugar to dextrose and galactose. This
inverting action is necessary to prepare the carbohydrate food for
nutritive purposes. Double sugars can not be used by the tissues
and would escape in the urine, but in the form of dextrose or
dextrose and levulose they are readily used by the tissues in their
normal metabolic processes.

4. Nuclease. There is some evidence that this enzyme which acts- upon

the nucleic acids is found normally in the small intestine and that it
may play a part in the digestion of the nucleins of our food.

5. Lastly, the substance secretin, which, as explained above, plays

such an important role in the control of the secretion of the pan-
creas, is formed in the walls of the small intestine. It is not an
enzyme, but a more stable and definite chemical substance which
is secreted or formed in the intestinal mucosa in a preliminary form,
prosecretin, and under the influence of acids is changed to secretin.
In this latter form it is absorbed, carried to the pancreas, and
causes a flow of pancreatic secretion.

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

* Cohnheim, " Zeitschrift f. physiol. Chemie, " 33, 451, 1901 ; also 35, 134
rt seq.

772 PHYSIOLOGY OF DIGESTION AND SECRETION.

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 lias passed the ileocecal valve; this estimate includes, of course,
the time in the stomach. During this passage absorption of the
digested products takes place nearly completely. In the fistula case
referred to above it was found that 85 per cent, of the protein had
disappeared, and similar facts are known regarding the other food-
stuffs. The problems that have excited the greatest interest have
been, first, the exact form in which the digested products are ab-
sorbed, and, second, the means by which this absorption is effected.
With regard to the last question, much work has been done to
ascertain whether the known physical laws of diffusion, osmosis,
and imbibition are sufficient to account for the movements of the
absorbed substances or whether it is necessary to refer them in
part to some unknown activities of the living epithelial cells. It
would seem that diffusion and osmosis occur in the intestines.
Concentrated solutions of neutral salts, — sodium chlorid, for instance,
—if introduced into a Thiry-Vella loop, cause a flow of water into
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,*
a presumably the same concentration and osmotic pres-
sure as the animal's blood, is absorbed completely from an isolated
intestinal loop. So also it has been shown that in the absorption of
salts from the intestine J the rapidity of absorption stands in no
dii-eci relation to the diffusion velocity. The energy thai effects
the absorption is furnished, therefore, by the wall of the intestine,
presumably by the epithelial cells. It, constitutes a special form
of imbibition which is no1 yet understood. That this particular
form of energy is connected with the living structure is shown by

the fad that when the \v;ill- are injured l.\ the action of sodium

* Macfadyen, Nendo, and Sieber, "Arohiv f. experiment. Pathol, u.
Phannakol.,' 28, 31 I. L891.

t Heidenhain, "Archivf. diege ammte Physiologic," 56, 579, 1894.

,f Wallace and Cushny, "Archiv f. die gesammte Physiologie," 77, 202,

DIGESTION AND ABSORPTION IN THE INTESTINES. 773

fluorid, potassium arsenate, etc., their absorptive power is dimin-
ished and absorption then follows the laws of diffusion and.
osmosis.*

Absorption of the Carbohydrates. — Our carbohydrate food is
absorbed, for the most part, as simple sugars, — monosaccharids.
As has been said, there is reason to believe that but little sugar is
absorbed in the stomach. Cane-sugar and milk-sugar are inverted
in the small intestine by invertase and lactase, the first being con-
verted to dextrose and levulose, the second to dextrose and galactose.
If, however, these substances are fed in excess they are absorbed in
part without conversion to simple sugar, and in that case may be
eliminated in the urine. The bulk of our carbohydrate food is taken,
however, in the form of starch, and the conditions for absorption in
this case are more favorable. The time required for the digestion of
the starch to maltose and dextrin, and the subsequent inversion of
these substances to dextrose, insures a slower and more complete
absorption. Five hundred grams or more of starch may be digested
and absorbed in the course of the day and it all reaches the blood in
the form of dextrose. This dextrose enters the portal vein and is
distributed first to the liver. In this organ the excess of sugar is
withdrawn from the blood and stored as glycogen, so that the amount
of sugar in the general circulation is thereby kept quite constant, —
about 0.15 per cent. When a large amount of carbohydrate food is
eaten, however, it is possible that the liver may not be able to remove
the excess completely. In that case the amount of sugar in the gen-
eral circulation may be increased above normal, giving a condition
of hyperglycemia. In such cases the excess is likely to be excreted
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 desig-
nated by Hofmeisterf as the assimilation limit of that carbo-
hydrate. If taken beyond this limit there is a physiological excess,
and some sugar 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. That starch may be eaten in larger
amounts than sugar without raising the percentage of sugar in
the systemic blood above the normal level is in accord with what
we know of the digestion of the two forms of carbohydrates.
Dextrose requires no digestion, it is absorbed as such, while cane-
sugar needs only to be inverted. Starch, on the contrary, requires
the action of ptyalin or amylase and subsequent inversion by

* Cohnheim, " Zeitschrift f . Biologie," 37, 443, 1899.

t Hofmeister, " Archiv f. exper. Pathol, u. Pharmakol.," 25. 240, 1889,
and 26, 355, 1890.

774 PHYSIOLOGY OF DIGESTION AND SECRETION".

maltase. Its absorption will, therefore, be much slower than that
l>f the sugars: In fact, it probably goes on for the period of four
or five hours, during which an ordinary meal is making its progress
from pylorus to ileocecal valve. During this period the entire
quantity of blood in the body is passed through the mesenteric
arteries over and over again, and it is probable that even in the
portal vein the quantity of sugar at any one moment rises but
little above the normal level, and this small excess is held back
by the liver colls, so that the systemic circulation is protected
from becoming hyperglycemic.

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,* 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 hit is not mechanically ingested as oil drops.
But, granting thai the fat is absorbed in solution, as fatty acids and
glycerin, the mechanism of absorption remains unexplained. It is

known lh:il the bile as well as the pancrent LC juice plays an important

part in the process. The pancreatic juice furnishes i he lipase, (lie bile
furnishes the bile salts (glycocholate and taurocholate of sodium)

which aid the lipase in splitting the neutral fat, and moreover aid
greatl) the absorption of the split fats. This latter function is due

probably to the fad thai the bile (bile salts) dissolves (he fat ty acids
* Macfadyen, Nencki, .-nil Sieber, loc. dt.

DIGESTION AND ABSORPTION IN THE INTESTINES. I (Q

readily* and thus brings them into contact, in soluble form, with the
epithelial cells. When the bile is drained off from the intestine
by a fistula of the gall-bladder or duct, a large proportion of
the fatty foods escapes absorption and appears in the feces. Direct
observation shows that the fat after passing the epithelial lin-
ing and entering the stroma of the villus is taken up by the
lymphatic vessels, the so-called lacteals. This fact is beautifully
demonstrated by the mere appearance of the lymphatics of
the mesentery after a meal containing fats. These vessels are
injected with milky chyle during the period of absorption so that
their entire course is revealed. The chyle on microscopical exami-
nation is found to contain fat in the form of an extremely fine
emulsion. In this form it is carried to the thoracic duct and thence
to the venous circulation. For hours after a meal the blood contains
this chyle fat. If a specimen of blood is taken during this time and
centrifugalized in the usual way, the chyle fat may be collected at
the top in the form of a cream. It is an easy matter to insert a
cannula into the thoracic duct at the point at which it opens into the
subclavian and jugular veins and thus collect the entire amount of fat
absorbed from the intestines by way of the lacteals. Experiments
of this kind show that, after deducting the amount of fat that escapes
absorption and is lost in the feces, the amount that may be recovered
from the thoracic duct is less than that taken in the food. It seems
probable, therefore, that some of the fat is absorbed directly by the
blood-vessels of the villi, probably in the form of fatty acids or soaps.
The portion thus absorbed enters the portal vein and passes through
the liver before reaching the general circulation. The liver holds
back more or less of the fat taking this route, as it is found that
during absorption the liver cells show an accumulation of fat droplets
in their interior .f The amount of fat that may be absorbed from
the intestines varies with the nature of the fat. Experiments show
that the more fluid fats, such as olive oil, are absorbed more com-
pletely,— that is, less is lost in the feces than in the case of the more
solid fats. Comparative experiments have given such results as the
following: Olive oil, — absorption, 97.7 per cent. ; goose and pork fat,
97.5 per cent.; mutton fat, 90 to 92.5 per cent.; spermaceti, 15 per
cent. The amount of fat that may be lost in the feces varies also
with other conditions. If, for instance, an excess is taken with the
food, or if the bile flow is diminished or suppressed, the percentage
in the feces is increased. The usual amount of fat allowed as a
maximum in dietaries is from 100 to 120 gms. daily.

Absorption of Proteins. — Most of the experimental work on
record shows that the digested proteins are absorbed by the blood-
vessels of the villi, although after excessive feeding of protein a

*See Moore and Rockwood, "Journal of Physiology," 21, 58, 1897;
also Moore and Parker, " Proceedings, Roval Society," London, 58, 64, 1901.
t See Frank, " Archiv f. Physiologie, " 1892, 497, and 1894, 297.

776 PHYSIOLOGY OF DIGESTION AND SECRETION.

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 I is ligated, so as to shut off the lym-
phatic circulation, an animal will absorb and metabolize the usual
amount of protein as is indicated by the urea excreted during the pe-
riod. Second (Munk), if a fistula of the thoracic duct is established
and the total lymph How from the intestines is collected during
the period of absorption after a diet of protein, it is found that there
is no increase in the quantity of the lymph or in its protein contents.
The form in which protein is absorbed and circulates in the blood
is not satisfactorily determined. Under normal conditions the
protein food is digested by the successive actions of pepsin, trypsin,
and probably erepsin. During this digestion peptones and proteoses
are formed and may be absorbed as such, or they may be further
broken down by trypsin and erepsin to the amino-bodies, leucin,
tyrosin, arginin, etc.. and the intermediate compounds, the poly-
peptids or peptoids (see p. 767), and be absorbed in the form of
these split products. Some observers claim to have found peptones
or proteoses as a normal constituent of the blood, but this claim
has not been satisfactorily established. Others have shown the
presence of traces of the amino-acids,f but much uncertainty exists
as i'i the precise form in which the protein nourishment for the body
exists normally in the blood. Several possibilities have been sug-
gested. It is conceivable that the peptones or the more simple
split products may be synthesized in the wall of the intestine or in
the liver to the proteins of the blood, the serum-albumin or globulin;
it i- possible that many of the end-products of the digestive splitting
may be further oxidized and converted to urea in the liver and only a
fractional part be really synthesized into the proteins of the body,
or it is possible that the absorbed protein exists in the blood in
some special form not as yet recognized. Perhaps the most
importanl fad to be emphasized in this connection is the dis-
covery thai animals may lie nourished when fed only with tin;
split products of protein, thai is to Bay, with the products of a
complete pancreatic digestion (p. Nf)7). It is evident that in
such cases the body must take some of these split products and
build 1 hem up again to t he protein form. The prevailing bypol n-
i- thai 1 his synthesis takes place in the walls of the intestine
ami that the body protein thus reconstructed constitutes a part

of the proteins of the blood. It must, be borne in mind, however,
that this, hypothesis is far from having been demonst rated. Atten-

* Sec Mendel, "American Journal of Physiology," 2, 137. L899.
f For reference . see Howell, "American Journal of Physiology," 1906,
17, 273.

DIGESTION AND ABSORPTION IN THE INTESTINES. 777

tion should also be directed to the fact that many forms of protein
may be absorbed apparently without previous digestion. This fact
has been demonstrated for isolated loops of the small intestine and
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 protein 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 proteins,
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 protein 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
protein 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. This difference is not due, however, to any peculiarity
of the vegetable proteins; it is probably an incidental result of the
presence of the indigestible cellulose found in our vegetable foods.
It is stated that from 17 to 30 per cent, of the protein 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

* See Munk, "Ergebnisse der Physiologic," vol. i., part i., 1902, article,
"Resorption," for literature and discussion.

7<S PHYSIOLOGY OF DIGESTION AND SECRETION.

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 whoso small intestine (70 to 83 per cent.) had been
removed.* These animals could digest and absorb well, and formed
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 protein 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 fermental ion of protein material
is limited or absenl in t his part of the intestine as long as the products
of protein digestion are promptly absorbed. Conditions that pre-
vent or retard this absorption favor the occurrence of protein
putrefaction. Opinions among investigators differ as to the means
by which the protein contents are protected from the action of the
bacteria. It lias been shown that the presence of carbohydrate
material lias a restraining effect upon protein putrefaction. The
simplesl explanation of this relation is that the fermentation of the

carbohydrates gives rise to ;i number of organic acids -lactic,
acetic, etc. and the-' acids inhibit the action of the protein bac-
teria. To make this explanation satisfactory, however, it is neces-
sary to show thai the contents of the small intestine possess an acid

reaction. ( loncerning 1 his point opinions also differ. The secretions

of the small intestine are all alkaline and we should expect their
contents to have this reaction: Examination shows thai the con-
bents of the small intestine are acid or not according to i\\i^ indicator
used. With phenolphthalein they may give an acid reaction, while
with litmus, lakmoid, etc., no such reaction is obtained. f Such a
resull as this indicates thai no strong organic acids, such as acetic

Erlanger and Hewlett, "American Journal of Physiology," 6, L, L902.
< on nil Macfadyen, Nencki, and Sieber, loc. tit.; Moore and Bergin,
"American Journal of Physiology," :;, 316, L900; Munk, " Cen1 ralblatt f.
ogie," L6, 33, and L46, L902.

DIGESTION AND ABSORPTION IN THE INTESTINES. 779

and lactic, are present, the phenolphthalein being affected possibly
by the C02. As Munk has stated it seems that the contents of the
small intestine throughout the duodenum and jejunum are at least
never alkaline, and when carbohydrates are used the reaction may
not only be acid to phenolphthalein but also to the stronger indica-
tors. On the whole, therefore, it would seem probable that the
small amount or total lack of protein putrefaction in the small intes-
tine is due in part to the rapid absorption of the digested protein
and in part to an unfavorable reaction. Some observers contend
that there is a struggle for existence or antagonism between the
bacteria acting upon carbohydrates and those living upon proteins.
When the former have conditions favorable for growth, their increase
in some way affects injuriously the protein bacteria.*

Bacterial Action in the Large Intestine. — In the large intestine
protein putrefaction is a constant and normal occurrence. The
reaction here is stated to be alkaline, and whatever protein may have
escaped digestion and absorption is in turn acted upon by the bac-
teria and undergoes so-called putrefactive fermentation. The split-
ting up of the protein molecule by this process is very complete, and
differs in some of its products from the results of hydrolytic cleavage
as caused by acids or by trypsin. The list of end-products of putre-
faction is a long one. Besides peptones, proteoses, ammonia, and
the various amino-acids, there may be produced such substances as
indol, skatol, phenol, phenylpropionic and phenylacetic acids, fatty
acids, carbon dioxid, hydrogen, marsh gas, hydrogen sulphid, etc.
Many of these products are given off in the feces, while others are
absorbed in part and excreted subsequently in the urine. In this
latter connection especial interest attaches to the phenol, indol, and
skatol. Phenol or carbolic acid, C6H5OH, after absorption is com-
bined with sulphuric acid, to form an ethereal sulphate (conjugated
sulphate) or phenolsulphonic acid, C6H5OS02OH, and in this form
is found in the urine. So also with cresol. The indol, G8H7N, 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 C9H8NOSO,OH,
skatoxyl-sulphuric acid. These bodies have long been known to
occur in the urine, and the proof that they arise primarily from putre-
faction of protein material in the large intestine is so conclusive as
not to admit of any doubt. The amount to which they occur in
the urine is, therefore, an indication of the extent of the putrefaction
in the large intestine.

Is the Putrefactive Process of Physiological Importance?—
Recognizing that fermentation by means of bacteria is a normal
occurrence in the gastro-intestinal canal, the question has arisen

*See Bienstock, "Archiv f. Hygiene," 39, 390, 1901.

780 PHYSIOLOGY OF DIGESTION AND SECRETION.

whether this process is in any way necessary to normal digestion and
nutrition. It is well known that excessive bacterial action may lead

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
Tbierf elder* report some very interesting experiments upon guinea
pigs in which the young animals from birth were kept sterile and fed
with perfectly sterile food. They found that the animals lived and
increased in weight, and concluded therefore that the intestinal
bacteria are not necessary to normal nutrition. This conclusion is
supported by the observations of Levin,f who finds that animals in
the Arctic regions in many cases have no bacteria in their intestines.
SchotteliusJ reports contrary results upon chickens. When kept
sterile they lost steadily in weight and showed normal growth only
when supplied with food containing bacteria. The idea that the
relations between the bacteria and the animal that harbors them
constitutes a kind of symbiosis in which each derives a benefit
from the other has certainly not been demonstrated. The con-
trary view, that bacterial putrefaction is the occasion for constant
danger to the human organism, lias been stated in extreme form,
perhaps, by Metchnikoff. According to this author the constant
production and absorption of bacterial toxins from the intestine is
one of the important causes of a loss of resistance on the part of
the body to the changes which bring on senescence and death.
At present it seems wise to take the conservative view that while
the presence ol the bacteria confers no positive benefit, the organ-
ism has adapted itself under usual conditions to neutralize their

injurious acl ion.

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 amounl and dark
in color; with an ordinary mixed diet the amount is increased ; and
it i- largest with an exclusively vegetable diet, especially with vege-
tables containing a large amount of cellulose. The average

• Nuttall and Thierfelder, "Zeitschrifl f. physiol. Chemie," 21, L09,
1895; 22. 62, L896; 23, 231, L897.

f'Skandinavi che Irchiv I Phyaiologie, " 16,249, L904.
X "Archiv f. Hygiene," 12, 48, 1902.

DIGESTION AND ABSORPTION IN THE INTESTINES. 781

weight of the feces in twenty-four hours upon a mixed diet is
given as 170 gins., 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 alwajrs
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
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 together with the cellular debris thrown
off from the walls of the intestines. (4) Products of bacterial
decomposition. The most characteristic of these products are
indol and skatol. They are crystalline bodies possessing a dis-
agreeable, fecal odor; this is especially true of skatol, to which
the odor of the feces is mainly due. (5) Cholesterin, or a deriva-
tive, which is found always in small amounts, and is probably
derived from the bile. (6) Some of the purin bases, especially
guanin and adenin. (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, but chiefly the last three together
with phosphoric acid. The significance of the calcium and iron
salts will be referred to in a subsequent 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 proteins, although some of the N may be derived from air
swallowed with the food.

* Prausnitz, "Zeitschrift f. Biologie, " 35, 335, 1S97; and Tsuboi, ibid.,
p. 68.

CHAPTER XLIV.
PHYSIOLOGY OF THE LIVER AND THE SPLEEN.

The liver plays an important part in the general nutrition of the
body. Its functions are manifold, but in the long run they depend
upon the properties of the liver cell, which constitutes the anatomical
and physiological unit of the organ. These cells are seemingly
uniform in structure throughout the whole substance of the liver, but
to understand clearly the different functions they fulfill one must
have a clear idea of their anatomical relations to one another and
to the blood-vessels, the lymphatics, and the bile-ducts. The histol-
ogy of the liver lobule, and the relationship of the portal vein, the
hepatic artery, and the bile-duct to the lobule, must be obtained from
the text-books upon histology and anatomy. It is sufficient here to
recall the fact that each lobule is supplied with blood coming in part
from the portal vein and in part from the hepatic artery. The blood
from the former source contains the soluble products absorbed from
the alimentary canal, such as sugar and protein, and these absorbed
products are submitted to the metabolic activity of the liver cells
before reaching the general circulation. The hepatic artery brings to
the liver cells the arterialized blood sent out to the systemic circu-
lation from the left ventricle. In addition, each lobule gives origin
to the bile capillaries which arise between the separate cells and which
carry off the bile formed within the cells. In accordance with these
facts, the physiology of the liver cell falls naturally into two parts, —
one treating of the formation, composition, and physiological signifi-
cance of bile, and the other dealing with the metabolic changes pro-
duced in the mixed blood of the portal vein and the hepatic artery
as it flows through the lobules. In this latter division the main
phenomena to be studied are the formation of urea and the forma-
tion and significance of glycogen, but it cannot be doubted that
the liver possesses other important metabolic functions which
a1 present are only guessed at or imperfectly understood.

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 ot her ways. Ifile is a continuous secret ion, Put 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, tn ome cases the entire supply of bile has been diverted in

782

PHYSIOLOGY OF THE LIVER AND SPLEEX. 7S3

this way to the exterior, and it is an interesting physiological fact
that such patients may continue to enjoy fair health, showing that,
whatever part the bile takes normally in digestion and absorption,
its passage into the intestine is not absolutely necessary to the nu-
trition of the body. The quantity of bile secreted during the day
has been estimated for human beings of average weight (43 to 73
kgms.) as varying between 500 and 800 c.c. This estimate is based
upon observations on cases of biliar}^ 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

Fa?*111 } 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.

t Reported in " Centralblatt f. Physiologie," 1894, No. 8.

784 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. Indeed, it is probable that
in some animals at least still other pigments, such as urobilin,
may be present in the bile, together with the bilirubin or biliverdin.
Biliverdin is supposed to stand to bilirubin in the relation of an
oxidation product. Bilirubin is given the formula Cu.H,8N,03,
and biliverdin, C16H18N204, the latter being prepared readily from
the former by oxidation. These pigments give a characteristic
reaction, known as "Gmelin's reaction," with nitric acid con-
taining some nitrous acid (nitric acid with a yellow color). If
a drop of bile and a drop of nitric acid are brought into con-
tact, 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. The bilirubin
is formed from the hematin of the hemoglobin by a process which
involves the splitting off of its iron. It is very significant that
the iron separated by this mean- from the hematin is. for the most
retained in the liver, a small portion only being secreted in
the bile. It seems probable thai the iron held back in iheliver is
again used in some way to make new hemoglobin in the hema-
topoietic organs. Since the hematin constitutes only I per cent.
of the hemoglobin molecule, it is evidenl that in the production
of the bilirubin a considerable amounl of globin must be formed
also, hut nothing is known of the fate of this portion of the hemo-
globin molecule. Quantitative data, in fact, are conspicuously
Lacking in regard to the amounl of bile pigment secreted daily.
Owing to the lack of a satisfactory method of estimating this
substance, it- percentage in the bile, as given by different authors,
reatly, from .04 per cent, to 0,25 per cent. The bile
pigm< e carried in the bile to the duodenum and are mixed

PHYSIOLOGY OF THE LIVER AND SPLEEN. 785

with the food in its long passage through the intestine. Under
normal conditions neither bilirubin nor biliverdin occurs in the
feces, but in their place is found a reduction product, urobilin
or stercobilin, formed in the large intestine. Moreover, 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.
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:

C26H43N06 + H20 = C^H^Os + CH2(NH2)COOH.

Glycocholic acid. Cholic acid. Glycocoll (amino-acetic-acid).

C26H4SNSO? + H20 = C24H40O5 + C2H4NH2S02OH

Taurocholic acid. Cholic acid. Taurin (amino-ethyl-

sulphonic acid).

These reactions are interesting not only in that they throw light on
the structure of the acids, but also because similar reactions doubtless
take place in the intestine, cholic acid having been detected in the
intestinal contents. As the formulas show, cholic acid is formed in
the decomposition of each acid, and we may regard the bile acids as
compounds produced by the synthetic union of cholic acid with
glycin 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

* "Archives de physiologie normale et pathologique, " 1S92, p. 577.
50

7S6 PHYSIOLOGY OF DIGESTION AND SECRETION.

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
than in the liver. It is more difficult to ascertain from what sub-
stances they are formed.' The fact that glycocoll and taurin con-
tain nitrogen, and that the latter contains sulphur, indicates that
some protein constituent is broken down during their production.

From the standpoint of nutrition the taurocholate is interesting as giving
one of the forms in which the sulphur of protein material is eliminated. Some
light has been thrown upon the origin of taurin by the discovery (Friedmann*)
that it may be formed from cystin. This latter body, (,(;H1.,N.JS204, or its
reduction product cystein, is known to occur as one of the end-products in the
acid hydrolysis of proteins, and it is possible that it occurs also in the tryptic-
erepsin hydrolysis in the small intestine, represent bag the end-product in which
the sulphur of the protein molecule is found. Cystin may be oxidized to
cysteimc acid I ( ,OOHC,H3NH,SO.iOH) and from this taurin i'(',U4NH,SO,OH)
may be obtained. It is probable, therefore, that the taurin is formed nor-
mally from cystin in the body and that the latter represents one of the split
products of protein. f Some of the sulphur of the cystin appears also in the
urine in oxidized form as sulphate. Under certain pathological conditions
the cystin itself appears in the urine, giving the phenomenon of cystinuria.

A circumstance of considerable physiological significance is that
these acids or their decomposition prodticts 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
reabsorptioD may lie in the fad 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 if economizes material.
In. in 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 in their
value have been made: In the firs! place, they serve as a menstruum
for dissolving the cholesterol which is constantly present in the l>ile

and which is an excretion to l»' removed; secondly, they facilitalc

greatly 'lie splitting and the absorption of fats in the intestine. It.
♦ Friedmann, " Hofmeister'e Beitrage, " '■'>, I, 1902.

t See Simon, ".Johns Hopkins Hospital Bulletin," l.r>, .'{(if), 1004.

PHYSIOLOGY OF THE LIVER AXD SPLEEX. 787

is an undoubted fact that when bile is shut off from the intestine the
absorption of fats is very much diminisned, and it has been shown
that this action of the bile in fat absorption is due chiefly to the
presence of the bile-acids, and in the same way the known acti-
vating influence of bile upon the activity of pancreatic lipase has
been traced to the bile-acids. The bile-acids, the taurocholate, at
least, possess the property of precipitating proteins in acid solu-
tions. This property probably explains the fact that the acid
chyme as it passes into the duodenum is precipitated by coming
into contact with the bile, a fact which has long been known,
although its physiological significance is not clear.

Cholesterin. — Cholesterin is a non-nitrogenous substance of
the formula C27H460. (See p. 79.) It is a constant constituent of
the bile, although it occurs in variable quantities. Cholesterin
is very widely distributed in the body, being found especially in
the white matter (medullary substance) of nerve fibers. It
seems, moreover, to be a constant constituent of all animal and
plant cells. It is assumed that cholesterin 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 by the liver
cells proper, but is added to the secretion while in the bile pas-
sages— the gall-ducts and gall-bladder. That it is an excretion-
is indicated by the fact that it is eliminated in the feces. Choles-
terin 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, C42H84-
XP09, is a compound of glycerophosphoric acid with fatty acid
radicals (stearic, oleic, or palmitic) and a nitrogenous base, cholin
(see p. 79). When hydrolyzed by boiling with alkali it splits
up into these three substances. 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 significance. According
to Hewlett and others it may serve to activate the lipase of the
pancreatic secretion.

788 PHYSIOLOGY OF DIGESTION AND SECRETION.

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
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 suhstances 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
thai cause- .hi 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
lory 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
ecretion. This effect is due both to the bile acids and bile pigments.
Since the bile acids have a hemolytic effect on n^\ corpuscles, it
might at firsl be assumed that their action as cholagogues is due
indirectly to this circumstance. The net ion of the bile acids is,
however, much more pronounced than that of other hemolytic agents,
and it eeme certain, therefore, that they exert a specific effect on the

PHYSIOLOGY OF THE LIVER AND SPLEEN. 789

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,f no bile appears
in the duodenum as long as the stomach is empty. When, how-
ever, a meal is taken, the ejection of the chyme into the duodenum
is followed by an ejection of bile. J It would seem, therefore, that
each gush of chyme into the duodenum excites, probably by reflex
action, a contraction of the gall-bladder, and an inhibition of the
sphincter closing the opening into the intestine.

An interesting application of this fact has been made in surgical practice.
After operations upon the gall-bladder trouble is experienced at times owing
to the failure of the fistulous opening to heal, so that there is constant oozing
of gall. It is found that frequent feeding of the patient facilitates the per-
manent closure of the fistula, because apparently the sphincter is kept inhibited
and the pressure in the gall-bladder is lowered.

The substances in the chyme that are responsible for the stim-
ulation have been investigated by Bruns. He finds that acids,
alkalies, and starches are ineffective, and concludes that the reflex
is clue to the proteins and fats or some of the products of their
digestion. The gall-bladder has a muscular coat of plain muscle,
and records made of its contractions show that the force exerted
is quite small. According to Freese,§ the maximal contraction

* See Falloise, quoted in Maly's " Jahres-bericht der Thier-chemie," 33,
611, 1904.

t " Archives des sciences biologiques," 7, 87, 1899.

j See also Klodnizki, quoted from Maly's "Jahres-bericht der Thier-
chemie," 33, 617, 1904.

§ "Johns Hopkins Hospital Bulletin," June, 1905.

790

PHYSIOLOGY OF DIGESTION AND SECRETION.

does not exceed that necessary to overcome the hydrostatic pressure
of a column of water 220 nuns, in height, — a force, therefore, which
is about equivalent to the secretion pressure of bile as determined
by Heidenhain. The innervation of the gall-bladder and gall-ducts
has been studied especially by Doyon.J It would seem, from the
experiments made by this author together with later experiments
reported by others, f that the bladder receives both motor and in-

10

8
6

4

Z

30'

JO'

30'

JO'

JO'

JO'-

JO'

JO'

30'

JO'

30'

30'

30'

JO'

JO'

/

v

1

,

\

I

\

/

j

\

8

6,

2

1

\

I

\

.-"-

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t

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\

',

\

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e

z

/

/

j

\

,-

''

\

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--..

FiK. 2S7. — Curves showing the velocity of secretion of bile into the duodenum on
(1) a dial "I r 1 1 i 1 k , uppermost curve; (-) a diet of meat, middle curve; (3) a diet of bread,
[owe i curve. The divisions on the ab ci B represent intervals of thirty minutes; the
figures on the ordinates represent the volume of secretion in cubic centimeters. — (firiins.)

hibitory fibers by way of the splanchnic nerves. These fibers emerge
from the spinal cord in the roots of the sixth thoracic to the first
lumbar spinal nerve, and pass to the celiac plexus by way of the
splanchnic nerves. Motor fibers may occur also in the vagi. Sensory
liber- capable of causing :i icilex constriction or dilatation of the
bladder are found in both the vagus and splanchnic nerves. Stim-
ulation of the central end of the cu1 splanchnic causes a dilatation
of the bladder (reflex Btimulation of the inhibitory libers), while
stimulation of the centra] end of the vagus causes a contraction
of the bladder and a dilatation (inhibition) of the sphincter muscle

Doyon, "Archive* de phy iologie," L894, p. I'd.

Bainbridge and Dale, 'Journal or Physiology," L905, \\\iii., L38.

PHYSIOLOGY OF THE LIVER AXD SPLEEN. 791

at the opening of the common duct into the intestine. Since these
last movements are the ones that occur during normal digestion,
it is probable that the afferent fibers from the duodenum, which
are concerned in this reflex, run in the vagus.

Effect of Complete Occlusion of the Bile-duct. — When the
flow of bile is prevented by ligation of the bile-duct, or when this
duct is occluded by pathological changes the bile eventually gets
into the blood, producing a condition of jaundice (icterus). There
has been much discussion as to whether the bile is absorbed directly
into the blood from the liver cells or the liver lymph-spaces, or
whether it is carried to the blood by way of the lymph-vessels and
thoracic duct.* Experimental evidence points to both possibili-
ties. The increased pressure in the bile system leads possibly to a
rupture of the delicate bile capillaries, and the bile thus escapes
into the lymph-spaces. From these spaces it may be absorbed
directly by the blood-vessels of the liver, or it may be carried off
in the lymph-stream toward the thoracic duct.

General Physiological Importance of Bile. — The physiological
value of bile has been referred to in speaking of its several constitu-
ents. Bile is of importance as an excretion in that it removes from
the body waste products of metabolism, such as cholesterin, lecithin,
and bile pigments. With reference to the pigments, there is evidence
to show that a part at least may be reabsorbed while passing through
the intestine, and be used again in some way in the body. The bile
acids represent end-products of metabolism involving the proteins
of the liver cells, but they are undoubtedly reabsorbed in part, and
can not be regarded merely as excreta. As a digestive secretion, the
most important function attributed to the bile is the part it takes in
the digestion and absorption of fats. It accelerates greatly the action
of the lipase of pancreatic juice in splitting the fats to fatty acids and
glycerin, and it aids materially in the absorption of the products
of this hydrolysis. A number of observers have shown that when a
permanent biliary fistula is made, and the bile is thus prevented from
reaching the intestinal canal, a large proportion of the fat of the food
escapes absorption and is found in the feces. This action of the
bile may be referred directly to the fact that the bile acids serve as a
solvent for the fats and fatty acids. It was formerly believed that
bile is also of great importance in restraining the processes of putre-
faction in the intestine. It was asserted that bile is an efficient
antiseptic, and that this property comes into use normally in prevent-
ing excessive putrefaction. Bacteriological experiments made by a
number of observers have shown, however, that bile itself has very
feeble antiseptic properties, as is indicated by the fact that it putrefies

* See Mendel and Underbill for literature, "American Journal of Phys-
iology," 1905, xiv., 252.

792 PHYSIOLOGY OF DIGESTION AND SECRETION.

readily. The free bile acids and eholalic acid do have a direct retard-
ins: effect upon putrefactions outside the body; but this action is not
very pronounced, and has not been demonstrated satisfactorily for
bile itself. It seems to be generally true that in cases of biliary fistula
the feces have a very fetid odor when meat and fat are taken in the
food. But the increased putrefaction in these cases may possibly be
an indirect result of the withdrawal of bile. It has been suggested,
for instance, that the deficient absorption of fat that follows upon the
removal of the bile results in the protein and carbohydrate material
becoming coated with an insoluble layer of fat, so that the penetration
of the digestive enzymes is retarded and greater opportunity is given
for the action of bacteria. We may conclude, therefore, that, while
there does not seem to be sufficient warrant at present for believing
that the bile exerts a direct antiseptic action upon the intestinal
contents, nevertheless its presence limits in some way the extent of
putrefaction.

Glycogen. — One of the most important functions of the liver is
the formation of glycogen. This substance was found in the liver in
1857 by Claude Bernard, and is one of several brilliant discoveries
made by him. Glycogen has the formula (C6H10O5)n, which is also
the general formula given to vegetable starch ; glycogen is therefore
frequently spoken of as " animal starch." It gives, however, a port-
wine-red color with iodin solutions, instead of the familiar deep blue
of vegetable starch, and this reaction serves to detect glycogen not
only in its solutions, but also in the liver cells. Glycogen is readily
soluble in water, and the solutions have a characteristic opalescent
appearance. Like starch, glycogen is acted upon by ptyalin and
other cliastatic 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 (lie iodin reaction for glycogen. Kven
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,

* The extensive literature of glycogen is collected und reviewed by Cre-
mer in the " Ergebni e der Phyeiologie, " vol. i, part i, 1902; and by Pfliiger,
" \n-hiv f. die gesammte Physiologic," 90, I, L903.

PHYSIOLOGY OF THE LIVER AND SPLEEN. 793

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,
glycogen is formed directly from them or from the products into
which they are converted during digestion. The bulk of our car-
bohydrate food reaches the liver as dextrose, or as dextrose and levu-
lose, and these forms of sugar may be converted into glycogen in the
liver cells by a simple process of dehydration, such as may be repre-
sented in substance by the formula 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-
* Voit, "Zeitschrift f. Biologie," 28, 285, 1891.

794 PHYSIOLOGY OF DIGESTION AND SECRETION.

jeeted under the skin, it has a very feeble effect in the way of increas-
ing the amount of glycogen in the liver, since under these conditions
it is probably absorbed into the blood without undergoing inversion.
Experiments -with subcutaneous injection of lactose gave similar
results, and it is generally believed that the liver cells can not convert
the double sugars to glycogen, at least not readily; hence the value
of the hydrolysis of these sugars in the alimentary canal before
absorption. We may assume, therefore, that dextrose, levulose, and
galactose are the true glycogen-formers that occur normally in the
blood, and that the disaccharids (cane-sugar, milk-sugar, etc.) and
the polysaccharids (starches) are true glycogen-formers to the ex-
tent that they are converted into dextrose, levulose, or galactose.

Effect of Protein on (rh/cogen Formation. — In his first studies
upon glycogen Bernard asserted that it may be formed from protein
material. Since that time there have been much discussion and
experimentation upon this point. The usual view is that protein
must be counted among the true glycogen-formers in the sense that
some of the material of the protein molecule is directly converted to
glycogen. The protein in digestion undergoes, it will be remem-
bered, a splitting process, the limits of which are not definitely settled.
It i- assumed, however, that the nitrogenous split products are
acted upon in the liver, the nitrogen being converted first to an
ammonia compound and then to urea, while the non-nitrogenous
residue is converted to sugar by a synthetic process. Positive
results have been obtained showing that some, at least, of the
amino acids, such as glycin, alanin, and aspartic acid, may be
converted to sugar in the body. Experimentally observers find
for the warm-blooded animals, at least, that feeding with proteins,
even in the case of those proteins, such as casein, that contain
no carbohydrate grouping, causes an increased production of
glycogen.* The conclusion to be drawn from these experiments
engthened by clinical experience upon human beings suffer-
ing from diabetes. In severe forms of this disease the carbo-
hydrate material of the food escapes oxidation in the
bod}' and i.^ secreted unchanged in the urine. If under
these conditions the individual is given an exclusively protein
diet, sugar still continues to appear in the urine, and it would
seem that this sugar can only arise from the protein food. In
the similar condition of severe glycosuria that may be pro-
duced by the use of phloridzin it has been shown that the animal

continues to excrete Ugar even when U-<\ on protein alone or when

starved. Under such conditions the amount of dextrose in the

urine bears a definite ratio to the amount of nitrogen excreted

D:N::3.65: I (Lusk), which would indicate that both arise from

* Bee Stookey, Ami rican Journal of Physiology," '■), L38, L903.

PHYSIOLOGY OF THE LIVER AND SPLEEN. 795

the breaking down of the protein molecule. On this supposition
58.4 per cent, of the protein may be converted to sugar. So also
the fact that during prolonged starvation, lasting for forty or even
ninety days, the blood retains a practically constant composition
in sugar indicates that this material is being formed from either
the protein or fat supply of the body. Other considerations tend
to exclude the fat, and we are, therefore, led to the belief that the
protein can give rise to sugar in the body. If this change is part
of the normal metabolism of the body it would make protein a gly-
cogen-former, since the sugar formed from the protein may, of course,
be converted to glycogen. Whether or not all proteins yield gly-
cogen or sugar in the body is not entirely determined. Some
authors have thought that only those proteins that contain a
carbohydrate residue have this property; but, as stated above,
casein and other proteins that do not possess this grouping seem
also to increase the glycogen supply when fed alone.

Effect of Fats upon Glycogen Formation. — A large number of
substances have been found by some observers to increase the store
of glycogen in the liver. In some of these cases at least it is evident
that the substance is not a direct glycogen-former in the sense that
the material is itself converted to glycogen. It may increase the
supply of liver glycogen in some indirect way, — for example, by
diminishing the consumption of glycogen in the body. The most
important substance in this connection from a practical standpoint
is fat. Whether or not the body can convert fats into sugar or
glycogen is a question about which at present there is much
difference of opinion, and much evidence might be cited on each side.
Cremer, however, has furnished apparent proof that glycerin acts
as a direct glycogen or sugar-former. When fed, especially in the
diabetic condition, it causes an increase in the sugar which can not
be explained as a result of protein metabolism. Since in the body
neutral fats are normally split into glycerin and fatty acid, the fact
that glycerin can be converted to sugar seems to carry with it the
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, cannot be decided at present. Since, however, the glycerin
radicle constitutes but a small fraction of the fat molecule, the
quantitative importance of a change of this kind cannot be very
great under any circumstances.

The Function of Glycogen — Glycogenic Theory. — The
meaning of the formation of glycogen in the liver has been, and
still is, the subject of discussion. The view advanced first by
Bernard is perhaps most generally accepted. According to
Bernard, glycogen forms a temporary reserve supply of carbo-

796 PHYSIOLOGY OF DIGESTION AND SECRETION.

hydrate 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 low limit a condition of hyperglycemia
prevails, and the excess is excreted through the kidney and is
lost. But as the blood from the digestive organs pusses 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. An objection has been made to this
part of the glycogenic hypothesis by Paw on the ground that
if all the carbohydrates of a meal were absorbed into the blood
as free sugar, a condition of hyperglycemia and glycosuria must
evidently result. We know that glycosuria does occur when the
carbohydrates are eaten in excess (alimentary glj-cosuria) for
this very reason. But within what we may call the normal
limits of a carbohydrate diet it seems most probable that the
contents of the portal vein never rise much above the usual level,
since the carbohydrate is absorbed slowly during a period of four
to five hours, and during this period a very large amount of blood
must flow through the intestines, as much perhaps in five hours
as 180 to 190 liters, if one may apply to man the results of Burton-
Opit z, obtained for the dog, namely, a flow of 31 cc. per minute
for each 100 gms. of intestine. From time to time the glycogen
of the liver 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 ill dextrose occurs. Within a

comparatively short time all the glycogen is gone and only dextrose

is found. It is for this reason that in t lie estimation of glycogen in the
liver it ifi necessary to mince the organ and to throw it, into boiling
water a- quickly as possible, sincp by this means the liver cells are

PHYSIOLOGY OF ^HE LIVER AND SPLEEN. 797

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 protein foods, once it is formed in the liver, has, of course,
the same functions to fulfil. It is converted into sugar, and
eventually is oxidized in the tissues. For the sake of completeness
it may be well to add that some of the sugar of the blood formed
from the glycogen, when an excess is eaten beyond the energy
needs of the tissues, may be converted into fat in the adipose
tissues instead of being burnt, and in this way it may be retained
in the body as a reserve supply of food of a more stable character.
Glycogen in the Muscles and other Tissues. — The history of
glycogen is not complete without some reference to its occurrence in
the muscles. Glycogen is, in fact, found in various places in the body,
and is widely distributed throughout the animal kingdom. It occurs,
for example, in leucocytes, in the placenta, in the rapidly growing
tissues of the embryo, and in considerable abundance in the oyster
and other molluscs. But in our bodies and in those of the mammals
generally the most significant occurrence of glycogen, outside the
liver, is in the voluntary muscles, of which glycogen forms a normal
constituent. It has been estimated that the percentage of glycogen
in resting muscle varies from 0.5 to 0.9 per cent., and that in the
musculature of the whole body there may be contained an amount
of glycogen equal to that in the liver itself. Muscular tissue, as
well as liver tissue, has a glycogenetic function — that is, it is cap-
able of laying up a supply of glycogen from the sugar brought
to it by the blood. The glycogenetic function of muscle has been
demonstrated directly by Kulz,f 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

* Tebb, "Journal of Physiology," 22, 423, 1897-98.
t "Zeitschrift f. Biologie," 72, 237, 1890.

79S PHYSIOLOGY OF DIGESTION AND SECRETION.

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. Observations on isolated muscles have shown
definitely that the local supply of glycogen is diminished when the
muscle is made to contract (see p. 66). In a starving animal
glycogen finally disappears, except perhaps in traces, but this
disappearance occurs much sooner if the animal is made to use its
muscles at the same time. It has been shown also by Morat and
Dufourt that if a muscle has been made to contract vigorously
it takes up much more sugar from an artificial supply of blood sent
through it than a similar muscle which has been resting ; on the
other hand, it has been found that if the nerve of one leg is cut
so as to paralyze the muscles of that side of the body, the amount
of glycogen is greater in these muscles than in those of the other
leg that have been contracting meantime and using up their gly-
cogen. The further history of glycogen is considered in the section
on Nutrition.

Formation of Urea in the Liver. The nitrogen contained in
the protein material of our food is finally eliminated, mainly in the
form of urea. It has been definitely proved that the urea is not
formed in the kidneys, the organs that eliminate it. It has long been
considered a matter of the greatesl importance to ascertain in what
organ or tissues urea is formed. Investigations have gone so far as
to demonstrate thai it arises in part at least in the liver; hence the
property of forming urea must be added to the other important func-
tions of the liver cell. Schroder* performed a number of experi-
ments in which the liver was taken from a freshly killed dog and

irrigated through its blood-vessels with a supplj 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 dogj the amount

" Arcbiv f. experimentelle Pathologie unci Pharmakologie," 15, 364, L882,
and I'.i, 373, L885.

PHYSIOLOGY OF THE LIVER AND SPLEEN. 799

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 equation (NH4)2C03— 2H20 = CON2H4. Schon-
dorff * 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 be detected; but if the blood, after
irrigation through the hind legs, is subsequently passed through the
liver, a marked increase in urea results. Obviously, the blood in this
experiment derives something from the tissues of the leg which the
tissues themselves cannot convert to urea, but which the liver cells
can. Finally, in some remarkable experiments upon dogs made by
four investigators (Hahn, Massen, Nencki, and Pawlow), which are
described more fully in the next chapter, it was shown that when the
liver is practically destroyed there is a distinct diminution in the
urea of the urine. In birds uric acid takes the place of urea as the
main nitrogenous excretion of the body, and Minkowski has shown
that in them removal of the liver is followed by an important
diminution in the amount of uric acid excreted. From experiments
such as these it is safe to conclude that urea is formed in the liver
and is then given to the blood and excreted by the kidney. In
treating of the physiological history of urea an account will be given
of the views proposed with regard to the antecedent substance or
substances from which the liver produces urea.

Physiology of the Spleen. — Much has been said and written
about the spleen, but we are yet in the dark as to the distinctive
function or functions of this organ. The few facts that are known
may be stated briefly without going into the details of theories that
have been offered at one time or another. The older experimenters
demonstrated that this organ may be removed from the body without
serious injury to the animal. An increase in the size of the lymph-
glands and of the bone-marrow has been stated to occur after ex-
tirpation; but this is denied by others, and, whether true or not, it
gives but little clue to the normal functions of the spleen. Some
observers t find that the removal of the spleen causes a marked

* Pfluger's "Archiv f. die gesammte Physiologie, " 54, 420, 1893.
f Laudenbach, " Centralblatt fur Physiologie," 9, 1, 1895.

800 PHYSIOLOGY OF DIGESTION AND SECRETION.

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
to this slow movement, Royf 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 refiexly cause the organ to diminish in
volume. According to 8chaefer,J 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
percent age 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
change,-- of some kind occur in the spleen. As to the theories of the
splenic functions, the following may be mentioned: (1) The spleen
been supposed fco 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 then; is no reliable evidence that the

; Paton, Gulland, and Fowler, "Journal of Physiology," 28, 83, L902.
Journal of Physiology," 3, 203, L881. :|: Ibid., 20, L, L896.

PHYSIOLOGY OF THE LIVER AND SPLEEN. 801

function is retained in adult life in man or in most of the mammals.
The presence of a large amount of iron in organic combination
suggests, however, that the spleen may play a part in the prepara-
tion of new hemoglobin, or in the perservation of the iron set free
by the death of the red corpuscles. This suggestion is strengthened
by the fact that after extirpation of the spleen there is a distinct
increase in the daily loss of iron from the body, in dogs an increase
from 11 to 18 or 29 mgm.* (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 cannot be considered at present as satisfactorily demon-
started. (3) It has been suggested that the spleen is concerned in
the production of uric acid. This substance is found in the spleen,
as stated above, and it was shown by Horbaczewsky that the
spleen contains substances from which uric acid or xanthin may
readily be formed by the action of the spleen-tissue itself. More
recent investigations f have shown that the spleen, like the liver
and some other organs, contains special enzymes (adenase, guanase,
and xanthin oxydase), by whose action the split products of the
nucleins may be converted to uric acid, and it is probable, therefore,
that this latter substance is constantly formed in the spleen. (4)
Lastly, a theory has been supported by Schiff and Herzen, according
to which the spleen produces something (an enzyme) which, when
carried in the blood to the pancreas, acts upon the trypsinogen con-
tained in this gland, converting it into trypsin. This view has been
corroborated by a number of observers, but it is difficult at present
to decide whether such an action occurs normally during digestion.
As already stated, the general testimony at present indicates that
the pancreatic juice when secreted contains its trypsin in inactive
form. It is activated only after reaching the duodenum under the
influence of the enterokinase.

* Grossenbacher and Asher, " Zentralblatt f. Physiol," No. 12, 1908.
f Consult Jones and Austrian, "Zeitschrift f. physiol. Chem.," 1906,
xlviii., 110.

51

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-

Fiir. 288. — Portions of the various divisions of the uriniferous tubules drawn from
■ections of human kidney: A, Malpighian body: x, squamou epithelium lining the cap>
sule and reflected over the glomerulus; y, z, afferent and efferent ve els "f the tuft; >■.,
nuclei of capillarie ; n, con tricted neck marking pa age "i cap ule into convoluted tu«
bule; /-'. proximal convoluted tubule; C. irregular tubule; /' and F, piral tubules; /.',
aacending limb of Henle' loop; 0, traighf collecting tubule. {Pieraol.)

logical bearing, although for a complete description reference must
be made to works on histology.

The arrangemenl of the glandular epithelium in the capsule with
reference to the bloods essels of I he glomerulus is worl hy of special
attention. If will be remembered that each Malpighian corpuscle con-
■ if t wo principal parts, a I nil of blood-vessels, the glomerulus, and
an enveloping expansion of the uriniferous tubule, the capsule. The
glomerulus is an interesting structure (see Fig. 288, A I. If consists

802

KIDNEY AND SKIN AS EXCRETORY ORGANS. 803

of a small afferent artery which after entering the glomerulus, breaks
up into a number of capillaries. These capillaries, although twisted
together, do not anastomose, and they unite to form a single efferent
vein of a smaller diameter than the afferent artery.' The whole
structure, therefore, is not an ordinary capillary area, but a rete
mirabile, and the physical factors are such that within the capil-
laries of the rete there must be a greatly diminished velocity of the
blood-stream, owing to the great increase in the width of the stream
bed, and a high blood-pressure as compared with ordinary capil-
laries. Surrounding this glomerulus is the double-walled capsule.
One wall of the capsule is closely adherent to the capillaries of the
glomerulus; it not only covers the structure closely, but dips into
the interior between the small lobules into which the glomerulus is
divided. This layer of the capsule is composed of flattened, endo-
thelial-like cells, the glomerular epithelium, to which great impor-
tance is attached in the formation of the secretion. It will be no-
ticed that between the interior of the blood-vessels of the glomerulus
and the cavity of the capsule, which is the beginning of the urin-
iferous tubule, there are interposed only two very thin layers, — ■
namely, the epithelium of the capillary wall and the glomerular
epithelium. The apparatus would seem to afford most favorable
conditions for filtration of the liquid parts of the blood. The epi-
thelium clothing the convoluted portions of the tubule, including
under this designation the so-called irregular and spiral portions
and the loop of Henle, is of a character quite different from that of
the glomerular epithelium (Fig. 288, 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-

S04 PHYSIOLOGY OF DIGESTION* AXD SECRETION.

posed that in these structures water filtered through from the blood,
carrying with it not only the inorganic salts, but also the specific
elements (urea, etc.) of the secretion. There was thus formed at
the beginning of the uriniferous tubules a complete but diluted
urine, and in the subsequent passage of this liquid along the con-
voluted tubes it became concentrated by diffusion with the more
concentrated lymph surrounding the outside of the tubules.

Bowman's theory of urinary secretion, which has since been
vigorously supported and extended by Heidenhain, was based orig-
inally mainly on histological grounds. It assumes that in the
glomeruli water and inorganic salts are produced, while the urea
and related bodies are eliminated through the activity of the epi-
thelial cells in the convoluted tubes.

The first of these theories (Ludwig) is sometimes spoken of as
the mechanical theory, since as originally proposed it attempted
to explain the formation and composition of the urine by reference
only to the physical forces of filtration and diffusion. Adherents
of this view in recent years have modified it, however, to the extent
that the absorption supposed to take place in the convoluted tubules
is designated as a selective absorption, or selective diffusion, the
characteristics of which depend upon unknown peculiarities of struc-
ture in the epithelial cell, so that it is no longer a purely mechanical
theory. The difference between the Ludwig and the Bowman
theories may be stated briefly in this way. The former assumes that
in the glomerulus all of the constituents of the urine are produced
from the blood, probably by nitration, and that the function of the
epithelium lining the convoluted tubules is absorptive, like the
epithelium of the intestines, and not secretory. The Bowman view
as formulated by Heidenhain teaches that the glomerular epithe-
lium forms the water and salts of the urine by an act of secretion,
the ultimate chemistry or physics of which is not known. The
theory asserts that the epithelial cells participate actively in the
process of secretion and do not serve simply as a passive membrane.
The cells of the convoluted tubules are also secretory, their special
activity being limited mainly to the organic constituents, urea, etc.,
although, iri this respect, — namely, in the precise distinction be-
tween the secretory products of the glomerular epithelium and those
of the convoluted tubules, — the theory is not very explicit. Much
interest and a large literature have been stimulated by controver-
sy- based on these theories, and to-day the facts accumulated are
qo1 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 bo the extent at least of recognizing that the physical
laws of filt ration, diffusion, and imbibition, so far as they are known,

KIDNBY AND SKIN AS EXCRETORY ORGANS. 805

do not suffice for a satisfactory explanation of the facts.* As in
other similar cases, our knowledge of the physical structure and
chemical properties of the walls of the living cells is still very de-
ficient, and it seems necessary to designate these activities by the
indefinite term secretion.

Function of the Glomerulus. — As stated above, the structure
of the glomerulus is peculiar and suggestive of a special adaptation.
Ludwig's theory looks upon it as a filter, the pressure of the blood
in the glomerular capillaries driving the water and salts through
the endothelium of the capillaries and the glomerular epithe-
lium into the cavity of the urinary tubule. If we consider
only the water and assume that the membranes traversed are freely
permeable to its molecules, then it is evident that, upon this theory,
the quantity of urine formed will depend upon the filtration pres-
sure, and that this filtration pressure can be expressed by the formula
F=P — p, in which P represents the blood-pressure in the glom-
erular capillaries and p the pressure of the urine in the capsular
end of the uriniferous tubules. Some of the interesting facts de-
veloped by experiment may be presented in connection with this
formula. According to the mechanical theory, the amount of urine
formed should vary directly with P and inversely with p. The
factor P may be increased in two general ways: First, by those
changes which raise general arterial pressure and therefore the
pressure in the renal arteries, — such changes, for instance, as are
brought about by an increased force of heart beat or a large vaso-
constriction. Second, by obstructing or occluding the renal veins.
Experiments have been made along these lines. With regard to
the first possibility it has been found in general, although not invar-
iably, that raising arterial pressure increases the quantity of urine
if the means used are such as may be assumed to raise the pressure
in the glomerular capillaries.

The reverse experiment, however, of raising P by blocking the
venous outflow fails entirely to support the theory. When the renal
veins are compressed the capillary pressure in the 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

* For discussion and literature see Magnus, "Munchener med. Wochen-
schrift," 1906, Nos. 28 and 29.

806 PHYSIOLOGY OF DIGESTION AXD SECRETION.

the chance for removal of CO.,, — that is, by producing local as-
phyxia. The latter explanation seems the simpler of the two, and it
is very strongly supported by the opposite experiment of clamping
the renal artery. When this is done the blood-flow through the
kidney ceases and the secretion of urine also stops, as would be
expected. But when after a few minutes' closure the artery is un-
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 a contrary result. 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 I he 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 />. Normally the pressure
of i he urine in the capsule must be very low, owing to the fact that
i he secretion drains away as rapidly as if is formed. If the ureter

LS 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, nianojn-

KIDNEY AND SKIN AS EXCRETORY ORGANS. 807

eter, it is found to rise to 50 or 60 mms. of mercury and then to
remain stationary. This fact might be explained b}^ supposing
that when p = P the secretion stops on account of the failure of
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 nitration theory. Moreover, experiments show * that
when a certain moderate resistance is established in the ureters
(p = 10 cms. H20) the flow of urine is actually increased instead
of falling off, a fact entirely opposed to the mechanical theory, but
explicable on the secretion theory on the assumption that the
resistance acts as a stimulus.

Function of the Convoluted Tubule. — By the term convoluted
tubule is meant here the entire stretch from the glomerulus to the
straight tubules. Its epithelium varies in character; its cells are
distinguished in general, as contrasted with the glomerular epithe-
lium, by a relatively large amount of granular protoplasm. The
question of interest at present in regard to this epithelium is whether
it is secretor}r or absorptive. The original view of Ludwig that
diffusion takes place in these tubules between the urine and the
blood (lymph) in accordance with simple physical laws and that
by this action alone the dilute urine is brought to its normal concen-
tration must be abandoned. The mere fact that the urine may be
more concentrated in certain constituents than the blood is suffi-
cient evidence that other factors must co-operate. Those who be-
lieve that the main function of the tubules is absorptive are obliged
to regard this process as physiological, as a selective absorption
depending upon the living structure and properties of the epithelial
cells. The kind of evidence upon which this view is based is some-
what indirect; a single example may suffice. Cuslmy statesf that
if certain diuretics — for example, sodium chlorid and sodium sul-
phate— are injected simultaneously into the blood and in such
amounts that an equal number of the anions (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

* Brodie and Cullis, "Journal of Physiology, " 1906, xxxiv., 224.
t "Journal of Physiology," 27, 429, 1902.

SOS PHYSIOLOGY OF DIGESTION AND SECRETION.

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) Microchemical reactions
indicate that the iron secreted from the kidney as well as the uric
acid is given off through the epithelium of the convoluted tubules.

(4) Several observers (Van der Stricht, Disse, Trambasti, Gur-
witsch*) 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 indi-
cate the discharge of these vesicles into the cavity of the tubules.

(5) 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 deprived completely of
blood, and that as a result the flow of urine ceases. If under
these conditions urea is injected into the circulation, it is excreted
together with some water, thus proving the secretory activity of
the tubules with regard to urea. These results, although denied
at one time, have recently been confirmed and extended.! (6)
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 t'nchsin, is injected into the dorsal lymph-sac of a frog, and an
hour or so later the kidneys are examined, it will l>e found that the
convoluted tubules are colored red, while the capsular end is
colorless, indicating that the secretion at the latter point has an

alkaline react ion. The experiment shows that t he acid substances

in the urine arc produced in the convoluted tubules. The sim-
plesl explanation is that they are formed by a, secretory activity

of the epil hclial cells. (7) St udics of the gaseous exchanges in the

kidney during diuresis} and during the; glycosuria caused by
phlorhizinf tend to support the secretion hypothesis to the

Gurwil ch, "Archiv I'. die gesammte Phyeiolocie, " 91, 71, L902.
I Bainbridge and Beddard, "Journal of Physiology, moo, xxxiv. (Proc.
I'liv iol. Soc ); al o Cullis., ibid., p. '_'.">().

; Barcroft and Brodie. "Journal of Physiology," 1906, xxxiii., 52.
I' •■■ y, Brodie, and Siam, ibid., 1903, xxix., l<>7.

KIDNEY AND SKIN AS EXCRETORY ORGANS. 809

extent that they prove an increased metabolism during func-
tional activity. (8) The action of diuretics (see below). On the
whole, it must be admitted that the weight of evidence is in favor
of the Bowman-Heidenhain theory of secretion, and it remains
for future investigations to explain more definitely what is meant
by the obscure term "secretory activity."

Under pathological conditions it has been shown satisfactorily
that the albumin and sugar which may be present in the urine are
secreted or eliminated at the glomerular end of the tubule.

Action of Diuretics. — An important side of the theories of
secretion of urine is their application to the action of diuretics.
Water; various soluble substances, such as salts, urea, and dextrose;
and certain special drugs, such as caffein or digitalis, exert a diuretic
action on the kidneys. Much experimental work has been done
to ascertain whether the action of these substances can be explained
mechanically by their influence on the blood-flow or the blood-
pressure in the kidney capillaries, or whether it is necessary to fall
back upon a specific stimulating effect exerted by them upon the
epithelial cells of the tubules. Adherents of the original Ludwig
theory are forced to explain their action by the effect they pro-
duce upon the pressure in the kidney capillaries, and, indeed, it
has been shown with reference to the saline diuretics that their
effect upon the secretion is in proportion to the osmotic pressure
they exert. It has been suggested, therefore, that the action of
these diuretics lies in the fact that they attract water from the tis-
tues into the blood and thus cause a condition of hydremic plethora.
But whether the elimination of this excess of water is due to filtra-
tion or to an active secretion by the glomerular epithelium is a
question that revives the discussion that has been presented briefly
above. Most observers find that the vascular changes in the kid-
ney, particularly after the administration of caffein and digitalis,
do not explain satisfactorily the phenomenon of diuresis, and al-
though it is necessary to admit that the diuretics, or some of them,
act in part by the changes which they cause in the circulation in
the kidney, it is not possible to demonstrate that all the phenomena
under this head can be thus explained. The bulk of the work
published indicates that some at least of the known diuretics act as
stimulants to the secreting cells. In the case of the inorganic salts
it may be said (Magnus) that there is for each salt a "secretion
threshold." An increase in concentration above this level leads
to the elimination of the excess of salt and an increased secretion
of water.

The Blood-flow through the Kidneys. — It will be inferred
from the discussion above that, other conditions remaining the same,
the secretion of the kidney varies with the quantity of blood flowing
through it. It is, therefore, important to refer briefly to the nature

810 PHYSIOLOGY OF DIGESTION AND SECRETION.

and especially the regulation of the blood-flow through this organ,
although the same subject is referred to in connection with the
general description of vasomotor regulation (see Circulation). It
has been shown by Landergren* and Tigerstedt that the kidney
is a very vascular organ, at least when it is in strong functional activ-
ity such as may be produced by the action of diuretics. They esti-
mate that in a minute's time, under the action of diuretics, an amount
of blood flows through the kidney equal to the weight of the organ;
this is an amount from four to nineteen times as great as occurs in
the average supply of the other organs in the systemic circulation.
Taking both kidneys into account, their figures show that (in strong
diuresis) 5.6 per cent, of the total quantity of blood sent out of the
left heart in a minute may pass through the kidneys, although the
combined weight of these organs makes only 0.56 per cent, of that
of the body (see table p. 453).

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-
stalment 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 (he flow of urine during these changes can be
determined by inserting a cannula info the ureter and measuring
directly the outflow of urine. By this and other means it has
been shown that the kidney receives a rich supply of vasoconstrictor
nerve fiber- thai reach it between and around Hie entering blood-
Is. rhese fillers 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

* " Skandinavischea Axchiv f. Physiologic, " 4, 241, 1892.

KIDNEY AND SKIN AS EXCRETORY ORGANS. 811

the small arteries of the kidney, a shrinkage in volume of the whole
organ as measured by the oncometer (see Fig. 232), 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 thoracic spinal nerves. Under normal conditions these fibers
are probably thrown into action by reflex stimulation and lead to
an increased functional activity. It will be seen, therefore, that the
kidneys possess a local nervous mechanism through which their
secretory activity may be increased or diminished' by correspond-
ing alterations in the blood-supply. So far as is known, this is the
only way in which the secretion in the kidneys can be directly af-
fected by the central nervous system. It should be borne in mind,
also, that the blood-flow through the kidneys, and therefore their
secretory activity, may be affected by conditions influencing general
arterial pressure. Conditions such as asphyxia, strychnin poison-
ing, or painful stimulation of sensory nerves, which cause a general
vasoconstriction, influence the kidney in the same way, and tend,
therefore, to diminish the flow of blood through it ; while conditions
which lower general arterial pressure, such as general vascular dila-
tation of the skin vessels, may also depress the secretory action of
the kidney by diminishing the amount of blood flowing through it.

In what way any given change in the vascular conditions of the
body will influence the secretion of the kidney depends upon a num-
ber of factors and their relations to one another, but any change
which will increase the difference in pressure between the blood in
the renal artery and the renal vein will tend to augment the flow
of blood unless it is antagonized by a simultaneous constriction in
the small arteries of the kidney itself. On the contrary, any vas-
cular dilatation of the vessels in the kidney will tend to increase
the blood-flow through it unless there is at the same time such a

SI 2 PHYSIOLOGY OF DIGESTION* AND SECRETION*.

general fall of blood-pressure as is sufficient to lower the pressure
in the renal artery and reduce the driving force of the blood to an
extent that more than counteracts the favorable influence of dimin-
ished resistance in its small arteries. Although the kidney does
not possess specific secretory nerve fibers, it is possible that there
may be formed in the body specific chemical excitants or diuretics
belonging to the general group of hormones (p. 749). Schafer* has
recently shown that such a substance occurs normally in the
nervous lobe of the pituitary gland, and it is possible that the
internal secretion of this lobe may play toward kidney activity a
role similar to that of the adrenalin toward muscular metabolism.

The Composition of Urine. — The urine of man is a yellowish
liquid that varies greatly in depth of color. It has an average
specific gravity of 1.020 and usually an acid reaction. This acid
reaction is attributed generally to the presence of acid phosphates,
particularly acid sodium phosphate (NaH2P04); but, according to
Folin,f the acidity is due partially and indeed in larger part to or-
ganic acids. When tested by the usual indicators (litmus) human
urine may show an alkaline reaction, and, in fact, observations
indicate that the reaction may vary in accordance with the
character of the food. Among carnivora the urine is uniformly
acid, and among herbivora it is alkaline so long as they use a veg-
etable diet. During starvation, however, or when living upon the
mothers' milk,-r-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 (l)rechsel) 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
vegetal )lc 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 neutral blood and lymph the excess of
acid salts and thus maintains a normal balance between the acid
and basic equivalents in the blood, but the fact that on an ordinary
mixed diet the urine has an acid reaction indicates that the acids
formed in the body during metabolism must exceed the bases.

The composition of the urine is very complex. In addition to
the water and inorganic salts the following elements an; important,
namely, urea, the purin bodies (uric acid, xanthin, hypoxantbin),
creatinin, hippuric acid, oxalic acid (calcium oxalate), several
conjugated sulphates and conjugated glycuronates, several aromatic
OXyacidfl and nitrogenous acids, fatty acids, dissolved gases (N and

C02)> :u"' the urinary pigments urochrome and urobilin. This list
is not complete; a Dumber of additional substances have been de-

* Schflfer and Herring, "Phil, Trans." L906, B. excix., 1.
t "American Journal of Physiology," 9, -<).">, L903.

KIDNEY AND SKIN AS EXCRETORY ORGANS. 813

scribed as occurring constantly or occasionally in traces within the
limits of health, and some substances are secreted whose composi-
tion is unknown. Under pathological conditions the composition
may be still further modified. The complexity of the composition
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 proteins — the end-prod-
ucts of their destruction or physiological oxidation in the body are
water, carbon dioxid, and nitrogenous waste products (and sulphates
and phosphates from the sulphur and phosphorus in the proteins).
The water is eliminated in the urine, the sweat, saliva, etc., and the
expired air. The 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 protein 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 protein metabolism in the body, both as regards its char-
acter and extent, the quantitative study of this excretion is of par-
amount importance. In order to determine the total amount of
protein metabolism it is customary to determine the total nitrogen
eliminated in the urine, without regard to its specific form. This
determination is made usually by the method of Kjeldahl. The
total weight of nitrogen multiplied by 6.25 gives the amount of pro-
tein broken down, since nitrogen forms, on the average, 16 per
cent, of the weight of the protein molecule. In an average-sized
man the total nitrogen eliminated in a day varies, let us say, between
14 and 18 gms., which would correspond to 88 and 117 gms. of pro-
tein. It being often necessary to distinguish between the forms in
which this nitrogen is eliminated, the following distinctions are made:
(1) The urea nitrogen, — that is, the nitrogen eliminated as urea.
According to some recent analyses by Folin,* the urea nitrogen in
man averages 87.5 per cent, of the total nitrogen. (2) The am-
monia nitrogen, — that is, the nitrogen found in the form of am-
monia salts which liberate free ammonia on the addition of a fixed
alkali. The proportion of this ammonia nitrogen often varies,
especially under pathological conditions affecting the liver. Its
*" American Physiological Journal," 13, 45, 1905

S14 PHYSIOLOGY OF Dl'GESTION AND SECRETION.

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-
olism (3.6 per cent, of total nitrogen). (4) The purin nitrogen
(uric acid, xanthin, hypoxanthin), also indicative of a special
metabolism. (5) The unknown nitrogen. A considerable portion
of the nitrogen is eliminated in compounds whose composition
as yet has not been determined satisfactorily. According to
some analyses this portion of the nitrogen may amount to more
than 5 per cent, of the total nitrogen. The so-called oxyproteic
acid constitutes a part of this unknown residue. This nitrogenous
substance is said to yield leucin and other amino acids on hydroly-
sis,* a fact which would suggest that it belongs to the protein
group or is derived from a protein, possibly it is a polypeptid.

Origin and Significance of Urea. — Urea has the formula, CO-
N,H4. It may be considered as an amid of carbonic acid, and

has, therefore, the structural formula of CCX^h2- It occurs in the
urine in relatively large quantities (2 per cent.). As the total quan-
tity of urine secreted in twenty-four hours by an adult male may
be placed at from 1500 to 1700 c.c, it follows that from 30 to 34
gms. of urea are eliminated from the body during this period. It
is the most important of the nitrogenous excreta of the body, the
chief end-product, so far as the nitrogen is concerned, of the phys-
iological metabolism of the proteins and the albuminoids of the
foods and the tissues. If we know how much urea is secreted in a
given period, we know approximately how much protein has been
broken down in the body in the same time. In round numbers,
1 'Jin. of protein will yield l gm. of urea, as may be calculated easily
from I lie amount of nitrogen contained in each. Since, however,
some of the nitrogen of protein is eliminated in other forms uric
acid, creatinin, etc even an exact determination of all the urea
i- not sufficient to determine with accuracy the total amount of

protein of all kind.- I hat has keen met abolized. This fact is arrived
at more perfectly, as slated ahove, by a determination of the total
nitrogen of 'he urine and ot her exc ret ions. In addition I o t he urine,
urea ifi found in slighl quantities ill other secretions in milk (in

trace I and in sweat. In the latter liquid the quantity of urea in
twenty-four hours may be quite appreciable asmuch, for instance,
as 0.8 gm. although such a large amount is found only after active

exerci e. I' ha€ been ascertained definitely that urea is not formed

by the kidneys; it is brought to the kidneys by the blood for elimi-
nation. That urea is not made in the kidneys is demonstrated

I on nil 'im berg, Hofmeiater's " Beitr&ge, " L0, 411, 1907.

KIDNEY AND SKIN AS EXCRETORY ORGANS. 815

by such facts as these: If blood, on the one hand, is irrigated through
an isolated kidney, no urea is formed, even though substances (such
as ammomium carbonate) from which urea is readily produced are
added to the blood; on the other hand, urea is constantly present
in the blood (0.0348 to 0.1529 per cent.), and if the two kidneys
are removed, it continues to accumulate steadily in the blood as
long as the animal survives. It has been ascertained that the urea
is produced in part in the liver. The most important questions
to be decided are: Through what steps is the protein molecule
metabolized to the form of urea? and What is the antecedent
substance brought to the liver, from which it makes urea? It is
impossible to answer these questions perfectly, but recent investi-
gations have thrown a great deal of light on the whole process,
and they give hope that before long the entire history of the deriva-
tion of urea from proteins will be known. The results of this
work may be stated briefly as follows:

1 . Urea arises from ammonia salts which in the liver are converted
to urea by a process equivalent to dehydration. It has long been
known that when ammonium carbonate is added to blood perfused
through a liver it is converted to urea.* The reaction may be
represented as follows:

ro^ONH, wo- m<^NH-2

LO<ONH, 2±1*u _ LU<NH2

Ammonium carbonate. Urea.

Moreover, the experiments made by Hahn, Pawlow, Massen, and

Nencki f show that in dogs removal of the liver is followed by a

decrease in the amount of urea in the urine and an increase in the

ammonia contents. In these remarkable experiments a fistula

(Eck fistula) was made between the portal vein and the inferior

vena cava, the result of which was that the whole portal circulation of

the liver was abolished, the organ receiving blood only by way of

the hepatic artery. If now the latter artery was ligated and the

liver was cut away as far as possible, the result was practically a

complete extirpation of the organ. Later investigations J showed

that in normal animals the ammonia contents of the blood of the

portal vein may be three to four times as great as in arterial blood,

but that after removal of the liver the ammonia in the general

circulation increases to a point equal to that observed for the

portal blood and produces symptoms of poisoning which may

result fatally. It would seem, therefore, that the liver protects the

body from the poisonous action of the ammonia compounds by

converting them to urea. Now in the normal digestive hydrolysis

*Schroeder, "Archiv f. exp. Pathol, u. Pharmakol.," vols. xv. andxix.,
1882, 1885.

f See "Archiv f. exp. Pathol, u. Pharmakol.," 1893, xxxii., 161.

J See Nencki and Pawlow, "Archives des sciences biologiques," v., 213.

S16 PHYSIOLOGY OF DIGESTION AND SECRETION.

of proteins brought about by the successive action of pepsin, tryp-
sin, and erepsin the evidence at present indicates that the protein
material is split largely or entirely into its constituent elements
and its nitrogen appears mainly in three forms — as ammonia, as
monamino-acids, and as diamino-bodies. The ammonia produced
is probably carried to the liver and there converted to urea. In
what form the ammonia exists in the blood is not positively known:
it may be present as a carbonate or possibly, as some observers
have thought, as a carbamate. Ammonium carbamate might be
changed to urea according to the following reaction :

co<0Nl:-^o=co<Ng:-

Ammonia salts may arise similarly in the other protein tissues
of the body. It is known, for instance, that the percentage of
ammonia compounds in the tissues is greater than in the blood.
Since the cells of many of the protein tissues of the body contain
intracellular enzymes capable of causing hydrolytic cleavage of the
protein molecule it is probable that some ammonia may be thus
formed in various parts of the body; and so far as it is produced
it will be converted to urea by the action of the liver and possibly
by a similar action in other tissues.

2. Urea arises from the monamino-acids by a process of deami-
dization, whereby the NH2 group is converted to ammonia and
then probably to urea. It is known, for example, that when a
monamino-acid such as glycocoll or leucin is given to an animal the
nitrogen of the compound is promptly eliminated as urea. Since,
as stated above, these monamino-acids form the chief constituent
of the end-products formed in the digestion of proteins, it is very
probable that in passing through the liver their nitrogen is removed
by a process of deamidization and eliminated as urea. The organic
acid radicle that remains may suffer oxidation and thereby furnish
heal energy to the body, or it may possibly be used for the con-
struction by synthetic processes of carbohydrate or of fat. Doubt-

klso in the metabolism of the proteins of the tissues, as in the
digestion of the food proteins, monamino-acids are likewise formed
and suffer a similar fate, so (:iv as the nitrogen is concerned.

3. Urea arises from the diamino bodies (arginin), formed in the
cleavage of the protein molecule, by conversion of the contained
guanidin radicle. Kossel and Dakin * have demonstrated the

■nca of a ferment, arginase, which is capable of splitting
arginin into urea and ornithin. The reaction may be represented
by the following equation:

NHCKjJh'CCHj l8< : 1 1 XH2COOH i- 11,0 - C0< JJJJ2 I NH2(CHa):iCHNH,COOH
Arginin (guanidin diamino'valerianic acid. Urea. Diamino-valerianio acid.

♦"Zeitechriftf. Physiol. Chemie," L904, sdii., L81.

KIDNEY AND SKIN AS EXCRETORY ORGANS. 817

Unlike cases 1 and 2, the urea in this instance is formed directly
from the guanidin residue contained in the arginin. Since this
latter substance constitutes one of the split-products of the protein
during digestion and probably also one of the split-products in
the metabolism of the proteins of the tissues, there is reason to
believe that part of the urea actually formed in the body arises
by this method.

4. Urea arises from a further metabolism of uric acid. As is
stated below in describing the history of the origin of uric acid
there is positive evidence that not all of the uric acid produced
in the body is excreted as such. A portion is further acted upon
by a uricolytic enzyme and converted to urea. The portion so
affected varies in different animals. In man it is estimated that
about one-half of the uric acid arising in the body metabolism
proper (endogeneous uric acid) suffers this fate.

It is a very significant fact that the relative and absolute amount
of urea nitrogen in the urine varies directly with the amount of
protein taken as food, while other nitrogenous constituents of the
urine (creatinin, purin bases) are practically not affected by the
food, if care is taken to have the food free of these substances to
begin with. Folin has laid emphasis upon this fact,* and suggests
that most of the urea may come directly from protein of the
food which is hydrolyzed during digestion and absorption (action
of trypsin and erepsin) into simpler amino-acids. These amino-
bodies by further hydrolysis and oxidation may be converted, so
far as their nitrogen is concerned, into ammonia compounds and
eliminated at once as urea by the liver without entering into tissue
formation at all.

Even after the removal of the liver some urea is still found in
the urine. It seems as though the urea-forming power of the liver
is shared by some of the other tissues, just as its glycogenic functions
are.

Origin and Significance of the Purin Bodies (Uric Acid,
Xanthin, Hypoxanthin, Adenin, Guanin). — These bodies are
related chemically, and appear also to have a common physiological
significance. Their chemical relations have been described by
Emil Fischer, to whom we owe the term purin bodies. Fischer
pointed out that these and other substances belonging to this
group have a common nucleus:
N — C

C — K which he named the purin nucleus. The

>

N — C — N

hydrogen compound of this nucleus would be designated as purin,

* Folin, "American Journal of Physiology," 13, 117, 1905.
52

SIS PHYSIOLOGY OF DIGESTION AND SECRETION.

N = CH

and would have the formula: HC C— XH , C5H4N4. Addi-

X — C — N^CH
tion of an atom of oxygen gives hypoxanthin, C5H4N40:
HX — CO

HC C — NH

11 '] -^yCH. Addition of two atoms of ox}Tgen gives xan-

HX — CO

thin, C5H4N40,: CO C — XH

I II \

H^- q N ^CH. And addition of three atoms

HX — CO
of oxvgen gives uric acid, C5H.N403: CO C — XH , which

I II >co

HX — C — XH
from this standpoint might be named trioxypurin. If one of the H
atoms in the purin is substituted by an amino-groiip, NH2, the com-
pound, adenin (C5H5N5), is obtained, and the substitution of an
NH., group in hypoxanthin gives the compound guanin (C5H5N50).
Moreover, caffein, the active principle of coffee and tea, and theo-
bromin, the active principle of cocoa, are respectively trimethyl
and dimethyl compounds of xanthin. We have to distinguish,
therefore, three classes of purin compounds, namely, the oxypurins,
comprising monoxypurin or hypoxanthin, dioxypurin or xanthin,
and trioxypurin or uric acid; the aminopurins, comprising adenin or
aminopurin and guanin or aminohypoxanthin, and the methyl-
purins, comprising caffein or trimethyl xanthin (CHH10N4O., or C-H-
(CH3)3N402) and theobromin or dimethyl xanthin (C7HsN,02 or
C5H2(CH3)2N402). Uric acid, xanthin, and hypoxanthin are found
constantly in the urine and in the feces small amounts of xanthin,
hypoxanthin, adenin, and guanin may also occur. It has been
pointed out* that these substances come partly from purin bodies
taken as food, [f materials containing the purin bodies, such as
meat, are fed, these bodies are excreted in pari in the urine. It is
proposed to designate the uric acid, etc., thai has this origin as the
exogenous purin material. A portion of the amount daily secreted
comes, however, from a metabolism of the protein material of the
body, and this portion may be distinguished as the endogenous purin
bodies. This latter amounl 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 change in the quantity or character of the food,
but varies within certain limits with the manner of life. Evidently

♦ See J5uria.il and Schur, "Arehiv f. die geaammte Phyeiologie, " 94, 273,

mo::.

KIDNEY AND SKIN AS EXCRETORY ORGANS. 819

the endogenous purin nitrogen represents a special metabolism,
propably of the living tissues, that goes on independently, in great
measure, of the mere oxidation of food. According to Siven, the
production during sleep is much less than during the waking
hours. Since the purin bodies may be obtained readily by
hydrolytic cleavage of the nuclein or nucleic acid constituent
of the nucleoproteins, and since nucleoprotein material or nucleins
when fed to animals cause an increase in the amount of purin
nitrogen eliminated in the urine, it is most probable that
in the body these purin bases represent the end-products of
the metabolism of nuclein material. The intermediate processes
in this metabolism, whether it affects the nuclein taken as food
or the nuclein contained within the tissues of the body, are
supposed to take place according to the following general schema:
The nucleins that are split off from the nucleoprotein are acted
upon first by an enzyme, nuclease, which has been demonstrated to
exist in various tissues, e. g., in the spleen, liver, lungs, and kidneys.
By the action of this enzyme the nuclein is split with the formation
of some of the purin bodies, adenin, guanin, xanthin, or hypoxan-
thin. The adenin and guanin are then deamidized and converted
respectively to hypoxanthin and xanthin. Jones * has given reasons
to believe that two specific deamidizing enzymes of this character
may exist in the body, namely, adenase and guanase. Their action
may be represented by the following equations :
C5H5N5 + H20 = CsH4N40 + NH3

Adenin. Hypoxanthin.

C5H5N50 + H20 = C5H4N402 + NH3

Guanin. Xanthin.

The hypoxanthin and xanthin thus formed are in turn oxidized
to uric acid by the action of an oxidase to which the specific name
of xanthinoxidase has been given. Its action upon the hypoxanthin
or xanthin is represented by the series:

C5H4N40 + O = C5H(N402

Hypoxanthin. Xanthin.

C3H4N"402 + O = C5H4N403

Xanthin. Uric acid.

Finally, as stated above, it can be shown that a portion of the uric
acid may be further metabolized by the action of a specific urico-
lytic enzyme and give rise to urea. The portion of the uric acid under-
going this last change varies in different animals, as may be demon-
strated by giving definite amounts of uric acid in the food. Ex-
periments of this kind have shown that in man about one-half
of the uric acid formed gives rise to urea, while in dogs and cats
only about -^ suffers this change. In rabbits the proportion is £.
According to a former view (Horbaczewsky) it was supposed that
* Jones and Austrian, "Zeitschrift f. physio! . Chem.," 1906, xlviii., 110.

SJH PHYSIOLOGY OF DIGESTION AND SECRETION.

the endogenous purin nitrogen represents an end-product of the
metabolism of the nuclein found in the nuclei of cells, especially
in the nuclei of the leucocytes. But Burian has shown, on the
contrary, that most of this nitrogen in the excreta arises from a
metabolism in the muscular tissues* Increased muscular activity
is followed within an hour or two by an increased output of uric
acid, and when an isolated muscle is perfused with a mixture of
defibrinated blood and Ringer's sedation, uric acid is given off to
the circulating liquid. When the muscle under these last-mentioned
conditions is made to work a distinct increase in the hypoxanthin
and uric acid can be determined. It would seem, therefore, that
under normal conditions the uric acid and other purin bases are
derived mainly from a metabolism of the muscular substance
whereby hypoxanthin is produced. This substance is then
oxidized to uric acid and a part of the uric acid is further changed
to urea.t

Origin and Significance of the Creatinin and Creatin. —
Creatinin (C4H7N30) occurs in the urine, and it has been assumed
that it is derived from the creatin (C4H9N30,) found in muscle. Its

/NH — CO
structural formula is given as NHC/ and its chemical re-

XN(CH3)CH2

lations are indicated by the fact that it may be prepared synthetically
from methyl-glycocoll and cyanamid, — that is, the union of these
two substances gives creatin, from which in turn creatinin may be
obtained.

X=C-NH2 + NH(CH8)CH2COOH - NHC<3^£H/X)0Hi

Cyanamid. Methyl-glycocoll. Creatin.

Creatinin occurs in the urine constantly and in amounts equal to
1 in 2 gms. per day, or, according to Shaffer, J there is an excretion
of from 7 to 11 nig. of creatinin nitrogen per kilogram of body-
weight. Next to the urea and the ammonia compounds it forms
the mosl important of the known nitrogenous constituent of the
urine. Its physiological history is imperfectly known. Under
constanl conditions of life the amounl of creatinin formed in the
body i independenl of the quantity of protein eaten, and this
fact indicates (Folin) thai it represents an end-product of the
metabolism of living or organized protein tissue rather than one
of the results of the metabolism of the food protein. This con-
elusion is strengthened by the fad that in fevers and other patho-

* Burian, "Zeitachrift f. physiol. Chemie," \liii., p. ■r>'-'<~-
(•For :i review of the exten ive literature, see Block, "Bioehemisches
Centralblatt." 1906, v., Nob. 12 I I

Con nil Shaffer, "American Journal of Physiology," '■>'■'>, I, L908.

KIDNEY AND SKIN AS EXCRETORY ORGANS. 821

logical conditions in which there is an increased breaking down of
tissues the creatinin excretion is increased.* As stated above,
the usual view has been that the creatinin of the urine is derived
from the creatin of the muscles, but the effort to demonstrate that
this relationship actually exists has met with many difficulties.
The older observers pointed out what seems to be an objection
to this view, namely, the lack of relationship between the amount
of creatin in the musculature of the body (about 90 gms.) and
the small amount of creatinin (1 to 2 gms.) excreted daily. If
the creatin is a nitrogenous waste constantly formed at this rate
and excreted as creatinin, there ought to be a larger amount of the
latter substance. To meet this difficulty it was suggested that
some of the creatin may be converted to urea, but as a matter of
fact the possibility of such a conversion in the body has not been
demonstrated. Moreover, the conversion by the body of creatin
into creatinin is not so simple a matter as was supposed. When
creatinin is added to the diet it is excreted as creatinin. When
creatin, on the contrary, is fed, there is no apparent increase in the
creatinin of the urine. In fact, in the experiments reported the
creatin nitrogen was not recovered in any form in the urine. The
newer analyses seem also to show that normal muscular work
causes no increase in the excretion of creatinin in the urine.
Experimental work, in fact, upon the relationship, if any, and
significance of the creatin and creatinin has got only so far as to
show that the story is more complex and difficult than was formerly
supposed. Normally, creatin exists in the muscular tissue of the
vertebrate animals — not in that of the invertebrates. Creatinin,
on the contrary, does not occur in detectable amounts in the blood
or tissues of the body, but is a constant constituent of the urine.
Creatin is not present normally in the urine, but under conditions
which involve a destruction of the organized body-proteins, for
example, in fevers, starvation, in women after delivery, during
the period of involution of the uterus, etc., it may be secreted
by the kidney in distinct amounts. Several investigators have
assumed that the liver is concerned in the history of these two
substances, but the part played by this organ is interpreted
differently by those working at the subject; and it seems abso-
lutely necessary at present to suspend judgment in regard to the
connection and significance of these two substances until inves-
tigations have reached more satisfactory results, f

Hippuric Acid. — This substance has the formula C9H9N03. Its
molecular structure is known, since upon decomposition it yields

* Hoogenhuyze and Verploegh, "Zeitschrift f. physiol. Chemie, " 57, 161,
1908.

f For a recent review and the literature, consult Mendel, "Science," April
9, 1909.

822 PHYSIOLOGY OF DIGESTION AND SECRETION.

benzoic acid and glycocoli, and, moreover, it may be produced syn-
thetically by the union of these two substances. Hippuric acid
may be described, therefore, as a benzoyl-amino-acetic acid (CH2-
NH[CGH5CO]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 mine, on an average diet, about 0.7 gm. are excreted in
twenty-four hours. If the diet is Largely vegetable, this amount may
be much increased. This last fact is readily explained, for it has been
found that if benzoic acid or substances containing this grouping
are fed to animals they appear in the urine as hippuric acid. Evi-
dently a synthesis occurs in the body, and Bunge and Schmie-
deberg proved conclusively that in dogs the union of benzoic acid
and glycocoli to form hippuric acid takes place in the kidney
itself. Later it was discovered* that the same synthesis may be
effected by ground-up kidney tissue, mixed with blood and kept
under oxygen pressure. It seems possible, therefore, that the
synthesis is due to some specific constituent of the kidney cells,
possibly an enzyme. Vegetable foods contain benzoic acid com-
pounds, and we can understand, therefore, why when fed they in-
crease the hippuric acid output of the urine. Since, however, in
starving animals or animals fed upon meat hippuric acid is still
present in the urine, although reduced in amount, it is evident that
it arises in part as a result of the body metabolism. It should be
added finally that some of the hippuric acid may be derived from
the process of protein putrefaction that occurs in the large intestine.

The Conjugated Sulphates and the Sulphur Excretion. —
The sulphur excretion of the urine possesses an importance similar
to that of nitrogen. Sulphur constitutes an element in most of the
proteins, and in some form, therefore, it will be represented in the
end-products of protein metabolism. The sulphur elimination in
the urine, like I be nil rogen eliminal ion, has been taken as a measure
of the amount of protein destruction. In the urine the sulphur
occur- in three forms: (1) In an oxidized form as inorganic sul-
phates. Some of the sulphates are undoubtedly derived or may be
derived from the mineral sulphates ingested with the food, bu1 the
larger pari arises from the oxidation of the sulphur of the proteins.
(2 The 30 called conjugated or ethereal sulphates are combinations
een lulphuric acid and Indoxyl, skatoxyl, phenol, and cresol,
giving us phenoisulphuric acid (C6H8OS02OH), cresolsulphuric acid
"II OS02OH), Indoxylsulphuric acid or indican (C8HaNOS02OH),
and skatoxylsulphuric acid (C9H8NOS02OH). The indol, skatol,
phenol, and cresol are formed in i he large intestine as a result of bac-
terial putrefaction. They are eliminated in part in the feces, but

* Ba hford and Cramer. "Zeit ichrift f. phyi iol. Chemie," 35, 324, 1902.

KIDNEY AND SKIN AS EXCRETORY ORGANS. 823

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, incloxyl, and skatoxyl may be secreted in the urine as con-
jugated glucuronates, — that is, in combination with glycuronic 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 protein putrefaction in the
intestine, by virtue of the indol and phenol constituents. All con-
ditions that increase the putrefactive processes in the intestine
are accompanied by a parallel increase in the ethereal sulphates.
By virtue of the sulphuric acid component these bodies represent
also one of the forms in which sulpftur 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
the amounts of water secreted through kidney and skin stand in
something of an inverse proportion to each other ; that is, the greater
the quantity lost through the skin, the less will be secreted by the
kidneys. Through these three organs, but mainly through the
kidneys, the blood is being continually depleted of water, and the
loss must be made up by the ingestion of new water. When water
is swallowed in excess the superfluous amount is rapidly eliminated
through the kidneys. The amount of water secreted may be in-
creased by the action of diuretics, such as potassium nitrate and
caffein.

The inorganic salts of urine consist chiefly of the chlorids, phos-
phates, and sulphates of the alkalies and the alkaline earths. It
may be said, in general, that they arise partly from the salts ingested
with the food, and are eliminated from the blood by the kidney
in the water secretion; and in part they are formed in the destruc-
tive metabolism that takes place in the body, particularly that

$24 PHYSIOLOGY OF DIGESTION AND SECRETION.

involving the proteins and related bodies. Sodium chlorid occurs
in the largest quantities, averaging about 15 gms. per day, of
which the larger part, doubtless, is derived directly from the salt
taken in the food. The phosphates occur in combination with cal-
cium and magnesium, but chiefly as the acid phosphates of sodium
or potassium. The acid reaction of the urine is usually attributed
to these latter substances. The phosphates result in part from the
destruction of phosphorus-containing tissues in the body, but
chiefly from the phosphates of the food. The sulphates of urine
are found partly in an oxidized form as simple sulphates or con-
jugated with organic compounds, as described above.

Micturition. — The urine is secreted continuously by the kid-
neys, is carried to the bladder through the ureters, and is then at
intervals finally ejected from the bladder through the urethra by
the act of micturition.

Movements of the Ureters. — The ureters possess a muscular coat
consisting of an internal longitudinal and external circular layer.
The contractions of this muscular coat form the means by which
the urine is driven from the pelvis of the kidney into the bladder.
The movements of the ureter have been carefully studied by Engel-
mann.* According to his description, the musculature of the ureter
contracts spontaneously at intervals of ten to twent}'" 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
bladder has been observed in the human being. Suter and Mayerf
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 th<- ureter or of ii 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
nerve-, and thai the contraction wave propagates itself directly
from muscle cell to muscle cell, the entire musculature behaving

*"PflUger' Arcbiv f . die gesammte Phy iologie, " 2, 243, L 869, and 4, 33;
see al o Luca , ' Mnerican Journal of Physiology," 17, 392, L906.

"Archivf. e per Pathologic und Pharmakologie," 32, 241, L893.

KIDNEY AND ,SKIN AS EXCRETORY ORGANS. 825

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
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 vesicae 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 urethras. 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

826 PHYSIOLOGY OF DIGESTION AX*) SECRETION".

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 Avail 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
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 Golfcz,* the scries 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
fii-i drops, however, that enter the urethra stimulate the sensory
nerves there and give rise to a conscious desire to urinate. If no

cle i- 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 urethras, which opposes the effect
of the contraction of the bladder. If the bladder is not too full
and the sphincter is kepi in :ic.tion for some time, the contractions
'Archiv f. die gesammte Phj iologie," 8, 478, 1874.

KIDNEY AND SKIN AS EXCRETORY ORGANS. 827

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 Pellacani* 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 even* psychical
act and every sensor}* 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
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.t 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
the hypogastric nerves and plexus (Fig. 277). Stimulation of
these nerves causes a comparatively feeble contraction of the blad-
der. (2) From the sacral spinal nerves, the fibers originating
in the second and third sacral spmal nerves, or in the rabbit in

* "Archives italiennes de biologie, " 1, 1S82.
t " Journal of Physiology, " 19, 71, 1895.

828 PHYSIOLOGY OF DIGESTION AND SECRETION.

the third and fourth, and taking their course through the so-called
nervi erigentes and the hypogastric plexus. 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,* 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. 152). According to Elliott the innervation of the bladder
varies in the different mammals. Speaking generally, the fibers
passing by way of the nervi erigentes when stimulated cause
contraction of the bladder (and inhibition of the sphincter).
These fibers, therefore, are mainly concerned in the act of micturi-
tion. The fibers supplied through the hypogastric nerve, on the
contrary, cause mainly relaxation of the bladder musculature,
and their stimulation, by inhibiting the tonus of the musculature,
would seem to provide a means for holding the urine.

The immediate spinal center through which the contractions
of the bladder max' lie reflexly stimulated or inhibited lies, accord-
ing to the experiments of ( roltz, 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, mic-
turition still ensued when the bladder was sufficiently full, and it
could be called forth reflexly by sensory stimuli, especially by
Blight irritation of the anal region. This localization lias been
confirmed by others X but Elliot stales thai the sacral portion
of the cord, which gives rise to the fibers of the nervi erigentes,
may also serve as a reflex center for the bladder.

Excretory Functions of the Skin. — The physiological activi-
ties of the .-kin are varied. It forms, in the first place, a sensory
surface covering the body, and interposed, as it were, between the

*"Archivf. die gesammte Physiologie, " 49, 111, L891.
i Elliot, "Journal of Physiology," ■ >■'>, 367, 1907.

Stewart, "American Journal of Physiology, " 2, L82, 1899.

KIDNEY AND SKIN AS EXCRETORY ORGANS. 829

external world and the inner mechanism. Nerve fibers of pressure,
temperature, and pain are distributed over its surface, and bv means
of these fibers reflexes of various kinds are effected which keep the
body adapted to changes in its environment. The physiology of
the skin from this standpoint is discussed in the section on special
senses. Again, the skin plays a part of immense value to the body
in regulating the body temperature. This regulation, which is
effected by variations in the blood supply or the sweat secretion,
is described at appropriate places in the sections on Nutrition and
Circulation. In the female, during the period of lactation, the mam-
mary glands, which must be reckoned among the organs of the
skin, form an important secretion, the milk; the physiology of this
gland is referred to in the section on Reproduction. In this section
we are concerned with the physiology of the skin from a different
standpoint, — namely, as an excretory organ. The excretions of
the skin are formed in the sweat-glands and the sebaceous glands.

Sweat. — The sweat or perspiration is a secretion of the sweat
glands. These latter structures are found over the entire cutaneous
surface except in the deeper portions of the external auditory meatus,
the prepuce, and the glans penis. They are particularly abundant
upon the palms of the hands and the soles of the feet. Krause
estimates that their total number for the whole cutaneous surface
is about two millions. In man they are formed on the type of
simple tubular glands; the terminal portion contains the secretory
cells, and at this part the tube is usually coiled to make a more or
less compact knot, thus increasing the extent of the secreting sur-
face. The larger ducts have a thin, muscular coat of involuntary
tissue that may possibly be concerned in the ejection of the secre-
tion. The secretory cells in the terminal portion are columnar in
shape, possess a granular cytoplasm, 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
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) ,

* "Archiv f. Physiologie," 1893, 116; see also Willebrand, " Skandi-
navisches Archiv f. Physiologie," 13, 337, 1902.

830 PHYSIOLOGY OF DIGESTION AND SECRETION.

when there is a marked increase in the water eliminated, the in-
crease being simultaneous with the formation of visible sweat. At
the same tune there is a sudden increase in the CO, eliminated from
the skin. It is possible that the sudden increase in CO, 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 chloric!. 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
flirt codes 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 fillers
at the point of stimulation, and not to a genuine fatigue of the
sweat glands or the sweat filters, since moving the electrodes to a
new point on the nerve farther toward the periphery calls forth a
new scent ion. The secret ion so formed is thin and limpid, and has

a marked alkaline read ion. The anatomical course of I bese libers
* "ArHiiv I', die gesammte Physiologic," ll, 71, L875.

KIDNEY AND SKIN AS EXCRETORY ORGANS. 831

has been worked out in the cat with great care by Langley.* He
finds that for the hind feet they leave the spinal cord chiefly in the
first and second lumbar nerves, enter the sympathetic chain, and
emerge from this as postganglionic fibers in the gray rami which
pass from the sixth lumbar to the second sacral ganglion, but chiefly
in the seventh lumbar and first sacral, and then join the nerves of
the sciatic plexus. For the forefeet the fibers leave the spinal cord
in the fourth to the tenth thoracic nerves, enter the sympathetic
chain, pass upward to the first thoracic ganglion, whence they are
continued as postganglionic fibers that pass out of this ganglion by
the gray rami communicating with the nerves forming the brachial
plexus. The action of the nerve fibers upon the sweat glands can
not be explained as an indirect effect, — for instance, as a result of
a variation in the blood-flow. Experiments have repeatedly shown
that, in the cat, stimulation of the sciatic still calls forth a secre-
tion after the blood has been shut off from the leg by ligation of
the aorta, or indeed after the leg has been amputated for as long
as twenty minutes. So in human beings it is known that profuse
sweating may often accompany a pallid skin, as in terror or
nausea, while, on the other hand, the flushed skin of fever is char-
acterized by the absence of perspiration. There seems to be no
doubt that the sweat nerves are genuine secretory fibers, causing
a secretion in consequence of a direct action on the cells of the sweat
glands. In accordance with this physiological fact histological
work has demonstrated that, special nerve fibers are supplied to
the glandular epithelium. According to Arnstein, the terminal
fibers form a small, branching, varicose ending in contact with the
epithelial cells. The sweat gland may be made 'to secrete in many
ways other than by direct artificial excitation of the sweat fibers, —
for example, by external heat, dyspnea, muscular exercise, strong
emotions, and by the action of various drugs, such as pilocarpin,
muscarin, strychnin, nicotin, picrotoxin, and physostigmin. In all
such cases the effect is supposed to result from an action on the
sweat fibers, either directly on their terminations or indirectly upon
their cells of origin in the central nervous system. In ordinar}'
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
gland or its terminal nerve fibers. We must. suppose, therefore,
that the high temperature acts upon the sensory cutaneous nerves,
* "Journal of Physiology," 12, 347, 1891.

S32 PHYSIOLOGY OF DIGESTION AND SECRETION.

possibly the heat fibers, and reflexly stimulates the sweat fibers.
Although external temperature does not directly excite the glands,
it should be stated that it affects their irritability either by direct
action on the gland cells or upon the terminal nerve fibers. At a
sufficiently low temperature the cat's paw does not secrete at all,
and the Irritability of the glands is increased by a rise of temper-
ature up to about 45° C.

Dyspnea, muscular exercise, emotions, and many drugs affect
the secretion, probably by action on the nerve centers. Pilocarpin,
on the contrary, is known to stimulate the endings of the nerve
fibers in the glands, while atropin has the opposite effect, com-
pletely paralyzing the secretory fibers.

Sweat Centers in the Central Nervous System. — The fact that
secretion of sweat may be occasioned by stimulation of afferent
nerves or by direct action upon the central nervous system, as in
the case of dyspnea, implies the existence of physiological centers
controlling the secretory fibers. The precise location of the sweat
center or centers has not, however, been satisfactorily determined.
Histologically and anatomically the arrangement of the sweat
fibers resembles that of the vasoconstrictor fibers, and, reasoning
from analogy, one might suppose the existence of a general sweat
center in the medulla comparable to the vasoconstrictor center,
but positive evidence of the existence of such an arrangement is
lacking. It has been shown that when the medulla is separated
from the cord by a section in the cervical or thoracic region the
action of dyspnea, or of various sudorific drugs supposed to act on
the central nervous system, may still cause a secretion. On the
evidence of results of this character it is assumed that there are spinal
sweat centers; but whether these are few in number or represent
simply the various nuclei of origin of the fibers to different regions
is not definitely known. It is possible that in addition to these
spinal centers there is a general regulating center in the medulla.

Sebaceous Secretion. — The sebaceous glands are simple or
compound alveolar glands found over the cutaneous surface, usually
in association with the hairs, although in some cases they occur
separately, as, for instance, on the prepuce and glans penis, and
on the lips. When they occur with the hairs the short duct opens
into the hair follicle, so that the secretion is passed out upon the

hair near the point at which it projects from the skin. The alveoli are

filled with cuboidal or polygonal epithelial cells, which are arranged

iii everal layers. Those uearesl (lie 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
from the layer nearest the basement membrane, and thus the glands
continue to produce a slow but continuous secretion. The sebaceous

KIDNEY AND SKIN AS EXCRETORY ORGANS. 833

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 of the sweat and possibly is
important in other ways in maintaining the physiological integrity
of the external surface.

Excretion of C02. — In some of the lower animals — the frog,
for example — the skin takes an important part in the respiratory
exchanges, eliminating C02 and absorbing 0. 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
C02 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.
53

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-
S6quard's extension of the idea of internal secretion has not been
justified by subsequent work, and to-day we must limit the term
to tissues that have a glandular structure. Experience has shown,
however, that not only the duel less glands, but some at least of the
typical glands provided with duds may give rise to internal secre-
tions, 1 he pancreas, for example. In some of the ductless glands,
on the '-out rary, the existence or non-existence of an internal secre-
tion is -till :m open question. The work done since 1889 has, how-
ever, demonstrated fully that some of the ductless glands play a
file of the very greatest importance in general nutrition, and this
knowledge has proved useful in widening our conception of the
nutritional relatione in the organism and besides has found a valuable
application in practical medicine. The conception that certain
glandular organs may give rise to chemical products which on
entering the circulation influence the activity of one or more other
organs has recently found a fruitful application in the study of the
digestive secretions. The gastric and pancreatic secretins may

834

SECRETION OF THE DUCTLESS GLANDS. 835

be regarded as examples of internal secretions. Chemical products
of this kind which stimulate the activity of special organs Starling
designates as hormones* From this point of view the active
substances formed in the thyroids, adrenal glands, etc., may all
be classified as specific hormones. Starling suggests that this
means of coordinating the activities of the various parts of a
complex organism may be regarded as the most primitive, while
the better-known coordination through the medium of a nervous
system is of later development. In the mammalian body both
methods, as we have seen, are employed.

Liver. — We do not usually regard the liver as furnishing an
internal secretion. As a matter of fact, it does form two products
within its cells — glycogen (sugar) and urea — which are subsequently
given off to the blood for purposes of general nutrition or for elim-
ination. The processes in this case fall under the general defini-
tion of internal secretion, and, in fact, may be used to illustrate
specifically the meaning of this term. The history of glycogen and
urea has been considered.

Internal Secretion of the Thyroid Tissues. — The most im-
portant and definite outcome of the work on internal secretions has
been obtained with the thyroids. Recent experimental work on
this organ makes it necessary for us now to distinguish between the
thyroid and the parathyroid tissues. The thyroids proper form
two oval bodies lying on the sides of the trachea at its junction with
the larynx. They have no ducts, and are composed of vesicles of
different sizes, which are lined by a single layer of cuboidal epithe-
lium and contain in their interior a material known as colloid. A
number of histologists have traced the formation of this colloid to
the lining epithelial cells, and have stated, moreover, that the vesicles
finally rupture and discharge the colloid into the surrounding lym-
phatic spaces. Accessory thyroids varying in size and number may
be found along the trachea as far down as the heart. They possess
a vesicular structure and no doubt have a function similar to that
of the thyroid body.

The parathyroids are, according to most authors, quite different
structures. Four of these bodies are usually described, two on each
side, and their positions vary somewhat in different animals or,
indeed, in different individuals. 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. They
may be imbedded in the thyroid tissue. 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.

* For general discussion, consult Starling, "Recent Advances in the
Physiology of Digestion," Chicago, 1906.

836 PHYSIOLOGY OF DIGESTION AND SECRETION.

The tissue has a structure quite different from that of the thy-
roids, 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 chronic malnutrition. On the other
hand, it became known that atrophy of the thyroids in the young
is responsible for the condition of arrested growth and deficient
mental development designated as cretinism, and in the adult the
same cause gives rise to the peculiar disease of myxedema, character-
ized by distressing mental deterioration, an 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 protein bodies, from which it may be separated by diges-
tion with gastric juice or by boiling with acids.

The Function of the Parathyroids. — Most of the results des-
cribed above were obtained before the existence of the parathy-
roid- was recognized. Early in the history of the subject it was
recognized that complete removal of the thyroids proper inherbiv-
orous animals (rats, rabbits) is not attended by a fatal result.
Gley and others, however, proved thai if the parathyroids also are

* For a general accounl of the development of the subject and the liter-
ature see "Transactions of the Congress of American Physicians and Sur-
Howell, Chittenden, Adami, Putnam, Kinnicutt, Osier), L897, and
Jeandelize, 'In umsance thyroidienne et parathyroidienne, " Nancy, l(.)()2;
also Vincent, 'Internal Secretions," etc., Lancet, A.ug. II and \x, 1906.
Zeitschrifl f. phy iolog. Chemie," 21, 319, and 481, L896.

SECRETION OF THE DUCTLESS GLANDS. 837

removed these animals die with the symptoms described in the
case of dogs, cats, and other carnivorous animals. This result
attracted attention to the parathyroids. Numerous experiments
by Moussu, Gley, Vassale and Generale, and others * have seemed
to show a marked difference between the results of thyroi-
dectomy and parathyroidectomy. When the parathyroids alone are
removed the animal dies quickly with acute symptoms, muscular
convulsions (tetany), etc.; when the thyroids alone are removed
the animal may survive for a long period, but develops a condition
of chronic malnutrition, — a slowly increasing cachexia which may
exhibit itself in a condition resembling myxedema in man. This
distinction has been generally accepted, and it throws much light
upon the discrepancy in the results obtained by some of the earlier
observers. Complete thyroidectomy with the acutely fatal results
usually described includes those cases in which both thyroids and
parathyroids were removed, while probably many of the apparently
negative results obtained after excision of the thyroids are expli-
cable on the supposition that one or more of the parathyroids were
left in the animal. It should be stated, however, that two recent
observers, Vincent and Jolly, as the result of numerous experi-
ments made upon different varieties of animals, throw some doubt
upon these conclusions. They contend that in herbivorous animals
fully half of those operated upon survive complete removal of all
thyroid tissue, showing no evil symptoms except perhaps a di-
minished resistance to infection. Carnivorous animals, on the con-
trary, usually die after such an operation. In spite of such con-
tradictory results in the hands of some observers the general opinion
prevails that complete removal of the parathyroids is followed by
acutely toxic results which develop rapidly and the most prom-
inent symptom of which is muscular tetany. This tetany exhibits
itself as fibrillar contractions of the muscles, a general muscular
tremor, tonic and clonic spasms of the muscles or "intention
spasms," that is, spasmodic or uncoordinated contractions follow-
ing upon an effort to make a voluntary movement.* As is well
known, similar symptoms are often observed under other condi-
tions, infantile tetany, gastro-intestinal tetany, etc., and it has
been suggested that in all such cases the initial difficulty may
consist in the insufficiency of active parathyroid tissue. Several
observers have reported that injections of extract of the parathy-
roids cause the tetany to disappear without, however, protecting
the animal from a fatal outcome, but the most striking results
have been obtained by Macallum and Voegtlin.f These observers

* For literature and Summary, see Bing, "Zentralblatt f. d. Physiol, u.
Pathol, d. Stoffwechsels," 190S, Nos. 1 and 2.

t Macallum and Voegtlin, "Johns Hopkins Hospital Bulletin," March,
1908.

838 PHYSIOLOGY OF DIGESTION AXD SECRETION.

find that injection or ingestion of solutions of calcium salts removes
completely the symptoms of tetany and restores the animal to
an apparently normal condition. They have obtained similar
results upon human beings suffering from tetany as a result of
unintentional removal of the parathyroids. The experimental
evidence in the case of the parathyroids tends to support the
view that their function consists in neutralizing in some way
toxic substances formed elsewhere in the body, and that, therefore,
after removal of these glands death occurs from the accumulation
of such toxic bodies in the blood and tissues. Thus Macallum
states that in animals in which tetany has developed as a conse-
quence of extirpation of the parathyroids, bleeding and infusion
of salt solution causes the tetany to disappear. The results
quoted above in regard to the therapeutic value of calcium salts
would seem, moreover, to connect the parathyroid function with
the calcium metabolism and to relate the development of toxic
substances with an insufficiency of calcium, but at present no
precise statement can be made in regard to the way in which
these bodies perform their very important function. The view
that the parathyroids are simply immature thyroid tissue is still
supported by some observers, being based chiefly on the his-
tological assertion that after removal of the thyroids the para-
thyroids may hypertrophy and show thyroid cysts containing
colloidal material. Most observers, however, take the view
outlined above, that the parathyroids have a functional signifi-
cance essentially different from that of the thyroids, and that the
parathyroids as they exist in the body are not simply undeveloped
or immature thyroid tissue. At the same time it is becoming
generally recognized that different as the functions of these two
tissues may be, they are in some way correlated, and that the
removal of oik; of them influences the activity of the other.

The Function of the Thyroid. — According to the opinion
of most writers on the subject, removal of the thyroid alone,
Leaving, .-it Least, the external parathyroids uninjured, is followed
by the development of a, state <>l chronic malnutrition which
expresses itself finally in a condition of cachexia. Following a
terminology sometimes used in medical Literature, this cachectic
condition may be designated as "cachexia fh\Teopriva, " whereas
the convulsive phenomena or tetany, formerly also described as
nptom <>t' loss of I he thyroid, may be characterized as "tetania
paral hyreopriva. " No adequate explantion has been furnished of
the influence exercised by the thyroid on the nutrition of the
body, h ie usually assumed I ha1 the thyroid cells form an internal
secretion which is contained possibly in the colloid material
found in the vesicles. This view assumes thai the thyroid forms

SECRETION OF THE DUCTLESS GLANDS. 839

a specific hormone which acts as a chemical stimulus to other
tissues, particularly those of the central nervous system. Some
justification for this view is found in the effect of feeding thyroid
tissue to normal individuals. There may be produced under
these circumstances a condition which may be designated as
hyperthyroidism, that is to say, the metabolism of the tissues is
augmented as is shown by an increase in the excretion of nitrogen,
carbon dioxid, and phosphoric acid, and by an increased con-
sumption of oxygen, the heart-rate is also accelerated, and other
evidences are given of an excitation of the nervous system. Simi-
lar symptoms are observed in the pathological condition known
as exophthalmic goiter, which is now usually explained as being
due to a hyperthyroidism resulting from an hypertrophy of the
thyroid tissue. As was stated above, Baumann isolated from the
thyroid a peculiar substance, iodothyrin, which is characterized
chemically by its large percentage of iodin, and physiologically
by the fact that when used upon pa,tients suffering from a defi-
ciency in functional activity of the thyroid (myxedema, goiter) it
gives the same beneficial results as thyroid tissue itself. In the
gland this iodothyrin is combined with protein to form a thyreo-
globulin or thyreoprotein. There has been much discussion
regarding the iodin constituent of the thyroid tissue. Extensive
observations have shown that in some entirely healthy animals
iodin is absent or is present only in traces, and in animals in which
it is present the amount may vary greatly with the character of
the food. Hunt gives the following table:

Per cent, of iodin.

Children's thyroid none.

Maltese kid thyroid none.

Guinea-pig thyroid 0.05

Dog thyroid 0.061

Cat thyroid 0.08

Sheep thyroid 0.176

Beef thyroid 0.25

Hog thyroid 0.33

Human (Wells) 0.236

Human (goitre) 0.04

Opinions in regard to the significance of the iodin have varied
from the view, on the one hand, that it is an essential constituent
of the physiologically active substance secreted by the gland, to
the opposite extreme that it is an injurious substance which is
bound and made innocuous by the thyroid cells. The balance
of evidence seems to favor the first point of view,* and at present
we may conclude that the iodin in some way intensifies the
activity of the internal secretion of the thyroid. That it is abso-

* For discussion and literature, consult Hunt, "Studies on Thyroid,"
"Hygienic Laboratory Bulletin," 1909, No. 47, Washington, D. C.

840 PHYSIOLOGY OF DIGESTION AND SECRETION.

lutely necessary to this activity is rendered improbable by the
fact that iodin-free thyroids appear still to exercise their normal
influence upon metabolism, but administration of iodin in the
food not only raises the iodin percentage in the gland but also
increases proportionately the physiological activity of extracts
of the tissue. Experiments show also that the known effects of
thyroid extracts are greater in the iodin-rich than in the iodin-
poor glands.

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
tin's 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.

Thymus. — The physiology of the thymus gland is very obscure,
indeed, practically nothing is known about its functions. Its prox-
imity to the thyroids and parathyroids and its general similarity
in origin would indicate that like them it may have some impor-
tant specific influence upon metabolism, but physiological experi-
iii nts so far have failed to discover what this influence is. Ac-
cording to Verdun the thymus arises from the endothelial pouches
belonging to the branchial clefts, chiefly from that of the third
cleft. Formerly it was supposed to reach its maximal develop-
ment at birth and subsequently to atrophy, being replaced by a
growth of lymphoid and fatty tissues. More recently doubt has
been thrown upon this belief. Several observers have stated that
it continues to increase in size after birth until the appearance of
puberty, and that true thymus tissue may persist throughout life.
Siohr, in fact, insists that what has usually been taken as lymphoid
tissue in the adult thymus is, in reality, epithelial or endothelial
tissue which presumably has some specific function. The organ,
in fact, seems to be an unusually labile structure. Deficient
nutrition lead- to ;i rapid decline in weight. According to Jonson,
chronic underfeeding in rabbits lor ;i, period of four weeks
will reduce the weight to ;■!„ of its normal, and from this con-
dition it recovers rapidly upon the restoration of a normal
diet. On the physiological side, Abelous and Billard have stated
thai extirpation of these glands in the frog is followed by
the death of the animal, but later observers have failed to con-
firm this result either up«m frogs or mammals, so that we
musl believe that whatever their function may be if is not
absolutely essential to the life of the organism. Removal of the

SECRETION OF THE DUCTLESS GLANDS. 841

gland in young dogs (Basch) is said to cause a retarded growth
of the bony tissues and to induce a condition resembling rickets.
At the same time the peripheral nervous system shows an in-
creased excitability as determined by the response of the nerves
to galvanic stimulation. Injections of extract of the gland
(Svehla) cause a fall of blood-pressure and some quickening of the
heart-beat, but these effects are not specific. Unlike the thyroid
and parathyroid glands, the thymus contains no iodin (Mendel).
The only definite suggestion made regarding its influence is that
there is some sort of reciprocal relationship between it and the re-
productive glands. Castration (Henderson) causes a persistent
growth and retarded atrophy of the thymus, while removal of the
thymus (Paton) hastens the development of the testes.*

Adrenal Bodies. — The adrenal bodies — or, as they are frequently
called in human anatomy, the suprarenal capsules — belong to the
group of ductless glands. It was shown first by Brown-Sequard
(1856) that removal of these bodies is followed rapidly by death.
This result has been confirmed by many experimenters, and so far
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 f and Schaefer, and, about the
same time, Cybulski and Szymonowicz,J 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

* References: Friedleben, "Die Physiologie der Thymusdriise, " 1858;
Verdun, "Derives branchiaux chez les vertebres," 1898; Hammar, "Pfluger's
Archiv, " ex., and "Anatom. Anzeiger, " xxvii.; Henderson, "Journal of Phys-
iology," 1904, xxxi., 222; Stohr, "Beit. z. Anat. u. Entwick, Anatom.,"
Hefte, 1906, xxxi., 409; Jonson, "Archiv f. mik. Anat." 73, 390, 1909; Basch,
" Jahrbuch f. Kinderheilkunde." 64, 1906, and 68, 1908.

t "Journal of Physiology," 18, 230, 1895.

% "Archiv f. die gesammte Physiologie," 64, 97, 1896.

S42 PHYSIOLOGY OF DIGESTION AND SECRETION.

of action by section or by the use of atropin the heart rate is ac-
celerated, -while the blood-pressure is increased sometimes to an
extraordinary extent. These results are obtained with very small
doses of the extracts, and only from extracts which include the
medullary substance of the gland. The medullary cells contain
a chromogen substance (chromaffin) which gives a yellow reaction
with chromates. The physiological activity of the gland, so far
as ilie effects on the circulatory system are concerned, seems to
be proportional to the amount of chromaffin material in the
medullary cells. Schaefer states that as little as 5V mgms. of
the dried gland may produce a maximal effect upon a dog weigh-
ing 10 kgms. The effects produced b}r such extracts are quite
temporary 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, al-
though where or how this destruction occurs is not known. Ac-
cording to .Schaefer, the kidneys and the adrenals themselves are
n< >t responsible for this prompt elimination or destruction of the
active substance. Several observers have shown satisfactorily
that the material producing this marked effect on the heart and
blood-pressure 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 injection,
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 libers. More recently it has been claimed
by Schur and Wiesel Hint adrenalin is present in detectable
amounts in the general circulation alter partial or complete
nephrectomy, in rases of chronic nephritis and after prolonged
muscular exercise. In such cases of excessive secretion the
chromaffin substance in i he gland is apparently used up, since
the reaction with chromates can no Longer be obtained. Abelf
has succeeded in isolating a substance from the gland that pro-
duce- the effecl on Mood-pressure and heart rale, and proposes
for il the name epinephrin hydrate. He assigns to it, the formula
C,0H13NO8 . III./), and describes it, as a peculiar, unstable, basic
body. Salts of epinephrin may be obtained which when injected
into the circulation cause the typical effects produced by injection
of ex1 pacts of the gland.

The acl ive principle of the »land has been prepared in crystalline
form and named adrenalin (Takamine, Aldrich); its formula is

* "American Journal of Physiology," 2, 203, 1899.

f Abel, " Berichte d. 'lent. chem. Gesellschaft," 37, 368, 1904.

SECRETION OF THE DUCTLESS GLANDS. 843

given as C9H13N03. This substance is much used practically in
minor surgical operations as a hemostatic to check the flow of blood.
The constriction of the blood-vessels seems to be due to a direct
effect upon the walls of the vessels, either upon the musculature
itself or upon the endings of the peripheral nerve fibers distributed
to these muscles. That the effect is not entirely central is indicated
by the fact that after destruction of the vasoconstrictor center and
removal of the spinal cord injection of the extracts causes a rise
of blood-pressure of 100 per cent, or more. Langley has called
attention to the peculiar fact that the action of adrenal extracts
or solutions of adrenalin on plain muscle resembles always the
effect of stimulating the sympathetic nerves supplying the same
tissue. It has been proposed, therefore, to use these solutions to
determine whether or not given vascular areas, such as those of the
brain or lungs, are provided with vasoconstrictor nerve fibers.
When adrenalin is injected into a normal animal it may have an
influence upon the nerve centers of the vasomotor nerves as well
as upon the peripheral endings. Meltzer* has shown that mod-
erate doses under such conditions may cause a dilatation, while
in parts whose connection with the nerve center is destroyed only
a constriction is obtained. Under normal conditions at least
these extracts when injected into the circulation soon lose their
effect. This fact may explain why injection of the extracts has
failed to give permanent relief in animals from whom the adrenals
had been removed or in human beings suffering from Addison's
disease. Bearing in mind the results obtained in the case of thy-
roidectomy, it has been suggested that grafts of the adrenals under
the skin or into the peritoneal cavity may prove more effective.
Results by this method have been chiefly negative, owing apparently
to the fact that in such grafts the medullary substance, which con-
tains the material that causes constriction of the blood-vessels,
readily undergoes atrophy and absorption, but Busch and Van
Bergen f report at least one successful transplantation of the adrenal
(rabbit) in which the medulla persisted, and in which the grafted
gland preserved the animal from the usual fatal result following
total extirpation. It seems probable that if the method of grafting
is perfected the procedure may prove effective as a therapeutical
means in the treatment of Addison's disease.

The Physiological Role 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-

* S. J. and Clara Meltzer, " American Journal of Physiology," 9, 252, 1903.
t Busch and Van Bergen, " American Journal of Physiology," 1906, xv., 444.

S4-4 PHYSIOLOGY OF DIGESTION AXD SECRETION.

fore, has been that one at least of the functions of the adrenals is
the internal secretion of this material. It is assumed that its con-
tinued formation is necessary to the maintenance of the normal
metabolism of the muscular tissues either by a direct effect or
indirectly by influencing the activity of the nerve centers. Removal
of this secretion results in a marked loss of muscular tone and vigor,
exhibited by the blood-vessels, the heart, and the skeletal muscles, and
death follows rapidly. This general view is in accord with the
facts so far as they are known, but it must be confessed that it goes
somewhat beyond the facts. Another permissible, although less
probable view is that the adrenals produce an antitoxic substance
whose function is to neutralize or destroy certain (unknown) poi-
sonous products of body metabolism. Removal or disease of the
adrenals, on this theory, causes death because it allows these
toxic products to accumulate. It should be noted that this sug-
gestion regarding the functions of the adrenal glands refers only
to the medullary portion, in which alone the substance caus-
ing a rise of blood-pressure is found. Regarding the functions of
the relatively large cortical portion of the gland we have no
definite information, although some comparative observations
indicate that it may have important specific relations to the growth
of the body, particularly of the genital organs. Comparative
observations show that the mammalian adrenals are charac-
terized by the large development of the cortical substance.*

Pituitary Body (Hypophysis). — This body is usually
described as consisting of two parts — a large anterior lobe of
distinct glandular structure and a much smaller posterior lobe
of nervous origin and composed chiefly of neuroglia cells and
fi Ikts. Embryologically the two lobes are entirely distinct.
The anterior lobe arises from an invagination (Rathke's pouch)
of the buccal ectoderm. A portion of this epithelium soon
develops into a glandular structure belonging to the type of glands
which have no excretory dud and which probably, therefore, form
an internal secretion. The posterior lobe arises as an outgrowth
from the floor of the third ventricle of the brain, the infundibulum,
which comes into contact with the epithelial pouch forming the
anterior lobe. The epithelial cells of the latter soon show a
differentiation into two parts, one of which gives rise to the
anterior lobe, while the other invests the body and neck of the
rior or nervous lobe. To this latter the special name of
the pars intermedia has been given. When fully formed the
posterior lobe consists of two parts, the pars nervosa, composed of
neuroglia cells and fibers and ependymal cells, and an investing

of epithelial cells, derived from the buccal ectoderm and
* Klliott and Tuckett, "Journal of Physiology," 34, 332, L906.

SECRETION OF THE DUCTLESS GLANDS.

845

known as the pars intermedia* (see Fig. 289). The cells of the
pars intermedia may also penetrate more or less into the sub-
stance of the pars nervosa. Howellf and others have shown that
extracts of the anterior lobe when injected intravenously have
little or no physiological effect, while extracts of the posterior
lobe, 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. It
was subsequently shown by Schafer and Herring! that extracts

Fig. 289. — Mesial sagittal section through developing pituitary body of a human fetus
(fifth month;. Drawing from a photograph. — (Herring.) a, Optic chiasma ; b, tongue-
like process of epithelium ; c, third ventricle ; d, anterior lobe ; e, neck of posterior lobe ;
/, epithelium surrounding neck ; g, epithelial cleft ; h, posterior lobe.

made from the posterior lobe when injected into the blood cause
a dilatation of the renal vessels and an increased secretion of
urine. Evidence was thus obtained that the posterior lobe
furnishes an internal secretion which has a specific effect upon the
organs of circulation and upon the kidneys. Further work by
Herring§ has made it very probable that this internal secretion

* See Herring, "Quarterly Journal of Experimental Physiology, " 1, 121,
161, 1908. **

t "Journal of Experimental Medicine," 3, 245, 1898; also Schafer and
Vincent, " Journal of Physiology, " 25, 87, 1899; and Herring, "Quarterly
Journal of Experimental Physiology," 1, 261, 1908.

X Schafer and Herring, "Philosophical Transactions, Royal Society,"
London, 1906, B. cxcix., 1.

§ Herring, loc. tit., and 1, 281, 1908.

S46 PHYSIOLOGY OF DIGESTION AND SECRETION.

is furnished by the epithelial cells of the pars intermedia and
possibly also by the ependymal cells which belong properly to
the posterior lobe. In the pars intermedia some colloid material
is formed, and this is transported through the pars nervosa and
excreted finally into the third -ventricle of the brain. There is
some evidence also from histological appearances that this secre-
tion is augmented after complete thyroidectomy, a fact which
has led to the view that there is a functional relationship between
this lobe of the pituitary body and the thyroid tissue. Physio-
logical experiments upon the large glandular anterior lobe have
given mostly negative results. Injections of its extracts cause no
specific reaction. Indirect evidence, however, indicates that it
has an important function connected in some way with body
metabolism. On the pathological side, tumors or hypertrophies
of the pituitary have been associated with the conditions known
as acromegaly and gigantism. The former term applies to cases
of disturbed nutrition in which there is abnormal growth, shown
especially in the enlargement of the bones of the face and the
extremities, while gigantism includes less distinctly pathological
cases of overgrowth, particularly of the skeleton. That this
abnormal nutrition is connected with a disturbance (hypertrophy)
of the pituitary seems probable, but is not conclusively shown.
It is assumed in these cases that it is the anterior lobe which is
involved, and that, therefore, normally it controls in some way
skeletal growth. A number of observers have attempted to remove
all or a portion of the pituitary body, and in this way to arrive
at a conception of its physiological importance. The results are
somewhat conflicting. Yassale and Sacchi reported that com-
plete removal of the pituitary body (hypophysectomy) results
in the death of the animal with symptoms such as muscular
tremors, apathy, and dyspnea, which resemble the effects of a
complete thyroidectomy. Paulesco* has obtained more decisive
results. Complete removal of the gland was followed by death
in a short time twenty-four hours on the average. Mere separa-
tion of the gland from the brain by division of the stalk gave an
equally fatal result. As between the anterior and the posterior
Lobes his experiments indicate thai the quickly fatal result is
due to i he loss of 1 Ik; former. Ablation of the nervous lobe caused
no appreciable evil effect. In this country the work of Paulesco
has been confirmed by Eieford and Cushing,t so far, at least, as
the fatal resull of a total hypophysectomy is concerned. Their
animals soon after the operation exhibited a, condition of lethargy
which passed rapidly into a coma that ended in death, but, the

; Paulesco, "Journal de Physiologie el <!<■ Path. g6n<Srale," |». Ill, L907.
t Eieford and ( lushing, "Johns I [opkine I lospital Bullel in, " April, L909.

SECRETION OF THE DUCTLESS GLANDS. 847

fatal result did not develop so quickly as in the experiments of
Paulesco. Quite contrary results are reported by Gemelli,* from
a series of experiments made upon cats. In this animal no injurious
effects followed complete removal of the hypophysis in the cases
in which the operation was entirely successful. The interesting
work that has been done and is being done upon this organ is for
the most part suggestive only, and at present nothing specific
can be said with confidence in regard to its precise functional
value, or in regard to the difference in function between the
anterior and the posterior lobes.

Organs of Reproduction. — Some of the earliest work upon the
effect of the internal secretions of the glands was done upon the
reproductive glands, especially the testis, by Brown-Sequard.f Ac-
cording to this observer, extracts of the fresh testis when injected
under the skin or into the blood may have a remarkable influence
upon the nervous system. Mental and physical vigor, and the
activity of the spinal centers, are greatly improved, not only
in cases of general prostration and neurasthenia, but also in the
case of the aged. Brown-Sequard maintained that this general
dynamogenic effect is due to some unknown substance formed
in the testis and subsequently passed into the blood, although he
admitted that some of the same substance may be found in the ex-
ternal secretion of the testis — i. e., the spermatic liquid. PoehlJ
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. Zoth§ and also
Pregel|| 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.

* Gemelli, "Archives ital. de Biologie, " 50, 157, 1908.
t "Archives de phvsiologie normale et patholosique," 1889-92.
t "Zeitschrift f. kfinische Medicin," 26, 133, 1894.

'i "Pfluger's Archiv f. die gesammte Physiologic, " 62, 335, 1896; also 69,
386, 1897.

|| Ibid., p. 378.

848 PHYSIOLOGY OF DIGESTION' AND SECRETION".

Similar ideas in general prevail as to the possibility of the ova-
ries furnishing an internal secretion that plays an important part
either m general nutrition or in the specific nutrition of the other
reproductive organs. 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 f also reports a case in which the entire ovary from
one woman was transplanted into another patient upon whom com-
plete ovariotomy had been performed two years before. The result
of the operation was a return of menstruation and sexual desire,
and a marked alleviation of the disagreeable symptoms following the
artificial menopause. Similar results have been reported upon
the lower animals. After complete ovariotomy a condition of
"heat'' may be reproduced by grafting ovarian tissue,* and
several observers agree in stating that removal of the ovaries in
young animals prevents the normal development of the uterus,
while in adult animals it causes the organ to undergo a fibrous
degeneration (see section on Reproduction). In the natural
menopause, as well as in the premature menopause following
operations, it is a frequent, though not invariable, result for
the individual to gain noticeably in weight. An effect of the
ovaries on general nutrition is indicated also by the interesting
facl that in cases of osteomalacia, a disease characterized by
softening of the bones, removal of the ovaries may exert a favor-
able influence upon the course of the disease. These indi-
cations have found some experimental verification in a research
by Loewy and Richter§ made upon dogs. These observers found
thai complete removal of the ovaries, although at first apparently
without effect, resulted in the course of two to three months in a
marked diminution in the consumption of oxygen by the animal,
ured per kilogram of body-weight. II' now the animal in this
condition was given ovarian extracts (oophonn tablets), the amount
of oxygen consumed was not only brought to its former amount,

* Morris, " Medical Record'," L901, p. 83.

■ Medical News," 1899, p. 523.
| Mar hall and Jolly, " Philo opn. Trail actions," B. exeviii., ".)!), L905.
I ioewy .ni' I Richter, " Archiv f. Physiologie," L889, suppl. volume, p. 174.

SECRETION OF THE DUCTLESS GLANDS. 849

but considerably increased beyond it. A similar result was obtained
when the extracts were used upon castrated males. The authors
believe that their experiments show that the ovaries form a specific
substance which is capable of increasing the oxidations of the body.
In addition to the internal secretion of the ovaries which is respon-
sible for the phenomenon of menstruation, other similar secretions
have been assumed to account for changes connected with the
process of reproduction. Thus the implantation of the fertilized
ovum in the uterine mucous membrane and the development of
the placenta have been supposed to be effected through the agency
of some chemical stimulus arising in the cells of the corpus luteum.
So also the development of the mammary glands during pregnancy
is attributed to the action of a hormone formed in the tissues of
the fetus itself (see section on Reproduction).

Pancreas. — The importance of the external secretion, the pan-
creatic juice, of the pancreas has long been recognized, but it was
not until 1889 that von Mering and Minkowski * proved that it fur-
nishes also an equally important internal secretion. These observers
succeeded in extirpating the entire pancreas without causing the
immediate death of the animal, and found that in all cases this
operation was followed by the appearance of sugar in the urine in
considerable quantities. Further observations of their own and of
other experimenters have corroborated this result and added a num-
ber of interesting facts to our knowledge of this side of the activity
of the pancreas. It has been showm 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,
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

♦Minkowski, "Archiv f. exper. Pathologie u. Pharmakologie, 31, 85,
1893.

54

850 PHYSIOLOGY OF DIGESTION AND SECRETION.

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 may be markedly
affected. They show signs of hyaline degeneration or atrophy or in
severe cases may be absent altogether. It should be added that
this connection of the islands of Langerhans with the internal
secretion of the pancreas is by no means a demonstrated fact.
Several observers f contend that the islands represent a stage in the
development of the ordinary secreting alveoli of the pancreas.
When the pancreas is subjected to prolonged and excessive activity,
by the injection of secretin, for example, the number of islands is
greatly increased, and the same result follows periods of prolonged
inactivity, as in fasting.

Several theories liuve been advanced to explain the action of
the internal secretion of the pancreas. It has been suggested that

* " Virchow's Archiv," His, 91, 1902
\ Dale
Thompson

i I >.-.]*-, " Philosophical Transactions," JJ. excvii., 1904 ; also Vincent and
, "Journal of Physiology, " L9O0, xxvii., xxxiv.

SECRETION OF THE DUCTLESS GLANDS. 851

the secretion contains an enzyme which is necessary for the hydros
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 (hormone) . Other
investigators adopt an entirely different view of the relation of
the pancreas to carbohydrate metabolism. They believe that the
internal secretion 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 (hyperglycemia) above normal, and the excess passes
out in the urine.

Kidney. — Tigerstedt and Bergman f 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. Other
observers claim that the kidneys furnish an important internal
secretion that affects the metabolism. The absence of this secretion
after complete nephrectomy leads to the production of uremia.!

* 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.

J Suner, " Zentralblatt f. d. ges. Physiol, u. Path, des Stofferechsel,"
1907, ii., 3.

SECTION VIII.

NUTRITION AND HEAT PRODUCTION AND
REGULATION.

CHAPTER XLVIL
GENERAL METHODS-HISTORY OF THE PROTEIN FOOD.

Under the head of nutrition or general metabolism we include
usually all those changes that occur in our foodstuffs from the time
that they are absorbed from the alimentary canal until they are
eliminated in the excretions. In many of these processes the oxj'gen
absorbed from the lungs takes a most important part, and the
changes directly due to this element, the physiological oxidations
of the body, can not be separated from the general metabolic phe-
nomena of the tissues. As was said in another place, the respiratory
history of oxygen ceases after this element has reached the tissues;
its subsequent participation in the chemical changes of the organ-
ism forms an integral part of the nutritional processes. These latter
processes are varied and complex and only partially understood.
For the sake of simplicity in presentation it is convenient to con-
sider separately each of the so-called foodstuffs, — the proteins,
carbohydrates, fats, water, and inorganic salts, — and attempts
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 desirable to
full attention to certain general methods and conceptions that
have been developed in connection with this part of physiology.

Nitrogen Equilibrium. — Among our main foodstuffs the pro-
teins (and albuminoids) are characterized by containing nitrogen.
After this materia] 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
presenl some undigested protein which, although taken with the
food, has never really entered the body. It is evident that the
urine, feces (and sweat) may be collected during a given period and
analyzed to determine their contents in nitrogen. The sweat is»

852

GENERAL METHODS HISTORY OF PROTEIN FOOD. 853

usually neglected except in observations upon conditions in which
muscular activity has been a prominent feature. As a rule, the
amount of nitrogen is determined by some modification of the Kjel-
dahl method. In principle this method consists in heating the
material to be analyzed with strong sulphuric acid. The nitrogen
is thereby converted to ammonia, which is distilled off and caught
in a standardized solution of sulphuric acid. By titration the
amount of ammonia can be determined, and from this the amount of
nitrogen is estimated. Nitrogen forms a definite percentage of the
protein molecule (about 16 per cent.) ; so that if the weight of nitro-
gen is multiplied by 6.25 the weight of protein from which it is de-
rived is obtained. If, on the other hand, the nitrogen is determined
in the food eaten during the period of the experiment it is evident
that a balance may be struck which will determine whether the
body is receiving or losing nitrogen. If the balance is even the body
is in nitrogen equilibrium — that is, it is receiving in the food as
much protein nitrogen as it is metabolizing and eliminating in
the excreta. If there is a plus balance in favor of the food it is
evident that the body is laying on or storing protein tissue, while
if the balance is minus, the body must be losing protein. During
the period of growth, in convalescence, etc., the body does store
protein, and under these conditions the balance is in favor of the
food nitrogen. But throughout adult life under normal conditions
our diet is so regulated by the appetite that a nitrogen equilibrium
is maintained through long periods. Under experimental condi-
tions, involving, for instance, a special diet, it often becomes neces-
sary to make the analyses for nitrogen in order to determine whether
or not the individual is losing or gaining protein or is in equilibrium.
It is important also to bear in mind that nitrogen or protein
equilibrium may be established at different levels. If, for instance,
a man is in nitrogen equilibrium on a diet containing 10 gms. of
nitrogen, what will happen if the protein in this diet is doubled ?
Our experience teaches us that the extra 10 gms. of nitrogen or
62.5 gms. of protein is not stored in the body indefinitely. As a
matter of fact, the extra protein is metabolized in the body and
nitrogen equilibrium becomes established at a higher level. Where-
as under the first condition 62.5 gms. of protein were eaten and 62.5
gms. of protein were lost from the body, either in the form of nitrog-
enous excreta or in the feces as undigested protein, under the
second condition 125 gms. of protein are eaten and 125 gms. of pro-
tein are lost. The total mass of protein tissue in the body may
remain the same, or if any increase takes place at the beginning of
the change in diet it soon ceases. Experimentally it is found that
there is a certain low limit of protein which just suffices to maintain
nitrogen equilibrium, and between this level and the capacity of

854 NUTRITION AND HEAT REGULATION.

the body to digest and absorb protein food nitrogen equilibrium
may be maintained upon any given amount of protein.

Carbon Equilibrium and Body Equilibrium. — The term car-
bon equilibrium is sometimes used to describe the condition in which
the total carbon of the excreta (in the carbon dioxid, urea, etc.) is
balanced by the carbon of the food. It is possible that an individual
may be in nitrogen equilibrium and yet be losing or gaining in
weight, since, although the consumption of proteins may just be
covered by the proteins of the food, the comsumption of non-protein
material, particularly the fats of the body, may be greater than the
supply furnished by or manufactured from the food. An animal
may lose or gain in carbon when his nitrogen supply is in equilib-
rium. In the same way under special circumstances we may
speak of a water equilibrium or a salts equilibrium, although these
terms are not generally used. An adult under normal conditions
lives so as to maintain a general body equilibrium; his ingesta of
all kinds are balanced by the corresponding excretions, and the
individual maintains a practically constant body-weight.

Complete Balance Experiments — Respiration Chamber. —
According to the statements made in the last paragraph, it is obvious
that if the analytical work is properly done, an exact balance may
be drawn between the proteins, fats, and carbohydrates eaten as
food and the proteins, fats, and carbohydrates destroyed in the
body as represented by the nitrogen and carbon contained in the
excreta. Complete experiments of this kind were attempted first
by Voit * and Pettenkofer, to whose work much of our fundamental
knowledge is due. In the experiments of these authors, made upon
men as well as animals, the total nitrogen of the urine and feces was
determined and the total quantity of 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, which were analyzed for 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 carbon eliminated, it was possible to estimate the
amount of protein and fat or carbohydrate destroyed in the body.
From the nitrogen the quantity of protein metabolized was
obtained by multipying by b\25, as explained above. If then
the carbon belonging to the amount of protein metabolized was

deducted from the total carbon excreta, what was left represented

either fa1 or carbohydrate burnt in the body, and, knowing the
* See Hermann's "Handbuchder Physiologic, " vol. vi., 1881.

GENERAL METHODS HISTORY OF PROTEIN FOOD. 855

amount of these materials taken in the diet, it was possible to
ascertain whether the corresponding amount of carbon had all
been excreted. By experiments of this kind a nearly perfect
balance may be struck between the income 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 secretions 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. 907) by means of which the heat given
off by the person could be measured. The heat value of the diet
being known, it is possible in this way to ascertain whether or not
this theoretical amount of heat is actually given off from the body.
Atwater's respiration chamber is described as a respiration calorim-
eter; some of the results obtained from its use are referred to later on.
The Effect of Non-protein Food on Nitrogen Equilibrium. —
By use of the methods referred to above the general influence of
the non-protein foods (fats, carbohydrates, albuminoids) upon the
protein consumption of the body has been made evident. An ani-
mal may be brought into nitrogen equilibrium on protein food alone,
the amount of protein required being relatively large. If now
non-protein foodstuffs are added to the diet it is found that the
amount of protein necessary to maintain nitrogen equilibrium may
be reduced correspondingly. With reference to the consumption
of protein in the body the non-protein foods are all protein-spar ers,
and herein lies one great peculiarity of their nutritional value.
On a mixed diet of protein and non-protein food the proportion of
the latter may be increased and that of the former decreased to a
marked extent without breaking down nitrogen equilibrium —
that is, without causing a loss of protein tissue from the body.
This fact is explained by the consideration that in our body the
food fulfils two great functions. First, it furnishes the material
for the formation of new living matter or the replacement of
the loss of this matter that is continually going on; second,
it furnishes a supply of energy for the work done by the various
cells, the contraction of the muscle, the secretion of the gland, the
discharges of the nerve cells, etc. This second function, the
energy requirement, is met by any of the three energy-yielding
food-stuffs, carbohydrates, fats, or proteins, especially, as we shall
* Atwater, Bulletins 45, 63, 69, United States Department of Agriculture.

S56 NUTRITION AND HEAT REGULATION.

find, by the carbohydrates. For the first, function protein (or its
split-products) is absolutely needed, and perhaps is alone needed.
In any event, if the supply of non-protein is sufficiently large,
then the amount of protein can be lowered to a certain irreducible
minimum which is required for purposes of genuine assimilation,
that is, the construction of living material.

The Nutritive History of the Protein Food. — The digestive
changes undergone by protein and its subsequent absorption have
been described in the section on Digestion. It will be remembered
that the products of protein digestion are absorbed mainly into the
blood-vessels of the intestine, and therefore must pass through the
liver before reaching the general circulation. It will also be remem-
bered that we are as yet ignorant of the precise form in which these
products enter the portal blood. This deficiency in our knowledge
constitutes a serious obstacle to a satisfactory explanation of the
nutritional history of the protein. Three general views have been
advanced concerning the ultimate fate of the absorbed material.
In two of these theories it is assumed that the digested material
is all synthesized into a new protein, during or after absorption,
being converted into what we might call a body protein charac-
teristic of the animal. Although it is not specifically stated the
assumption seems to be that this body protein is serum-albumin
or, at least, one of the blood-proteins.

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 (Vatabolism or disassimilation) of thai tissue.

The second theory, advanced by Voit, assumes that some of the
absorbed material is assimilated to form living protoplasm, so far
as this is necessary to replace the wastes of the tissue or to provide
new material for growth. The portion of the absorbed protein
tli.it subserves this function is designated as tissue protein. It is
obvious l hut this function cannot be replaced by the non-protein —
th:it is, the uon-nitrogenous— foodstuffs. The larger portion of the
absorbed material, however, after distribution to the tissues is
dest rayed, 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 thai they decompose into alcohol and
carbon dioxid. The portion of the protein that undergoes this fate
i- de ignated a the circulating protein, on the hypothesis that it
enter- the circulating liquids of the body, the blood, and lymph.

The third general point of view represents perhaps the trend
of modern investigation, it starts from the belief now generally

GENERAL METHODS — HISTORY OF PROTEIN FOOD. 857

accepted that the digestive processes do not stop at the peptone
stage, but result in splitting the protein molecule more or less
completely into its constituent amino bodies, or into a mixture of
such amino bodies and polypeptids. From this group of split
products, none of which is of sufficient complexity to be desig-
nated as a protein, some protein is reconstructed by processes
of synthesis taking place in the wall of the intestine or in the liver.
That this is a possibility, that, in other words, the body may
build its own prorein out of the split products of a complete
pancreatic hydrolysis, has been demonstrated by the work of
Loewi and others.* Dogs fed on the split products of a pancreatic
digestion, together with sufficient carbohydrates and fats, may be
kept in nitrogenous equilibrium or may even store up protein in
the body. It is interesting to know that the split products of pro-
tein obtained by complete hydrolysis with boiling acids cannot be
utilized in this way by the body. The end products of pancreatic
and acid hydrolysis of protein are very similar, but evidently
the latter either goes too far or results in the production of sec-
ondary reactions which unfit the split products for synthesis by
the tissues of the body. It is possible, as was suggested first by
Abderhalden, that in the normal digestion of protein in the body
some polypeptids remain which serve as a sort of nucleus for the
reconstruction of the body protein. Any way, the view that we
are now describing assumes that the protein material of the food
is first broken down quite completely in digestion and then a new
body protein is reconstructed from some of this material. In
other words, out of the various pieces into which the food-protein
is split by the processes of digestion a certain number are united
by synthetic processes to form the special body-protein of the
animal. The balance of the amino bodies not thus used is of
value to the body only as a source of energy, but not for tissue
building. The nitrogen in them is useless to the body and con-
sequently it is promptly split off, probably in the liver, as ammonia,
which is then converted to urea and excreted. The organic acid
group left behind is important as a source of energy. It can be
oxidized with the production of heat, or if the food is in excess of
the energy requirements of the body, it may be converted to glyco-
gen or fat and stored as a reserve. On this view, therefore, one
would not speak of circulating protein as contrasted with tissue-
protein. So much of the food protein as is not resynthesized into
tissue protein for the construction of tissue, is used or destroyed
for purposes of energy without again passing into the protein
form.

* For discussion and literature, consult "Luthje in Ergebnisse der Physi-
ologie," vii., 1908.

858 NUTRITION AND HEAT REGULATION.

Folin* has called attention to the fact that the proportions
of the different nitrogen compounds in the urine vary with the
amount of protein food. Upon an average diet containing 16 to
17 gms. of nitrogen (100 to 106 gms. of usable protein) the urea
forms S7 to 88 per cent, of the total nitrogen of the urine, while
when the protein intake is reduced to 3 or 4 gms. of nitrogen the
urea forms only 61 to 62 per cent, of the total nitrogen of the
urine. On the other hand, the creatinin and the purin bodies
(uric acid, xanthin, etc.) are not diminished in amount with a
decrease in the protein food. He suggests, therefore, that the
hitter bodies, creatinin and purin bases, arise from the breaking
down of the living tissues, the catabolism or wear and tear of the
living machinery, and may be taken as an index of the extent
of this metabolism. The urea, on the other hand, represents in
part that portion of the protein food which, from the present
point of view, is not used for construction of living matter, but
which acts simply as an energy food. The amount of urea, there-
fore, while a reliable index of the weight of protein destroyed in
the body, is not an index, as was formerly supposed of the amount
of living tissue protein broken down, since a portion of it may
arise from the food-protein as described above.

The Amount of Protein Necessary for Normal Nutrition. —
As was stated above, nitrogen equilibrium may be maintained on
different amounts of protein food. It is important, from a
scientific and from an economic standpoint, to determine the low
limit for this equilibrium and to ascertain whether, for the purpose
of the best as well as the most economical nutrition, this low
limit is as good as or preferable to a higher amount of protein in
the diet. Examination of the dietaries of civilized races shows
that, on the average, 100 to 120 gms. of protein are used daily by
an adult man. Voit gives 118 gms. of protein as the average
daily consumption. A variable portion of this amount passes
into the feces in undigested form, but we may assume that about
100 to 105 gms. are absorbed and actually metabolized in the body.
If we take into account the weight of the body, this amount of
protein may bo estimated as equivalent in round numbers to
1.5 gms. of pTot fin for 0.23 gm. nitrogen) per kilogram of body-
weight. In recent years serious attempts have been made to
lain how low this daily quota of protein may be reduced
without destroying nitrogen equilibrium or injuring the effective-
ness of the body for muscular or mental work. Siven was able

for short periods to red u re his daily diet of protein to as little as

0.5 gm. (0.08 gm. N.) per kilo of body weight, but probably the

iiio.-I important experiments of this kind were those carried out

* Folin, "American Journal of Physiology," xiii., l.r>, <>(>, and 1 17, L905.

GENERAL METHODS HISTORY OF PROTEIN FOOD. 859

by Chittenden.* In this work the experiments were continued
over long periods of time, and were made upon three different
groups of men, five university teachers, a detail of thirteen men
from the Hospital Corps of the Army, and eight university students
classed as athletes. The general result of the investigation
showed that the body can be maintained in protein equilibrium
and in a normal state of efficiency upon a diet containing only
30 to 50 gms. of protein per day, according to the weight of the
individual — or, expressed in more general terms, the daily quota
of protein per kilo of weight may be reduced from 1.5 gms.
(0.23 gm. N.) to about one-half, that is, 0.75 gm. of protein or
0.12 gm. of nitrogen per kilo. This general result has been
confirmed on a large scale by the studies made by McCabef of
the metabolism of the Bengalis of India. He finds that the
average Bengali metabolizes in his body, so far as may be judged
from the nitrogen excreted in the urine, only about 37.5 gms. of
protein daily, corresponding to a consumption per kilo of 0.7 gm.
of protein or 0.113 gm. of nitrogen. A corresponding average
amount of protein was, of course, eaten daily, and on this low
protein diet they exist in apparent health. Rubner % also empha-
sizes the fact that milk, which forms the sole diet of the infant, is
& protein poor food. The usual daily diet of the adult has a heat
value of from 2400 to 3000 calories (see p. 900). Of this total
heat value the protein food in the diets usually recommended
forms about 15 to 20 per cent. In milk, however, according to
Kubner's estimates, the protein constitutes only about 10 per
cent, of the total heat value. As the result of these and similar
investigations, the practical question presents itself as to what
constitutes the optimum daily quota of protein. If the body can
be kept in good condition upon 0.75 gm. per kilo per day, will an
ingestion of more than this, say twice as much, prove injurious
or beneficial or indifferent to the body? Outside its hygienic
aspect the question is important from an economical standpoint,
since the proteins are the most expensive foods, and in the feeding
of large masses of individuals — armies, schools, asylums, etc. —
it is not desirable to waste money on protein food if it is not
needed. The full and satisfactory answer to this question must
be deferred until more experience is obtained. The report upon
the Bengalis, noted above, would seem at first to constitute a
satisfactory demonstration of the practicability of a low protein

* Consult Chittenden, "Physiological Economy in Nutrition," New York,
1905, for discussion and literature.

f McCabe, " The Metabolism of the Bengalis, Calcutta," 1908. (Scientific
Memoirs, Medical Department Government of India, No. 34.)

% Rubner, "Das Problem des Lebensdauer," 1908; Cohnheim, "Die
Physiologie der Verdauung u. Ernahrung," 1908.

860 NUTRITION AND HEAT REGULATION.

diet, but McCabe states that the Bengali is inferior physically to
the average European, and is particularly deficient in capacity
for muscular work, and he is inclined to attribute this inferiority
to the diet. Moreover, the Bengali is quite susceptible to kidney
troubles, a fact which seems to destroy one prediction often
made by those who advocate a low protein diet, namely, that the
smaller amount of work thus thrown on the kidneys would result
in a diminution of diseases of the kidney. The newer conceptions
in regard to the digestion and nutritive history of the protein
foods certainly seem to favor the adoption of a low protein diet.
If protein is eaten in excess of the real assimilation needs of the
tissues, all the excess, so far as we can see, might just as well be
substituted by carbohydrate or by carbohydrate and fat. The
excess nitrogen thus eaten appears to be so much useless ballast
which the body very promptly gets rid of. The uncertain point,
however, is what constitutes the assimilation need of the tissues.
The experiments given above would place this need very low,
according to the lowest estimate, at about 5 per cent, of the total
energy value of the food. That is to say, if the daily diet contains
heat energy equivalent to 2400 calories, only 5 per cent, of this,
120 calories, needs to be in the form of protein, an estimate which
would bring the protein to about 30 gms. daily. Against this line
of reasoning it may be urged, in the first place, that our positive
knowledge of the history of protein in the body is too incomplete
to justify its application in a wholesale way to such an important
matter as the daily diet. Serious blunders have been made in
the past, notably in the nutritive employment of gelatin, by a
premature application of incomplete knowledge. Secondly, it
must be remembered that mankind, left to the guidance of the
natural appetites and the eliminating influence of natural selec-
lion, has always, when possible, adopted the high protein level of
90 to 100 gms. per day. Indeed, the uniformity with which this
level has been unconsciously maintained is a striking fact. Among
the rich as well as the poor, and in races very differently placed
ae regards quantity of available food, substantially the same
amounl of protein (80 to LOO gms.) is consumed daily by each
Individual. The element of the diet which varies most widely,
iinlicim points oul in an interesting discussion of this ques-
tion, is, on the contrary, the non-protein, particularly the carbo-
hydrate material. Those who arc obliged to do much muscular
work to earn a Living or for the sake of pleasure (spoils, athletics)
add to their daily quota of protein an excess of carbohydrate
food to furnish the requisite energy. On the contrary, those whose
daily Life requires bul little muscular exertion, cut down the carbo-
hydrates and fats, and make their diet relatively but not abso-

GENERAL METHODS HISTORY OF PROTEIN FOOD. 861

lutely richer in protein. That mankind has made a mistake
in adopting the higher protein level can hardly be claimed on the
basis of our present knowledge. We must be content to await
until the matter is tested more completely on a larger scale or
until our knowledge of the details of protein metabolism is more
satisfactory.

The Intermediate Stages in Protein Metabolism. — The urea
found in the urine and in lesser amounts in the sweat and other
secretions may arise in two general ways: 1. As an end-product
of the digestive hydrolysis of the protein food. As was explained
above, the protein material is split by the successive actions of the
pepsin, trypsin, and erepsin into products which no longer give
the biuret reaction for protein. As a result of this process much
of the nitrogen appears in the form of ammonia, monamino-acids,
and the so-called diamino-bodies, such as arginin, and we may
suppose that in these forms some of it is carried to the liver.
In this organ the ammonia, as ammonia salts, is transformed into
urea. The monamino-acids, some of them, at least, are deamidized,
that is, their NH2 group is split off as ammonia which then is like-
wise converted to urea. The organic acid radicles left after removal
of the NH2 group may subsequently be oxidized through various
stages to carbon dioxid and water, or they may be synthesized to
form a carbohydrate body or possibly a fat, and thus be kept
temporarily as storage, although their eventual fate is to suffer
oxidation to carbon dioxid and water. Regarding the diamino-
compounds like arginin it is known that when this substance is
injected subcutaneously its nitrogen is excreted for .the most part
if not entirely as urea. Since Kossel and Dakin have shown that
the liver especially contains a hydrolytic enzyme, arginase, which
is capable of splitting off the guanidin residue of arginin to form
urea, we may assume that the arginin formed during protein diges-
tion actually undergoes this fate. The process is represented by
the following equation :

NHC<NH(CHp3CHNH2COOH+H2° = CO<NH22 + NH^CH^3CHNH2COOH

Arginin or guanidin diamino-valerianic acid. Urea. Ornithin or diamino-valerianic

acid.

The ornithin, in turn, may suffer deamidization, its (NH2) groups
being converted to ammonia and urea.

By these possible processes it is evident that some of the nitro-
gen of the food, the amount depending on the quantity of protein
eaten, may be excreted promptly as urea without entering at any
time into the formation of living protoplasmic tissue. It seems
clear also that so far as the protein undergoes these intermediary
changes its nitrogen constituent is without value to the body.

862 NUTRITION AND HEAT REGULATION.

The body gets rid of the nitrogen and utilizes the balance of the
protein molecule as a source of heat energy or as material for the
synthesis of its non-nitrogenous storage fuel. Folin's estimates,
quoted above, showing that the urea of the urine rises and falls
promptly with the amounts of protein in the food, indicate that
part of the protein food undergoes this series of changes. Since
some of the nitrogenous food material must be actually synthe-
sized into living protoplasm, acting as a "tissue protein" in Voit's
sense, to make new tissue or to repair tissue waste, it follows that
a portion of the absorbed split products of digested protein must
undergo an entirely different process, but concerning the inter-
mediary steps of this process we have little or no knowledge.
2. The urea of the excretion may arise in the tissues at large
from the breaking down of the organized or living protein or of
the protein material included in the cell liquids. As has been
stated in another place, most of the living tissues con-
tain intracellular enzymes capable of causing hydrolysis of
the proteins. When the excised tissues are kept warm but
protected from the action of the bacteria they undergo self
digestion or autolysis. As a result of this process the protein
molecule is split into its constituent parts, which in general are the
same as those formed during digestion. Assuming that these
intracellular enzymes act in this way during life it is evident that
the fate of the split products may be the same as that described
above. The ammonia compounds are converted to urea by the
liver and quite probably by other tissues; the monamino-bodies.
lose their NHL, group by a process of deamidization and the am-
monia compounds thus produced are in turn changed to urea, and
such compounds as arginin will probably under the influence of
arginase yield their nitrogen as urea. In the protein that undergoes
metabolism in the tissues, as well as in the protein of the food that
is metabolized before reaching the tissues at large, the urea is formed
by two general methods at least, by the intermediate production
of ammonia compounds and by the conversion of a guanidin residue.
For the sake of completeness a third method of producing urea in
the body may be added, namely, a derivation from uric acid.
This mode of origin is considered in the following paragraph.

Tin Intermediary Metabolism <>f the Nuclcoprotcins.—Nudeo-
proteins are taken in our fond and likewise are found in the tissues

of the body. Their metabolism, so far as the nuclein portion is
concerned, gives rise to the formation of uric acid and the purin
bases. It will be remembered that in the urine we find some uric
acid and some xanthin and hypoxanthin. In the feces small
amounts may be detected of xanthin, hypoxanthin, adenin, and
guanin. These bodies all contain the purin group or radicle (see

GENERAL METHODS — HISTORY OF PROTEIN FOOD. 863

p. 817) and are closely related chemically. By hydrolytic processes
outside the body one may obtain their purin bases from nucleins
or nuclein acids, and inside the body the metabolic processes give
similar products. The history of the intermediary metabolism
may be outlined as follows: When nucleoprotein is eaten the
nuclein is split off apparently by the action of the pepsin, the
protein portion then undergoing the digestive and metabolic changes
already described. The nuclein is not acted upon further by the
pepsin or trypsin, except that under the influence of the latter it is
rendered soluble possibly by an act of hydration.* Once within
the body the nuclein is submitted to the action of a series of enzymes
as follows: Under the influence of nuclease it is split with the
production of some of the purin bases, adenin, guanin. The amino-
purins so far as they are formed are converted to the corresponding
oxypurins by the action of a deamidizing enzyme. According
to Jones two such enzymes may occur in the body, namely, adenase
and guanase. Their action takes place as follows:

C5H5N5 + H20 = C8H<N40 + NH3

Adenin. Hypoxanthin.

C5H5N50 + H20 = C5H4NA f NH3

Guanin. Xanthin.

The xanthin and hypoxanthin in turn are converted to uric acid
by the action of an oxidase, known as xanthinoxydase, and finally
the uric acid formed may in turn be partly split under the influence
of a special uricolytic enzyme so that part of its nitrogen is elimi-
nated as urea. Eventually, therefore, we may believe that the
nitrogen of the nuclein is excreted largely as uric acid and urea,
and to a smaller amount as xanthin, hypoxanthin, adenin, or guanin.
The proportion of the uric acid which is further split to form urea
varies in different animals (see p. 819). In man the proportion is
estimated at about one-half. Burian has given reasons for be-
lieving (see p. 820) that most of the purin nitrogen excreted arises
in the metabolism of the muscle, and represents presumably the
break down of organized structure. The action of the series of
enzymes just described seems adapted simply to remove the waste
nuclein with little corresponding profit to the body from the stand-
point of liberated heat energy. It is to be borne in mind, however,
that the activity of some of these enzymes, the nuclease, for example,
may be concerned in the synthesis of nucleins and nucleoproteins
within the body, a process about which at present little or nothing
is known.

It is usually believed that the creatinin of the urine is formed
from the creatin found in muscular tissue and that the latter is

* See Abderhalden and Schittenhelm, "Zeit. f. physiol. Chem.," 1906,
xlvii., 452.

S64 NUTRITION AND HEAT REGULATION.

derived from a metabolism of the living muscular tissue, but no
entirely satisfactory demonstration of the correctness of these
views has been obtained (see p. 820).

The Specific Dynamic Action of Proteins. — This some-
what indefinite term is used by Rubner to designate the fact that
protein foods seem to stimulate the metabolic processes of the body
to a greater extent than the fats or carbohydrates. This pecu-
liarity may be demonstrated, for instance, in the case of a starving
animal living upon its own substance and metabolizing a certain
amount of its tissues daily. The amount thus metabolized may
be expressed in terms of the heat production and it represents the
minimal consumption of material requisite for the maintenance
of body-temperature and the other energy-needs of the body.
If this minimal daily consumption is expressed in calories and
the animal is given food containing the same amount of avail-
able energy the consumption of body material is not completely
covered, since the food leads to an increased total metabolism
which is especially marked in the case of proteins. Expressing the
minimal daily metabolism during starvation by 100, Rubner esti-
mates that the minimal amounts of the three foodstuffs requisite
to give a heat equilibrium would be for proteins 140.2, for fat 114.5,
and for sugar 106.4. The fact that protein food tends to increase
the total metabolism of the body has been explained by some
authors on the assumption that a greater amount of secreting and
muscular work is required for its digestion. The proteins are
retained for a longer time, for instance, in the stomach, and the
continued muscular movements of the organ involve, of course, a
consumption of tissue material. This explanation does not seem
to be entirely satisfactory and the term "specific dynamic action"
expresses the view that the protein food actually stimulates the
tissues to a greater metabolism, in somewhat the same way as in
the case of increased muscular work. Rubner's explanation of
this fact is that before protein can be used for the energy needs
of the body it must be split into a nitrogenous and anon-nitrog-
enous part. This splitting process liberates a certain amount
of heat, free heat as he calls it, which, while helping to keep up the
body temperature, is not utilizable for the energy needs of the
working cells. This amount of energy is, therefore, wasted, so
to speak, and more protein has to be taken to supply the body
than would be the case if all of its potential chemical energy were
utilizable. On the view of protein metabolism given above a
large part of this loss may be accounted for as is suggested by
Lusk,* by the process of deamidization of those amino acids

* For further discussion, sec Rubner, "Geaetze dee Energieverbrauchs,"

1002, or Lusk, " Elements of t be Science <>r Nul ril i<>n," Philadelphia, L906.

GENERAL METHODS HISTORY OF PROTEIN FOOD. 865

which are formed in digestion, but are not reconstructed into
protein. Thus one gram of alanin has a heat value of 4.37 cal.
and may be considered as giving one gram of lactic acid after
removal of its NH2 group — one gram of lactic acid has a heat
value of 3.66 cal., hence in the process 0.7 cal. of heat has been
liberated, a loss of about 16 per cent.

Nutritive Value of Albuminoids. — The albuminoid most fre-
quently occurring in food is gelatin. It is derived from collagen
of the connective tissue. Collagen of bones or of connective tissue
takes up water when boiled and becomes converted into gelatin.
We eat gelatin, therefore, in boiled meats, soups, etc., and, besides,
it is frequently employed directly as a food in the form of table
gelatin. Collagen has the following percentage composition: C,
50.75 per cent.; H, 6.47; N, 17.86; 0, 24.32; S, 0.6. It resembles
the protein molecule closely in percentage composition and, in
fact, is now classified as one of the varieties of protein. It would
seem that the tissues might use it as they do protein for the for-
mation of new protoplasm. Experiments, however, have demon-
strated clearly that this is not the case when it is employed without
other protein food. Animals fed upon albuminoids together
with fats and carbohydrates do not maintain nitrogen equilibrium.
The final result of such a diet would be continued loss of weight
and malnutrition and death. Some light is thrown upon the
inability of the gelatin to act as a tissue former by a considera-
tion of the split products formed from it in hydrolytic cleavage.
While it yields a number of the products usually given by the
proteins, there are others which are lacking, such as cystein
(thioaminopropionic acid), tyrosin (oxyphenylaminopropionic
acid), serin (oxyaminopropionic acid), and tryptophan (indol-
aminopropionic acid). On the hypothesis that proteins during
digestion are normally split more or less completely into then
constituent parts, and that the characteristic body-protein of the
animal is reconstructed synthetically by a new arrangement of
these groups, it is apparent that the gelatin, when used without
protein, may fail to furnish some of the groupings necessary to
such a synthesis. Gelatin is readily digested, gelatoses and
gelatin peptones and eventually some split products being formed;
these are absorbed and oxidized in the bod}*, with the formation
of C02, H,0, and urea. Gelatin serves, then, as a source of energy
to the body in the same sense as do carbohydrates and fats.
When any one of these three substances is used in a diet, the
proportion of protein necessary for the maintenance of nitrogen
equilibrium may be reduced greatly. Actual experiments have
shown that gelatin is more efficacious than either fats or carbo-
hydrates in protecting the protein in the body. The relative
55

S66 NUTRITION AND HEAT REGULATION.

value of fats, carbohydrates, and gelatin in protecting protein
from destruction in the bod)' is illustrated by an experiment
report ed by Yoit: A dog weighing 32 kgms. was fed alternately
upon protein and sugar, protein and fat, and protein and gelatin,
with the following result:

Nourishment (Gms.) Calculated Destruction of

Meat. Gelatin. Fat. Sugar. Flesh in Body (Gms.).

400 200 450

400 250 439

400 200 356

This greater efficacy of the gelatin is doubtless connected with
its nitrogen-containing groups and would indicate an ability to
partly replace protein material in its assimilative functions.
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. A number of observers have attempted to
determine experimentally just how far the protein of the food may
be replaced by gelatin without causing a loss of body-protein.
Munk states, from experiments upon dogs, that when about six-
sevenths of the nitrogen necessary to maintain equilibrium was
given in the form of gelatin, the animal could be kept in nitrogen
equilibrium for a few days at least. Murlin,* in more careful
experiments, has shown that if abundant carbohydrate food is
used a dog may be kept in nitrogen equilibrium at or near the
fasting level on a diet in which two-thirds of the protein (meat)
nitrogen is substituted by gelatin nitrogen. Kaufniannf claims
to have kept himself in nitrogen equilibrium for a short time upon
a diet in which no protein was contained, all the nitrogen being
supplied in the form of gelatin, together with small amounts of the
amino-acids, which are lacking in the gelatin molecule (cystin,
tyrosin, tryptophan).

The history of gelatin as a food is very interesting and, Indeed, instructive,
since it Berves or should serve as n warning againsl a premature application
of the results of scientific investigation. A condensed account of the subject
is given l<y Voi1 in Hermann's Handbuch der Physiologie, vol. vi., p. 396.

It would Kcr-m ilia i on account of the high nitrogen content of the gelatin and
the fact thai it is soluble, there was a tendency to attribute to it an unusual
nutritive value. The fact, too. that the gelatin could beobtainedfr bones

which otherwise were l.urned or thrown away was important in suggesting

a meant for the economical feeding of the poor. The matter was inquired
into by a committee during the French Revolution and subsequently by a

* Murlin. "American Journal of Physiology," L9, 285, 1907, and 20,234,
1907.

t Kaufinatui, "Pfltiger's Archiv f. d. ges. Physiol," 1906, cix., 140.

GENERAL METHODS HISTORY OF PROTEIN FOOD. 867

commission of the French Academy, who made favorable reports. The success
of d'Arcet, in making gelatin economically by a new process, led the Philan-
thropic Society of Paris to request the Academy of Medicine to investigate
whether gelatin is really a nutritious and healthy food. The Academy
appointed a commission for the purpose and the report of this commission,
published in the Annales de Chimie, vol. 92, 1814, was most enthusiastic.
They recommended gelatin as a most nutritious and healthful food, when its
natural insipidity was corrected by the addition of salts and savory herbs.
On the basis of this report the article was largely used in the nourishment of
hospital patients, but in course of time complaints became so emphatic that
doubt was again raised as to its real value. In fact, a reaction set in. The
second gelatin commission of the French Academy, 1841; a commission of
the Netherlands Institute, 1844, and a report from the Academy of Medicine,
Paris, 1850, all condemned gelatin as useless from the standpoint of nourish-
ment, and as injurious rather than beneficial. Thus, as so often happens,
public opinion oscillated from one extreme to the other. The true value
of the gelatin, as we understand it to to-day, was established by Voit's experi-
ments, but from the brief account given above it is evident that something
remains to be explained. It is not clear why it cannot be borne better in a
diet when used in quantity.

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 protein tissues of the body, and
possibly also from the body fat, although this latter source is
disputed. The supply of glycogen under normal conditions is
maintained chiefly by the carbohydrate food. As was explained
in the section on Digestion, the starches, sugars, gums, etc.,
which constitute the carbohydrate foodstuffs are eventually
absorbed into the blood as simple sugars, chiefly dextrose, but
probably also some levulose and galactose. These simple sugars
constitute the important glycogen formers. With regard to the
proteins there is still some difference of opinion as to whether all
of them 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 synthe-
sized to sugar in the liver, and thus become a possible source of
glycogen. Others hold that only those proteins, such as egg-
albumin, which contain a carbohydrate grouping in the molecule,
are capable of yielding glycogen in the body.* The store of
glycogen in the body is about equally divided between the liver
and the: muscular tissues, and it is estimated that in man each of
these di'i'ots may contain, at a maximum, about L50 gms. The
regulation of t be supply of sugar to the blood is usually attributed
to the liver. This regulation is adjusted so thai the percentage
of sugar in the blood is kept astonishingly constant, between
o.l and 0.2 per cent., tiol only during the conditions of ordinary
living, but under such an abnormal condition as prolonged starva-
tion. It is assumed thai this constancy of composition is effected
mainly by an enzyme formed in the liver cells, which converts the

■ 3ee Pfluger, in "Arcbiv I. < 1 i<- gesammte Physiologie, " 96, l, L903, for
literal lire and di cu ion.

CARBOHYDRATES AND FAT. 869

glycogen to dextrose in proportion as the sugar of the blood is
used up by the tissues.

The Intermediary Metabolism of the Carbohydrate in the
Body. — Eventually the carbohydrate of the body is oxidized in
the tissues with the formation of carbon dioxid and water. Much
uncertainty prevails, however, as to the steps and means by which
this oxidation is effected. Reference has already been made to the
important fact that the internal secretion of the pancreas is neces-
sary to this process (p. 849). According to Cohnheim's experi-
ments, this secretion furnishes an activating substance which
enables the enzymes of the muscles and other tissues to attack
the sug'ar. The sugar is probably broken down and oxidized by
the successive action of a number of enzymes, with the formation,
therefore, of a number of intermediate products, the entire process
being designated frequently by the term glycolysis. Our know-
ledge at present is not sufficient to warrant positive statements
concerning the exact nature of these intermediate processes. Two
general points of view have been advocated. According to some
observers the sugar molecule first undergoes a splitting process,
and the split products are subsequently acted upon by oxidases
and converted to carbon dioxid and water. The following steps
have been suggested.* First a cleavage to form lactic acid:

C6H1206 = 2(C3H603)

Dextrose. Lactic acid.

Then a second cleavage to form alcohol and carbon dioxid:
C3H603 = C03 + C2H5OH

Lactic acid. Ethyl alcohol.

Thus far the process would resemble that which takes place in
alcoholic fermentation, in which the sugar is broken down to
alcohol and carbon dioxid by the action of zymase. This primary
splitting action, in which only a small part of the chemical energy
contained in the sugar molecule is liberated in the form of heat,
is then followed by the strongly exothermic reactions of oxidation.
The alcohol is oxidized successively to acetic and formic acid and
finally to carbon dioxid and water. Others have assumed that the
sugar undergoes a series of oxidations, without preliminary cleav-
age, with the formation of such intermediate products as glycuronic
acid and oxalic acid, both of which are undoubtedly formed in the
body, since they are found in small quantities in the urine. A
series of oxidations may occur such as is represented in the follow-
ing formulas:

* See Biichner and Meisenheimer, "Berichte d. deutsch. Cheni. Gesell-
schaft," 38, 620, 1905; and Stoklase, ibid., p. 664.

870 NUTRITION AND HEAT REGULATION.

CH..OH

COOH

COOH

COOH

(CHOH)4

(CHOH),

(CHOH)4

COOH

COH

COH

COOH

Dextrose.

Glycuronic acid.

Saccharic acid.

Oxalic acid.

We are certain at present only of the fact that the final products
are carbon dioxid and water — that is, complete oxidation products
— and that in some way the internal secretion of the pancreas is
essential to the process.

Regulation of the Sugar-supply of the Body. — This regula-
tion is of the greatest importance to the body, since any distinct
increase in the percentage of dextrose in the blood, a condition
known as hyperglycemia, is followed promptly by glycosuria, that
is, the appearance of sugar in the urine. It has been suggested
that the regulation of the output of sugar from the liver is con-
trolled reflexly through the nervous system. Some evidence for
this view is found in the following facts: Bernard discovered (1855)
that a puncture of the medulla, made between the levels of origin
of the vagus and auditory nerves, causes the development of a
condition of glycosuria. This puncture, known as the "piqure"
or "sugar puncture," fails to cause glycosuria if the animal has been
starved previously so as to remove most of the glycogen from the
liver or if the splanchnic nerves have been cut. Moreover, stimula-
tion of various sensoiy nerve trunks, the vagus, for example, causes
the same phenomenon, and in human beings lesions of the central
nervous system may likewise develop a condition of glycosuria.
These results have been explained in two ways. The puncture or
sensory stimulation may act upon the vasomotor center of the
medulla, cause a dilatation of the blood-vessels in the liver, and
thus indirectly accelerate the output of sugar; or these stimuli may
act upon a distinct su^ar-regulating center and through it augment
directly the conversion of glycogen to sugar in the liver. According
to this latter view the efferent fibers from the center reach the liver
via the splanchnic nerves. If such a nervous mechanism exists
it affords ;i suitable means for the adjustment of the supply of
sugar to the needs of the tissues, particularly the muscles. The
contract ions of the muscles and the heart by exciting their contained
Sensory fibers mighl lie supposed to stimulate reflexly the sugar
center and thus provide an increased output of sugar in proportion
t<. the extent of the contractions (Tfliiger). While this theory is

attractive, it has not yet received definite experimental proof.

It i certain, however, that by some means, chemical or nervous,

ipply of sugar from (he liver is regulated, and that under

various unusual and pathological conditions this regulation is

broken down with the production of conditions of hyperglycemia
and glycosuria. It is interesting, from a physiological standpoint,
to recall that glycosuria may result temporarily from too great

CARBOHYDRATES AND FAT. 871

an ingestion of carbohydrate food (see Alimentary Glycosuria, p.
773). The liver in this case gets more sugar than it can convert to
glycogen, and an excess gets through into the general circulation.

Pancreatic Diabetes. — Some of the facts regarding this form
of diabetes are described on p. 849. The immediate cause of
the diabetes is the increased percentage of sugar in the blood
(hyperglycemia). This result finds its most probable explanation
in the view that the loss of the internal secretion of the pancreas
robs the tissues of their power to metabolize the sugar.

Diabetes Mellitus. — In this severe and usually fatal disease the
amount of sugar lost daily in the urine may be very large. In severe
forms of the disease practically all the carbohydrate of the food may
be eliminated in the urine in the form of sugar ,, and even when the
diet contains no carbohydrate, or during complete starvation, sugar
continues to be secreted in the urine in considerable amounts. In
these latter cases the sugar is supposed usually to have its source
in the proteins of the food or of the body, a view which is supported
by the fact that the amount of nitrogen and dextrose excreted in
the urine may exhibit a constant proportion to each other. The
ratio of dextrose to nitrogen (D : N) is given as 3.65 to 1.*
Special cases have been reported, however, in which the ratio
exceeded these figures. The general and specific symptoms observed
in diabetes mellitus closely resemble those observed upon dogs
suffering from pancreatic diabetes. It seems probable, therefore,
that in man the condition of diabetes may also be due in the first
place to some trouble in the pancreas which prevents it from giving
off its normal internal secretion. Whether or not the activity
of the pancreas is impaired in all these cases, the majority of those
who have studied the subject agree that the final difficulty lies
in the fact that the tissues, especially the muscular tissues, can
not utilize the sugar brought to them by the blood. Some writers
take an entirely different point of view, holding that the difficulty
lies not in the consumption of sugar by the tissues, but at the
other end, namely, in the proper handling or assimilation of the
sugar as it is absorbed from the alimentary canal. f But assuming
the correctness of the usual view, it has been a question as to what
part of the process of glycolysis is affected. According to experi-
mental results,! it would seem that the diabetic individual can
still oxidize substances, such as glycuronic acid or saccharic acid,
which are closely similar to the sugar in structure, and form
possibly normal intermediary products in its metabolism. It has

* Lusk, "Elements of the Science of Nutrition," Philadelphia, 1906.

t For this point of view, see Pavy, "Lancet," Nov. 21 and 28, and Dec. 12,
1908; and for literature on the metabolism of Diabetes, see Lusk, "Archives
of Internal Medicine," Feb., 1909.

J See Baumgarten, "Zeit., f. exp. Path. u. Therapie, " 2, 53, 1905.

872 NUTRITION AND HEAT REGULATION.

been suggested, therefore, that the difficulty lies in the preparatory
cleavage of the sugar, which fits it for oxidation. The enzymes
that produce this preliminary cleavage may be inactive. In
addition to the sugar found in the urine in diabetes, this secretion
may also contain considerable amounts of the acetone bodies,
namely, ,'-oxybutyric acid, aceto-acetic acid, and acetone. It
is probable that these bodies represent intermediary products
in the metabolism of the fats of the body which escape oxidation,
and they appear in the urine of the diabetic either because the
power of the tissues to oxidize their fatty foods has also become
impaired or, as seems possible in the beginning, at least, simply
because in the loss of the power to utilize the energy of the carbo-
hydrates the tissues consume more fat, and whenever the fat
consumption is large it is likely to be incomplete, that is, some of
the intermediary products fail of oxidation and pass into the
general circulation (see p. 875).

Phlorhizin Diabetes. — Phlorhizin is a vegetable glucoside ob-
tained from the roots of certain trees — e. g., apple, pear. When
injected into an animal it causes a glycosuria which is temporary,
but which may be renewed by repeated injections. Examination
of the blood in this case reveals the fact that the percentage of
sugar is not increased, so that the immediate cause of the glycosuria
is different from that responsible for the diabetes of man or of
animals without the pancreas. A satisfactory explanation of the
action of the phlorhizin has not yet been obtained, but it would
seem that the drug acts in some way upon the kidney itself— that
is, the tissues of the body are probably still able to metabolize the
sugar, but the blood is continually depleted of this substance
through the kidney ; it leaks off through the kidney faster than it
can be utilized by the tissues. The evidence at, hand seems to indi-
cate that the sugar (in part at least) exists in the blood in some
form of colloidal combination, and that under the influence of the
phlorhizin the kidney breaks up this combination and eliminates
the sugar.*

From this brief description of the fate of the carbohydrate
in the body it is evident that its history as a food-stuff might
he considered conveniently under three heads, namely, its supply,
its storage, and its consumption. The supply is regulated by the

diet. In the usual did carbohydrate constitutes the chief and
also the most variable factor. Us cheapness, its ease of digestion
and of consumption make it the most convenient and economical
source of energy to the body. When our energy needs are large,
.1- in muscular work, the carbohydrate portion of the diet is
* For more complete details and the literature, see Macleod, "The Metab-
oli m of tin- Carbohydrates" in "Recenl Advances in Physiology," London
and New York, 1906, and Lusk, loc. tit.

CARBOHYDRATES AND FAT. 873

increased; when the energy needs are small, as in a sedentary
life, the amount of carbohydrate is reduced. The storage of
carbohydrate in the body is provided for temporarily by the
glycogenetic function of the liver and the muscles. This function
may be deranged for a time by injuries to the central nervous
system, in which case hypoglycemia and glycosuria result. Or
the gbycogenetic function may be inadequate to handle all the
sugar absorbed from the alimentary canal (alimentary glycosuria),
and in this case also there is a temporary hyperglycemia and
glycosuria. At the consumption end the amount of suger
destroyed is controlled by the energy needs of the tissues, espe-
cially of the muscles. Failure to destroy the sugar at this point
brings on also a hyperglycemia and glycosuria of a more serious
nature.

Our sugar-regulating mechanism in fact may break down in
one of four general ways, which may be tabulated briefly as
follows:

1. Conversion of sugar to glycogen (liver) breaks down in
alimentary glycosuria.

2. Conversion of glycogen to sugar (liver) breaks down in
injuries to the central nervous system, etc.

3. Glycolysis of sugar (muscles and other tissues) breaks down
in diabetes mellitus and pancreatic diabetes.

4. The normal impermeability of the kidney breaks down in
phloridzin diabetes.

Functions of the Carbohydrate Food. — The general value of
the carbohydrate food to the organism may be summarized as
follows: (1) It furnishes a source of energy for the needs of the
tissue cells and particularly for muscular work. It will be remem-
bered that the glycogen of a muscle disappears in proportion
to the work done by the muscle, and, indeed, prolonged muscu-
lar 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 oxida-
tion of the sugar furnishes energ}r 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

S74 NUTRITION AND HEAT REGULATION.

muscles during contraction take the form of heat, and even dur-
ing muscular rest the condition of tone is probably attended by a
constant oxidation of this material. (3) The oxidation of the sugar
protects the protein of the bod}'. Attention has already been
called to the fact that an animal may be kept in nitrogen equilibrium
on a relatively small protein diet provided carbohydrates (or fats)
are also eaten. One may say. in fact, that as the carbohydrate food
is increased the protein food may be diminished, down to a certain
irreducible minimum which is probably the amount necessary
for the reconstruction of new tissue. From the chemical com-
position of carbohydrates it is evident that they alone cannot serve
to build up protoplasm. An animal fed on carbohydrate food
alone, no matter how abundant the supply, would eventually
starve to death. Within certain limits, however, the carbohy-
drates are protein sparers ; the energy provided by their oxidation"
keeps up the supply of heat and enables the muscles and the other
tissues to obtain the energy necessary for their special kind of
work, and to this extent the carbohydrates protect the living
protein from consumption and enable us to reduce the protein
material in our diet. Experiments show, in fact, that carbo-
hydrate is much more efficient as a sparer of protein than fat.
An animal fed on carbohydrates alone loses less protein from the
body than when kept on a fat diet containing the same amount of
heat energy, and the minimal amount of protein upon which the
body may be kept in nitrogen equilibrium is much lower when
the protein is combined with an abundant supply of carbohydrate
than in the case of a diet of protein and fat together. It would
seem that the body must always have sugar to oxidize. If this
material is not furnished in the food, it is obtained by breaking
down the body protein itself, as is indicated by the continued
formation of sugar in diabetes and also by the fact that even in
prolonged starvation the sugar contents of the blood are kept at
a normal level. (4) Any excess of carbohydrate, taken as fond,
beyond the power of the tissues to store as glycogen may be
synthesized to form tat. Nutritional experiments, described
below, leave no doubt that the fat of the body may ho formed
from carbohydrate food, it is stated that the fat of the body
having this origin, so-called carbohydrate fat, is of a more solid
consistency than the tat derived from other sources.

Nutritive Value of Fats. — The fats of food are absorbed into
the lacteals, chiefly as neutral fats the so-failed chyle fat,. The
chyle fa1 is transported to the blood by way of the; great thoracic

duct, and after it is poured into the Mood it remains in the cir-
culation for a considerable lime, being slowly picked out, by the

tissues which can use it in their metabolic processes. Within

CARBOHYDRATES AND FAT. 875

these tissues it is oxidized to supply the energy needs of the cells.
The final products of the oxidation are the same as when fat is
burnt outside the body — namely, C02 and H20 — and a corre-
sponding amount of energy must be liberated. Speaking generally,
then, the essential nutritive value of the fats is that they furnish
energy to the body, and, from a chemical standpoint, they must
contain more available energy, weight for weight, than the proteins
or the carbohydrates. In a well-nourished animal a large amount
of fat is found normally in the adipose tissues, particularly in the
so-called "panniculus adiposus" beneath the skin, in the folds
of the peritoneum, etc. Physiologically, this body fat is to be
regarded as a reserve supply of nourishment. When fatty food
is eaten and absorbed in excess of the actual metabolic processes
of the body, the excess is stored in the adipose tissue as fat, to be
drawn upon in case of need — as, for instance, during partial or
complete starvation. A starving animal, after its small supply
of glycogen is exhausted, lives entirely upon body proteins and
fats; the larger the supply of fat, the more effectively will the
protein tissues be protected from destruction. In accordance with
this fact, it has been shown that when subjected to complete
starvation a fat animal survives longer than a lean one. Our
supply of fat is called upon not only during complete abstention
from food, but also whenever the diet is insufficient to cover the
oxidations of the body, as in deficient food, sickness, etc.

The Intermediary Metabolism of the Fat. — 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. — 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. 71S). 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

876 NUTRITION AND HEAT REGULATION.

takes place, but through how many stages is not known. It seems
probable that the long carbon chain of the fats (stearic acid = CH3-
(CH.,\,.COOH> is deprived in succession of its carbon atoms by-
oxidation, with the formation of simple fatty acids, but little
positive evidence has been obtained of intermediate products.
Perhaps the most significant fact known bearing upon this point
is that under conditions which involve a large destruction of fat
in the body, as in starvation, fevers, and especially in diabetes,
/9-oxybutyric acid together with aceto-acetic acid and acetone are
excreted in the urine. These three substances are designated as
the acetone bodies, and their appearance in the urine makes the
condition known as acetonuria. The oxybutyric acid may be
regarded as the source of the other two. as may be inferred from
their formulas. ,5-oxybutyric acid = CH3CHOHCH2COOH. By
oxidation this yields aceto-acetic acid. CH3COCH2COOH, and
this by loss of CO, is converted to acetone, CH,C~OCHr The
evidence seems to show that the oxybutyric acid arises from the
fats, and it represents probably one of the simpler fatty acids
formed in the intermediate metabolism of the fats. There is
some indication also that the liver cells, along with their numerous
other functions, are concerned in some of the intermediary stages
of fat metabolism. Under abnormal conditions, such as phos-
phorus-poisoning, the fat of the adipose tissues is transported
to the liver, and it is suggested that this transportation may be
a normal process, that before the neutral fat is actually oxidized
or is converted into the phosphorus-containing fats of the tissues
(lecithin, etc.), it is acted upon by the liver, possibly in the way of
desaturating the fatty acids, since the fat actually found in the
liver contains more unsaturated fatty acids than the storage
fat of the adipose tissues. Whatever may be the real nature of
the connection, both microscopic and chemical evidence indicates
that the liver is concerned in some phase of fat metabolism.*

According to the experiments of Knoopf the oxidation of the fatty acids
begins with the carbon occupying 1 1 1 * - beta position. In the case of butyric
acid this would result al once in the formation of /i-oxybutyr ic acid. In the
Case of higher fatty acids containing an even number of carbon atoms a

Bunilar process would result in the formation, first, of butyric acid and then

of the '-oxybutyric acid. The series of oxidations of caproie acid may be

represented as follows: %

(\ll;uil,r!l,rooii + o = C,H,CHOHCHjCOOH
Caproie acid. Oxycaproic acid.

• 1 1 / 1 1 o 1 1 u i I zoo 1 1 f- 6o - cjicooii i 2HaO + 2C02

Butyric acid.

CH,CHjCH,COOH t 0 - CH,CHOHCH,,COOH
Butyric acid. /9-oxybutyric acid,

* For discussion and facts, sec Leathes, "Lancet," Feb. 27, L909.

1 Knoop, " Ilofmeistcr's licit rage, " 6, 150. L904.

X Lusk, "Archives of internal Medicine/' Feb., 1909.

CARBOHYDRATES AND FAT. 877

On this view, fatty acids with an odd number of carbon atoms cannot yield
/3-oxybutyric acid. Some of the amino-acids derived from the hydrolysis of
protein may, however, serve as a source of this acid, leucin, for example, so
that in this way the protein of the food as well as the fat may be responsible
for the presence of this acid in diabetes. The inability of the tissues to oxidize
sugar in the case of diabetes is associated in many instances with a loss of the
power of oxidizing the /3-oxybutyric acid, but the reason for this relationship
is not clear. To the extent that the /3-oxybutyric acid is not burnt and not
excreted, it accumulates in the body and produces a condition of acidosis which,
in turn, is responsible for the development of diabetic coma.

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 ox each species of
animal is more or less peculiar, the fat of the sheep having a higher
melting point than pork fat, and both differing in composition from
the fat taken as food. "In hay or the other fodder of oxen no
beef suet exists, and no hog's lard can be found in the potato refuse
given to swine." He was led to attribute the source of body fat
chiefly to the carbohydrate food, and this belief agreed well with
the experience of agriculturists as to the use of such foods in fatten-
ing animals for market. This view, in turn, was displaced by the
theory of Voit, supported by elaborate feeding experiments. Voit
believed that the fat of the body is formed mainly or entirely from
the protein of the food, the carbohydrate and the fat of the diet
being useful only to protect a part of this protein from oxidation.
Voit's experiments have been shown by Pniiger to have been based
upon erroneous analyses of the meat used in his experiments. Voit
assumed that in this meat the ratio -<j- 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 Irhe
food, especially in herbivora, in whose diet this foodstuff forms
such a large part. Whether under any circumstances the pro-
tein food may also serve as a source of body fat is still an open
question. According to the view of protein metabolism given
in the preceding pages, the possibility of a formation of fat from
protein food must be held in view. So far as the amino-acids

* Pfliiger, "Archiv f. die gesammte Physiologie, " 51, 229, 1892, and 77,
521, 1899.

878 NUTRITION AND HEAT REGULATION.

formed from the food protein during digestion are not reconstructed
into the body-protein of the animal, they are deamidized, ami the
organic acid grouping left may be converted to sugar and glycogen,
hence probably also to fat. The modern point of view, however,
seems clearly to be that body fat is formed in the first instance
from food fat and food carbohydrates.

Origin of Body Fat from Food Fat. — The first proofs that
the food fats ma}' 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.* Linseed oil, rape-seed oil, and mutton-fat
were used in these experiments. Secondly, it has been made
probable by feeding experiments that the normal fat of the food
undergoes a similar fate. Thus, Hofmann used a dog weighing
26 kgms. and allowed it to starve until its weight was reduced to
16 kgms. It was then fed for five days on a little meat and large
quantities of fat. At the end of that time it was killed and analyzed.
The body contained 1353 gms. of fat, of which only 131 gms. could
have come from the protein used, assuming that this material
can serve as a fat former. Much of the fat found, therefore, was
probably derived from the fat of the food.

Origin of Body Fat from Carbohydrates. — That the body
fat may have this origin has been made probable or certain by
feeding experiments. Thus, Rubner fed a dog (5.89 kgms.) for
two days on a diet of sugar, starch, and fat whose total carbon
content was equal to 176.6 gms. During this period the animal
excreted 87.1 gms. of carbon. There were retained in the body,
therefore, 89.5 gms. carbon. The fat fed, 4.7 gms., contained
(4.7 X 0.77) 3.6 gms. C. The total nitrogen excreted during this
period was 2.55 gms., which indicated a metabolism, therefore, of
16 gms. (2.55 X 6.25) of body protein. Making the improbable
assumption that all of the carbon of this protein was retained in
the body, this would account for 8.32 gms. C (16 X 0.52); so that
:;.() 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 oidy as

glycogen or fat. Allowing for the greatest possible storage of

glycogen, 78 gms. or 34.6 gms. C, there would still remain 42. 0 gms.
of (', which could have been retained only as fat. Numerous other

fattening experiments of different kinds have been made in which
it has been shown that the fat laid on by the animal could not be

accounted for by the fat of the food, nor by assuming with Voit that

•Lebedeff, "Centralblatt t die med. Wise.," 1881, and Munk, " Vir-
chow'e Archiv," 95, 407, 1884.

CARBOHYDRATES AND FAT. 879

it originated from the protein. The combined testimony of these
experiments have satisfied physiologists that the tissues can pro-
duce fat from sugar. The chemistry of the change is not understood
and cannot be imitated in the laboratory.

The Source of Body Fat in Ordinary Diets. — For the pur-
poses of demonstration the experiments made to prove the origin
of body fat from carbohydrate or the fat of food have made use
of abnormal diets and conditions. It would be a matter of practical
interest to ascertain whether upon normal diets the fat of the
body arises more easily from the fat or from the carbohydrate of
the food. While the question is one to which a positive answer
cannot be given, it seems to be probable that the result varies with
conditions and the nature of the animal. Experience seems to
show that carnivorous animals can be fattened more easily on a
fat diet, herbivora on a carbohydrate diet. In animals, like our-
selves, there is reason to believe that the carbohydrates are more
easily and more quickly destroyed in the body than the fats, and
that, therefore, the latter may be more readily deposited in the tis-
sues, although an excess of carbohydrate beyond the actual needs
of the body will also be preserved in the form of fat or glycogen.*

The Cause of the Deposit of Body Fat — Obesity. — Our
experience shows that individuals differ greatly in the ease with
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 to a small
extent as glycogen, but chiefly as body-fat. As stated above, this
holds true, especially for fat and carbohydrate foods, which, speak-
ing generally, are the variable parts of our diet. A diet which will
give such an excess to one individual, may in the body of another
of the same weight be all consumed. The oxidizing or metab-
olizing 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. Fun-
damental 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
fat or carbohydrate 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

* Consult Rosenfeld, "Ergebnisse der Physiologie," vol. i., part i, 1902.
Complete literature.

880 NUTRITION AND HEAT REGULATION.

opposite effect. Men who lead a very muscular life — farmers,
fishermen, etc. — are rarely disposed to accumulate fat to a notice-
able degree. So also the use of alcoholic beverages may indirectly
favor accumulation of fat, partly because the oxidation of the
alcohol protects the fats and carbohydrates from oxidation, and
partly also, perhaps, because long-continued use of alcohol may
depress the oxidizing capacity of the tissues. The tendency to
form fat may exhibit itself in some cases to such an -extent as to con-
stitute an almost pathological condition. Obesity may be coun-
teracted by altering the mode of life, especially by taking much
muscular exercise, and by reducing the diet, so that the total amount
of calories represented do not exceed one-half to three-fifths that
recognized as the usual average (see p. 900). The diet for such
purposes should not only be reduced in amount, but should be as
free as possible from excess of fats and carbohydrates, consisting of
such material as eggs, fish, lean meat, salads, fruits, etc.*

Summary of the General Functions of Fat. — The general
functions fulfilled by the fats may be summarized briefly under
the following heads: (1) It provides a store of reserve food which
is used by the body in case of deficiency of food or complete starva-
tion. The fattening of hibernating animals before their winter
sleep and the humps of the camel give conspicuous examples of this
peculiarity. (2) By its oxidation in the body it furnishes a part
of the heat energy necessary to maintain the body temperature.
On account of its high combustion equivalent (1 gm. of fat yields
9.3 Calories) fat is very effective in this respect. Inhabitants
of cold regions choose a diet rich in fat. (3) It is a protein saver.
Like the carbohydrate food, its oxidation protects the protein from
consumption. In starvation, therefore, the amount of protein
destroyed daily is smaller as long as any fat remains, and, under
ordinary conditions of life, the larger the amount of fat in the diet,
the less the amount of protein necessary to maintain the body
in nitrogen equilibrium. Experiments show that in this respect
the fat is not, so effective as an equivalent amount of carbohydrate
food. The difference is referable to the greater difficulty of

dation of the fatty material.

* For practical directions concerning the breatmenl of obesity by dieting
eeeGautier, " [/alimentation et les regimes," Paris, L904.

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 in-
clude the bones, which are rich in mineral matter, the average
amount of ash in the body amounts to about 4.3 to 4.4 per cent,
of its weight. The bones, however, in the adult contain most of
this ash (five-sixths). In the soft tissues, like the muscle, the ash
constitutes about 0.6 to 0.8 per cent, of the moist weight. The
ash consists of chlorids, phosphates, sulphates, carbonates, fluorids,
or silicates of potassium, sodium, calcium, magnesium, and iron;
iodin occurs also, especially in the thyroid tissues. In the liquids
of the body the main salts are sodium chlorid, sodium carbonate,
sodium phosphate, potassium and calcium chlorid or phosphate.
In considering the organic foodstuffs weight was laid upon their
value as sources of energy, as well as upon their function in con-
structing tissue. The salts have no importance from the former
standpoint. Whatever • chemical changes they undergo are not
attended by any liberation of heat energy — none at least of suffi-
cient importance to be considered. They have, however, most
important functions. They maintain a normal composition and
osmotic pressure in the liquids and tissues of the bod}', and by
virtue of their osmotic pressure they play an important part in
controlling the flow of water to and from the tissues. Moreover,
these salts constitute an essential part of the composition of living
matter. In some way they are bound up in the structure of the
living molecule and are necessary to its normal reactions or irrita-
bility. Even the proteins of the body liquids contain definite
amounts of ash, and if this ash is removed their properties are
seriously altered, as is shown by the fact that ash-free native pro-
teins lose their property of coagulation by heat. The globulins
are precipitated from their solutions when the salts are removed.
The special importance of the calcium salts in the coagulation of
blood and the curdling of milk has been referred to, as also the
peculiar part played by the calcium, potassium, and sodium salts
in the rhythmical contractions of heart muscle and the irritability
of muscular and nervous tissues. The special importance of the
56 881

sv- NUTRITION AXD HEAT REGULATION.

iron salts for the production of hemoglobin is also evident without
comment. There can be no doubt, in fact, that each one of the
salts of the body has a special nutritive value and a special met-
abolic history. The time will doubtless come when the special
importance of the potassium, sodium, calcium, and magnesium will
be understood as well, at least, as we now understand the signifi-
cance of iron, and quite possibly this knowledge will find a direct
therapeutic application, as in the case of iron.* .

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 wrhich 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 10 to 20 gms. a day. This amount seems to be in excess
of the actual necessities of the body, since on experimental diets
individuals have been kept in good condition when the total
content in sodium chlorid was reduced to one or two grams.
This desire for salt is exhibited also by many animals. The
farmer provides sail for his slock and wild animals visit the salt-
licks at intervals. Bunge lias called attention to the fact that
among men and animals the desire lor salt is limited, for the most,

pari at least, t" those thai use vegetable food. From the accounts
of travelers he shows that when a purely animal diet is used there
is no desire for Bait; hut on a vegetable diet there is acravingfor
it which may become very intense and unpleasant when circum-
stances prevenl its being obtained. He offers an ingenious

* For :i brief summary of facte and speculations, sec Allia and Neuberg,
"Pbysiologie a. Pathologic des Mineral-Stoffwechsels," 1906.

INORGANIC SALTS, STIMULANTS, AND CONDIMENTS. 883

explanation for this relation. Most vegetables 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 potas-
sium 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.* K6ppe,f on the contrary, emphasizes the
fact that while vegetable foods have much ash, most of it is in
organic combination and not in diffusible form. Vegetable food
contains but little salt in soluble form as compared with animal
foods, hence the necessity of adding sodium chlorid. The con-
tent of the blood in sodium chlorid remains remarkably constant.
When an excess is taken in the food it is removed by the kidneys.
On a salt-free diet or in starvation the amount of sodium chlorid
secreted in the urine soon falls to a low figure (0.6 gm.), showing
that the tissues are holding on to this constituent. It cannot be
doubted, however, that under ordinary conditions we use salt in
quantities much larger than 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 satisfactory 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. 549).
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

* For an interesting discussion, see Bunge, "Physiologie des Menschen, "
vol. ii., p. 103, 1901.

t Quoted from Alba and Neuburg.

^s4 NUTRITION AND HEAT REGULATION.

that some calcium is constantly eliminated from the inner surface
of the intestine. The amount is small, not exceeding perhaps 0.15
to 0.16 grams per day. There is some evidence that the amount
of calcium in the tissues increases with age. This is certainly
true of the bones, which become exceedingly brittle in advanced
life, and is evident also in the arteries, whose elasticity diminishes
as the calcium salts deposited in their coats are increased. Under
pathological conditions deposition of calcium salts (calcium car-
bonate) in the tissues may be markedly increased, as is shown
by the condition of the arteries in arterial sclerosis and the con-
dition of the crystalline lens in senile cataract.

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 contain iron in milligrams, as follows :

White of egg trace Apples 13

Rice 1 to 2 Cabbage (green leaves) ... 17

Wheat flour (bolted) . . 1.6 Beef '. 17

Cows' milk 2.3 Asparagus 20

Potatoes 6.4 Yolk of egg . . '. 10 to 24

Peas 6.2 to 6.6 Spinach 33 to 39

Carrots 8.6

In conditions of malnutrition, particularly in the simple anemias,
it becomes necessary to select a diet with reference to its contents
in iron or to add iron deliberately to the diet. Therapeutically
iron may be given in the form of simple salts with organic or mineral
acids or in more complex organic combination. There has been
much controversy as to whether the body is capable of taking
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 heniatogen. 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 iii the U-crs rather than in the urine. The experiments
Of \ oit upon isolated loops of the intestine, referred to above, show

thai 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

INORGANIC SALTS, STIMULANTS, AND CONDIMENTS. 885

takes place, as to its final stages, in the red marrow, but it is possible
that other organs may take part in the formation of intermediate
products. As regards its elimination, we know that the breaking
down of the hemoglobin (formation of bile pigments) occurs prob-
ably in the liver, but the final excretion of the iron takes place
mainly through the walls of the intestine.

Accessory Articles of Diet. — Under this general term we may
include all those bodies classed as condiments, flavors, and stimu-
lants, which we habitually take in our diet in order to enhance the
attractiveness of the food. These substances may or may not
have some heat value to the body — that is, they may undergo
oxidation with the liberation of heat energy; but, in general, their
value in nutrition is due to other properties.

The Flavors and Condiments. — Perhaps the most important
influence exerted by these bodies is that by making the food appe-
tizing they increase the secretion of gastric juice. The origin of
the so-called psychical secretion has been described (p. 746), 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.

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. 747). Meat extracts of various
kinds contain secretogogues which stimulate the gastric glands to
secretion. In themselves they may contain very little actual
foodstuff. Liebig's extract contains some protein, gelatin, and gly-
cogen, which form an actual nourishment, but its specific value
as a gastric stimulant depends upon other constituents, possibly the
nitrogenous extractives, — creatin, xanthin, camin, 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:

SS6 NUTRITION AXD HEAT REGULATION.

HX- CO CHaX— CO

CO C— NH CO C— N<CHs

\CH —I- II -^°H

[X— 0— n'

//^1X CH3X-C— X

HX

Xanthin. Caffein.

This alkaloid has a diuretic action on the kidneys and a stimulating
effect on the nerve centers, as is illustrated by its effect in raising
blood-pressure by an action on the vasoconstrictor center. The
influence of tea and coffee in preventing sleepiness may be referred
to this action on blood-pressure. The use of these substances,
according to general experience, augments muscular energy and
diminishes the sense of fatigue. Cocoa, or the chocolate made
from it by the addition of sugar, contains considerable nourish-
ment in the form of fats, carbohydrates, and proteins, but its stimu-
lating effect is referred to the alkaloid theobromin or dimethyl-
xanthin, and to some extent possibly to the essential oils developed
in roasting. The theobromin exerts stimulating effects similar to
those of the caffein, and experiments indicate that in moderate
doses of from 20 to 30 grams per day cocoa has no perceptible
injurious effect. The methylxanthins are in part oxidized in
the body and in part (one-third) excreted in the urine.

Alcohol. — The physiological effects of alcohol are of peculiar
interest to mankind, owing to its widespread use, and especially
to the disastrous results following its intemperate consumption.
Those who employ it in excess are in danger of acquiring an alco-
holic thirst or habit toward which the body possesses no counter-
acting regulation. When food is eaten in excess we experience a
feeling of satiety which destroys the desire for more food, and the
same regulation prevails in the case of water. With alcoholic
drinks, however, the desire may continue long after the alcohol
taken has begun to exert an injurious action upon the tissues
The evil effects of excessive use of alcohol are so continually demon-
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
re lilting from excessive doses. On the other hand, it is known
that many individuals use alcohol in moderate doses throughout

lifewit h no not iceably evil result, bu1 , on the contrary, with possible

♦ See Welch. '''I'll'' Pathological Effects of Alcohol," in "Physiological
A peel of the Liquor Problem," vol. ii., 1903.

INORGANIC SALTS, STIMULANTS, AND CONDIMENTS. 887

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, but the experimental evidence is of an uncer-
tain nature. Some observers have claimed that the reaction
time is diminished after the use of alcohol, but most of the recent
investigation goes to show that in the work of skilled labor, in
which the neuromuscular machinery is involved, alcohol even
in small quantities decreases the efficiency.* It has been sug-
gested, therefore, that as regards the higher nerve centers it acts
from the beginning as a narcotic or paralysant to the inhibitory
centers. By thus removing inhibitory control there is an apparent
increase in activity which is not due to a direct stimulating effect.
On other mechanisms different results are reported. Thus it is
stated that the secretion of the gastric and of the pancreatic juice
is markedly increased by the use of alcohol in samll doses, so far,
at least, as the water secretion is concerned. The content of the
secretion in digestive ferments seem to be diminished. 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 dilatation of the skin vessels, giving
a feeling of warmth and leading to increased loss of heat; but
whether this effect is due to a stimulation of the vasodilator centers
or, as seems more probable, to a narcotic or depressing action
upon the vasoconstrictor centers has not been definitely demon-
strated. The experience of explorers bears out the general view
that under conditions of stress and of maintained exertion alcohol
is of little value as a stimulant to the neuromuscular apparatus.
Whatever action it has in this direction is temporary. After the
day's 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-

* For literature and discussion, see Abel, "The Pharmacological Action of
Alcohol," in "Physiological Aspects of the Liquor Problem," vol. ii., 1903;
and Horsley and Sturge, "Alcohol and the Human Body," 1907.

888 NUTRITION AND HEAT REGULATION.

jurious effect upon the tissues, and moreover a material whose
consumption protects some of the other foodstuffs — fats, carbo-
hydrates, and protein — from destruction. In the first place, there
is no doubt that alcohol is oxidized in the body. Various observers
estimate that as much as 90 to 98 per cent, of the alcohol absorbed
is destroyed.* Since 1 gm. of alcohol, when burnt, yields 7 calories
of heat, it is evident that its oxidation in the body must yield a
large supply of heat energy. The question arises whether this
oxidation of the alcohol occurs in addition to the normal metab-
olism of the protein and non-protein foodstuffs, or whether it pro-
tects and takes the place of these foodstuffs. With regard to the
non-proteins a number of observers have attempted to determine
the point by ascertaining the total carbon excretion during an
alcohol period. If the usual amount of material is burnt, and the
alcohol in addition, it is evident that the carbon excretion should be
markedly increased. Most observers, however, find that it re-
mains practically the same. Such results as the following have
been obtained:

, t, ... f Alcohol-free days. . 251.9 ems. carbon.
At water and Benedict | Ak.ohol dayg * 238.5 "

— 13.4 "

T3. f Alcohol-free days. .212.58 gms. carbon.

BJerre I Alcohol days ...... 220.84 "

8.26 "
,,, / Alcohol-free days. . 214.83 gms. carbon.

u"!';i" I Alcohol days 220.87 "

: 6.04 "

These results indicate that the alcohol is used by the body in place
of the other carbon-containing foodstuffs. Geppert and Zuntz have
also found that on alcohol days there is no material increase in
the carbon dioxid eliminated or the oxygen absorbed.

Theoretically if the alcohol takes the place of the other material the
amount of carbon dioxid excreted should be diminished. One gram <>f
alcohol when oxidized furnishes as much heat as 1 .7 gms. of sugar or 0.75 gm.
of fat. But I gm. of alcohol when burnt yields only 1.91 gms. of ('<>.,, while
1.7 gin-, of sugar yield 2.77 gms. CO,, and 0.75 gm. of fat, 2.13 gms. of CO,.
If f.-it were replaced by the alcohol the amount of COa should be reduced
about L0 per cent., while if the sugar were replaced the reduction should
amount i" 31 per rent. Thai such a reduction is not actually observed is
ined by the fact thai the alcohol leads to more muscular activity and
i | heal from the congested skin, thus indirectly augmenting
tin- i) cidatione of I be body.

To determine whetherthe combustion of the alcohol protects the
protein material from metabolism to the same extent as is done by
carbohydrates and fats, experiments have been made in which the
individual was broughl into nitrogen equilibrium on a mixed diet.

, and Benedict, Bulletin 69, I oited States Department of
Agriculture, L889.

INORGANIC SALTS, STIMULANTS, AND CONDIMENTS. 889

Then for a given period a portion of the carbohydrate was omitted
and alcohol in isodynamic amounts was substituted. The result
was an increase in the nitrogen excretion, showing that the alcohol
did not protect fully the protein tissue. In a third period the
first diet was resumed, and after nitrogen equilibrium had again
been established the same proportion of carbohydrate was omitted
from the diet, but this time alcohol was not substituted. If the
diet was poor in protein it was found that less protein was lost from
the body when the alcohol was omitted than when it was used.
Hence alcohol not only did not take the place of the carbohydrate
in protecting the protein, but it actually caused an increased pro-
tein consumption.* Other observers (Neumann, Rosemann f ) have
found that, although the effect just described may occur in the first
few days, yet if the alcohol diet is maintained the injurious effect
exercised by it disappears, the body ceases to lose its protein tissue,
and may even lay on protein. These results, taken with those
given above, indicate, therefore, that the alcohol may actually
take the place physiologically of fat or carbohydrates as a source
of energy and as a protector of protein metabolism. J Under these
circumstances, therefore, it acts as a true foodstuff. It is perhaps
scarcely necessary to emphasize the fact that this scientific con-
clusion does not mean that alcohol can be regarded as a prac-
tical food. Its expensiveness, its dangers when the dose is too
large, etc., prevent us from regarding it in this light. As Rosemann
says, however, it is possible that on account of its ready absorption
and palatableness it may form a useful substitute for the solid,
non-nitrogenous foodstuffs in sickness. This suggestion seems
to be supported by many reports of cases in which alcohol has served
as the sole or main nutriment during the critical periods of fevers
and in other conditions, but it needs to be tested more carefully by
direct experiments before it can be accepted generally for prac-
tical purposes. In line with this suggestion there are some
results upon diabetic patients (Benedict and Torok) which indi-
cate that in this condition alcohol used as a food diminishes the
production of acetone bodies and protects the protein.

'* See Miura, "Zeitschrift fur klin. Medicin," 20, 1892. _
f See Rosemann, "Archiv f. die gesammte Physiologie, " 86, 307, 1901,
and 100, 348, 1903, for discussion and literature.

| See also Atwater and Benedict, "Memoirs of National Academy of
Sciences,'' 1902; and Atwater, "The Nutritive Value of Alcohol," in "Physi-
ological Aspects of the Liquor Problem," vol. ii., 1903.

CHAPTER L.

EFFECT OF MUSCULAR WORK AND TEMPERATURE ON

BODY METABOLISM— HEAT ENERGY OF

FOODS— DIETETICS.

The Effect of Muscular Work. — It is a matter of common
knowledge that muscular exercise increases the food consumed,
and scientific experiments have shown that it greatly augments
the consumption of material in the body. Physiologists have
attempted to determine which of our energy-yielding foodstuffs
is directly affected by muscular activity. A brief statement of
the development of our knowledge upon this point will make clear
our present theories. According to Liebig, our foods fulfill two
general purposes in the body : they are burnt to supply heat, respira-
tory foods — fats, and carbohydrates, or they are used to construct
tissue, plastic foods — proteins. It seemed to follow, from this
generalization, that muscular tissue in activity should use protein
material, and it was believed at that time that the metabolism of
protein furnished the source of muscular energy. That it is not
the sole source was demonstrated by the interesting experiments
of lick 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, kick'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,
v.,,- estimated at 30,000 kilogrammeters. There was, moreover,
a certain amount of muscular work performed in the move-
incut- 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
hour.- afterward their food was entirely non-nitrogenous, so that

the urea eliminated came entirely from the protein of the body.

i [i '.hen the urine was collected and the urea estimated,

it was found that the energy contained in the protein destroyed,

reckoned as heal 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

890

EFFECT OF MUSCULAR WORK AND TEMPERATURE. 891

the experiment has been accepted as showing conclusively that the
total energy of muscular work does not come necessarily from the
oxidation of protein. Later experiments made by Yoit upon a
dog working in a tread-wheel and upon a man performing work
while in the respiratory chamber gave the surprising result that
not only may the energy of muscular work be far greater than the
heat energy of the protein simultaneously oxidized, but that the
performance of muscular work within certain limits does not
affect at all the amount of protein metabolized in the body, since
the output of urea is the same on working days as during days of
rest. Careful experiments by an English physiologist, Parkes, made
upon soldiers, while resting and after performing long marches,
showed also that there is no distinct increase in the secretion of urea
after muscular exercise. It followed from these latter experiments
that Liebig's theory as to the source of the energy of muscular
work is incorrect, and that the increase in the oxidations in the
body, which undoubtedly occurs during muscular activity, must affect
only the non-protein material — that is, the fats and carbohydrates.
Subsequently the question was reopened by experiments made
under Pfliiger by Argutinsky.* In these experiments the total
nitrogen excreted was determined with especial care in the sweat
as well as in the urine and the feces. The muscular work done
consisted in long walks and mountain climbs. Argutinsky found
that work caused a marked increase in the elimination of nitrogen,
the increase extending over a period of three days, and he estimated
that the additional protein metabolized in consequence of the work
was sufficient to account for most of the energy expended in per-
forming the walks and climbs. A number of objections have been
made to Argutinsky's work. It has been asserted that during his
experiment he kept himself upon a diet deficient in non-protein
material, and that if the supply of this material had been sufficient
there would not have been an increase in protein metabolism.
These experiments were repeated in various forms by many ob-
servers (Zuntz, Speck, et 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 protein, and
the Voit theory, that it comes only from the oxidation of non-pro-
tein material. It has been found that in muscular work carried to
the ordinary extent protein material, in excess of that destroyed in
conditions of rest, may or may not be used according to the amount
of fats and carbohydrates contained in the diet. If these latter
elements are in sufficient quantity they furnish the energy required,
and the protein metabolism is not increased by work. If, however.

* Argutinsky, "Pfluger's Archiv f. die gesammte Physiologie, " 46, 552.
1890.

892 NUTRITION AND HEAT REGULATION.

the non-proteins are not sufficient in quantity some of the energy-
is obtained at the expense of the protein of the body, and there is
an increase in the nitrogen excretion. We may believe, in fact,
that the energy necessary for muscular work may be obtained from
any of the heat-yielding foodstuffs — carbohydrates, fat, or proteins.
It seems probable that the sugar (glycogen) of the muscle is, so to
speak, the easiest source; but, when the carbohydrates are deficient
or absent altogether in the diet, muscular exercise is accompanied
by an increase in the consumption of fats or proteins or both.
According to the view adopted in the preceding pages, it will lie re-
membered that when protein-food is used as a source of energy it
is used not as protein, but after the nitrogen has been split off in
the liver by the process of deamidization of the ammo-acids.
According to this view, therefore, the working muscle cells obtain
their energy always by oxidation of non-nitrogenous material,
although a portion of this material may have been derived ulti-
mately from the protein of the food. The Voit theory is correct
to the extent that on an abundant non-protein diet much muscular
work may be done without any increase in the consumption of
protein tissue. The muscle is a protein machine for the accom-
plishment of work, but in the performance of moderate work
there is apparently no greater wear and tear of the machinery, no
greater tissue waste, than under resting conditions. If, however,
the muscular work is excessive, the tissue waste may be increased.
Argutinsky found an increased nitrogen elimination lasting two or
three days after the cessation of the work. It is probable that this
result indicates a greater waste of the protein apparatus itself, and
this idea is borne out by the fact that under similar conditions
other observers have detected an increase in the creatinin and
uric acid excretion, nitrogenous wastes that are derived from
muscle. The effect of muscular work on the carbon excretion, car-
bon dioxid, is, of course, marked and invariable. Some extra ma-
terial iuu-t be oxidized to furnish the energy, and since this material
is usually sugar, or sugar and fat, or the non-nitrogenous portion
of the protein of the diel . the effeel , so far as the excret ions are con
cemed, will be mo I manifesl in the amounl of carbon dioxid
-.riven off. Pettenkofer and Voit found thai 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 :i corresponding increase in the absorption
of oxygen.

Metabolism During Sleep. It- has been shown that during
sleep there is no marked change in the total nitrogen excreted,
and therefore no distinct decrease in the protein metabolism.
According to Siven there La a distinct diminution in the secretion

EFFECT OF MUSCULAR WORK AND TEMPERATURE. 893

of the endogenous purin nitrogen. On the contrary, the carbon
dioxid eliminated and the oxygen absorbed are unquestionably
diminished. This latter fact finds its simplest explanation in the
supposition that the muscles are less active during sleep. The
muscles do less work in the way of contractions, and, in addition,
probably suffer a diminution in tonicity, which also affects their
total metabolism.

Effect of Variations in Temperature. — In warm-blooded
animals variations of outside temperature within ordinary limits
do not affect the body temperature. An account of the means by
which this regulation is effected will be found in the chapter upon
Animal Heat. So long as the temperature of the body remains con-
stant, it has been found that a fall of outside temperature may
increase the oxidation of non-protein material in the body, the in-
crease being in a general way proportional to the fall in tempera-
ture. That the increased oxidation affects the non-protein con-
stituents is shown by the fact that the urea remains unchanged in
quantity, other conditions being the same, while the oxygen con-
sumption and the carbon dioxid elimination are increased. This
effect of temperature upon the body metabolism is due mainly to a
reflex stimulation of the motor nerves to the muscles. The tem-
perature nerves of the skin are affected by a fall in outside tempera-
ture, and bring about reflexly an increased innervation of the
muscles of the body. Indeed, it is stated * that unless the lowering
of the temperature is sufficient to cause shivering or muscular
tension no increase in the excretion of C02 results. This fact suf-
fices to explain, therefore, the physiological value of shivering and
muscular restlessness when the outside temperature is low. The
fact that variations in outside temperature affect only the con-
sumption of non-protein material falls in, therefore, with the concep-
tion of the nature of the metabolism of muscle in activity, given
above. When the means of regulating the body temperature
break down from too long an exposure to excessively low or ex-
cessively high temperatures, the total body metabolism, protein
as well as non-protein, increases with a rise in body temperature
and decreases with a fall in temperature. In fevers arising from
pathological causes it has been shown that there is an increased
excretion of nitrogen as well as of carbon dioxid.

Effect of Starvation. — A starving animal must live upon the
material present in its body. This material consists of the fat
stored up, the circulating and tissue protein, and the glycogen.
The latter, which is present in comparatively small quantities, is
quickly used, disappearing more or less rapidly according to the
extent of muscular movements made. Thereafter the animal lives

* Johannson, " Skandinavisches Archiv f. Physiologie," 7, 123, 1897.

$94 NUTRITION AND HEAT REGULATION.

on its own protein and fat, and if the starvation is continued to a
fatal termination the body becomes correspondingly emaciated.
Examination of the several tissues in animals starved to death has
brought out some interesting facts. Yoit 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:

Loss TO
Supposed Weight Actual, Loss Each 100 Gms.
of Organs Before of Organs of Fresh Organ
Starvation. in Cms. (Percentage Loss)

Bone 393.4 54.7 13.9

Muscle 140S.4 429.4 30.5

Liver 91.9 49.4 53.7

Kidney 25.1 6.5 25.9

Spleen 8.7 5.8 66.7

Pancreas 6.5 1.1 17.0

Testes 2.5 1.0 40.0

Lungs 15.8 2.8 17.7

Heart 11.5 0.3 2.6

Intestines 118.0 20.9 18.0

Brain and cord 40.7 1.3 3.2

Skin and hair 432.8 89.3 20.6

Fat 275.4 267.2 97.0

Blood 138.5 37.3 27.0

Remainder 136.0 50.0 36.8

According to these results, the greatest absolute loss was in the
muscles (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 (he protein materials, particularly in the voluntary muscles,
pi - into solution in the blood, and are then used to nourish the
tissues generally and to supply the heat necessary to maintain the
body temperature. Examination of the excreta in starving ani-
mals has shown that a greater quantity of protein is destroyed dur-
ing the first day or two than in the subsequent days. This fact
plained on the Supposition that the body is at first supplied

with a certain excess of protein material derived from its previous
food, and that after this is metabolized the animal lives entirely,
so far as protein consumption is concerned, upon its "tissue

protein." If the animal remains quiet during starvation, the
amount of nitrogen excreted daily soon readies a nearly constant
minimum, showing that a practically constant amount of protein
(together with fat) is consumed daily to furnish body heat, and

material for the energy needs and tissue waste in the active organs,
Buch as the heart,. Shortly before death from starvation the

POTENTIAL ENERGY OF FOOD. 895

daily amount of protein 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 proteins alone. The general
fact that the loss of protein is greatest during the first one or two
days of starvation has been confirmed upon men in a number of
interesting experiments made upon professional f asters. For
the numerous details as to loss of weight, variations of temperature,
etc., carefully recorded in these latter experiments, 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 hunger, 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 liberation 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. As an example of this fact one may take the inversion
of the double sugars — one molecule of maltose yields two molecules
of dextrose. The heat value of a gram molecule of maltose is
1350.7 calories. The heat value of the dextrose resulting from its
inversion is 1347.4 cal., so that the process of hydrolysis liberates
only 3.3 cal. or about 0.2 per cent, of the total available energy in
the maltose.f 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 substance take place constantly as a part of general
nutritional metabolism. On the other hand, many of the chemical
processes occurring in the body are especially valuable on account
of the heat liberated. These reactions, for the most part, at
least, are oxidations; 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 necessary and that the carbon and
the hydrogen contained in the substances acted upon appear
eventually in the form of oxidation products — namely, carbon
dioxid and water — Liebig designated the fats and carbohydrates
as respiratory foods on the hypothesis that their fate in the body

*"Virchow's Archiv," vol. 131, supplement, 1893; and Luciani, "Das
Hungern," 1890. See also Weber, "Ergebnisse der Physiologie, " vol. i.,
part l., 1902.

fSee Herzog, "Zeit. f. physiol. chem.," 37,383,1903, and Tangl,
"Pfluger's Archiv," 115, 1, 1906.

896 NUTRITION AND HEAT REGULATION.

is to be oxidized and furnish heat. While this view is, in the
main, correct, it is evident now that a portion at least of the
protein molecule, after the splitting off of the nitrogen, may
also undergo oxidation and furnish heat. In Liebig's sense,
therefore, the proteins play the part of respiratory or heat-pro-
ducing foods as well as acting as tissue formers. On the other
hand, fats and carbohydrate material may enter to some extent,
together with the protein, into the synthesis of cell material, and
thus play the role of a plastic or tissue-forming as well as of a
respiratory food. We cannot divide the foodstuffs, therefore,
strictly into two such classes, but we may perhaps consider the
chemical processes in the body under the two heads mentioned
above — namely, the oxidation or energy-producing changes and
those due to hydrolytic cleavages, synthesis, etc., which are
attended by a small liberation of energy, or, indeed, may be accom-
panied by an absorption of energy (synthesis). The great supply
of heat energy needed by the body to maintain its temperature
comes from the oxidation processes. This classification is
employed by some physiologists, and is helpful in emphasizing
the fact that many chemical changes occur in the body that
are of no importance from the standpoint of heat production, and
that the changes that do give rise mainly to heat form, as it were,
a special group, which is not connected with the building up or
breaking down of the living matter, but furnishes the energy by
means of which these latter changes and perhaps other functions,
such as muscular work, are made possible. Roughly speaking, an
adult man forms in his body and gives off to the surrounding air
about 2,400,000 calories of heat per day. By calorie or small
calorie (c) is meant the quantity of heat necessary to raise 1
gm. of water 1° in temperature. This great supply of heat is derived
from the physiological oxidation of the carbohydrate, fat, and
protein material of the food. These same materials may be oxi-
dized outside the body by burning them at a high temperature or
under a high pressure of oxygen, and the heat that they give off in
the process can be measured directly. So far as the fats and carbo-
hydrates are concerned, the end-products of the oxidation in the
body are the same as in their combustion out of the body, and we
may believe, therefore, that the amount of heat produced is the
same in both cases. Consequently the heat value of a gram of fat
or carbohydrate burnt outside the body is spoken of as its combus-
tion equivalent, and it measures the amount of potential energy
of these foodstuffs which is available for the production of heat
or for the supply of energy in other forms to the working cells.
With regard to the protein, the case is somewhat different. Its
end-products in the body are carbon dioxid, water, and urea

POTENTIAL ENERGY OF FOOD. 897

or some other of the nitrogenous waste products. These nitrog-
enous wastes are capable of further oxidation with liberation
of heat, so that, as far as they are eliminated, the body
loses a possible supply of heat energy, which must be subtracted
from the total heat energy that the protein gives upon oxida-
tion outside the body, in order to determine the available heat
energy yielded within the body. The figures obtained for the heat
equivalents of the foodstuffs by burning them outside the body in
some form of calorimeter are as follows: 1 gm. of fat yields an aver-
age of 9300 calories, or 9.3 large calories (C), 1 gm. of carbohydrate
yields an average of 4100 calories (4.1 C). These figures may be
taken, therefore, to express the quantity of heat given to the body
by the oxidation within its tissues of these elements of our food.
A gram of protein when burnt outside of the body yields on the aver-
age 5778 calories. The heat value of the urea is estimated as 1
gm. = 2523 calories. If we assume that all the nitrogen of the pro-
tein appears as urea and that 1 gm. of protein yields J gm. of urea,
then the available heat energy of a gram of protein should be equal
to 5778 — 841 (or £ 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-
portion is given off in the feces. Rubner has calculated the avail-
able-heat energy of proteins by direct experiments upon animals.
In these experiments the heat value of the protein fed was directly
determined by burning a sample in a calorimeter. Then after feed-
ing a known amount of the protein the urine and feces were col-
lected and their heat value was determined in the same way. The
difference between the total heat value of the protein fed and the
heat value lost in its excreted products in the feces and urine gave
the actual heat energy obtained from the protein by the animal
body. Results obtained by this method give an average value
for 1 gm. protein of 4100 calories (4.1 C), or, since protein contains
an average of 16 per cent, of nitrogen, we may say that 1 gm. of ni-
trogen ingested as protein has a heat value of 4.1 X 6.25 = 25.6 C.
The figures that are used, therefore, in estimating the heat value
of our foodstuffs are:

1 gm. proteid = 4100 calories (4.1 C).

1 gm. carbohydrate = 4100 calories (4.1 C).
1 gm. fat = 9305 calories (9.3 C).

Making use of these values, it is obvious that we can calculate the
total heat value of any given diet. If we analyze the food for its
composition in the three principal foodstuffs we may determine how
many calories will be furnished to the body. In many of the tables
published to show the composition of the different foods figures are
57

898

NUTRITION AND HEAT REGULATION.

Fat. Cahbohy- Ash_

Heat Value
in Calories

DRATE.

Per Pound.

17.9

0.8

1110

2.4

1.2

475

18.7

4.0

1280

3.7

1.1

520

5.3

1.3

575

10.3

0.9

740

14.2

1.3

1060

24.2

0.8

1270

12.3

0.7

775

4.8

0.7

380

3.8

2.6

1.5

600

10.7

0.7

680

4.0

5.0

0.7

325

7.2 67.5

1.9

1860

0.3 79.0

0.4

1630

1.9 71.9

1.0

1675

0.5 ]

16.9

1.0

465

0.1 18.4

1.0

385

0.3

3.2

2.1

110

0.4

3.9

0.5

105

0.5 14.2

0.3

290

0.6 22.0

0.8

460

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 ordinal foods
are as follows : *

Protein.

Beefsteak, porterhouse 19.1

Beefsteak, round (lean) 20.2

Corned beef (canned) 26.3

Veal, les; (lean) 19.4

Veal liver 19.0

Mutton, leg (lean) 16.5

Pork, ham (fresh, lean) 24.8

Pork chops, medium fat 13.4

Chicken (fowl) 13.7

Shad 9.4

Shad roe 20.9

Eggs 11.7

Milk 3.3

Oatmeal 16.1

Rice 8.0

Wheat flour (entire wheat) 13.8

Green peas 7.0

Potatoes (raw) 2.2

Spinach 2.1

Tomatoes 0.9

Apples 0.4

Bananas 1.3

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 material — 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 supplying the energy needs of the living
cells. In the work that these cells perform, whether it is contrac-
tion, secretion, or nervous activity, energy is needed, and this
energy is carried into the body in the potential chemical energy
of the proteins, fats, and carbohydrates.

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. f The general principles upon which practical
dieting 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

* Selected from At water and Bryant, Bulletin 28 (revised edition),
United States Departmenl of Agriculture, L889.

f For practical directions, see Guiltier, " L'aliinentation et les regimes, "

I'.ioi: Blyth, "foods: their Composition and Analysis."

DIETETICS. 899

maintain the body in an equilibrium of material and of energy —
that is, the diet must furnish the material for the regeneration of
tissue and the material for the heat produced and the muscular
work and other work done. Nutritional experiments prove that
this object may be accomplished by protein food alone, together
with salts and water. It is doubtful, however, whether, in the
case of man, such a diet could be continued for long periods without
causing some nutritional disturbance, directly or indirectly. It
will be remembered that a pure meat diet is not entirely protein,
since all flesh contains some fats and carbohydrates (glycogen).
The functions of a diet are accomplished more easily and more
economically when it is composed of proteins and fats, or proteins
and carbohydrates, or, as is almost universally the case, of proteins,
fats, and carbohydrates. The experience of mankind shows
that such a mixed diet is most beneficial to the body and most
satisfying to that valuable regulating mechanism of nutrition,
the appetite. Expressed in its most general form the cells of our
body need food for two purposes: first, to supply the energy
needs; second, to furnish the material for the construction of their
own living substance, that is, for assimilation. The first of these
purposes is fulfilled by any of the three energy-yielding foodstuffs,
carbohydrates, fats or proteins, but as a matter of fact we use
chiefly the carbohydrates on account of their economy and the
ease with which they are utilized by the body. For the second
purpose, the construction of protoplasm or living matter proteins
(or their cleavage products) are absolutely necessary. Whether fats
or carbohydrates participate at all in this process is perhaps an
open question. In accordance with this specific and necessary
function of the protein we find that the amount used in the daily
diet is fairly constant, about 100 grams, while the proportions of
fat and carbohydrate show wide variations. Since from the energy
standpoint the fats and carbohydrates have a common function,
serving as fuel for the energy needs of the body, 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, sIioav that this substitution can be
made in a general way, although it is not advisable to eliminate
either of these foodstuffs entirely from the diet. The fact that
within certain limits fats and carbohydrates may be substituted
for each other is illustrated in a general way by the different diets
recommended by various physiologists, since it will be noticed

900 NUTRITION AND HEAT REGULATION.

that in those in which the proportion of fat is large the amount of
carbohydrate is reduced.

AVERAGE DIETS AND THEIR HEAT VALUES.

MOLESCHOTT. RANKE. VoiT.

Calories. Calories. Calories.

Protein 130 gms. . . . 533 100 gms. . . .410 118 gms. ... 483

Fats 40 " ... 372 100 " ... 930 56 " ... 520

Carbohydrates . . . 550 " . . . 2275 240 " . . . 984 500 " . . . 2050

2980 2324 3053

FORSTER.

. .930
. . 984

56

500

"

2324

Atwater.

Calories.

125 gms.
125 "

400 "

512

1172
1640

Calories.

Protein 131 gms. . . . 567

Fats 68 " ... 632

Carbohydrates . .494 " . . .1825

"2024 3324

The average heat value of these diets is equal to 2742 calories,
of which about 18 per cent, is furnished by the protein. Generally
speaking, it will be found that in the dietaries selected voluntarily
by mankind the protein furnishes from 15 to 20 per cent, of the
total heat value of the diet. According to some physiologists
this proportion is unnecessarily large and it might be reduced
to as little as 5 or 10 per cent. Whether or not such a change is
justified has already been discussed to some extent (p. 858).
Leaving aside this point, it is usually estimated in round numbers
that the diet should furnish daily 2400 calories for an individual
weighing 60 kgms., or about 40 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 abundance, and its ease of digestion and
oxidation in the body, constitutes 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
4770 to 6005 calories. Chittenden, in the work previously re-
ferred to,* 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 con-
taining a total heat value of only 1600 calories or 28 calories per
kgm. of body weight instead of 40 calories. The diet in this
case, it will be remembered, contained only 36 to 40 gms. of protein
in place of the 100 to l.'iO gins, recommended in the diets mentioned
above. The question thus raised is one that must bo decided by
actual experience, but from the numerous statistical and experi-
mental results riow availablef it would appear, as has been stated

* Chittenden, "Physiological Kconomy in Nutrition," L905.
f See especially the numerous Bulletins of the U.S. Department of
Agriculture, Nos. 28, I L6, L29, L49, etc.

DIETETICS. 901

above, that the total energy necessary in a diet, estimated in
terms of its heat value, varies chiefly with the amount of muscular
work to be done. Persons who lead a very muscular life require
a correspondingly large amount of energy in the diet, and this
demand is met usually by augmenting the proportion of carbo-
hydrate and fat, especially the carbohydrate. Since the amount
of protein is not varied greatly in such cases the diet is relatively
poor in this foodstuff. On the contrary, those who lead a sedentary
life, including, broadly speaking, all the well-to-do class, require
less energy in their diet, and they can afford to reduce the pro-
portion of carbohydrate and fat. The diet in such cases may be
relatively rich in protein, although the amount per kilogram of
body weight is not increased, in fact, is usually diminished some-
what. These facts are illustrated in Atwater's estimate of the
diet necessary for men performing different amounts of muscular
work.

Protein. Carbohydrate
and Fat.

Man doing hard muscular work 600 cal. 3550 cal.

Man doing moderate muscular work 500 " 2900 "

Man doing no muscular work 360 '; 2040 ';

On comparing these diets it will be observed that in per-
forming hard muscular work the diet contained 1700 calories of
energy beyond that used when no work was done. About six-
sevenths of this increase was provided for by the carborrydrates
and fats. It will be seen also that in this case the proportion
of the total energy obtained from protein remained practically
identical.

Mankind is guided and has been guided in all times by
the control of the appetite, using this term in a general sense to
designate the conscious desire for food, and also the desire, more
or less clearly recognized, for special kinds of food. If scientific
experiments indicate that this regulatory apparatus leads us to
ingest more food than is actually required for the assimilation
needs and the energy needs of the body, it remains for observa-
tion and experiment to determine whether this excess is beneficial
or useless or, perhaps, even harmful.

Munk gives an interesting table showing how much of certain
familiar articles of food would be necessaiy , if taken alone, to supply
the requisite daily amount of protein or non-protein material ; his
estimates are based upon the percentage composition of the foods
and upon experimental data showing the extent of absorption of the
foodstuffs in each food. In this table he supposes that the daily
diet should contain 110 gms. of protein = 17.5 gms. of N. and non-
proteins sufficient to contain 270 gms. of C:

902

NUTRITION AND HEAT REGULATION.

Milk

Meat (lean) . .
Hen's eggs...
Wheat flour. .
Wheat bread.
Rye bread . . .

Rice

Corn

Peas

Potatoes ....

For 110 Gms. Proteih
(17.5 Gms. N).

2900 gms.

540 "
18 eggs.

800 gms.
. . 1650 "
. . 1900 "
. . 1870 "

990 "

520 "
. . 4500 "

For 270 Gms. V.

3800 gms.
2000 "
37 eggs.

670 gms.
1000 "
1100 "

750 "

660 "

750 "
2550 "

As Munk points out, this table shows that any single food, if taken
in quantities sufficient to supply the nitrogen, would give too much
or too little carbon and the reverse; those animal foods which, in
certain amounts, supply the nitrogen needed furnish only from one-
fourth to two-thirds of the necessary amount of carbon and, vice
versa, the vegetable foods if taken in sufficient quantity to supply
the carbon would not give sufficient nitrogen, or if used alone to
furnish the requisite nitrogen would give an excess of carbon.
This same fact is illustrated in another way in a table compiled
by Cohnheim.* To furnish the body with its necessary daily
quota of 100 grams of protein the following amounts of different
foods, expressed in their heat values, would be required:

Meat 495

Eggs 1133

Cheese 1704

Milk 2070

Corn 4104

Coarse bread 4552

Fine bread 4720

Potatoes 5000

Rice 5600

It is evident from this table that a person leading a sedentary
life who used a vegetable diet alone would be required, in order to
obtain his necessary protein, to consume much more carbohy-
drate than from an energy standpoint was needed by the body.
As ( 'ohnheim points out, the animal foods are for this reason espe-
cially suited to supply the protein needs of those who lead a com-
paratively inactive life. In practical dieting we are accustomed
to get our supply of proteins, fats, and carbohydrates from both
vegetable and animal foods. To illustrate this fact by an actual
case, in which the food was carefully analyzed, an experimenter
weighing 67 k^ms. records that he kept himself in nitrogen equilib-
rium upon a diet in which the protein was distributed as follows:

N.

:;nii •/hi,-, meal

=

63.08 gms. protein

=

9.78 gms

(106.3 <-.c. milk

=

18.74 "

=

2.905 "

loo gms. rice

=

7.74 "

=

1.2

loo " bread

=

11.32 "

=

1 .755 "

500 c.c. wine

=

1.17 "

=

0.182 gin.

102.05 " " = 15.868 gms. "

* Cohnheim, "Die Physiologie der Verdauungund Ernahrung," 1908.

DIETETICS. 903

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; they may be relied upon, at least, to protect the
body from undernutrition. The opposite danger of overeating
is a real one, particularly among those who do not lead an active
life. It is, however, a hygienic offence that is usually committed
knowingly and may consequently be controlled by those who have
sufficient wisdom. Physiological knowledge emphasizes clearly
enough the great fact that the mechanisms of nutrition and
digestion, like the other mechanisms of the body, should not be
subjected to unnecessary strain. For those who are in health,
the important rule to follow in the matter of diet is to avoid an
excess in eating. In conditions of disease, in regulating the diet
of children or of collections of individuals, as in the army, navy,
etc., it is necessary for purposes of hygiene or for purposes of
economy to arrange the diet in accordance with the knowledge
obtained from experience and from scientific investigations.
In this direction much has already been accomplished, but more
remains to be done, particularly perhaps in the relation of diet to
pathological conditions.

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
[ess 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-

904

BODY TEMPERATURE. 905

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 da}rs
their temperature is low, approximately that of the surrounding
air or water, and in summer their body temperature rises to cor-
respond with that of the outside. Strictly speaking, they are cold
blooded only in cold surroundings. This group may be designated
as the changeable-temperature animals (poikilothermous). The
warm-blooded animals maintain a constant high body temperature
on account of their relatively active oxidations and the existence
of a heat -regulating mechanism. In the cold-blooded animals the
oxidations are not so intense and a heat-regulating mechanism is
absent or poorly developed. The hibernating animals form a group
intermediate in many ways between these two classes. They possess
a heat-regulating apparatus that maintains a constant body tem-
perature under most conditions, but breaks down in very cold
weather; so that during the period of winter sleep their tem-
perature is but little above that of the surrounding air. In
some of the cold-blooded animals the production of heat is more
rapid during warm weather than its loss; so that they exhibit
a body temperature slightly higher than the surrounding me-
dium. A hive of bees in activity may raise the temperature
within the hive through a number of degrees and snakes and
many reptiles show a temperature of 2° to 8° C. above that of
the air. So also some reptiles possess a rudimentary means of
protecting their bodies from too great a rise of temperature, —
for instance, by accelerated breathing whereby more water is evap-

906 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 bodjr (rectal) is slightly higher than on the
surface of the skin. The average temperature in the rectum is 37.2°
C. (9S.960 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. gOnOrale," 1902,
249.

CALORIMETRY. 907

Among physiological conditions that influence the body tempera-
ture, muscular work and meals, as stated above, have the most posi-
tive effect. Marked muscular activity implies a great increase in
the production of heat in the body and most observers find that
the initial result at least is a small rise in body temperature, — a fact
which indicates that the heat regulation is not perfect; the excess
of heat produced is not dissipated promptly. In the period of rest
following upon work, on the contrary, the body temperature may
fall, owing probably to the fact that more heat is lost through the
flushed skin than is produced within the body. In this matter of
the effect of muscular work individual variations are to be expected,
since the perfection of the heat-regulating mechanisms may vary
somewhat in different persons. Meals also cause a slight rise in
body temperature, which reaches its maximum about an hour and
a half after the ingestion of the food. The explanation in this case
also is to be found doubtless in a greater production of heat, due to
the increased metabolism in the secreting glands, the liver, and the
musculature of the gastro-intestinal canal. The excessive production
of heat is not compensated completely by a corresponding increase in
the heat dissipated.* It is sufficiently obvious, perhaps, from these
facts that the temperature as measured by the thermometer is a
balance between the amount of heat produced and the amount of
heat lost or dissipated. The thermometer alone gives us no cer-
tain indication of the quanity of heat produced in the body. A
temperature higher than normal, fever temperature, may be due
either to an excessive production of heat or to a deficient dissipa-
tion. To understand and control the processes by which the body
temperature is kept normal it is necessary to discover a means for
ascertaining at any time the actual quantities of heat produced
and dissipated, and the effect upon each factor of different normal
and pathological conditions. The method used for determining
the quantity of heat is designated as calorimetry. It is necessary,
therefore, to describe the principle and construction of calorimeters
and the methods of calorimetry before attempting to explain the
mechanism of heat regulation.

Calorimetry. — A calorimeter is an instrument for measuring
the quantity of heat given off from a body. The unit employed in
these determinations is the calorie, — that is, the amount of heat
necessary to raise 1 gm. of water 1° C.,or more accurately the amount
of heat required to raise 1 gm. of water from 15° to 16° C. This
unit is sometimes designated as a small calorie to distinguish it
from the large calorie (C), — that is, the quantity of heat necessary
to raise 1 kgm. of water 1° C. The large calorie is equal to 1000

* For further details see Puchet, "La chaleur animate," 1889; and Pem-
brey, " Animal Heat, " Schaefer's " Text-book of Physiology, " vol. i, 1898.

908

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

CT\ EWT

Fig. 290. — Reichert's water calorimeter.

and which is filled with oxygen. The combustion of the foodstuff
is initiated by means of a spiral of platinum wire heated by an
electrical current. The bomb is immersed in water and the heat
given off raises the water to a measured extent of temperature.
The weight of water being known, the amount of heat is easily
expressed in calories. For the purpose of measuring the heat
given off by living animals two principal forms of calorimeter are
used, each form having a number of modifications. These two
forms are the water calorimeter and the air calorimeter. The
water calorimeter was the form used in the first experiments on rec-
ord (Crawford, 1779). In principle it consists of a double-walled
box with a known weight of water between the walls. The animal
is placed in the inner box and the heat given off is absorbed by the

CALORIMETRY. 909

water. Knowing the weight of the water and how much its tem-
perature is raised, the data are at hand for determining the number
of calories given off during the experiment. One form of this
variety of calorimeter, used in this country by Reichert, is shown
in Fig. 290. It consists of two concentric boxes of metal with a
space between them of about 1-y inches. The animal is placed
in the inner box (A). The two boxes are inclosed in a large wooden
box, the space between the metal and wooden boxes being filled
with shavings (SH). The object of this outer box is to prevent
radiation of heat from the metal boxes. The tubes EN and EX,
which lead into the interior chamber containing the animal, are for
the entrance and exit of the ventilating air. A thermometer is
placed in each to determine the heat carried off by the air. The
thermometer, CT, measures the temperature of the water, and S is
a stirrer to keep the water well mixed and thus insure a uniform
temperature. When the animal is placed in the apparatus the
heat given off warms not only the water, but also the metal; so
that to determine the total heat the weight of metal must be re-
duced to an equivalent amount of water by multiplying its weight
by its specific heat, or, a more simple method, the calorimetric equiv-
alent of the apparatus is determined, — that is, the actual amount of
heat necessary to raise the temperature of the apparatus, water and
metal, one degree. This value is obtained by burning in the appa-
ratus a known weight of some substance (alcohol, hydrogen) whose
heat of combustion is known. Knowing how much heat is given
off by this combustion and how much the temperature of the
apparatus is raised, the calorimetric equivalent is easily calcu-
lated and may be used subsequently in estimating the results ob-
tained from animals. In the use of the apparatus many precau-
tions must be observed. These practical details need not be des-
cribed here except to say that account must be taken of the warm-
ing of the air used to ventilate the apparatus and of any changes
in the amount of its moisture. The calorimeter used in this way
measures directly the amount of heat given off from the animal
during the period of observation. The amount of heat produced in
the animal's body during this time may be the same, or may be
more or less. To arrive at a knowledge of this factor observations
must be made upon the animal's body temperature by means of a
thermometer in the rectum. If this body temperature is the same
at the end as at the beginning of the experiment then it is obvious
that the heat produced must have been equal to the heat lost. If
the 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)
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

910

NUTRITION AND HEAT REGULATION.

experiment. The product is obtained in calories and is subtracted
from the amount of heat lost, as determined by the calorimeter, to
obtain the amount of heat produced. If, on the contrary, the ani-
mal's temperature has risen during the experiment the body has
produced more heat than it has dissipated. The increase may be
determined as above by multiplying the weight of the animal, the
specific heat of the body, and the difference in temperature. This
amount added to the heat lost gives the heat produced.

Many 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-

Fig. 291. — 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. 291, which gives a
schema of the form originally employed by d'Arsonval; 8 and 8'
represent the two calorimeters, in one of which the animal is placed
while the other acts as dummy. Each is double walled and the
air spaces are connected by tubes, 10 and 10', to small gasometers,
4, 4', suspended in water and hung on opposite sides of a balance.
The movements of these gasometers antagonize each other, and the
resultant may be recorded upon smoked paper, us indicated in the
figure.*

* For detailed accounts of special forms of air calorimeters see Rubner,
■ Calorimetrische Mefchodik," L891; and Rosenthal, "Arclriv f. Physiologie,"
1897, p. 170.

CALORIMETRY. 911

The Respiration Calorimeter. — When a calorimeter is so arranged
that the composition of the air drawn through the apparatus for
ventilation can be determined as well as the amount of heat pro-
duced, the apparatus becomes a respiration calorimeter. In such
an apparatus, if proper provision is made for analyzing the urine,
the feces, and the food, the total carbon and nitrogen excretion may
be obtained simultaneously with the heat loss. Since we may
calculate from the carbon and nitrogen excretion how much pro-
tein, fat, and carbohydrate have been burnt in the body, and since
the heat values of these constituents are known, it is evident that
we may reckon indirectly how much heat ought to be produced
from the combustion of so much material. This method of arriv-
ing at the heat production is designated indirect calorimetry . With
an adequate respiration calorimeter it is possible to ascertain
whether the results calculated by the method of indirect calorim-
etry really correspond with the heat obtained by direct measure-
ment. In the hands of good observers the correspondence is
very close, and gives substantial proof of the scientific belief
that in the living body the energy liberated as heat or as heat
and work is all contained in potential form in the foodstuffs
eaten. By means of the respiration calorimeter we can obtain a
balance between the energy income and outgo of the body as well
as between the material income and outgo, — that is, the carbon and
nitrogen equilibrium. The most complete and elaborate form of
respiration calorimeter used is that devised by Atwater and Rosa for
experiments upon man.* Considered as a calorimeter the appara-
tus used by these investigators belongs to the type of water cal-
orimeters. Instead, however, of having a stationary stratum of
water to be warmed by the heat given off from the body, the appara-
tus is arranged so that a stream of water may be circulated between
the walls, and this stream is so regulated, as to quantity and
temperature, as to keep the temperature of the calorimeter as a
constant point. In other words, the heat given off from the body
is carried away by the circulating water, and the quantity of the
heat may be calculated when the temperature and amount of the
water are known. By means of this apparatus many interesting
and important experiments have been made upon the nutrition
of man under special conditions. Such results as the following
have been obtained (Atwater and Benedict) in the case of a man
who, while in the apparatus, did much muscular work on a bicycle
ergometer:

*See Atwater and Rosa, Bulletin 63, United States Department of Agri-
culture, 1899; and for recent improvements, Atwater and Benedict, "A Respira-
tion Calorimeter," Carnegie Institution, Washington, 1905.

912 NUTRITION AND HEAT REGULATION.

Income: Potential energy of material metabolized in body = 5459 Cal.
Outor> i Energy given off from the bod}* as heat. . . . 4833 Cal.
° \ Heat equivalent of muscular work 602 Cal.

5435 Cal. 5435 Cal.

Experimental error 24 Cal.

Results of Calorimetric Measurements. — The actual results
obtained from direct calorimetric measurements corroborate those
deduced from the study of the energy given off in the oxidation of
the foodstuffs of the daily diet. They show that man gives off heat
from his body to the amount of 40 to 50 calories per kgm. of
weight during 24 hours under conditions of ordinary life, — a
total, therefore, of 2400 to 3000 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. This fact has been expressed by
Rubner in what he calls his "surface area law." According to
this law the metabolism is proportional to the surface area, or
for the same amount of surface area there will be the same pro-
duction of heat. He estimates that in man there is produced in
24 hours for each square meter of surface 1042 cal. The figures
for other mammals are nearly the same. In small animals of
a given species in which the surface area is greater relatively to
the mass than in the larger animals, the metabolism per kilogram
of weight will be larger — for example, in the human infant com-
pared with 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 :

*See Rubner, " Zeitschrift. f. Biologie," 19, 535, 1883; and Gesetze,
"des Energieverbrauchs," 1002.

REGULATION OF HEAT LOSS.

913

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 ah",

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 0.5 cal.

3. By evaporation of the sweat from the skin. The amount lost in this

way increases naturally with the amount of sweat secreted.

4. By conduction and especially by radiation of heat from the skin.

The relative values of these different means of heat loss are
estimated as follows by Vierordt:

1. By urine and feces 1.8 per cent, or 48 calories.

2. By expired air: Warming of air 3.5 " " 84

Vaporization of water from lungs 7.2 " " 182

3. By evaporation from skin 14.5 " " 364

4. By radiation and conduction from skin 73.0 " " 1792

Total daily loss =2470

It is obvious that the relative importance of these factors will vary
with conditions. Thus, high external temperatures will tend to
diminish the loss from radiation while increasing that from evapora-
tion, owing to the greater production of sweat. The variation
in this respect is well illustrated by the following table, compiled
by Rubner, from experiments made upon a starving dog:*

Temperature.

Calories lost by radia-

Calories lost by

Total calories of

tion and conduction.

evaporation.

metabolism.

7° C.

78.5

7.9

86.4

15°

55.3

7.7

63.0

20°

45.3

10.6

55.9

25°

41.0

13.2

54.2

30°

33.2

23.0

56.2

It will be noted that between 25° and 30° C. there was a marked
increase in the loss of heat through evaporation.

In man loss of heat is regulated chiefly by controlling the impor-
tant factors of evaporation and radiation. We accomplish this end in
part deliberately or voluntarily by the use of appropriate clothing.
Clothing of any kind captures a layer of warm and moist air between
it and the skin and thus diminishes greatly the loss by evaporation
and by radiation. In cold weather the amount and character of the
clothing is changed in order to diminish the heat loss. The ideal
clothing for this purpose is made of material, such as wool, which,
while porous enough to permit adequate ventilation of the air next
to the skin, is at the same time a poor conductor of heat and thus
diminishes the main factor of loss by radiation. The most impor-
tant means of controlling the heat loss, however, is by automatic

* Taken from Lusk, "Elements of the Science of Nutrition," Philadel-
phia, 1906.

58

914 NUTRITION AND HEAT REGULATION.

reflex control through the sweat nerves and the vasomotor nerves.
By these means the amount of perspiration evaporated from the
skin and the amount of warm blood sent through the skin are
controlled. Rubner speaks of this side of the heat regulation
as the phi/sical regulation. By its means the body may be safe-
guarded from an abnormal rise of temperature. In warm weather
the secretion of sweat is greatly increased by reflex stimulation
of the sweat nerves. The greater amount of water requires a
greater amount of heat to vaporize it, and thus the heat loss
is increased. The value of this control is illustrated by a case
recorded by Zuntz* of a man who possessed no sweat glands. In
summer this individual was incapacitated for work/ since even a
small degree of muscular activity would cause an increase in his
body temperature to 40° or 41° C.

The control through the vasomotor nerves is doubtless even
more important. The blood-vessels bring the warm blood to the
skin, where it loses its heat by conduction and especially by radia-
tion to the cooler air. When the surrounding air is much below the
temperature of the body the vasoconstrictor center is stimulated,
the blood-vessels in the skin are constricted, the supply of warm
blood to the skin is diminished, and therefore the amount of heat lost
is less. The reflex in this case may be attributed primarily to the
action of the cool air on the cold nerves of the skin. The impulses
carried by these fibers to the nerve centers stimulate the vasocon-
strictor center or that part of it controlling the vasomotor fibers
to the skin. On warm days, on the contrary, the blood-vessels
in the skin are dilated sometimes to an extreme extent, the
supply of warm blood is therefore increased, and more heat
is lost if the air is lower in temperature than the blood. The
reflex in this case may be regarded possibly as an inhibition of the
vasoconstrictor center through the warm nerves of the skin. Sub-
stances, such as alcohol, which cause a dilatation of the skin ves-
sels also increase the loss of body heat, in some cases to a sufficient
extent to lower the body temperature. To a smaller extent our
heat loss is controlled through an acceleration of the breathing
movements. The greatly increased respirations in muscular ac-
tivity must aid somewhat in eliminating the excess of heat produced,
although this factor must be much less important than the sweating
and the flushing of the skin which are produced reflexly during
muscular work. In some of the lower animals — the dog, for in-
stance— in which the sweat nerves are absent over most of the body
and in which the coat of hair interferes with the free loss by
radiation, it is found that the loss through the respiratory channel is

* Zuntz, " Deutsche medizinal-Zeitung," 1903, No. 25.

REGULATION OF HEAT PRODUCTION. 915

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 replacing the greater amount of
heat lost from the body without calling upon the tissues of the
body itself. In normal individuals this regulation is not, strictly
speaking, voluntary. Outside cold is most effective in stimulating
the appetite and thus leading us to increase the diet. In this, as in
other respects, the appetite serves to control the amount of food in
proportion to the needs of the body. The purely involuntary con-
trol of heat production consists of an involuntary reflex upon mus-
cular 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 maintain its body temperature when the outside temperature is
changed. The rabbit behaves, in fact, like a cold-blooded animal.
In the calorimeter it shows a marked loss of heat production, and its
temperature may be made to go up and down with the outside
temperature. The same result may be obtained by section of all
the motor nerves, — that is, section of the spinal cord in the upper
cervical region. Rubner has shown by calorimetric experiments
upon animals that although the body temperature, as we know,
may remain constant when the outside temperature is changed,
the heat production is increased as the outside temperature is
lowered. This fact is well shown by the following table, compiled
by Rubner, from experiments made upon a fasting guinea-pig :f

* Pfliiger " Archiv f. die gesammte Physiologie, " 18, 255, 1878.
f Taken from Lusk, loc. cit.

916

NUTRITION AND HEAT REGULATION.

Temperature

Temperature

Grams of CO^ eliminated per hour

of air.

of animal.

and per kilogram of animal.

0.0° c.

37.0° C.

2.905

11.1

37.2

2.151

20.8

37.4

1.766

25.7

37.0

1.540

30.3

37.7

1.317

34.9

38.2

1.273

40.0

39.5

1.454

From 0° to about 35° C. the animal's body temperature remained
practically constant, but the oxidations at the lower temperature
were over twice the amount of those at the higher temperature.
At about 33° C. the metabolism of the mammal, according to
Rubner, is at its minimum. From 35° to 40° C. the heat regula-
ting mechanism in the experiments quoted broke down, in that
heat loss was prevented to such an extent by the outside high
temperature that the body temperature rose in spite of the
diminution in heat production. The increased production of
heat in the body in consequence of a fall in external temperature
is a characteristic property of warm-blooded animals. Rubner
designates this side of the regulating mechanism as the chemical
regulation, and he calls attention, moreover, to the fact that in
mankind, owing to our custom of protecting the surface of the
body by clothing and by artificial heat, chemical regulation
plays less of a role than in the lower animals. Man, in fact,
keeps most of his skin surrounded by a warm layer of air at
about the temperature (33° C.) at which the metabolism, as
affected by temperature, is minimal. Cold baths, cold winds,
and various climatic conditions, such as high altitudes and sea-
side conditions, may cause a marked increase in body metabolism.
Johannson* has shown that the increased oxidations that occur
under the influence of outside cold, as measured by the C02 out-
put, occur only when muscular tension is increased or shivering
is noticed. We may believe, therefore, that the increased oxida-
tions caused by cold are due to motor reflexes upon the skeletal
muscles. These reflexes take place doubtless through the motor
filicvs. and lead to an augmented muscular tone or to small con-
tractions (shivering), according to their intensity. This fact
accords with one's personal sensations regarding the condition of
his muscles in cold weather.

The Existence of Heat Centers and Heat Nerves. — Physi-
ologists have long supposed that there may be in the body a special
set of heat nerves and heat centers, separate in their action from the
motor, secretory, and other efferent nerves that influence the me-

* Johannson, " Skandinavisches Arcbiv. f. Physiologic," 7, 123, 1897.

EXISTENCE OF HEAT CENTERS AND HEAT NERVES. 917

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* have found that section or
puncture of the brain at the junction of medulla and pons causes
an increase in heat production and a rise of temperature. Section
of the cord in the cervical region is, on the other hand, attended
usually by a fall in body temperature. These experiments might be
interpreted to mean that there exists in the brain anterior to the
medulla a general heat center of an inhibitory character. Under
normal conditions this center may hold the lower heat-producing
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,f 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,^ 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

* See Wood, "Fever," "Smithsonian Contributions to Knowledge,"
Washington," 1880.

t Ott, "Journal of Nervous and Mental Diseases," 1884, 1887, 1888;
also "Brain," 1889.

t Roily, "Deutches Archiv f. klinische Medicin," 78, 250, 1903.

918 NUTRITION AND HEAT REGULATION.

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.* The great amount of experimental work done along
these lines has been inspired doubtless by the hope of discovering
a special heat-regulating nervous apparatus which if demonstrated
would enable us to explain the causation of fevers. In its most
elaborate form this hypothesis assumes the existence of primary
heat-producing (thermogenic) centers in the cord and brain from
which the calorific or heat nerves arise. These centers in turn are
controlled by regulating (thermotaxic) centers of an augmenting
and inhibitory character in the higher portions of the brain. By
reflex influences upon these latter centers the activity of the thermo-
genic centers may be increased or diminished and the production
of heat in the body controlled. While such an apparatus may
exist, it is nevertheless true that the evidence in favor of it so far
produced has failed to convince the majority of physiologists. The
existence of a special set of heat nerves, in fact, is still unproved.
Most physiologists, perhaps, believe that variations in heat pro-
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 :

!1. The sweat centers and sweat nerves.

2. The vasoconstrictor center and the vasoconstrictor
nerve fibers to the skin.

3. The respiratory center.

( 1. The motor nerve centers and the motor nerve fibers

tt , i, *• J to the skeletal muscles.

neat production s 2 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

* See Reichert, " University Medical Magazine," 5, 406, 1894; also Kemp,
"Therapeutical Gazette," L889, pp. 66 and 155.

PHYSIOLOGICAL OXIDATIONS. 919

in the body — fats, carbohydrates, proteins — is consumed with a
certain rapidity, — in the case of muscular contractions with great
rapidity, — and we know that these same materials out of the body
at a temperature of 39° C. are oxidized with extreme slowness. It
became customary, therefore, to speak of the oxidations in the body
as indirect, meaning thereby that the material is not acted upon
directly by the molecular oxygen . Within recent years it has been
shown that the oxidation in ordinary combustions — the burning
of gaseous hydrogen, for instance — is not explained by assuming
that the oxygen unites directly with the hydrogen. It is stated,
for instance, that this combustion does not take place if both gases
are entirely free from water vapor; the presence of water is necessary
for the oxidation. Chemists are not agreed as to the exact nature
of simple combustion, and it is therefore increasingly difficult to
compare these processes with the oxidations in the body. Leaving
aside the details of the process, it may still be believed that tho
metabolism of material in the body by means of which its heat
energy is produced is at bottom comparable to ordinary combus-
tions. Oxygen is absolutely necessary to the process in each case;
the same end-products are formed and the same amount of heat is
liberated in the one case as in the other. The fundamental point
that the physiologist is attempting to solve is the means by which
the body accomplishes these oxidations at such a low temperature.
The theories suggested to explain this fact have changed naturally
with the advance of chemical knowledge. After the discovery of
ozone (Schonbein, 1840) and its great power of oxidation as com-
pared with oxygen it was suggested that in some way the oxygen
in the body is ozonized and is thus able to burn the food material.
Gorup-Besanez showed that some of the oxidations that take place
in the body can be successfully accomplished outside the body
with the aid of ozone, especially in the presence of alkalies or alka-
line carbonates. Others suggested that the oxygen in the body be-
comes converted to atomic oxygen and is thus enabled to attack the
tissue materials. Hoppe-Seyler formulated a theory according to
which the living molecule is first split into smaller molecules by the
hydrolytic action of ferments. In this process, as in fermentation, to
which he compared it, hydrogen is liberated in the nascent or atomic
state, and this hydrogen acting upon the oxygen forms water with
the liberation of some atomic oxygen, which in turn oxidizes the
split products of the fermentation. Others still (Traube) laid stress
upon the possibility of the formation of hydrogen peroxid or
similar organic peroxids which are then capable of effecting the
oxidation of the body material. This latter theory, in modified
form still prevails.*

* See Engler and Weissberg, "Kritische Studien uber die Vorgange der
Autoxydation, " 1904.

920 NUTRITION" AND HEAT REGULATION.

The great amount of experimental and theoretical work upon
the nature and cause of physiological oxidations has established
pretty clearly two general beliefs which it is important to keep
in mind. It has been shown, in the first place, that the amount of
the oxidation is governed by the tissue itself and not by the quantity
of oxygen present. The view that by increasing the amount of
oxygen offered to the tissue the intensity of the oxidations can
likewise be increased was formerly held and is still met with. It
is often supposed, for example, that by breathing pure oxygen the
oxidations of the body may be augmented. On the contrary, the
facts indicate that when a sufficient supply of oxygen is provided
any further increase has no immediate effect in aiding or hastening
the oxidations. The intensity of the process is conditioned by the
tissue itself. The initial stimulus or substance that sets going the
whole reaction arises within the tissues. The second generalization
that seems to be accepted more and more of recent years is that the
oxidations of the body, those reactions that give rise to much heat,
do not affect the living tissue itself. They take place under the
influence of the living matter, or by the aid of substances (enzymes)
formed by the living matter, but the material actually burnt is not
organized living substance. As the living yeast cells break down
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 Pfluger. 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 Pfluger expressed it, "The intramolecular heat
of the cell is its life." This point of view, however, has not found
acceptance of late years. It is implied or stated by most recent
authors that the food material is attacked and oxidized outside the
living molecule, in the form of fat, sugar, protein, etc. The ten-
dency for many years has been to show that these processes in the
body are chemical changes that do not differ fundamentally from
similar processes outside the body. The point of view actually
adopted by most workers is that the living matter effects its won-
derful changes in the food material with the aid of intracellular
ferments or enzymes. That such enzymes are formed, one may say
generally in the tissues of the body, has been brought out in the pre-
ceding chapters upon Digestion and Nutrition. It is necessary only

PHYSIOLOGICAL OXIDATIONS. 921

to recall the facts that lipase, the fat-splitting enzyme, has been iso-
lated from many tissues, and that in the liver and muscles and prob-
ably other tissues there exist enzymes capable of converting glycogen
to sugar or the reverse, and of destroying the sugar completely by the
serial action of several intracellular enzymes. Finally, with regard to
the protein material it is now recognized that proteolytic enzymes
are formed within many, if not all, of the living tissues. This point
is demonstrated by the fact of autolysis, — that is, if living tissue is
taken from the body, with precautions against contamination by
bacteria, and while under perfect aseptic conditions is kept warm
and moist, it will digest itself. The protein is split up into the
same simple hyclrolytic products as are obtained by boiling it with
acids. It has been shown that this digestion is due to enzymes —
autolytic enzymes — formed within the living tissue. There is no
doubt, therefore, of the existence of intracellular enzymes, and that
these substances play a conspicuous part in the metabolism of food
material. The lipase, the diastase, and the autolytic enzymes just
referred to all belong to the group that cause hydrolytic cleavages, —
that is, they induce splitting or decomposition of the material by
a reaction with water. The supposition has naturally been made
that probably the oxidations of the body are effected also by enzymes
which in some way activate the oxygen. Enzymes of this char-
acter have been found; they are designated in general as oxidases
or as oxidases and peroxidases, the former term referring to those
enzymes that effect oxidations in the presence of oxygen, while
the latter is applied to certain enzymes supposed to act only in the
presence of peroxids. According to Bach and Chodat the per-
oxidases act upon organic compounds of the nature of peroxides,
causing these latter to give off their oxygen in a form capable of
producing oxidations. The peroxides are produced from certain
organic substances which they designate as oxygenases. These
latter take up ox}^gen and are converted to peroxides, as H20
may take up oxygen and be changed to H202. According to
these authors all the oxidizing enzymes of the body are peroxidases,
what have been called oxidases being simply a mixture of per-
oxidases and oxygenase. Peroxidases have been described in the
blood (Kastle and Amoss), in pus-cells, lymphoid tissue generally,
and in sperm-cells (Czyhlarz and v. Fiirth). The most conspicuous
of the oxidases or peroxidases found in the animal body is the
one capable of oxidizing aldehydes (salicylic or benzoic aldehyde)
into the corresponding acids, and hence designated specifically
as aldehyclase. 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 tyrosin with the formation of

922 NUTRITION AND HEAT REGULATION.

homogentisinic acid. So also oxidases are described capable of
oxidizing xanthin to hypoxanthin or to uric acid.* The process
of destructive metabolism of sugar in the body, glycolysis, may
be effected, it will be remembered, by the tissue juices squeezed
from the organs, or even by extracts of the tissues of muscle, liver,
etc. It may well be believed, therefore, that the oxidation of
this most important food material is accomplished by the action
of one or more enzymes. Such facts as these lend great probability
to the belief that eventually it will be shown that the oxidations in
the body are effected by the influence of oxidases or peroxidases
acting singly, or in combination, or in sequence with the hydrolytic
enzymes.

While it is perfectly obvious that more facts are needed before
positive statements are warranted regarding the chemistry of the
oxidations in the body, the view entertained regarding the general
process in the body is that the material — protein, fat, or carbohy-
drate— is first split into simpler products by the action of a hy-
drolytic enzyme, or a series of hydrolytic enzymes, formed in the
cells. These reactions are not attended by any marked formation
of heat. The split products thus produced are then acted upon by
oxidases with the formation of certain intermediate products and
eventually of carbon dioxid, water, etc., and the liberation of heat.
A specific instance of this serial action has been given in reference
to the oxidation of sugar (p. 869) : According to Stoklasa, the sugar
is first split into lactic acid, and this into carbon dioxid and alcohol;
the alcohol then by the action of a series of oxidases is oxidized to
acetic acid, formic acid, carbon dioxid, and water. From our
present standpoint, the production of heat in the body, it is impor-
tant also to bear in mind the general view advocated by Speck and
others — namely, that the chemical changes or metabolism of the
body may be divided into two general classes: first, the heat-produc-
ing or energy-liberating metabolism, which results finally in the
oxidation of the great mass of the food material and which is
essential for the production of body heat, and, second, the tissue
metabolism proper — that is, the synthesis and disassimilation
of the living substance itself. This latter metabolism varies
probably in the different tissues; it is concerned with the building
up and breaking down of the living machinery and is attended by
the absorption as well as the liberation of heat, and the energy
necessary for effecting these reactions is obtained from the heat
energy liberated by the oxidation processes. In this last thought
there is contained a suggestion which may serve as an explanation
of the fundamental value of the physiological oxidations to the

* For further details see < >ppenheimer, "Die Fermente und ihre Wir-
kungen," second edition, V.W,,

PHYSIOLOGICAL OXIDATIONS. 923

body. It may be supposed that these oxidations furnish not only
the energy used in the work done generally by the cells but also
the energy necessary for the anabolic or synthetic metabolism of
living matter, that is to say, the construction of the complex
and unstable protoplasm. In those organisms or cells that lead
an anaerobic existence — that is, an existence in the absence of
free oxygen — the energy necessary for the process is obtained
perhaps from hydrolytic changes alone.

SECTION IX.
THE PHYSIOLOGY OF REPRODUCTION.

With the exception of the phenomenon of consciousness, na
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-
!< i more emphasis is laid upon this side, the accessory phenomena
of reproduction, than upon the deeper, more fundamental prob-

92 I

THE FEMALE REPRODUCTIVE ORGANS. 925

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 membrana granulosa and attached to one side
is a mass of the same cells, the discus proligcrus — within which
the ovum is imbedded. The follicular liquid lies between. This
liquid increases in amount, and when the follicle has reached the

926 THE PHYSIOLOGY OF REPRODUCTION.

surface it forms a vesicle projecting to the exterior. This projecting
portion is nearby 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, atwhich 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.

THE FEMALE REPRODUCTIVE ORGANS. 927

The majority of writers seem to favor the latter view.* Regarding
the physiological importance of the corpus opinions also differ.
Some regard it as simply a protective mechanism by means of
which the empty space in the follicle is filled up by a tissue which is
afterward easily absorbed, instead of by scar tissue. Others, how-
ever, attribute to the lutein cells secretory functions of the most
important character in connection with the subsequent develop-
ment of the egg and the activities of the uterus. Some reference
will be made to these views farther on.

Menstruation. — The attainment of sexual maturity or puberty
is marked by a number of visible changes in the body, but in the
female the characteristic change is the appearance of the men-
strual flow from the uterus. The age at which this phenomenon
occurs shows many individual variations, but the average for
temperate climates is given usually at 14 to 15 years. In the
warmer countries the age is earlier, — 8 to 10 years, — and in the cold
regions somewhat later, — 16 years. The racial characteristic in
this respect is said to be maintained, however, after generations of
residence 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

* For discussion and literature see Marshall, "Quarterly Journal Micro-
scopical Science," 1905, xlix., 189; and Loeb, "Journal of the American
Medical Association," 1906, xlvi., 416.

928 THE PHYSIOLOGY OF REPRODUCTION.

menstruation, and it is not infrequently associated with psychical
and physical disturbances of a serious character. If at any time
during sexual life the ovaries are completely removed by surgical
operation menstruation is brought to a close, this condition being
designated as artificial menopause.

Structural Changes in the Uterus During Menstruation. — Men-
struation is a phenomenon of the uterus. The lining mucous mem-
brane, the endometrium, in the period of four or five days preceding
the flow, becomes rapidly thicker and its superficial layers are con-
gested with blood, and indeed in places small collections of blood
may be noticed. Opinions differ very much as to the change under-
gone by this thickened membrane during the flow. According to
some authors, most of the membrane is thrown off and the blood
escapes from the denuded surface mixed with pieces of the mem-
brane. According to others, no material destruction of the mem-
brane occurs, the blood that escapes being due to small capillary
extravasations or perhaps mainly to a process of diapedesis. It
would seem that the amount of destruction of the endometrium
must be subject to individual variations. After the cessation of
the flow the mucous membrane is rapidly repaired by regenerative
changes in the tissues; the surface epithelium, if denuded, is re-
placed by proliferation of the cells lining the uterine glands and
the thickened, edematous condition of the membrane rapidly sub-
sides during a period of six or seven days. While the escape of
blood takes place only from the surface of the uterus, the other
reproductive organs — the ovary, the Fallopian tubes, and even the
external genital organs — share to some extent in the vascular con-
gestion exhibited by the uterus during the period preceding the
menstrual flow. The mucous membrane of the uterus may be said
to exhibit a constantly recurring menstrual cycle which falls into
four periods: (1) Period of growth in the few (5) days preceding
menstruation, characterized by a rapid increase in the stroma,
blood-vessels, epithelium, etc., of the membrane. (2) The men-
struation or period of degeneration (4 days), during which the
capillary hemorrhage takes place and the epithelium suffers de-
generative changes and is cast off more or less. (3) The period of
regeneration (7 days), during which the mucous membrane returns
to its normal size. (4) The period of rest (12 days), during which
the endometrium remains in a quiescent condition.

The Phenomenon of Heat (CEstrus) in Lower Mammals. —
The phenomenon known as heat in lower mammals resembles, in
many essential respects, menstruation in human beings, and they
may be regarded as homologous functions. Heat is a period of
sexual excitement which occurs one or more times during the year
and during which the female will take the male. The condition

THE FEMALE REPRODUCTIVE ORGANS. 929

lasts, as a rule, for several days, and in the female is accompanied
by changes which resemble those of menstruation. The external
genital organs become swollen and in many animals there is a
discharge of mucus or mucus and blood from the uterus. His-
tologically the mucous membrane of the uterus undergoes changes
similar to those of menstruation — that is, the membrane increases
in size and becomes congested with blood — and it exhibits a phase
of degeneration during which some of the epithelial lining may be
cast off and some hemorrhage occur. As in the case of the men-
strual period, the heat period or cestrous cycle may be divided into
four subperiods (Marshall and Jolly) : the procestrum, during which
the genital organs are congested and bleeding occurs, corresponds
with menstruation; the oestrus, the period of sexual desire; the
metoestrum, the period of repair and return to normal conditions,
and the anoestrum, the period of rest. If sexual union is prevented
during this period heat passes away in a few days, but recurs again
at intervals which vary in the different mammals: 4 weeks in the
monkey, mare, etc.; 3 to 4 weeks in the cow; 2\ to 4 weeks in the
sheep; 9 to 18 days in the sow; 12 to 16 weeks in the bitch, etc.
The recurrence of the period under these circumstances suggests
at once the essential resemblance to the monthly periods of women.
According to Heape's most interesting observations upon monkeys
(Semnopithecus),* some of these animals show a regular monthly
flow lasting for 4 days, except when conception takes place. The
changes during heat must be considered as physiologically ho-
mologous to those of menstruation. The sexual excitement that
attends the condition in the lower animals is not distinctly repre-
sented in man, although it is commonly said that in the period pre-
ceding or following menstruation the sexual desire is stronger than
at other times, but in the changes undergone by the uterus and the
fact that these changes are connected, as a rule, with the liberation
of an egg from the ovary (ovulation), the two phenomena are
physiologically similar.

Relation of the Ovaries to Menstruation. — It appears to be
clearly demonstrated that the phenomenon of menstruation is de-
pendent upon a periodical activity in the ovaries. When the
ovaries are completely removed menstruation ceases (artificial
menopause) and the uterus undergoes atrophy. When the ovaries
are congenitally lacking or rudimentary, a condition of amenorrhea
also exists. These facts and the connection of the ovaries with
menstruation are further corroborated in a striking way by experi-
ments upon transplantation or grafting of the ovary. This experi-
ment has been performed upon lower animals (apes) as well as upon

*Heape, "Philosophical Transactions, Royal Society," 185 (B), 1894,
and 188 (B), 1897.
59

930 THE PHYSIOLOGY OF REPRODUCTION.

human beings. Removal of both ovaries in apes is followed by a ces-
sation of menstruation. Transplantation of an ovary under the skin
serves to maintain menstruation, but if subsequently removed this
function disappears.* In the human being Morris and Glass ob-
tained similar results. f An ovary or a piece of an ovary trans-
planted into the uterus itself or the broad ligament caused a re-
turn of the menstrual periods which had ceased after surgical re-
moval of the glands, or brought on free menstruation in conditions
of amenorrhea or dysmenorrhea.

Man}- 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, as a rule,
the two acts occur together, not simultaneously, but in a definite
sequence, and the significance of menstruation is to be found in its
physiological connection with 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 Reinf have shown by
experiments upon dogs that when the nerves going to the uterus
are completely severed from their central connections the animals
can be fertilized, become pregnant, and give birth to a litter of
young. Moreover, the experiments upon transplantation referred
to above seem to show quite conclusively that a nervous connection
is not essential to the influence that the ovary exerts upon the
uterus. The present view, therefore, is that this influence is exerted
through the blood, — the other great system connecting the organs
with one another. The usual assumption is that the ovaries form an
internal secretion which is given to the blood or lymph and upon
reaching the uterine tissues serves to stimulate the mucous mem-
brane to a more active growth. This theory has been elaborated

* Halban, "Deutsche Gesellschaft f. Gynakol, " 9, L901.

tGlass, "Medical News," 523, L899; Morris, "Medical Record," 83, VjOl.

X Rein " Archiv I', die gesammte Physiologic," vol. xxiii.

THE FEMALE REPRODUCTIVE ORGANS. 931

most fully perhaps by Fraenkel,* who believes that this internal
secretion is furnished by the yellow cells of the corpus luteum.
This observer, from the results of operations upon women, believes
that the ovum is normally discharged two weeks before menstrua-
tion, and the resulting increased activity of the cells of the corpus
luteum is responsible for the secretion which stimulates the uterus
to the augmented growth that takes place in the premenstrual
period. Whether or not the monthly change in the endometrium
is directly dependent upon an internal secretion from the ovary or
is an independent cyclic process peculiar to this tissue, there seems
to be no doubt that the physiological integrity of the uterus as a
whole is dependent upon the ovaries. Removal of the ovaries
in the young prevents the normal development of the uterus,
while removal in the adult causes a degeneration of the uterus,
which, however, can be averted by a successful transplantation
of ovarian tissue, f In the lower animals Marshall and Jolly J
have been able to show that extracts of the ovaries, taken from
an animal in or just before heat (procestrous or cestrous period),
when injected into an animal during the ancestrum bring on a
transient condition of heat. These authors do not believe, how-
ever, that the chemical stimulus (hormone) formed in the ovary
is developed by the cells of the corpus luteum, since according
to their observation on cats and dogs ovulation does not occur
until after heat has begun (prooestrum).

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

* Fraenkel, "Archiv f. Gynakologie, " 68,2, 1903. See also Ihm,
" Monatssehrif t f. Geburtshiilfe u. Gynakol.," 21, 515, 1905, for discussion
and extensive literature.

f Carmichael and Jolly, "Proc. Roy. Soc.," B, 79, 1907, and Marshall
and Jolly, "Roy. Soc. Edinb.," 45, 589, 1907.

{Marshall and Jolly, "Philosophical Transactions, Royal Society,"
London, 1905, B. cxcviii., 99.

932 THE PHYSIOLOGY OF REPRODUCTION.

or a portion of it is cast off in the menstral flow, while the re-
mainder is absorbed. According to this view, menstruation is an
indication that fertilization has not taken place.* This view
falls in with the belief that ovulation normally precedes menstrua-
tion by a considerable interval. A modification or extension of
this general hypothesis is proposed by Bryce and Teacher. f
They believe that the process of menstruation is a cyclic one,
which has for its object the preparation of the endometrium for
the reception of the ovum. The monthly regeneration keeps
this membrane in that condition of youthful irritability which
enables it to respond promptly to the stimulus of the ovum by
the formation of a decidua. The other point of view was advo-
cated especially by Pfliiger in connection with his theory of a
common cause of ovulation and menstruation. He assumed that
menstruation occurs before the ovum reaches the uterus and that
its physiological value lies in the fact that a raw surface is thus made
upon which the ovum is grafted. Menstruation, according to him,
is an operation of nature for the grafting of the fertilized ovum
upon the maternal organism. This view finds considerable support
in the fact that in some of the lower animals (dogs) the flow of
blood (procestrum) precedes fertilization.

The Effect of the Menstrual Cycle on Other Functions. — It
is natural to suppose that such marked changes as occur in the
ovary and uterus during the menstrual cycle should have an in-
fluence upon other parts of the body. As a matter of fact, it is
known that in general the sense of well-being varies with the phases
of the cycle. At the time of or in the period just preceding the
menstrual flow there is usually a more or less marked sense of ill-
being or despondency, and a diminution in general efficiency.
Among the various observations made by objective methods upon
the functions of the different organs during these periods the most
significant, probably, are those upon blood-pressure. According
to Mosher,J 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
thai ilic author quoted above obtained similar periodical falls in

* This view finds expression in the aphorisms: ['Women menstruate
becau e they do no1 conceive," Powers, and "The menstrual crisis is the
physiological bomologue of parturition," Jacobi.

t Bryce and Teacher, " Early Developmenl and Imbedding of the Human
Ovum,"' L908.

% Mosher, "The Johns Hopkins Hospital Bulletin," 1901.

THE FEMALE REPRODUCTIVE ORGANS. 933.

blood-pressure in men, suggesting the idea that has frequently been
expressed, that in man as well as woman there is a rhythmical
activity of the genital organs, a reproductive cycle that in man
may be referred to the development and extrusion of the sperma-
tozoa in the testis, as in woman it is connected with the growth and
expulsion of the ova in the follicles of the ovary.

The Passage of the Ovum into the Uterus. — The means by
which the ovum gains entrance to the Fallopian tubes has given
rise to much speculation and some interesting experiments. It
was formerly believed (Haller) that at the time of ovulation the
fimbriated end of the Fallopian tube is brought against the ovary,
the movement being due to a congestion or a sort of erection of the
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 movements of the ovum. Attention has been called
to the fact that in animals with a bicornate uterus the ova may
be liberated from the ovary on one side, as shown by the presence
of the corpora lutea, while the embryos are developed in the horn
of the other side. As further evidence for the same possibility of
migration it has been shown that the ovary may be excised on one
side and the horn of the uterus on the other and yet the animal may
become pregnant after sexual union. It would seem probable,
therefore, that the ovum is discharged into the pelvic cavity and
may be caught up by the ciliary movements at the end of the tube
on the same side, or may traverse the pelvic cavity in the narrow
spaces between the viscera and be received by the tube on the
other side. Such a view explains the possible occurrence of true
abdominal pregnancies, and suggests also the possibility that ova
may at times fail to reach the uterus at all and may undergo de-
struction and absorption in the abdominal cavity. In some of
the lower animals — the dog, for example — provision is made for
the more certain entrance of the ova into the tubes b3^ 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 opposing
force of the ciliary contractions in the uterus. It is known that
the cilia of the tubes and uterus contract so as to drive inert

'

=y=i=

— — d

"

-n

./

/

934 THE PHYSIOLOGY OF REPRODUCTION.

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 fertilization 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 fol-
licular epithelium forming
the corona radiata, which
is subsequently lost. The
egg proper consists of cyto-
plasm and a nucleus or
germinal vesicle containing
a nucleolus or germinal
spot. Within the cyto-
plasm is a definite collec-
tion of food material or
yolk which is sometimes
designated as deutoplasm.
The whole structure is sur-

Fig. 292.— Human ovum (Lee, modified from rOUllded by a membrane

Nagel): n, Nucleus (germinal vesicle) containing l™nwT1 „c + U„ 7nn!, rnrlinfl

tne ameboid nucleolus (germinal spot); d, deu- KllOWn as Xtie ZOna raUlOXa

toplasmic zone; p, protoplasmic zone; z, zona /Tr^o- 9Q9\ T-iofnvp nv nfrpr

racliata; s, perivitellin space. \r l&- ***)• J^eiOie Ol dl lei

the egg reaches the Fal-
lopian tube its nucleus undergoes the changes preparatory to
a mitotic division. The changes that occur in an ordinary cell
division are represented schematically in Fig. 293. 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 (b) 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
ca'-h 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

Fig. 293. — Schematic representation of the processes occurring during cell division.-

CBoveri.)

THE FEMALE REPRODUCTIVE ORGANS. 935

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 membrane and the chromatin substance increases in
quantity. In the ovum during maturation two successive cell-
divisions occur which resemble the typical cell-division just
described, except that the daughter-cells are of very unequal size
and that they contain each only half the normal number of
chromosomes. In the first division, known sometimes as the
heterotypical division, the process is preceded by a fusion of the
chromosomes in pairs. In the division that ensues the pairs of
chromosomes are split, one part going to each cell, with the result
that each of the latter now contains half the number of chromo-
somes— and each chromosome is an entire one from the parent
cell, instead of half a one, as in the usual cell division. The two
resulting cells are of very unequal size, the larger one is designated
still as the ovum, the smaller one as the first polar body. The
ovum now divides again (homotypical division), throwing off a
second polar body. In this division the chromosomes, according
to some observers, divide transversely, according to others, they
divide longitudinally as in typical cell division.* In the formation
and extrusion of the two polar bodies the matured ovum has suf-
fered a quantitative and perhaps a qualitative reduction in chroma-
tin material, 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 abor-
tive 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. 294. The details of this process of forma-
tion of the polar bodies and of reduction in chromatin material
differ somewhat in different animals, f The process has not been
followed in the human ovum, but since it occurs in the eggs of all
animals with sexual reproduction, so far as they have been studied,
it is justifiable to assume that a similar change takes place in man.
From a biological standpoint the reduction of chromosomes and
the loss of the centrosome, or of the power to produce a centrosome,
throw much light upon the significance of fertilization by the male
cell. The spermatozoon before it is ripe undergoes a process of
maturation essentially similar to that described for the ovum.

* For further details see Bryce in Embryology, " Quain's Anatomy," 1908.
t For details see Wilson, " The Cell in Development and Inheritance,"
second edition, 1900, New York.

936

THE PHYSIOLOGY OF REPRODUCTIOX.

Two cell divisions take place with the formation of four spermatozoa,
each of which, however, is a functional spermatozoon. In the pro-
cess of division the number of chromosomes in each cell is reduced

—-First polar doqv

Mature egg vS^li T • * Abortive ova resulting

from division of first
polar body.

Second polar body (abortive ovum).
Fig. 294. — Schema to indicate the process of maturation of the ovum. — (Boveri.)

by half. When the matured ovum and the matured spermatozoon
fuse, therefore, each brings half the normal number of chromosomes,
and the resulting fertilized ovum is a cell with its chromosomes
restored to their usual number. The chromatin material is the
essential part of the reproductive element. We have reasons to
believe, in fact, that it is the substance which has the power of
development and which conveys the hereditary structure specific
to the animal. The process which causes each element to lose a
part of this material before its union with the cell of the opposite
sex is a provision by means of which the fertilized egg, from which
the offspring develops, shall inherit the characteristics of each parent,
without increase in the typical amount of the chromosomes. The
loss of the centrosome by the matured egg is interpreted by Boveri
as follows:* 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 develop-
ment, but in the act of fertilization the spermatozoon brings into
the egg a new centrosome, or causes the formation of a new centro-
some after its entrance, and thus initiates a process of cell mul-
tiplication. From this standpoint the loss of the centrosome by
the egg is a provision to necessitate sexual union, and thus insure
the benefits that presumably are associated with the fusion of two
cells originating from different individuals.

Fertilization of the Ovum. — The spermatozoon comes into
contact with the ovum probably at the beginning of the Fallopian
tubes. The meeting of the two cells is possibly not simply a matter
of accidental contact, although the number of spermatozoa dis-
charged by the male at coitus is so great that there would seem

* For :i popular presental ion sec Boveri, " Dun Problem der Befruchtung,"
Jena, 1902.

Fig. 295. — 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. 937

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. 295, taken from Boveri, the maternal and paternal chromo-
somes being indicated by different colors. According to this descrip-
tion, both egg and spermatozoon are incomplete cells before fusion.
The egg contains a nucleus and a large cell body, cytoplasm, rich in
nutritive material, but it lacks a centrosome or the conditions neces-
sary for the formation of an astrosphere, so that it cannot mul-
tiply. The spermatozoon has also chromatin for a nucleus, and
a centrosome or the material which may give rise to a centrosome,
but it lacks cytoplasm — that is, food material for growth. It
would seem that if the spermatozoon could be given a quantity
of cytoplasm it would proceed to develop an embryo without the
aid of an ovum. This experiment has, in fact, been made by

938 THE PHYSIOLOGY OF REPRODUCTION.

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,
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.f The further
development of the egg into a fetus, the formation of the decidua
graviditatis, and the placenta are anatomical features that need
nol be described here. Detail of these structures will be found

* Loeb, " University of California Publications," 2, pp. 83, 89, and 113,
1905. See also Wilson," "Archiv f. entwick. Mechanik," 12, L901.

f See Minot,0' Transactions of the American Gynecological Society," 1904.

THE FEMALE REPRODUCTIVE ORGANS. 939

in works on anatomy, embryology, or obstetrics. On the phys-
iological side it has been found that removal of the ovaries, or even
destruction of the corpora lutea, shortly after pregnancy has begun
brings the process to an end, while a similar operation later in
pregnancy has no effect upon the developing fetus or the subsequent
act of parturition. It seems, therefore, that the process of implan-
tation of the ovum in the uterine mucous membrane and the devel-
opment of a placenta are dependent in some way upon the ovaries.
The apparent explanation of the connection is given in the hypothe-
sis that the corpora lutea, during their rapid development at the
beginning of pregnancy, give off an internal secretion which controls
or influences in some essential way the processes connected with
the fixing of the fertilized ovum.*

The Nutrition of the Embryo — Physiology of the Placenta.
1 — 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 papilla? from
the fetus bathed in large blood-spaces in the decidual membrane of
the mother. The fetal and the maternal blood do not come into
actual contact ; they are separated from each other by the 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, protein, fat, and carbohydrate, and oxygen pass from
the maternal to the fetal blood, and the waste products of fetal
metabolism — carbon dioxid, nitrogenous wastes, etc., pass from the
fetal to the maternal blood. The nutrition of the fetal tissues is
maintained, in fact, in much the same way as though it were an
actual part of the maternal organism. That material passes from
the maternal to the fetal blood is a necessary inference from the
growth of the fetus. The fact has also been demonstrated repeat-
edly by direct experiment. Madder added to the food of the mother
colors the bones of the embryo. Salts of various kinds, sugar, drugs,
etc., injected into the maternal circulation may afterward be de-
tected in the fetal blood. But we are far from having data that
* Marshall and Jolly and Fraenkel, loc. cit.

940 THE PHYSIOLOGY OF REPRODUCTION.

would justify us in supposing that the exchange between the
two bloods is effected by the known physical processes of os-
mosis, diffusion, and filtration. The difficulties in understanding
the exchange in this case are the same as in the absorption of nour-
ishment by the tissues generally. It is perhaps generally assumed
that the chorionic villi play an active part in the process, func-
tioning, in fact, in much the same way as the intestinal villi. This
assumption implies that the epithelial cells of the villi take an active
part in the absorption of material by virtue of processes which can-
not be wholly explained, but which without doubt are due to the
chemical and physical properties of the substance of which they are
composed. This assumption does not mean that the simpler
and better understood physical properties of diffusion and osmosis
are not also important. The respiratory exchange of gases, the
diffusion of water, salts, and sugar, may be largely controlled in this
way. There are no facts at least which contradict such an assump-
tion. The passage of fats and proteins, 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 FEMALE REPRODUCTIVE ORGANS. 941

the meconium, which shows that the motor and, secretory functions
of the intestinal canal may be present in the last months of fetal
life. From the pancreas a proteolytic enzyme may be extracted at
the time of birth or before, but the amylolytic enzyme is not formed
apparently until some time later. It is stated, at least, that it is
not present at birth. In general, it is evident that for a long period
the maternal organism digests and prepares the food for the 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 fetus on the mammary
gland is treated in a separate paragraph below. In addition to
these two visible effects it is evident that the growth of the fetus
has an important influence on general metabolism and therefore
upon the whole maternal organism. This fact is indicated by the
marked changes often exhibited in the physical and mental con-
dition of the mother. It is shown more precisely by a study of the
nutritional changes. Numerous investigations have been made
upon this subject, especially as regards the nitrogen equilibrium.
During the latter part of pregnancy, especially, the nitrogen balance
is positive — that is, nitrogen is stored as protein — due doubtless
both to the growth of the embryo and the increase in material in
the uterus and mammary gland. The proportion of ammonia in

942 THE PHYSIOLOGY OF REPRODUCTION.

the urine increases during pregnancy and especially during labor
(Slemmons*).

Parturition. — The fetus " comes to term " usually in the tenth
menstrual period after conception — that is, about 280 days after
the last menstruation. The actual time of delivery, however
shows considerable variation. Delivery occurs in consequence of
contractions, more or less periodical, of the musculature of the-
uterus, and reflex as well as voluntary contractions of the abdom-
inal muscles. It has been shown that delivery ma}r 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-
aras. 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-

■■ Slemmons, "The Johns Hopkins Hospital Reports," 12, ill, 1904.

THE FEMALE REPRODUCTIVE ORGANS. 943

After delivery the gland evidently is again brought under the
influence of special stimuli. It becomes rapidly enlarged and a
more abundant secretion is formed. For the first day or two
this secretion still has the characteristics of colostrum, but on
the third or fourth day the true milk is formed and thereafter is
produced abundantly, during the period of lactation, under the in-
fluence of the act of milking. If during this period a new con-
ception occurs the milk secretion is altered in composition and
finally ceases. On the other hand, if the act of nursing is aban-
doned permanently the glands after a preliminary stage of turgid-
ity undergo retrogressive changes that result in the cessation of
secretory activity. The colostrum secretion that occurs during
pregnancy and for a day or two after birth differs from milk in
its composition and histological structure. It is a thin, yellowish
liquid containing a larger percentage of albumin and globulin
and a smaller percentage of milk-sugar and fat than normal milk.
Under the microscope it shows, in addition to some fat droplets,
certain large elements, — the colostrum corpuscles. These con-
sist of spherical cells filled with fat droplets, and are most probably
leucocytes filled with fat which they have ingested. Colostrum
corpuscles may occur in milk whenever the secretion of the gland
is interfered with, and their presence may be taken as an indi-
cation of an incomplete secretion.

The Connection Between the Uterus and the Mammary
Gland. — The physiological connection between the uterus and
the mammary gland is shown by the facts mentioned in the pre-
ceding paragraph. That the ovary also shares in this influence
either directly or through its effect on the uterus is shown by
the fact that after complete ovariotomy the mammar}^ 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 qualit}r 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

944 THE PHYSIOLOGY OF REPRODUCTION.

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, the}'' have been sub-
jected to adverse criticism — and they cannot, therefore, be ac-
cepted unhesitatingly.

After apparently complete separation of the gland from all its
extrinsic nerves, not only does the secretion, if it was previously
present, continue to form, although less in quantity, but in opera-
tions of this kind upon pregnant animals the glands increase in size
during pregnancy and become functional after the act of parturi-
tion.* This result confirms the older experiments of Goltz, Rein,
and others, according to which section of all the nerves going to
the uterus does not prevent the normal effect on lactation after
delivery. Regarding the question of the existence of secretory
nerves, Baschf reports that extirpation of the celiac ganglion or
section of the spermatic nerve does not prevent the secretion, but
causes the appearance of colostrum corpuscles.

Experiments, therefore, as far as they have been carried in-
dicate that the gland is under the regulating control of the cen-
tral nervous system, either through secretory or more probably
through vasomotor fibers. The bond of connection between the
mammary gland and the uterus is, however, established mainly
through the blood rather than through the nervous system. Some
direct evidence for this point of view is furnished by the interesting
experiments of Starling and Lane-Claypon.J These authors found
that extracts made from the body of the fetus, or rather from the
bodies of many fetuses, when injected repeatedly into a virgin rabbit
caused a genuine development of the mammary glands closely
simulating the growth that normally occurs during pregnancy.
Since similar extracts made from ovaries, placental and uterine
tissues had no effect, they conclude that a specific chemical sub-
stance (a hormone) is produced in the fetus itself and, after absorp-
tion into the maternal blood, it acts upon the mammary gland, stim-
ulating it to growth. Since the birth of the fetus is followed by
active secretion in the mammary glands they adopt further the
view that this substance, while promoting the growth of the gland
tissue, inhibits the catabolic processes which lead to the formation
of the secretion. With the birth of the fetus this substance is
withdrawn and secretion begins, and, on the contrary, the secretion
is suspended when a new pregnancy is well advanced.

*Mironow, "Archives des sciences biologiques, " St. Petersburg, 3, 353,
1894.

t Basch, "Ergebnisse der Physiologie, " vol. ii., part i, 1903.

+ Lane-Claypon and Starling, "Proceedings of the Royal Society," 1906,
B. lxxvii.; ee al o Starling in "Lancet," 1905.

THE FEMALE REPRODUCTIVE ORGANS. 945

As was said in speaking of the histology of the gland, the se-
creting alveoli are not fully formed until the first pregnancy. Dur-
ing the period of gestation the epithelial cells multiply, the alveoli
are formed, and after parturition secretion begins. As the liquid
is formed it accumulates in the enlarged galactophorous ducts, and
after the tension has reached a certain point further secretion
is apparently inhibited. If the ducts are emptied, by the infant
or otherwise, a new secretion begins. The emptying of the ducts,
in fact, seems to constitute the normal physiological stimulus to
the gland-cells, but how this act affects the secreting cells, whether
reflexly or directly, is not known.

Composition of the Milk. — The composition of milk is com-
plex and variable.* The important constituents are the fats, held
in emulsion as minute oil droplets, and consisting chiefly of olein
and palmitin; casein, a nucleo-albumin which clots under the in-
fluence of rennin; milk-albumin or lactalbumin, a proteid resem-
bling serum-albumin; lactoglobulin; lactose or milk-sugar; lecithin,
cholesterin, phosphocarnic acid, urea, creatin, citric acid, enzymes,
and mineral salts. It is well known also that many foreign sub-
stances—drugs, flavors, etc. — introduced with the food are secreted
in the milk. An average composition is: proteins, 2 to 3 per cent.;
fats, 3 to 4 per cent.; sugar, 6 to 7 per cent.; salts, 0.2 to 0.3 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.

K20 8.5

Na,0 8.2

CaO 35.8

MgO 1.6

Fe203 0.3-1

P,05 39.8

CI 7.3

On account of the use of cows' milk in place of human milk in
the nourishment of infants much attention has been given to

* For data as to composition and hygienic relations, sec Bulletin 41,
"Hygienic Laboratory," Public Health and Marine Hospital Service, U. S.,
Washington, 1908.

60

Dogs' Milk.

Dogs' Serum.

10.7

2.4

6.1

52.1

34.4

2.1

1.5

0.5

0.14

0.12

37.5

5.9

12.4

47.6

946 THE PHYSIOLOGY OF REPRODUCTION.

the relative composition and properties of the two secretions.
The chief difference between the two lies apparently in the casein.
The casein of human milk is smaller in amount, curdles in looser
flocks than that of cows' milk, and seems to dissolve more easily
and completely in gastric juice. The former also contains rela-
tively more lecithin and less ash, particularly the lime salts. On
the other hand, cows' milk contains less sugar and fat. In using
it, therefore, for the nutrition of infants it is customary to add
water and sugar. The composition of cows' milk is so well known
that it is easy to modify it for special cases according to the in-
dications. The rules for this procedure will be found in works
upon pediatrics.

CHAPTER LIII.
PHYSIOLOGY OF THE MALE REPRODUCTIVE ORGANS.

The sexual life of the male is longer than that of the female.
Puberty or sexual maturity begins somewhat later, — in tem-
perate climates at about the fifteenth year; but there is no dis-
tinct limitation of the reproductive powers in old age correspond-
ing to the menopause of the female. At the time of puberty and
for a short preceding period the boy grows more rapidly in stature
and weight, and the assumption of its complete functions by the
testis exerts a general influence upon the organism as a whole.
One of the superficial changes at this period which is very evident
is the alteration in pitch of the voice. Owing to the rapid growth
of the larynx and the vocal cords the voice becomes markedly
deeper, and the change is in some cases sufficiently sudden to cause
the well-known phenomenon of the breaking of the voice. The
neuromuscular control of the vocal cords becomes for a time un-
certain. The completion of puberty can not be determined in the
boy with the same exactness as in the girl, in whom menstruation
furnishes a visible sign of sexual maturity. Much of the sexual
mechanism may be functional long before the time of puberty,
as is shown by the presence of sexual desire and the possibility
of erection; but fully developed spermatozoa are not produced
until this period, and indeed the presence of ripe and functional
spermatozoa in the testis is the only certain sign that sexual ma-
turity has been attained. Puberty consists in the maturation of
the testis in the male, and of the ovary in the female.

The Properties of the Spermatozoa. — The development and
maturation of the spermatozoa in the testis has been followed
successfully by histological means. The mother-cells of the sper-
matozoa, the spermatocytes, give rise to four daughter-cells, sper-
matids, each of which develops into a functional spermatozoon.
The process in this case is something more than mere cell division,
since in the spermatozoa eventually produced the number of
chromosomes present in the nucleus — that is, the head of the sper-
matozoon— are reduced by one-half. The process of production
of the spermatozoa is therefore quite analogous to the maturation
of the ovum during the formation of the polar bodies. The forma-
tion and maturation of the spermatozoa may be represented by

947

94S

THE PHYSIOLOGY OF REPRODUCTION.

a schema similar to that used in the case of the ova, as follows
(Fig. 296) : In the case of the ovum four ova are produced, but
only one is functional, and this one, the ripe egg, is characterized
by its large amount of cytoplasm, its inability to undergo further
cell division until fertilized, owing possibly to its loss of the cen-
trosome, and the reduction of its chromosomes to half the num-
ber characteristic of the body cells of the species. In the case
of the spermatozoa, the four cells produced are all functional,*
and are characterized by the practical loss of cytoplasm, reduc-
tion of chromosomes by one-half, and inability to multiply until
cell material is furnished. The two cells supplement each other,
therefore. Their union restores the normal number of chromo-
somes, part of which are now maternal and part paternal; the egg
supplies the cytoplasm and the spermatozoon nuclear material and
the definite stimulus that leads to multiplication.

The spermatozoa are produced in enormous numbers. It is
calculated that at ejaculation each cubic centimeter of the liquid

contains from sixty to seventy
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. ;is in the case of the polar bodies of the egg.

t See Steinach, " Archivf. d. gesammte Physiologie," 56, 1894, and Walker,
"Archiv f. Anatomie u. Physiologie," ISO!), j>. 313.

Spermatids.

- Spermatozoa.

Fig. 296 — Schema to indicate the proc-
ess of maturation of the spermatozoa. —

(Boveri).

THE MALE REPRODUCTIVE ORGANS. 949

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 motilitj^ 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 great number that may be
present eventually perish. The changes that take place during
the process of fertilization have already been described (p. 936).

Chemistry of the Spermatozoa. — Much chemical work has
been done upon the composition of spermatozoa, particularly in
the fishes. The results have been most interesting from a chem-
ical standpoint, and biologically they are suggestive in that the
analytical work has been done upon the heads of the spermatozoa.
These heads consist entirely of nuclear material, and contain the
substance or substances which convey the hereditary characteristics
of the father. Whatever progress may be made in the understand-
ing of the chemistry of this material is a step toward the solution of
the most difficult and mysterious side of reproduction, the power
of hereditary transmission. Miescher, in investigations upon the
spermatozoa of salmon, discovered that the heads are composed
essentially of an organic combination of phosphoric acid, since
designated as nucleic acid, united with a basic albuminous body,
protamin. This view has been confirmed and extended by later
observers, especially by Kossel and his pupils.* The head of the
spermatozoon, the male pronucleus in fertilization, may be de-
fined, in the case of the fishes at least, as "a salt of an organic
base and an organic acid, a protamin-nucleic acid compound."
The term protamin is used now to designate a group of closely
related substances obtained from the spermatozoa of different
animals. The special protamin of each species is designated ac-
cording to the zoological name of that species; thus the protamin
of salmon is salmin, of hering (Clupea harengus) clupein, and so on.
The protamins are all strong bases; their aqueous solutions give
an intense alkaline reaction, and they unite readily with various
acids to form well-defined salts. They are albuminous bodies,
giving the biuret reaction readily even without the addition of

* For literature and details of the chemistry of spermatozoa see Burian,
in ' Ergebnisse der Physiologie, " vol. iii., part I, 1904, and 1906, v., 832.

950 THE PHYSIOLOGY OF REPRODUCTION.

alkali, and they are precipitated by most of the general precipitants
of proteins, such as the neutral salts, the alkaloidal reagents, etc.
Their solutions, however, are not coagulated by heat. The molec-
ular formula for salmin is given as C30H57N17O6. When decom-
posed by the action of acids they yield simpler basic products,
the so-called hexon bases or diamino-acids, and particularly the
base arginin (C6H14N402), which is contained in the protamin of
the spermatozoa in greater abundance than in any other protein.
The protamins differ from most other protein compounds by their
relative simplicity; they contain no cystin grouping, therefore no
sulphur; no carbohydrate grouping in most of the compounds
examined; and no 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 proteins,
and in general it may be said that the head of the spermatozoon,
like the nuclei of cells in general, consists chiefly of a nucleoprotein
compound, that is, a compound of nucleic acid with a protein body
of a more or less distinctly basic character.* The nucleic acid com-
ponent of the spermatozoon resembles the same substance as
obtained from the nuclei of other cells. In the spermatozoa of the
salmon this nucleic acid has the formula C40H56NuP4O26. On
decomposition by hydrolysis it yields at first some of the purin bases
(adenin, guanin), and on deeper cleavage a number of compounds,
including the pyrimidin derivatives, thymin, uracil, and cytosin.
While the chemical studies upon spermatozoa, thus briefly referred
to, have greatly extended our knowledge, it is still impossible to
say that they have given any information concerning the peculiar
functions of the spermatozoa in fertilization.

The Act of Erection. — In the sexual life of the male the act of
erection of the penis during coitus offers a most striking physical
phenomenon. During this act the penis becomes hard and erect,
owing to an engorgement with blood. The structure of the corpora
cavernosa and corpus spongiosum is adapted to this function, being
composed of relatively large spaces inclosed in trabeculse of connec-
tive and plain muscle tissue, — the so-called erectile tissue. Many
theories have been proposed to explain the mechanism of erection,
but it is generally agreed that the work of Eckhard f demonstrated
the essential facts in the process. This investigator discovered that
in the dog stimulation of the nervi erigentes causes erection. These
nerves are composed of autonomic fibers arising from the sacral por-
tion of the spinal cord (see Figs. 110 and 111). They arise from the

* Burian, loc. dt.

t Eckhard, "Beitrage zur Anatomie und Physiologie, " 3, 123, 1803, and
4, 69, 1869.

THE MALE REPRODUCTIVE ORGANS. 951

sacral spinal nerves, first to third (dog), on each side and help to
form the pelvic plexus. They contain vasodilator fibers to the penis,
as well as to the rectum and anus, and also visceromotor fibers to the
descending colon, rectum, and anus. Eckhard, Loven, and others *
have shown that when these fibers are stimulated there is a large
dilatation of the arterioles in the erectile tissue of the penis and a
greatly augmented blood-flow to the organ. If the erectile tissue
is cut or the dorsal vein is opened the blood-flow under usual con-
ditions is a slow stream, but when the nervus erigens is stimulated
the outflow is very greatly increased; according to Eckhard's
measurements, eight to fifteen times more blood flows out of the
organ. The act of erection is therefore due essentially to a vas-
cular dilatation of the small arteries whereby the cavernous spaces
become filled with blood under considerable pressure. The caver-
nous tissues are distended to the limits permitted by their tough,
fibrous wall. It seems probable that the turgidity or rigidity of
the congested organ is completed by a partial occlusion of the
venous outflow, which is effected by a compression of the efferent
vein by means of the extrinsic muscles (ischio and bulbocavernosus)
and possibly by the intrinsic musculature as well. This compres^
sion does not occlude the blood-flow completely, but serves to in-
crease greatly the venous pressure. This explanation of the act of
erection, while no doubt correct, so far as it goes, leaves undeter-
mined the means by which the dilatation of the small arteries is
produced. Vasodilator nerve fibers in general are assumed to pro-
duce a dilatation by inhibiting the peripheral tonicity of the
arterial walls. If this explanation is applied to the case under
consideration it forces us to believe that throughout life, except
for the very occasional acts of erection, the arteries in the penis
are kept in a constant condition of active tone. Moreover, on this
view we should expect that section of the vasoconstrictor fibers to
the penis, by abolishing the tone of the arteries, would also cause
erection. These constrictor fibers arise fiom the second to fifth
lumbar spinal nerves, and reach the organ by way of the hypo-
gastric nerve and plexus and the pudic nerve. No such result of
their section is reported and it seems that in the matter of erec-
tion the actual mechanism of the great dilatation caused by the
nervi erigentes still contains some points that need investigation.

The Reflex Apparatus of Erection and Ejaculaticn. — The
dilatation of the arteries of the penis during erection is noimally a
reflex act, effected through a center in the lumbar cord. This center
may be acted upon by impulses descending from the brain, as
in the case of erotic sensations, or by afferent impulses arising in

*See especially Francois-Franck, "Archives de Physiol, norm, etpathol.,"
1895, 122 and 138.

952 THE PHYSIOLOGY OF REPRODUCTION.

some part of the genital tract, — from the testes themselves, from
the urethra or prostate gland, and especially from the glans penis.
Mechanical stimulation of the glans leads to erection, and Eckhard
showed in dogs that section of the pudic nerve prevents this reflex
from occurring, proving, therefore, that the sensory fibers concerned
run in the pudic nerve. Stimulation of these latter fibers leads also
to erotic sensations and eventually to the completion of the sexual
orgasm. This latter act brings about the forcible ejection of the
sperm through the urethra. It is initiated by contractions of the
musculature of the vasa deferentia, ejaculatory duct, the seminal
vesicles, and the prostate gland, which force the spermatozoa, to-
gether with the secretions of the vesicles and prostate gland, into
the urethra, whence they are expelled in the culminating stage of
the orgasm by the rhythmical contractions of the ischiocavernosus
and bulbocavernosus muscles, together with the constrictor urethrse.
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 Physiologie/
vol. xi, 1903.

CHAPTER LIV.

HEREDITY— DETERMINATION OF SEX— GROWTH AND

SENESCENCE.

Heredity. — The development of the fertilized ovum offers two
general phenomena for consideration: First, the mere fact of mul-
tiplication by which an infinite number of cells are produced by
successive cell-divisions; second, the fact that these cells become
differentiated in structure in an orderly and determinate way so as
to form an organism of definite structure like those which gave
origin to the ovum and the spermatozoon. In other words, the
fertilized ovum possesses a property which, for want of a better
term, we may designate as a form-building power. The ovum
develops true to its species, or, indeed, more or less strictly in accord-
ance with the peculiarities of structure characteristic of its parents.
The object of a complete theory of heredity is to ascertain the me-
chanical causes — that is, the physicochemical properties — resi-
dent in the fertilized ovum which impel it to follow in each case a
definite line of development. The discussions upon this point have
centered around two fundamentally different conceptions designated
as evolution and epigenesis.

Evolution and Epigenesis. — The earlier embryologists found a
superficial explanation of this problem in the view that in the germ
cells there exists a miniature animal already preformed, and that
its development under the influence of fertilization consists in a
process of growth by means of which the minute organism is
unfolded, as it were. The process of development is a process of
evolution of a pre-existing structure. Inasmuch as countless in-
dividuals develop in successive generations, it was assumed also
that in the germ cell there are included countless miniature organ-
isms,— one incased, as it were, in the other. Some of the embry-
ologists of that period conceived that the undeveloped embryos are
contained in the ovum, — the ovists, — while others believed that
they are present in the spermatozoon, the animalculists. Other
embryologists pointed out that the fertilized egg shows no indication
of a preformed structure, and therefore concluded that development
starts from an essentially structureless cell, and consists in the
successive formation and addition of new parts which do not pre-

953

954 THE PHYSIOLOGY OF REPRODUCTION.

exist as such in the fertilized egg. This view in contradistinction
to the evolution theory was designated as epigenesis. Microscopi-
cal investigation has demonstrated beyond all doubt that 'the fer-
tilized ovum is a simple cell devoid of any parts or organs resem-
bling those of the adult, and the evolution theory in its crude form
has been entirely disproved. Nevertheless the controversy be-
tween the evolutionists and epigenesists still exists in modified
form. For it is evident that in the fertilized ovum there may exist
preformed mechanisms or complexes of molecules which, while in no
way resembling anatomically the subsequently developed parts of
the organism, nevertheless are the foundation stones, to use a figure
of speech, upon which the character of the adult structure depends.
Such a view in one form or another is probably held by most bi-
ologists, since it avoids the well-nigh inconceivable difficulties of-
fered by a completely epigenetic theory. If the fertilized ovum
of one animal is in the beginning substantially similar to that of
any other animal the epigenesist must ascertain what combination
of conditions during the process of development causes the egg,
in a clog, for instance, to develop always into a dog, and moreover
into a certain species of dog resembling more or less exactly the
parent organisms. The infinite difficulties encountered by such a
point of view are apparent.at once. In this, as in other similar prob-
lems, experimental work is gradually accumulating facts which
throw some light upon the matter and may eventually lead us to the
right explanation. It has been made highly probable that the chro-
matin material in the nuclei of the germ cells, the chromosomes,
constitute the physical basis of hereditary transmission. In the
fertilized egg, it will be remembered, half of the chromosomes come
from the mother and half from the father, and there is good reason
for believing that the maternal chromosomes are the bearers of the
maternal characteristics, and the chromosomes derived from the
spermatozoon convey the hereditary peculiarities of the father.
Such a view, it will be noticed, implies at once preformed structures
in the chromosomes and constitutes one form of an evolutionary
hypothesis. This view is further supported by the interesting ex-
periments of Wilson.*

This author has shown that in certain molluscs (Dentalium or
Patella) if a portion of the egg is cut off, the remaining portion upon
fertilization develops into a defective animal that is not a whole
embryo, but rather a piece or fragment of an embryo. Or if the
fertilized egg after its first segmentation is separated artificially
into two independent cells each develops an embryo, but neither one
is completely formed, — each is lacking in certain structures and

* Wilson, "Science," February 24, 1905, for a popular discussion; also
"Journal of Experimental ZoSlogy," 1, 1 and 197, 1904, and 2, 371, 1905.

HEREDITY. 955

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 all these theories, but a word may be
said regarding the work of cle Vries and Mendel, which have given
rise recently to so much discussion. For fuller information the
reader is referred to special treatises on the subject. f According
to the well-known views of Darwin in regard to the action of
natural selection it was assumed that new varieties and species
are formed by the cumulative action of selection upon small
fluctuating variations. By this cumulative selection certain
variations are preserved and strengthened until thejr are suffi-
ciently marked to constitute a specific difference, the process
requiring naturally a long period of time. In contrast with this
view de Vries has suggested what is commonly known as the
theory of mutations. According to this view the variability in
the germ plasm is such that it may at times give rise not to fluctu-
ating variations but to marked and permanent variations, and

* For a discussion of these facts and for various hypotheses, see Morgan,
"Regeneration," New York, 1901.

t Hertwig, "The Biological Problems of To-day"; Delage, "L'heredite-
et les grands problemes de la biologic generale," 1903; Thomson, "Heredity,"
1908; Kellogg, "Darwinism To-day," 1908; Jordan and Kellogg, "Evolution
and Animal Life," 1907.

956 THE PHYSIOLOGY OF REPRODUCTION.

these latter, if advantageous to the animal, are preserved by
natural selection. Such permanent variations are known as
mutations or ''sports/' and in consequence of their formation
and preservation the process of evolution may proceed much
more rapidly than was assumed to be the case in the original
form of Darwin's hypothesis. The contribution made to our
understanding of heredity by the work of Mendel and those who
have used his conceptions is most significant. By the Menclelian
law or Menclelian inheritance is meant in the first place the general
idea that characteristics handed down by inheritance from parents
to offspring may be treated as separate units. In some cases
parental characteristics may blend in the children, as for example,
in the case of color, the mulatto being in this regard a blend of a
white and a black parent. In other cases, however, there is no
blending, but an alternation of one or the other of a pair of con-
trasting characteristics. As regards such a pair of alternating
characteristics Mendel found that one will be dominant, the other
recessive, whenever they are brought together. That is to say,
if each parent possesses one of such alternating characteristics,
brown eyes and blue eyes, for example, the children will all show
the dominant characteristic, in this case brown eyes, but the
other characteristic will be present in a recessive or concealed
form. In the hybrids possessing both characteristics the germ
cells are so divided that half of them possess the dominant alone
and half the recessive alone. This constitutes the law of the
"purity of the germ cells" or of the " segregation of the gametes."
If two such hybrids breed together it follows from the law of
probabilities that in the offspring three out of four will show the
dominant characteristic and one the recessive characteristic.
Moreover, of those that show the dominant characteristic two will
be hybrids, containing also the recessive, but one will be a pure
dominant. This result may be understood from the following
formula, in which D and R represent respectively the dominant
and the recessive:

D— Tt

| | = 1 DD, 2D(R) and 1 RR.

U— R

If two pure recessives or two pure dominants breed together, only
a recessive or a dominant, as the case may be, will be exhibited
in the offspring, and in this way pure characteristics may be
selected and established. Such a process of selection is simple in
the case of the recessive characteristics; but in the case of the
dominant it is, of course, more difficult to distinguish between the
\)\) and the D(R). The distinction may be made by breeding

DETERMINATION OF SEX. 957

with an animal showing the recessive. If the dominant is pure,
all of the offspring will exhibit the dominant characteristics. If,
on the contrary, it is a hybrid, the offspring will be half dominant
and half recessive, according to the formula:

D— R

| |=DR, DR, RR, RR.
R— R

The many attempts to verify this law in breeding have shown that
it expresses probably a great truth, although the application of it
to the practical purposes of breeding is beset with many compli-
cations. In regard to mankind the chief lesson that may be
learned from these investigations is the very great importance of
hereditary transmission — characteristics, good or bad, that dis-
appear in one generation may simply be recessive, and in the
course of successive intermarriages may again come to the surface
in accordance with the Mendelian law.

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.* 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,
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. It may be added as a matter
of interest that this preponderance of the male is reversed at the
period of. adult life. Owing to the greater death rate of the male
the proportion of male to female in the adult population of Europe

* For accounts of the various theories and discussion, see Morgan, "Popular
Science Monthly," December, 1903, and "Experimental Zoology," 1907; Len-
hossek, "Das Problem der geschlechtsbestimmenden Ursachen," 1903.

958 THE PHYSIOLOGY OF REPRODUCTION.

is as 1000 to 1024. Examination of these statistics with reference
to determining conditions led to the formulation of the so-called
Hof acker-Sadler law or laws, which may be stated as follows:
(1) When the man is older than the woman the ratio of male
births is increased (113 to 100). (2) When the parents are
of equal age the ratio of female births is increased (93.5 males to
100 females). (3) When the woman is older the ratio of female
births is still further increased (88.2 to 100). These laws have
been corroborated by some statisticians and contradicted or modi-
fied bjr others. Ploss attempted to show that poor nutritive con-
ditions affecting the parents, especially the mother, favor the
birth of boys. Dusing combined these results in a sort of general
compensatory law of nature, according to which a deficiency in
either sex leads, by a process of natural selection, to an increase
in the births of the opposite sex. Thus, when males are few in
number, — as the result, for instance, of wars, — females marry
later and more males are produced. When males are in excess early
marriages are the rule and this condition favors an excess of female
births. However interesting these statistics may be, it is very
evident that they do not touch the real problem of the cause of the
determination of sex.

Modern work has turned largely to observations and direct
experiments upon the lower animals, particularly the inverte-
brates, with the result that a very large number of facts have
been collected of a most interesting kind, but difficult as yet to
interpret so as to formulate a general law. The trend of modern
work tends to oppose an older view founded largely upon experi-
ments on frogs, bees, and wasps, according to which the sex is not
determined at or before fertilization, but is controlled or may be
controlled by the conditions of nourishment during development,
favorable conditions of nutriment leading to the development of
female cells from the germinal epithelium of the embryo. In
contrast with this latter view an opinion that has been frequently
advocated is that the sex of the embryo is determined in the egg
before fertilization or at the time of fertilization. This view,
as first presented, assumed substantially 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 conclusiveness 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 invertebrates exhibit
the phenomenon of parthenogenesis — that is, the eggs of the
mother develop without fertilization. In some cases this method

DETERMINATION OF SEX. 959

forms the only means of reproduction, and the individuals of the
race are all females. But in other animals reproduction is effected
either by parthenogenesis or by fertilization, according to the
conditions — change of seasons, etc. Among these latter animals
it may be shown, in some cases at least, that the parthenogenetic
eggs may give rise either to males or females — a fact which
accords with the hypothesis of the existence of male and female
eggs in the mother. (3) In man twins may be born and these
twins may be of two kinds. First, those that are developed
from two different eggs, each of which has its own chorion and
develops its own placenta. This kind may be designated as false
twins, and in the matter of sex they may be male and female,
or both male, or both female. The matter varies as in the statis-
tics of births in general. In the other group, however, of true
twins or identical twins, the two embryos are developed from a
single ovum and are included in a single chorion. In such cases
the sexes of the twins are always the same, they are both boys
^or both girls. This fact favors the view that the sex may be pre-
determined in the ovum, which may be either male or female.
However, if we grant the fundamental fact, so far as the ova are
concerned, that they are either male or female at the time of forma-
tion or are made so during the process of growth and maturation,
it is still logically possible that there may also be male and female
spermatozoa, and that in the union of the two cells the sex of the
fertilized ovum may be referable either to the ovum or spermatozoon.
It is not justifiable to assert that the paternal organism is without
influence upon the sex of the offspring. In fact, in the case of
honey bees it is observed that if the egg of the queen bee is unfer-
tilized it develops into a male, but, if fertilized, into a female, thus
indicating a determining influence upon the part of the male ele-
ment. Moreover, Wilson* and others have obtained some inter-
esting results upon insects (hemiptera), which indicate that the
determination of sex in these animals is dependent upon or
correlated with a visible difference in the chromosomes of the
spermatozoon. In some cases one-half of the spermatozoa
contain an unpaired or accessor}^ chromosome. Those showing
this structure produce females on fertilization, while the others
give rise to males. In other cases all the spermatozoa exhibit
the same number of chromosomes, but one-half of them contain
a large " idiochromosome, " the other half a small one. The
former give rise on fertilization to females, the latter to males.
If, on the basis of such facts, we assume the existence of male
and female eggs- and male and female spermatozoa, the question
of the sex of the offspring would seem to depend upon which of
* Wilson, "The Journal of Experimental Zoology, " 1906, hi., 1.

960 THE PHYSIOLOGY OF REPRODUCTION.

the sex-determining structures in the two cells predominates
after union. While it is difficult or impossible to make any
generalizations in regard to sex determination which will hold
throughout the animal kingdom, or which convey any definite
suggestion of an explanation of the problem, two facts of impor-
tance may be especially emphasized: First, The capacity to
produce a male or a female is probably contained in both the eggs
and the spermatozoa, or, to quote Morgan's words, "In all species
with separate sexes the potentialities of producing both sexes
are present in all eggs and in all sperm, but the development of the
one or the other sex is determined by some unknown internal
relation." Second, In those cases in which an individual de-
velops from a fertilized ovum, the sex is probably determined at
the time of fertilization.

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 6^-
pounds. At the end of the first year it weighs 18^ pounds, a gain of
12 pounds. At the end of the second year it weighs 23 pounds, a
gain of only 4£ pounds, and so on, the rate of increase falling rap-
idly with advancing years. Jacksonf has published an interesting
series of observations upon the relative and absolute growth of
the human fetus and its different organs during the intra-uterine
period. Relative growth is defined as the "ratio of the gain
during a given period to the weight at the beginning of the period."
from this standpoint he finds that the maximum rate of growth
occurs during the first month of fetal life. As determined by
the volume of the fetus the ovum increases more than 10,000
times in size; during this period. In the succeeding months of
intra-uterine life the relative monthly growth rate may be expressed
by i he figures 74, 1 1 , 1 .75, .82, .67, .50, .47, .45. During this period
the absolute weight is, of course, increasing rapidly, and according
to Jackson's observations the total weight of the embryo may be

(A °*o fd*ivs>)\4
7 )

♦ See Minot, "Journal of Physiology," 12, 07.

f Jackson, "The American journal of Anatomy," 9, I I'.), L909.

GROWTH AXD SEXESCEXCE. 961

The actual statistics of growth have been collected and tabulated
with great care by a number of observers; for this country
especially by Bowditch, Porter, and Beyer.* 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
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 possibl}T the reproductive elements.
The course of metabolism is such that it is self-limited, and even if
perfect conditions were supplied natural death would eventually
result. We do not understand the nature of these limitations, — that
is, the ultimate causes of senescence. Many examples of unusual
longevity are on record, the most authentic being probably that of
Thomas Parr. An account of his life and the results of a postmor-
tem examination by Harvey are given in volume iii of the " Philo-
sophical Transactions of the Royal Society of London." "He died
after he had outlived nine princes, in the tenth year of the tenth of
them, at the age of one hundred and fifty- two years and nine
months." The immediate cause of his death was attributed to a

* 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.

61

962 THE PHYSIOLOGY OF REPRODUCTION.

change of food and air and habits of life, as he was brought from Shrop-
shire to London, "where he fed high and drunk plentifully of the best
wines."* With reference to the phenomenon of senescense as a neces-
sary attribute of living matter, Weissmann has called attention to the
fact that inasmuch as the species continues to exist after the in-
dividual dies, we must believe that the protoplasm of the repro-
ductive elements is not subject to natural death, but has a self-
perpetuating metabolism which under proper conditions makes it
immortal. Weissmann f designates the protoplasm of the germ cells
as germ-plasm, that of the rest of the body as somatoplasm, and
inasmuch as the former continues to propagate itself indefinite^
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-
clusive results have not been reached. Assuming that the poten-
tial immortality exhibited by the reproductive cells was originally a
general property of protoplasm, Weissman conceives that the phe-
nomenon of senescence and death exhibited by other cells, somato-
plasm, is a secondary property, which was acquired as a result of
variation and was preserved by natural selection because it is an
advantage in the propagation of the species. An actual immor-
tality of the entire organism, — that is, the property of indefinite
existence except as death might be caused by accidental occur-
rences of various kinds — would be a disadvantage in many ways.
The vast increase in the number of individuals might exceed the
capacity of nature to provide for; the retention of the maimed and
imperfect would make many useless mouths to feed, and perhaps
the evolution of higher and more perfect forms by the slow action
of variation and natural selection would be retarded. From this
point of view senility and natural death constitute a beneficial
adaptation, acquired because of its utility to the race, on the one
hand, and, on the other, because, after the beginning of a differen-
tiation in function among the cells, the possession of immortality
by all the cells was no longer of any value to the race, and therefore
was not brought under the preserving influence of natural selection.

* A picture of Parr painted by van Dyck (i635) is exhibited in the lioya'
Gallery, Dresden, No. L032.

f W< i man, "Essays upon Heredity and Kindred Biological Prob-
lems"; al o " Germ-plasm" in the "Contemporary Scieiri- Series.

J See Maupas, Archives de zodlogie exp6rimentale et gen6rale," (i,
165, 1888; Joukowsky, "Inaugural Dissertation," Heidelberg, ]898; Gotte,
"Ueber den Ursprung des Todes," 1883.

GROWTH AND SENESCENCE. 963

Perhaps the most significant and definite contribution to the
subject of growth has been made by Rubner* upon the basis of
the energy factor. His estimates were made upon data collected
for man and the following mammalia, horse, cow, sheep, pig,
dog, cat, rabbit, and guinea-pig — and they bring out the sur-
prising fact that human growth constitutes a type of its own
differing greatly from that shown by the other mammals named.
His conclusions are expressed in two general laws which are founded
upon calculations made upon these animals in the first period
after birth during the time necessary for doubling the weight of
the animal: First, the law of constant energy consumption. During
the first period of growth the total amount of energy necessary
for maintenance (metabolism) and growth, as expressed by the
heat value of the food consumed, is the same for all mammals
except man. To form one kilogram of animal weight requires
in round numbers 4808 calories in food; while for man about six
times this amount is needed. Since the several mammals con-
sidered require very different times to double their weight, it
follows from this law that the shorter the time necessary for this
result the more intense Avill be the metabolism, or, expressed in
another way, the rapidity of growth is proportional to the intensity
of the metabolic processes. Second, the law of the constant growth
quotient. In all the mammals considered, with the exception of
man, the same fractional part of the entire food energy is utilized
for growth. This fractional portion is designated as the "growth-
quotient," and it averages 34 per cent., that is to say, for every
1000 calories of food 340 calories are applied to growth. In man,
on the contrary, the growth quotient is only 5 per cent. This
growth quotient is a specific property of the cell and a charac-
teristic of youthful ness. It has its maximal value at birth, so
far as extra-uterine life is concerned, and then sinks slowly, so
that at maturity, that is, at the end of the growth period, it becomes
zero. Thence forward the energy of the food is utilized only for
the maintenance of the cells and for the work they perform, none
is applied to growth. Rubner suggests that the power to grow
possessed by the cells of the young organism depends upon some
special mechanisms of a chemical nature, that is, probably certain
special chemical complexes which he designates as the "growth
mechanism " (Wachstumstrieb) .

After the period of maturity has been reached the question
arises whether the subsequent duration of life can be foretold or
formulated in any definite way. The older naturalists conceived
that the duration of mature life might represent a definite multiple
of the period of youth. According to Buffon this multiple is 6 to

* Rubner, "Das Problem der Lebensdauer, " etc., Berlin, 1908.

964 THE PHYSIOLOGY OF REPRODUCTION.

7, according to Flourens it is 5 — that is, the mean duration of life
is 5 to 7 times that required for the completion of growth. The
data gathered in regard to the average duration of life among
different animals has not borne out these suggestions, and Rubner
discusses the matter again from the energy standpoint. He
estimates the number of calories of food which are required for each
kilogram of body weight in the different mammalia from the end
of the period of youth to the end of life. For man this period is
estimated at sixty years (20 to 80). On this basis he finds that
each human kilogram requires 725,770 calories, while for the other
mammalia for which data are accessible an average of only 191,600
calories is required, and the figures in the latter animals are so
close as almost to warrant the belief that the same amount is
required by each animal in spite of the great variation in the
duration of life. It follows from these figures that the human cell
is characterized, as compared with that of the other mammalia,
by its much greater total capacity for obtaining energy from the
foodstuffs. This capacity, the property of assimilation, implies
chemical changes and transformations in the living matter, and
the fact that eventually this property languishes and expires, that
is, the fact that there is such a thing as natural or physiological
death, means that the somatic protoplasm is capable of effecting
only a limited number of such transformations. In man a greater
number is possible than in the other mammals, and among the
latter the number is practically the same, but in the smaller
animals, with their more intense metabolism, the series is com-
pleted in a shorter time than in the case of the larger animals.
Rubner states, moreover, that if a cell, the yeast cell, for example,
by artificial means is forced to live without growing and multiply-
ing it dies in a very short time. In some way the processes of
growth contain the very source of the maintenance of life. The
injurious by-products which accompany simple metabolism in the
living matter are in some way obviated or neutralized by the
growth changes. On this basis Rubner suggests, somewhat in
the line of Darwin's theory of pangenesis and of Weissmann's
theory of the cause of death in the somatoplasm, that the body-
cells give off certain molecular complexes which are necessary to
the growth processes, and these complexes are taken up by the
reproductive cells. After the animal has reached the period of
puberty, of reproductive power, and provision is thus made for
the perpetuation of the species, the individual organism is
depleted of the power of growth, and senescence and death
become inevitable.

APPENDIX.

PROTEINS AND THEIR CLASSIFICATION.

Definition and General Structure. — Proteins or albumins are complex
organic compounds containing nitrogen which, although differing much in
their composition, are related in their properties. They are formed by
living matter, and occur in the tissues and liquids of plants and animals,
of which they form the most characteristic constituent. On ultimate analy-
sis they are all found to contain carbon, hydrogen, oxygen, and nitrogen;
most of them contain also some sulphur, and some, in addition, phosphorus
or iron. As usually obtained, they leave also some ash when incinerated,
showing that they hold in combination some inorganic salts. Percentage
analyses of the most common proteins of the body show that the above
named constituents occur in the following proportions:

Carbon 50 to 55 per cent.

Hydrogen 6.5 to 7.3 " "

Nitrogen 15 to 17.6 " "

Oxygen 19 to 24 "

Sulphur 0.3 to 2.4 "

The clearest insight into the structure of the protein molecule has been
obtained by a study of its decomposition products. When submitted to the
action of proteolytic enzymes, or putrefaction, or acid at high temperatures,
the large molecules split into a number of simpler bodies in consequence of
hydrolytic cleavage. These end-products are very numerous, and, while
they differ somewhat for the different proteins, yet a number of them are
the same or similar for all proteins. The great variety in the end-products is
an indication of the complexity of the molecule, while their similarity is proof
that the various proteins are all built, so to speak, upon a common plan, by the
union of certain groupings which may be more numerous in one protein than
in another. This fact becomes evident from a brief consideration of the prod-
ucts obtained by hydrolytic cleavage with acids. The groupings represented
by the following compounds may be supposed to exist preformed in protein
molecules, some possibly containing them all, some only a portion of the
list, while the different groups vary in their proportional amounts in the
various proteins:

Monamino Acids.

1. Glycocoll or glycin (amino-ace-tic acid).

2. Alanin (aminopropionic acid).

3. Valin (amino valerianic acid).

4. Leucin (aminocaproic acid).

5. Isoleucin (aminocaproic acid).

6. Serin (oxaminopropionic acid).

7. Cystein (aminothiopropionic acid).

8. Phenylalanin (phenylaminopropionic acid).

9. Tyrosin ioxy phenylaminopropionic acid).

10. Tryptophan (indolaminopropionic acid).

11. Aspartic acid (aminosuccinic acid)..

12. Glutaminic acid (aminoglutaric acid).

13. Prolin (pyrrolidin-carboxyhc acid).

14. Oxyprolin (oxypyrrolidin-carboxylic acid).

15. Histidin (imidazol aminopropionic acid).

Diamino Acids.

16. Lysin (diaminocaproic acid).

17. Arginin iguanidinaminovalerianic acid).
IS. Diaminotrioxydodecoic acid.

965

966

APPENDIX.

These split products are all amino-acids, some of them belonging to the
fatty acid (aliphatic) series of carbon compounds, some to the aromatic
(carbocyclic) series, and some to the heterocyclic (pyrrol, indol) series. In
what may be considered the simplest proteins occurring in nature — namely,
the protamins found in the spermatozoa — only from four to six of these groups
occur, while in some of the more familiar proteins, such as serum-albumin
or casein, a much larger number is found. This fact is illustrated by the
following table, taken from Abderhalden, which shows the composition of
several proteins belonging to different classes. It will be noted that except
for the salmin the known products sum up to less than 100 per cent., showing
that there is a large portion of the molecule as yet unknown.

Serum Serum Casein. Salmin.
Albumin. Globulin.

Glycin 0 3.5 0

Alanin 2.7 2.2 0.9

Valin present 1.0 4.3

Leucin 20.0 18.7 10.5

Prolin 1.0 2.8 3.1 11.0

Phenylalanine 3.1 3.8 3.2

Glutaminic acid 7.7 8.5 11.0

Aspartic acid 3.1 2.5 1.2

Cystin 2.3 0.7 .065.

Serin 0.6 .... 0.23 7.8

Tyrosin 2.1 2.5 4.5

Tryptophan present present 1.5

Diaminotrioxydodecoic acid .... 0.75'

Oxyprolin .... 0.25

Lysin .... 5.80

Arginin 4.84 87.4

Histidin 2.59

The «-amino-acids of which these end-products consist all contain the
H

grouping — C— NH2, and Fischer has shown that such bodies possess the

COOH

property of combining with one another to make complex molecules containing
two, three, or more groups of amino-acids. The combination takes place
with the elimination of water formed by the union of the OH of the carboxyl
(COOH) group in one acid and the H of the amino (NH2) group in another.
Thus, two molecules of amino-acetic acid (glycocoll) may be made to unite to
form a compound, glycylglycin, as follows:

NH2CH2COOH + NH2CH2COOH — H20 = NH2CH2CONHCH2COOH.

Glycocoll. Glycocoll. Glycylglycin.

Compounds <»f this kind are designated by Fischer as peptids. _ When formed
from the union of two amino-acids they are known as dipeptids; from three,
as tripeptids, etc. The more complicate;! compounds of this sort, the poly-
peptide, begin to show reactions similar to those of the proteins. Sonic of
them give tin; biuret reaction, some are acted upon and split by proteolytic
enzymes. It seems justifiable, therefore, to consider proteins as essentially
polypeptid compounds of greater or less complexity— that is, they are acid-
amids formed by the union of a number of a-amino-acid compounds. More
than ;i hundred* of these artificial polypeptids have been thus synthesized,
one of the most complex, an octa-deca peptid, consisting of eighteen mon-
amino acids, fifteen molecules of glycin, and three of leucin, with a total molec-
ular weight of 1213. This conception of the structure of the protein molecule
explains a number of their general characteristics — for instance: (I) The
fad i h.'t I hey are nil decomposed and yield similar products under the influence

PROTEINS AND THEIR CLASSIFICATION. 967

of proteolytic enzymes or boiling dilute acid. (2) The fact that the proteins
are all so alike in their general properties in spite of the great differences in
the complexity of their molecular structure. (3) The fact that they show
both basic and acid characters. (4) The fact that they all give the biuret
reaction* (see below).

In addition to the amino-acids some proteins — egg-albumin, for example
— yield a carbohydrate body upon decomposition. The carbohydrate ob-
tained is an amino-sugar compound, usually glucosamin, C6H]3N05. It is
detected by its reducing action and by the formation of an osazone. It seems
probable, therefore, that some of the proteins at least contain such a group-
ing as part of the molecular complex, but at present it is undetermined how
many possess this peculiarity of structure.

General Reactions of the Proteins. — It is evident from what has been
said in the preceding paragraph that proteins may give different reactions
according to the kinds of groupings contained in the molecule. The reac-
tions common to all proteins are few in number, the most certain perhaps
being the biuret reaction, the hydrolysis by proteolytic enzymes or putre-
factive organisms, and the nature of the split products formed by these latter
hydrolyses or by the action of boiling dilute acids. A very large number
of reactions, however, have been described which hold for some or all of
the proteins usually found in the tissues and liquids of the body. These
reactions may be described under two heads: (1) Precipitation of the protein
when in solution; (2) color reactions.

/. Precipitants. — For one or another protein the following reagents cause
precipitation :

1. The addition of an excess of alcohol.

2. Boiling (heat coagulation).

3. The addition of mineral acids, — e. g., nitric acid.

4. The salts of the heavy metals, — e. g., acetate of lead, copper sul-

phate, etc.

5. Addition of neutral salts of the alkalies to a greater or less degree

of concentration, — e. g., sodium chlorid, ammonium sulphate.

6. Ferrocyanid of potassium after previous acidification by acetic acid.

7. Tannic acid after previous acidification by acetic acid.

8. Phosphotungstic or phosphomolybdic acid in the presence of free

mineral acids.
9 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 protein.

12. Precipitins. In this connection a brief reference may be made to
the interesting group of bodies known as precipitins. As stated
on p. 412, the animal organism has the power, when foreign cells
are injected into it, of forming anti-bodies by a specific biological
reaction. It has been discovered that anti-bodies, or as they
are called in this case, precipitins, may be produced in the
same, way if protein solutions or solutions of animal tissue are in-
jected into the circulation. Thus, if cows' milk be injected under
the skin of a rabbit there will be produced within the rabbit's
blood a precipitin which is capable of precipitating the casein of
cows' milk, although it may have no action on the milk of other
animals. In the same way any given foreign protein, when injected

under the skin of an animal, may cause the production of a pre-

* For further details, see Cohnheim, "Chemie der Eiweisskorper, " second
'edition, 1904; or Abderhalden, "Physiological Chemistry," translated by
Hall and Defren, New York, 1908, and Rosenheim, in "Science Progress,"
April and July, 1908.

968 APPENDIX.

cipitin capable of precipitating that particular protein from its
solutions. The precipitin is not absolutely specific for the protein
used to produce it, but nearly so. If a rabbit is immunized with
human blood a precipitin is produced in the animal's blood
which causes a precipitate when mixed with human blood or
with that of some of the higher monkeys, but gives no reaction
with the blood of other mammals. The reaction may be used,
therefore, in a measure to test the blood-relationship of different
animals.* It has been suggested that the reaction may also be
of practical importance in medicolegal cases, in determining whether
a given blood-stain is or is not human blood. For such a pur-
pose a human antiserum is first produced by injecting human
serum into a rabbit. The serum of the rabbit is then mixed with
an extract of the suspected blood-stain made with salt solution;
if a precipitate forms it proves that the blood stain is human blood
provided the possibility of its being monkey's blood is excluded.
Concerning the nature of the precipitins, little is known. They
combine quantitatively with the protein precipitated and they
are inactivated (hematosera) by a temperature of 70° C. Their
reactions are not sufficiently specific to be used as a means of de-
tecting or distinguishing closely related proteins.
//. The Color Reactions of Proteins.
1. The biuret reaction. The protein solution is made strongly alkaline
with caustic socla or potash and a few drops of a dilute solution of
copper sulphate are added carefully so as to avoid an excess. A
purple color is obtained. Some proteins (peptones) give a red
purple, others a blue purple. If only a blue color, without any
mixture of red, is obtained, no protein is present. At present
this reaction gives the best single test for protein. It obtains

its name from the fact that it is given by biuret HN<p^-xttt'".. a

compound that may be formed by heating urea. Two molecules
of urea give off a molecule of ammonia and form biuret.

2. The Millon reaction. The protein solution is boiled with Millon's

reagent. The solution or the precipitate, if one is formed, takes
on a reddish color, which varies in intensity with different proteins.
Millon's reagent consists of a solution of mercuric nitrate in nitric
acid containing some mercurous nitrate. This reaction is supposed
to be given by the tyrosin (oxy-aromatic) grouping in the protein
molecule, and fails, therefore, with those proteins in which tyrosin
is not present.

3. The xanthoproteic reaction. Nitric acid is added to strong acid

reaction and the solution is then boiled. After cooling ammonia
is added. The ammonia causes the development of a deep-yellow
color if protein is present. This reaction is supposed to be due
to the presence in the molecule of the groupings belonging to the
aromatic series.

4. Adainkiewicz's reaction. A mixture is made of one volume of con-

centrated sulphuric and two volumes of glacial acetic acid ; if the
protein solution is added to this mixture and warmed a reddish-
violet color is obtained. According to Hopkins and Cole, the re-
action depends upon the presence of glyoxylic acid in the acetic
acid. This reaction seems to be due to the tryptophan grouping
in the protein molecule.

5. Liebermann's reaction. Dry protein purified with alcohol and ether

jrives a blue color upon boiling with strong hydrochloric acid.

6. The lead sulphid reaction. The protein solution is boiled with a

solution of a lead salt made strongly alkaline with soda or potash.
A black precipitate or black or brown coloration results, according
* For many interesting experiments and t lie literature see Nuttall, "Blood
Immunity and' Relationship." Cambridge, 1904.

PROTEINS AND THEIR CLASSIFICATION.

969

to the amount of protein. The color is due to the splitting off of
sulphur and formation of lead sulphid. It is given, therefore, by
the sulphur-containing groups in the protein molecule.
7. The Molisch reaction. A few drops of an alcoholic solution of a-
naphthol are added to the protein solution and then strong sul-
phuric acid. A violet color is obtained. This reaction is given
by the carbohydrate grouping in the protein molecule. The strong
acid forms furfurol from this group, which then reacts with the naph-
thol. The reaction is not given by those proteins that do not con-
tain a carbohydrate group.

Classification of the Proteins. — No classification of the proteins has
been proposed which is entirely satisfactory. Eventually a classification
may be obtained based upon the chemical structure of the various proteins,
the number and arrangement of the constituent amino bodies, but our know-
ledge at present is much too incomplete for this purpose. We must be con-
tent with a less satisfactory system based in part upon empirical reactions
which have gradually been recognized in the course of physiological inves-
tigations.

In the following classification the recommendations are followed of the
Joint Committee on Protein Nomenclature appointed by the American Physi-
ological Society and the American Society of Biological Chemists ("American
Journal of Physiology, Proc. Physiol. Soc," vol. xxi., 1908):

I. Simple proteins (protein sub-
stances which yield only
a-amino acids or their deriv-
atives on hydrolysis).

II. Conjugated proteins (sub-
stances which contain the pro-

f Albumins.
I Globulins.
I Glutelins.

«j Alcohol-soluble proteins (prolamines).
I Albuminoids.
| Histons.
[ Protamins.
f Glycoproteins.
I Nucleoproteins.
tein molecule united to some J Hemoglobins (chromoproteins).
other molecule or molecules | Phosphoproteins.
otherwise than as a salt). [ Lecithopoteins.

' Primary protein derivatives "]

(formed through hydrolytic | Proteans.
changes which cause only }■ Metaproteins.
slight alterations of the pro- I Coagulated proteins,
tein molecule). J

Secondary protein deriva- ) prntpn„pt,
(Products ol further

III. Derived proteins

fives.

hydrolytic cleavage of the
protein molecule.)

^Peptc
Peptids.

The Albumins. — In addition to the albumins found in the cellular tis-
sues, the cell albumins, the conspicuous examples of this group are serum-
albumin, milk-albumin (lactalbumin), and egg-albumin (ovalbumin). They
are characterized as a class by the fact that they are coagulable by heat in
solutions with a neutral or acid reaction, and are soluble in water free
from salts. In accordance, with the latter part of this definition they are not
precipitated by dialysis. They are precipitated from their solutions with
more difficulty by saturation with neutral salts, ammonium sulphate, than
the globulins with which they are usually associated. Empirically, as regards
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 sul-
phate unless the solution is made acid. They are rich in sulphur, containing
from 1 .6 to 2.2 per cent., and on hydrolysis they yield no glycocoll.

970 APPENDIX.

The Globulins. — Proteins belonging to this group are found in the cell
tissues together with albumins. The forms that have been most studied
are serum-globulin (paraglobulin) ami fibrinogen (blood, lymph, and transu-
data), milk-globulin ilactoglobulin), and egg-globulin. As contrasted with
the albumins, they are coagulable by heat, but are insoluble in pure water.
They are readily soluble in dilute solutions of neutral salts, that is, salts of
strong bases with strong acids. In consequence of their insolubility in water
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 neutral solutions the globulins are completely precipitated by saturation
with magnesium sulphate or half saturation with ammonium sulphate. In
the blood several different forms of globulin are distinguished by the degree
of saturation with ammonium sulphate necessary for their precipitation (see
Blood). The separations made by this method are not, however, satisfac-
tory. Nor, indeed, is the separation between globulins and albumins alto-
gether satisfactory. It would seem that these proteins are so closely related
that distinctive reactions are difficult to obtain on account of the existence
of forms intermediate between the extremes that are used as types.

The Glutelins. — These proteins occur in abundance in the seeds of
cereals. They are insoluble in all neutral solvents, but are readily dissolved
by very dilute acids or alkalies.

Alcohol-soluble Proteins (Prolamines). — Found in quantity in cereals,
but not in other seeds. They are soluble in alcohol (70-80 per cent.), but
insoluble in water or in absolute alcohol. Gliadin of wheat and rye and hor-
dein of barley are examples. On hydrolysis these proteins give a very large
percentage of glutaminic acid (20 to 37 per cent.) and from 20 to 30 per cent,
of their nitrogen is given off as ammonia.*

Albuminoids. — Simple proteins which are characterized by great in-
solubility in all neutral solvents. They form the principle constituent of
the skeletal tissues and connective tissues, epidermis, hairs, etc., including
such members as elastin, keratin, and collagen. Physiologically it has been
found that gelatin, a derivative of collagen, does not suffice for the construction
of living protein, and cannot be used in place of the other proteins to main-
tain nitrogen equilibrium. This peculiarity seems to be due to the absence
of certain necessary amino-acids in its molecule. (See p. 865.)

Protamins and Histons. — The histons are defined as being soluble in
water and insoluble in very dilute ammonia. They yield precipitates with
solutions of other proteins and give a coagulum on heating. Protamins
are soluble in water, not coagulated by heating, and, like the histons, have
the property of precipitating other proteins in aqueous solutions. They
possess strong basic properties and form stable salts. 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
Hi i In spermatozoa of different animals, and are, therefore designated according
to the zoological name of the fish from which they arise, as sahnin, sturin, clu-
pein, scombrin, etc. They show a biuret reaction, but in most cases fail to
give Millon's reaction. On hydrolysis they give split products, which consist
chiefly of the so-called dianiino-bodies (arginin, histidin, lysin) rather than the
monamino-acids. Some of the latter may occur, however, such as alanin,
serin, aminovalerianic or a-pyrrollidin-carboxylic acid. The protamins all give
an alkaline' reaction, form salts with acids, and are precipitated easily. Their
molecular structure is relatively simple. Sahnin is given the formula C30HW-
C17H„. The molecule contains no sulphur and is characterized also by its
large percentage of nitrogen. I'rotamin must be regarded as the simplest
form of protein occurring normally in the animal body, a protein in which

' For description of this and other vegetable proteins, see Osborne,
Science," Oct. 2, L908.

PROTEINS AND THEIR CLASSIFICATION. 971

many of the groupings, such as cystin, tyrosin, carbohydrates, found in the
usual protein molecule are entirely lacking and in which the basic groupings
(arginin) predominate. The histons form a series of compounds intermediate
in many ways between the protamins and the usual proteins. The reaction
usually considered as characteristic of the class is that they are precipitated
by ammonia. They are precipitated also by the alkaloidal reagents — e. g.,
phosphotungstic acid — in neutral solutions. Ordinary proteins give a pre-
cipitate with these reagents only in acid solutions, while the protamins give
one even in alkaline solutions. Protamins, histons, and the usual proteins
form a series, therefore, in which the basic reaction is less and less marked.
The best known of the histons is the globin obtained from hemoglobin ; an-
other form has been obtained from the nucleohiston in the white corpuscles,
from the spermatozoa of mackerel (scombron), codfish (gadushiston), sea-
urchin (arbacin), and frog (lotahiston). They do not occur free in the liquids
or tissues of the body, but in combination, as in the case of hemoglobin.
They give the biuret reaction, a faint Millon reaction, and also respond to the
tests for sulphur. The products obtained by their hydrolytic cleavage are
much more numerous than in the case of the protamins — a fact which would
indicate that their molecular structure is correspondingly more complex.

The Conjugated Proteins. — The chromoproteins or hemoglobins may be
defined as consisting of a simple protein in combination with a pigment
grouping, such as occurs in the case of hemoglobin. A number of such com-
pounds are known — hemoglobin, hemocyanin, hemerythrin, chlorocruorin —
all characterized 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).
Glycoproteins are compounds of a carbohydrate group with a simple protein.
Numerous bodies have been put in this class; some of them contain phos-
phorus (phosphoglucoproteins). Those free from phosphorus fall into two
divisions: one, the mucins, which on decomposition yield the carbohydrate
group in the form of an amino-sugar (glucosamin), and one, the chondropro-
teins, found in the connective tissues and in the pathological substance known
as amyloid, which yield their carbohydrate group in the form of chondroitin-
sulphuric acid (C18H27NS017). True mucin is obtained from the secretion
of the salivary glands and the mucous glands of the various mucous mem-
branes. The nucleoproteins constitute the most interesting of the group
of compound proteins. They are recognized as forming an important con-
stituent of the cell nuclei. They may be defined as consisting of a compound
of simple protein with a nucleic acid. In the nuclei (head) of spermatozoa
the compound, in some cases at least (fishes), contains a nucleic acid and a
protamin. In other cases the protein constituent is more complex. On
digestion with pepsin-hydrochloric acid the more complex nucleoproteins
split, with the formation, first, of a protein substance and a simpler nucleo-
protein, richer in phosphorus and designated as a nuclein. On further
decomposition this latter yields a nucleic acid. Nucleic acid is, therefore,
the characteristic constituent, and a number of different forms have been
described, all rich in phosphorus, such as thymonucleic acid, salmonnucleic
acid, guanylic acid, etc. On hydrolytic decomposition they yield some of the
purin bases — xanthin, guanin, adenin, etc.; some pyrimidin derivatives —
uracil, thymin, cytosin; a carbohydrate group — pentose, levulinic acid; and
phosphoric acid. These final decomposition products are characteristic of
the true nucleoproteins as distinguished from the phosphorus-containing
proteins, the nucleo-albumins or phosphoproteins, such as casein. The per-
centage of phosphorus in the nucleoproteins varies, according to the com-
plexity of the molecule, between 0.5 and 1.6 per cent.

The lecithoproteins consist of compounds of the protein molecule with
lecithin (lecithans, phosphatids), while the phosphoproteins are compounds
of the protein molecule with some, as yet undefined, phosphorus-containing
substance other than a nucleic acid or lecithin. This group contains such
proteins as the vitellin of the yolk and casein of milk, which were formerly
designated as nucleo-albumins.

The Derived Proteins. — Under this designation are included products

972 APPENDIX.

derived from the simple proteins by hydrolysis. When the hydrolytic change
involves only a slight change in the protein molecule we have what are known
as primary derivatives, of which three groups are made: (1) Proteans, cer-
tain insoluble products which result from the incipient action of water,
enzymes, or very dilute acids. (2) Metaproteins, products which result from
the further action of acids or alkalies, by means of which the protein is con-
verted into a form soluble in weak acids or alkalies, but precipitated on neu-
tralization. This group includes what was formerly designated as acid or
alkali albumin. (3) Coagulated protein — insoluble products formed by
the action of heat, alcohol, etc.

If the hydrolysis proceeds further, certain cleavage products result which
are simpler than these just named, but are more complex than the final
products of complete hydrolysis (amino-acids). These intermediate cleavage
products are grouped under the term secondary derivatives and include:
(1) Proteoses, products which are soluble in water, not coagulated by heat,
and are completely precipitated by saturation with ammonium sulphate or
zinc sulphate. (2) Peptones, products which are soluble in water, are not
coagulated by heat, and are not precipitated by saturation with ammonium
sulphate. (3) Peptids, products which consist of two or more amino-acids
in which the carboxyl group of one is united with the amino group of an-
other, with the elimination of a molecule of water. The peptones probably
are simply polypeptids or mixtures of polypeptids.

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-

* Consult Cohen, "Physical Chemistry for Physicians and Biologists,"
translated by Fischer, L903. E. C. Jones, "The Theory of Electrolytic Dis-
sociation," L900 ; "Diffusion Osmosis, and Filtration," by E. W. Reid, in
Schafer's "Text-book of Physiology," L898.

PROTEINS AND THEIR CLASSIFICATION. 973

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-
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

* 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 tins
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 voxume
of the entire solution.

974 APPENDIX.

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
a state of solution are believed to be dissociated into two or more parts,
known as ions. The completeness of the dissociation varies with the sub-
stance used, and for any one substance with the degree of dilution. Roughly
speaking, the greater the dilution, the more nearly complete is the dissocia-
tion. The ions liberated by this act of dissociation carry an electrical charge
and when an electrical current is led into the solution it is conducted in a
definite direction by the movements or migration of the charged ions. The
molecules of perfectly pure water undergo almost no dissociation, and water,
therefore, does not appreciably conduct the electrical current. If some
NaCl is dissolved in water, a certain number of its molecules become dis-
sociated into a Na ion charged positively with electricity and a CI ion charged
negatively, and the solution becomes a conductor of the electrical current.
Substances that exhibit this property of dissociation into electrical ly-charged
ions are known as electrolytes, to distinguish them from other soluble sub-
stances, such as sugar, that do not dissociate in solution and, therefore, do not
conduct the electrical current. Speaking generally, it may be said that all
salts, bases, and acids belong to the group of electrolytes. The conception of
electrolytes is very important for the reason that the act of dissociation ob-
viously increases the number of particles moving in the solution and thereby
increases the osmotic pressure, since it has been found experimentally that, so
far as osmotic pressures are concerned, an ion plays the same part as a mole-
cule. It follows, therefore, that the osmotic pressure of any given electrolyte
in solution is increased in proportion to the degree to which it is dissociated.
As the liquids of the body contain electrolytes in solution it becomes neces-
sary, in estimating their osmotic pressure, to take this fact into consideration.

Gram-molecular Solutions. — The concentration of a given substance
in solution may be stated by the usual method of percentages, but from the
standpoint of osmotic pressure a more convenient method is the use of the
unit known as a gram-molecular solution. A gram-molecule of any sub-
stance is a quantity in grams of the substance equal to its molecular weight,
while a gram-molecular solution is one containing a gram-molecule of the
substance to a liter of the solution. Thus, a gram-molecular solution of
sodium chlorid is one containing 58. 5 gms. (Na, 23; CI, 35.5) of the salt to
a liter, while a gram-molecular solution of cane-sugar contains 342 gms.
(C12H22On) 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 litei
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 II has the same number of
molecules of II in it as a liter of solution containing 342 gms. of sugar has
of sugar molecules. On the assumption thai 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 just died 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 II when compressed to the volume
of 1 liter. This tact gives a means of calculating the osmotic pressure of
solution- in certain cases according to the following method:

Calculation of the Osmotic Pressure of Solutions. — To illustrate this

PROTEINS AND THEIR CLASSIFICATION. 975

method we may take a simple problem such as the determination of the
osmotic pressure of a 1 per cent, solution of cane-sugar. One gm. of H at
atmospheric pressure occupies a volume of 11.16 liters; 2 gms. of H, there-
fore, under the same conditions will occupy a volume of 22.32 liters. A
gram-molecule of H — that is, 2 gms. of H — when brought to the volume
of 1 liter will exert a gas-pressure equal to that of 22.32 liters compressed
to 1 liter — that is, a pressure of 22.32 atmospheres. A gram-molecular solu-
tion of cane-sugar, since it contains the same number of molecules in a liter,
must therefore exert an osmotic pressure equal to 22.32 atmospheres. A
1 per cent, solution of cane-sugar contains, however, only 10 gms. of sugar
to a liter; hence the osmotic pressure of the sugar in such a solution will

be —■■ of 22.32 atmospheres, or 0.65 of an atmosphere, which in terms of

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 -j^., or 0.3. 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 t he
absorption of water and digested foodstuffs from the alimentary canal, in

976 APPENDIX.

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 satisfactorjr explanation of the
forces controlling the flow to and fro of the water and dissolved substances,
but there can be little doubt that in all of them the physical forces of fil-
tration, diffusion, and osmosis take an important part. Whatever can be
learned, therefore, concerning these processes must in the end have an im-
portant bearing upon the explanation of the nutritive exchanges between
the blood and tissues. Some additional facts may be mentioned to indicate
the applications that are made of these processes in explaining physiological
phenomena.

Osmotic Pressure of Proteins. — The osmotic pressure exerted by crys-
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, hoAvever, would soon
diffuse out into the tissues, and to the degree that this occurred its effect in
diluting the blood would tend to diminish because the part of the salt that
got into the extravascular lymph spaces would now exert an osmotic press-
ure in the opposite direction, drawing water from the blood. This fact,
together with the further fact that an excess of salts in the body is soon re-
moved by the excretory organs, gives to such substances a smaller influence
in directing the water stream than would at first be supposed when the inten-
sity of their osmotic action is considered. In addition to the crystalloids the
liquids of our bodies contain also a certain amount of protein, the blood,
especially, containing over 6 per cent, of this substance. It has been gen-
erally assumed that proteins in solution exert little or no osmotic pressure,
but Starling * and others have claimed, on the contrary, that they exert a
distinct, although small, osmotic pressure, and it is possible that this fact
is of special importance in absorption, because the proteins do not diffuse
or diffuse with great difficulty, and their effect remains, therefore, so to
speak, as a permanent factor. According to Starling, the osmotic pressure
exerted by the proteins of serum is equal to about 30 mms. of mercury. That
the osmotic pressure of the serum proteins is so small is not surprising if we
remember the very high molecular weight of this substance. In serum the
proteins are present in a concentration of about 7 per cent., but owing to
their. large molecular weight comparatively few protein molecules are present
in a solution of this concentration ; and, assuming that the dissolved protein
follows the laws discovered for crystalloids, its osmotic pressure would depend
upon the number of molecules in' solution. By meansof this weak but con-
stant osmotic pressure of the indiffusible protein it is possible to explain
1 heoretically the fact that an isotonic or even a hypertonic solution of diffusi-
ble crystalloid may be completely absorbed by the blood from the peritoneal
cavity. Eteid t has published experiments which indicate that pure proteins
exert no osmotic pressure ; that as they occur in the body liquids they are
combined or mixed with certain substances to which the feeble osmotic pres-
sure formerly attributed to the proteins really belongs. Since these unknown
substances are themselves indiffusible, the arguments just used still hold for
the conditions in the body. It seems probable, however, that in the method
used by Eteid to purify the proteins the nature of these substances was
altered, the state of aggregation of the molecules, forexample, and that, there-
fore, his negative results do not apply to the proteins as they exist in the
blood.

Isotonic, Hypertonic, and Hypotonic Solutions. — Tn physiology the
osmotic pressures exerted by various solutions are compared usually with
that of Hie 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-

* "Journal of Physiology," 24, 317, LS99.

t Reid, "Journal of Physiology," 1905.

PROTEINS AND THEIR CLASSIFICATION. 977

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
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 Ave 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 Avails 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, Ave may suppose that the functional actiA'ity
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 Avay, by diffusion, a constant supply of dissolved material is kept
in motion from the blood to the tissue elements. On the other hand, the
functional activity of the tissue elements is accompanied by a breaking down
of the complex protein molecule, with the formation of simpler, more stable
molecules of crystalloid character, such as the sulphates, phosphates, and
urea or some precursor of urea. As these bodies pass into the tissue lymph
they tend to increase its concentration, and thus by the greater osmotic
pressure developed they serve to attract 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 toAvard
the blood. By this means the waste products of actiA'ity are draAA-n off to
the blood, from Avhich, in turn, they are removed by the action of the excretory
organs.

Diffusion of Proteins. — This simple explanation on purely physical
grounds of the flow of material between the blood and the tissues can only
be applied, however, at present to the diffusible crystalloids, such as the
salts, urea, and sugar. The proteins of the blood, which are supposed to
be so important for the nutrition of the tissues, are practically indiffusible,
so far as Ave know. It is difficult to explain their passage from the blood
through the capillary Avails into the lymph. Provisionally it may be assumed
that this passage is due to filtration. The blood-plasma in the capillaries is
under a slightly higher pressure than the lymph of the tissues, and this higher
pressure tends to squeeze the blood constituents, including the protein, through
the capillary Avails. This explanation, however, cannot be said to be satis-
factory ; and in this respect the purely physical theory of lymph formation
waits upon a clearer knowledge of the nature of the nutritive proteins and
their relations to the capillary wall (see Lymph, p. 456).
62

NDEX.

Abdominal respiration, 624

type of respiration, 628
Absolute power of muscle, 38
Absorption coefficient, 652

in large intestine, 777

in small intestine, 771

in stomach, 756

of carbohydrates, 773

of fats, 774

of proteins, 775

spectra of hemoglobin, 419
Acapnia, 678, 683
Accelerator center for heart, 575

nerves, effect of, on heart rate, 577
of heart, 571

reflex stimulation of, 573
Accessory thyroids, 835
Accommodation in eye, limits of, 308
mechanism of. 305

reflex, 318
Acetone bodies, 876
Achromatic series of visual sensa-
tions, 341
Achroodextrin, 738
Acid albumin in gastric digestion, 752

aceto-acetic, 876

amino-acetic, 765, 965

aminocaproic, 766, 965

aminoglutaric, 965

amino-oxypropionic, 965

aminopropionic, 965

aminosuccinic, 766, 965

aminothiolactic, 965

aminovalerianic, 765, 965

cholic, 785

conjugated sulphuric, 779, 822

diaminocaproic, 965

diaminotrioxydodecoic, 965

glutaminic, 766

glycocholic, 785

glycuronic, 869

guanidinaminovalerianic, 965

hippuric, 821

lactic, 63

oxalic, 870

oxybutyric, 876

oxyphenylaminopropionic, 965

oxyproteic, 814

phenylaminopropionic, 965

phosphocarnic, 63

pyrrolidin-carboxylic, 965

Acid, saccharic, 870

taurocholic, 785
Acidosis, 877
Acromegaly, 846
Action current, diphasic, 104
in heart, 522
in muscle, 103
in nerve, 103
in retina, 329
monophasic, 104

relation of, to contraction wave,
107
to nerve impulse, 107
Activation of lipase, 770
of thrombin, 445
of trypsin, 763
Activators, 722
Adamkiewicz's reaction for proteins,

968
Addison's disease, 841
Adenase, 723, 819
Adenin, 64, 818

Adrenal bodies, functions of, 843
Adrenalin, 842
Aerial perspective, 367
Aerotonometer, 653
Afferent fibers in cranial nerves, 84
position of, in posterior roots,
82
nerve fibers, 80
After-images in eye, 343
Air, effect of variations in, on res-
pirations, 680
Alanin, 765, 965
Albumin, properties of, 969 (see also

Protein)
Albuminoids, nutritive value of, 865
Albumon, 440
Alcohol as food, 887

effect of, on gastric absorption, 757
physiological action of, 886
use of, in diabetes, 889
Alexins, 413

Alimentary canal, movements of, 689
glycosuria, 773
principles of food, 712
Altitude, effect of, on red corpuscles,
' 428

Amboceptors, 413
Ametropia, 311
Amino-acetic acid, 765, 965

979

9S0

INDEX.

Amino-acids as part of protein mole-
cule, 765, 965
Aminocaproic acid, 766, 965
Aruinoglutaric acid, 965
Amino-oxypropionic acid, 965
Aminopropionic acid, 765, 965
Aminopurins, 818
Aminosuccinic acid, 766, 965
Aminothiolactic acid, 965
Aininovalerianic acid, 765, 965
Ammonia compounds in urine, 813

salts, relation of, to urea, 815
Ammonium carbamate as precursor
of urea, 816

carbonate as precursor of urea, 816
Amylase, 768
Amylolytic enzyme, 720
Anacrotic pulse, 511
Anaglyph, 370
Anelectrotonic currents, 108
Anelectrotonus, 88

Anisotropous substance in muscle, 19
Anode as stimulus to muscle, 88
to nerve, 88

physical, 94

physiological, 94
Anorexia, 283
Anoxemia, 681
Anterior commissure, 186, 214

roots of spinal nerves, 82
Antidromic impulses in vasodilator

nerve fibers, 83, 599
Antilytic secretion, 735
Antiparalytic secretion, 735
Antipeptone, 764
Antithrombin, 449
Antrum pylori of stomach, 695
Anus preternatural is, 777
Apex beat of heart, 524
Aphasia, motor, 216

sensory, 2I§
Apnea, 676
Arginase, 816
Arginin, 766, 816, 950, 970
Argyll-Robertson pupil, 319
Arterial pressure (see Circulation)
Artificial muscle of Engelmann, 73

respiration, 633, 643

stimuli of nerve fibers, 85
Ascending paths in spinal cord, 170
Aspartic acid, 766, 965
Asphyxia, 676

effect of, on heart-rate, 579
Aspiratory action of thorax, 639
Association areas in brain, 219, 221

system of fibers in cerebrum, 186
Astereognosis, 200
A i igmatism, 314
Atrioventricular bundle of heart, 520,

556
Atropin, action of, on heart, 569
on iris, 320

Atropin, action of, on salivary secre-
tion, 734
on sweat secretion, 832
Auditory center in cortex, 209
nerve, course of, in brain, 210

effect of section of, 397
sensations (see Ear)
striae, 212
Auricle (see Heart)

Auriculoventricular bundle of heart,
520, 556
effect of compressing, 556
Auscultation, 531
Autolysis, 921
Autolytic enzymes, 722
Automaticity of heart beat, 548
Autonomic fibers from brain, 249
from sacral cord, 251
from spinal cord, 248
nerve fibers, normal stimulation of,

251
nervous system, general relations
of, 246
Axial stream in arteries and veins, 466
Axon reflexes, 153

Bacterial action in intestines, 778

Balance experiments in nutrition, 854

Balloon ascensions, effect of, 684

Barometric pressures, effect of, 682

Bartholin, duct of, 724

Basilar membrane, function of, 389

Bathmotropic nerve fibers to heart,
565

Bechterew's nucleus, 211, 231

Bell-Magendie law, 82

Bilateral representation in motor
areas, 196

Bile, composition of, 783
curve of secretion of, 790
effect of occluding bile ducts, 791
ejection of, into duodenum, 789
functions of, summary, 791
quantity of, 783
secretion of, 788

Bile-acids, composition of, 785

Bile-duct, sphincter of, 790

Bile-pigments, 425, 784

Bile-salts, importance of, in fat diges-
tion, 775, 791

Bilirubin, 784

Biliverdin, 784

Binocular perspective, 368, 371
vision, 359

horopter in, 365
struggle of visual fields in, 366
value of, in judgments of dis-
tance, 371
of size, 371

Biological reaction, 412

Births, ratio of male and female, 957

INDEX.

981

Biuret reaction for proteins, 968
Bladder, urinary, movements of, 825
sphincter of, 825

gall-, movements of, 789
Blind spat in eye, 329
Blood, blood-plates of, physiology
of, 432

circulation of (see Circulation).

coagulation of, 440

condition of carbon dioxid in, 656
of nitrogen in, 654

curve of dissociation of oxyhemo-
globin, 655

defibrinated, 405

gases of, 648

general properties of, 404

hemoglobin in, 408
amount, 4l4
nature, 414

hemolysis of red corpuscles, 409

histological structure of, 404

leukocytes of, 429

nucleoprotein in, 440

osmotic pressure of, 410

proteins of, 434, 436

reaction of, 405

reasons for not clotting in vessels,
448

red corpuscles of, 408
fate of, 425
origin of, 425

regeneration of, after hemorrhage,
453

specific gravity of, 407

total quantity of, 452

transfusion of, 455
Blood-plasma, composition of, 434
Blood-plates, part taken by, in coagu-
lation, 448

properties of, 432
Blood-pressure, 473

diastolic, 477

effect of menstruation upon, 932

in brain, 608

in capillaries, 483

in man, 485, 490

mean, 477

relation of, to heart rate, 577

respiratory waves of, 640

systolic, 477

Traube-Hering waves of, 596

venous and capillary, 491
Blood-serum, 405, 435
Body equilibrium in nutrition, 854

sense area, 200

temperature in man, 905
Bowman's theory of urinary secre-
tion, 804
Brachium conjunctivum, 231

pontis, 233 '
Brain, association areas of, 219

auditory center in, 209

Brain, center for taste, 215
for olfaction, 213

centers affected in aphasia, 215, 219

development of cortical areas, 222

effect of variations in arterial pres-
sure upon, 608

intracranial pressure in, 607

histological differentiation of cor-
tex of, 225

localization of function in, 190

motor areas of, 193

regulation of circulation in, 603

sensory areas of, 199

vascular supply of, 603
Brightness in visual sensations, 339
Bronchi, capacity of, 633

constrictor and dilator fibers of, 679
Buffy coat of blood, 441

Caffein, 885

Caisson disease, 682

Calcarine fissure, relation of, to vision,

207
Calcium, amount of, in cataract, 884
rigor, 54

salts, effect of, on heart, 549
in clotting of blood, 444
in curdling of milk, 754
nutritive value of, 882
secretion of, in milk, 458
Calorie, definition of, 907
Calorimeters, varieties of, 907
Calorimetric equivalent, 909

measurements, 912
Calorimetry, indirect, 911

principles of, 907
Cannula, washout, 475
Capillary blood-pressure, 483

electrometer, construction of, 99
Carbohemoglobin, 417
Carbohydrates, absorption of, 773
as glycogen formers, 793
as source of body fat, 879
fermentation of, in intestine, 778
general functions of, 873
metabolism of, in body, 869
of muscle, 62

regulation of supply of, 870
supply of, in body, 868
Carbon dioxid, action on respiratory
center, 674
condition of, in blood, 656
effect of, in inspired air, 674, 682
on dissociation of oxyhemo-
globin, 656
on respiratory movements, 674
excretion of, through skin, S33
in balance experiments, 854
in saliva, 727

production of, in muscle, 65
tension of, in alveolar air, 659

982

INDEX.

Carbon dioxid, tension of, in arterial
blood, 660
in tissues, 660
in venous blood, 659

equilibrium, 854

monoxid hemoglobin, 417
Cardiac cycle, 534

glands of stomach, 740

muscle, properties of, 57, 552

nerves (see Heart)

sphincter, 693
Cardiogram, 525
Cardio-inhibitory center, 566
Carnin, 64
Casein, 754, 945
Catalase, 717, 723
Catalysis, 717

Catelectrotonic currents, 108
Catelectrotonus, 88
Cathode as stimulus, 88

physical and physiological, 94
Centers in cerebrum (see Cerebrum)
Central field of vision, 333
Centrosome, 934

Cerebellum, ending of spinal tracts
in, 173, 232

experimental work upon, 234

general functions of, 237

localization of function in, 239

paths connecting with other parts
of brain, 231

psychical functions of, 239

structure of, 229
Cerebrin, 80
Cerebrosides, 79
Cerebrospinal liquid, 605
Cerebrum, association areas of, 219

center for hearing, 209
for olfaction, 213
for vision, 203

centers affected in aphasia, 216

•commissural system of fibers in, 186

•development of cortical areas in,
222

general physiology of, 182

histological differentiation of cor-
tex, 225

histology of cortex, 183

localization of function in, 190

motor areas of, 193

projection system of fibers in, 184

results of ablation of, 188

sensory areas of, 199

system of fillers in, 184

vasomotor supply of, 610
■ Cerumen, 833
Chemical heat regulations, 916

secrelion, gastric, 749
pancreatic, 703
Chemotaxis, 128
Cheyne-Stokes respiration, 686
Cholesterin, 79, 781, 787, 833

Cholic acid, 785

Cholin, 79

Chorda tympani nerve, 286, 725, 728

Chromatic aberration in eye, 310

visual sensations, 341
Chromatolysis, 130
Chromophile substance in nerve cells,

136
Chromoproteins, 971
Chromosomes, 934, 954
Chronotropic nerve fibers to heart,

565
Chyle fat, 775
Chymosin, 753

Ciliary muscle, action of, in accom-
modation, 307
nerves to, 316
Ciliated epithelium, 57
Circulating proteins, 856
Circulation, accessory factors in, 502
as seen under microscope, 466
curve showing pressures in, 478, 482,

483
data concerning pressures in (man),
490
mean pressures in, 481
diastole and systole of heart, 518
effect of adrenal extracts upon, 841
of heart beat and size of arteries
upon, 471
explanation of side-pressure in, 495
of velocity changes in, 471
pressure in, 496
factors of normal pressure and

velocity in, 498
form of pulse wave, 508
general curve of velocities in, 470
statement of pressure relations,
473
hydrostatic effects upon, 500
importance of elasticity of arteries,

497
in brain, 603
in kidneys, 809

means of determining blood-pres-
sure in, 473, 485
velocities in, 469
pressure in coronary system, 537

in pulmonary system, 503
pulse pressures in, 477
regulation of blood supply, 600
respiratory waves of pressure in, 640
systole and diastole of heart, 518
systolic, diastolic, and mean pres-
sures in, 477
velocities in, 469
time required for complete, 172
Traube-Hering waves of pressure

in, 596
velocity in capillaries, 469
in coronary system, 537
in man, 469

INDEX.

983

Circulation velocity in pulmonary-
system, 503
of pulse wave, 506
Clarke's column, 165
Claudication, intermittent, 34
Clotting (see Coagulation)
Coagulation, blood, 440

factors of, 443

intravascular, 449

means of hastening and retarding,
450

theories of, 442
Coagulin, 444
Cobra-lecithid, 413
Cocain, action of, on iris, 320
Cochlea, functions of, 388

sensory epithelium of, 382
Coefficient, temperature, 116

absorption, 652
Cold spots on skin, 272
Color blindness, 345

contrasts, 344

fusion, 342

saturation, 341

sense of retina, 348

vision, theories of, 352
Combustion equivalents of foods, 897.
Comma tract of Schultze, 180
Commissural system of fibers (cere-
brum), 186
Common sensations, 265
Compensatory pause in heart beat,

554
Complemental air, 632
Complementary colors, 343
Compound muscular contractions, 40
Condiments, 714, 885
Conduction as physiological property,
76

direction of, in nerve fibers, 115
Conjugate foci, 299
Conjugated sulphates, 822
Contraction, 17, 33 (see also Muscle)
Contralateral conduction in cord, 176
Convoluted tubules of kidney, 802,

807
Core-model of nerve, 109
Coronary arteries, effect of occlusion
of, 541
vasomotor supply of, 601
Corpora quadrigemina, relation of, to
visual apparatus, 205, 208

striata, functions of, 227
Corpus callosum, structure and func-
tion, 226

luteum, 926

trapezoideum, 212
Corresponding points of retina, 362
Cortex of cerebrum, general physi-
ology of, 186
histology of, 183, 225
Corti, rods of, 383

Costal respiration, 628
Cowper's glands, 948
Cranial nerves, afferent fibers in, 84
efferent fibers of, 84
nuclei of origin of, 241
Cranioscopy, 190
Creatin, 64, 69, 820
Creatinin, 64, 820
Cresol-sulphuric acid, 779, 822
Cretinism, 836
Crystalline lens, calcium of, in

cataract, 884
Curve, contraction, of artificial mus-
cle, 74
of arterial pulse, 509, 512
of plain muscle, 55
of skeletal muscle, 26
dissociation of oxyhemoglobin, 655
extensibility and elasticity of mus-
cle, 20
gastric secretion, 747
intensity of sleep, 255
pancreatic secretion, 761
pressures in vascular system, 478,

482, 483
relations of heart sounds, 532, 533
respiratory movements, 630
secretion of bile, 790
systolic, diastolic, and mean blood-
pressures, 477 •
velocity of blood-flow, 470
venous pulse, 514
visual acuity of retina, 336
work of muscle, 39
Cycloplegia, 320
Cystin, 786, 965
Cystinuria, 786
Cytozym, 444

Dead space of lungs, 633
Deamidizing enzymes, 720
Death rigor, chemical changes during,
69
in muscle, 51

theories of, 961
Deep reflexes, 161

sensibility, 271, 280, 282
Defecation, 706

Degeneration in nerve fibers, 127
Deglutition, 689

nervous control of, 693
Deiters' cells in cochlea, 382

nucleus, 211, 231
Demarcation current, muscle and

nerve, 96
Demilunes of salivary glands, 726
Depressor nerve fibers, 591

of heart, 594
Derived proteins, 971
Descending paths, spinal cord, 177,

180
Deuteranopia, 346

9S4

INDEX.

Deutero-albumoses, 752
DeVries's theory of mutation, 955
Diabetes, 870

mellitus, 871

pancreatic, S71

phloridzin, 872

use of alcohol in, 889
Dialysis, definition of, 977
Diaminotrioxydodecoic acid, 965
Diaphragm, action of, 624
Diaphragmatic respiration, 624
Diastase, 720

discovery of, 715
Diastasis of heart, 529
Diastole, duration of, in heart, 535
Diastolic arterial pressure, 477

method of determining, in

animals, 479
method of determining, in
man, 486
Dicrotic pulse wave, 510
Diet, accessory articles of, 714, 885

average daily, 899

effect of reduction of salts in, 882
Dietetics, general principles of, 898
Diffusion circles on retina, 305

definition of, 972
Digestion in large intestine, 777

in small intestine, 759

in stomach, 755-
Diopter, definition of, 309
Dioptrics of eye, 298
Diplopia, 361, 364
Direct field of vision, eye, 333
Discord, physiological explanation of,

391
Dissociation of oxyhemoglobin, 655
Diuretics, action of, 809
Dominant characteristics in heredity,

956
Dromograph, 468
Dromotropic nerve fibers to heart,

565
Duct of Bartholin, 724

of Rivinus, 724

of Stenson, 724

of Wharton, 724

of Wirsung, 759
Dyspnea, 027, 675

Ear, effect of section of auditory
nerves, 397
of stimulation of semicircular
canals, 397
Eustachian tube of, 381
Flourens's experiments on semi-
circular canals, 395
functions in analyzing sound waves,
388
of cochlea, 388
of ear-bones, 377

Ear, functions of sacculus, 402
of utriculus, 402

intrinsic muscles of, 380

limits of hearing, 392

position of bones in, 377

projection of auditory sensations,
382

semicircular canals of, 394

sensations of discord, 391
of harmony, 391

sensory epithelium in cochlea, 382

structure of, 383, 389
bones of, 377

theories of functions of semicircu-
lar canals of, 398

tympanic membrane of, 376
Eck fistula, 815
Efferent nerve fibers, 80

occurrence in anterior roots, 82
in cranial nerves, 84
Ejaculation of spermatic liquid, 951
Elasticity and extensibility of muscle,

20
Electrical changes in heart, 522, 669
in muscle and nerve, 96
with respiratory movements, 668
Electrocardiograms, 523
Electrodes, non-polarizable, 101

stimulating, 86
Electrolytes, effect of, on osmotic

pressure, 974
Electrotonic currents, 108
Electrotonus, 88
Eleventh cranial nerve, nucleus of,

245
Embryo, nutrition of, 939
Endogenous fibers of spinal cord, 171
Energy of muscular contraction, 36
Enterokinase, 763, 770
Entoptic phenomena, 357
Enzymes, adenase, 722, 819

amylase, 768

arginase, 816

chemistry of, 723

classification of, 720

deamidizing, 720

definition of, 720

enterokinase, 763, 770

erepsin, 767, 771

general properties of, 721

glycolytic, 722, 851

guanasc, 723, 819

historical account of, 715

intracellular, 921

inverting, 771

lipase, 768

nuclease, 723

of muscle, 64

oxidases, 720, 918

pepsin, 749

peroxidases, 921

ptyalin, 737

INDEX.

985

Enzymes, rennin, 753

reversible reactions of, 717

specificity of, 719

trypsin, 764
Epicritic sensations, 272

sensibility, 271
Epigenesis, 953
Epinephrin, 842
Erection, physiology of, 950
Erepsin, 771
Ergograph, 47
Erythroblasts, 427

Erythrocytes (see Red blood-corpus-
cles)
Erythrodextrin, 738 _
Eserin, action of, on iris, 320
Ethereal sulphates, 822
Eupnea, 627
Eustachian tube, 381
Evolution, hypothesis of, in heredity,

953
Exogenous fibers in spinal cord, 171
Expiration (see also Respiration)

definition of, 623

expiratory center, 670

muscles of, 626
Expired air, composition of, 644

injurious effects of, 645
Extensibility of muscle, 20
Extensor thrust reflex, 159
Eye, abnormalities in refraction of,
311

accommodation in, 305

action of drugs upon, 320

acuity of vision in, 335

after-images in, 343

as optical instrument, 298

binocular field of vision, 362
perspective, 368

chromatic aberration in, 310

color blindness of, 345
contrasts in, 344
vision in, 340

complementary colors, 343

corresponding points in, 362

dark adapted, 330, 338

diffusion circles in, 305

diplopia in, 361, 364

direct field of vision in, 333

entopic phenomena in, 357

far point of distinct vision, 309

function of cones, 349
of rods, 349

fundamental color sensations, 342

horopter, 365

indirect field of vision in, 333

inversion of image in, 303

light adapted, 330, 338
reflex in, 318

movements of, 359

muscular insufficiency, 361

nature of visual stimuli, 330

Eye, near point of distinct vision, 308
nodal point of, 302
ophthalmoscopic examination of,

323
optical defects of, 310

delusions, 372
physics of formation of image in,

301
qualities of visual sensations, 340
reduced schematic (Listing), 302
refractive power of, 309
size of retinal images, 304
spherical aberration in, 311
stereoscopic vision, 369
struggle of visual fields, 366
suppression of visual images, 365
theories of color vision, 352
threshold stimulus of, 337
visual field of, 332

judgments, 366

purple of, 330
Eye-muscles, action of, 359

Facial nerve, dilator fibers in, 596

nucleus of, 244
Far point of distinct vision, 309
Fat, absorption of, 774

as glycogen former, 795

digestion of, 768
in stomach, 758

excessive formation of, in obesity,
879

in bile, 788

metabolism of, in body, 875

nutritive value of, 874

of chyle, 775

origin of, from carbohydrates, 878
in body, 878

relation of fiver to, 876

mode of oxidation of, in body, 876
Fatigue in nerve fibers, 118

muscular, 48

of olfactory organs, 295

theories of, 69

toxin, 70, 647
Feces, composition of, 780
Fermentation in intestine, 778

of carbohydrates in small intestine,
774
Ferments, historical account of, 715
Fertilization of ovum, 936
Fibrillary contractions of heart, 541
Fibrin ferment, preparation of, 442

relations to blood-clot, 440
Fibrinogen, 438

preparation of, 442
Fibrinolysis. 447
Fictitious meal (Pawlow), 746
Fifth cranial nerve, 244
Fillet, lateral, 212

median, 201

986

INDEX.

Fistula, Eck's, 815

gall-bladder. 782

stomach, 743

Thiry-Yella, 770
Flavors, 714

dietary, importance of, 885
Flechsig's myelinization method, 166
Fluorid solution, effect on clotting, 451
Food, composition of, 712

definition of, 712

potential energy of, 895
Foodstuffs, definition of, 712
Fourth cranial nerve, nucleus of, 243
Fovea, center for, in occipital cortex,
207

of retina, size of, 334
Franklin theory of color vision, 355
Freezing-point, method of determin-
ing, 975
Fundic glands of stomach, 740
Fundus of stomach, 695

Gall-bladder, functions of, 789

nerves of, 790
Galvanometer, construction of, 97
d'Arsonval, 98
string, 100
Gases, laws governing absorption of,
651
of blood, 648
pressure of, 651
tension of, in solution, 653
Gas-pump, 649
Gastric glands, 740

histological changes in, during

secretion, 741
secretory nerves of, 746
secretion, acid of, 744
chemical, 749
composition of, 742
curve of, 748
means of obtaining, 742
nervous, 749

normal mechanism of, 747
Gelatin, history of, as a food, 866

nutritive value of, 865
Genital organs, vasomotor supply of,

614
Germ plasm, definition of, 962
Glans penis, sensibility of, 272
Globin, 414, 971
Globulicidal action of blood-serum,

411
Globulins, general properties of, 970
Glomerulus of kidney, functions of,

805
Glossopharyngeal nerve, dilator fibers
in, 596
nucleus of, 245
Glucosamin, 967
Glutaminic acid, 706, 965
Glutelins, 970

Glutolin, 437

Glycin, 765, 785, 965

Glycocholic acid, 785

Glycocoll, 965

Glycogen, amount of, in liver, 792

discovery of, 792

glycogenic theory, 795

importance of, in embryo, 940

in muscle, 62, 797

loss of, during muscular contrac-
tions, 66

metabolism of, in body, 874

origin of, 793

supply of, in body, 868
Glycolysis of sugars in body, 869
Glycoproteins, 971
Glycosuria, 870

alimentary, 773
Glycylglycin; 966
Gmelin's reaction for bile-pigments,

784
Golgi's nerve cells, second type, 135

pericellular nerve net, 137
Graafian follicle, structure of, 925
Gram-molecular solution, 974
Growth, 960
Guanase, 723, 819
Guanin, 64, 818
Gudden's commissure, 206, 213

Harmony, physiological cause of, 391
Hearing (see Ear)

cortical center of, 209

limits of, 392
Heart, accelerator center for, 575
nerves of, 571

action current of, 522
of inhibitory nerves, 561

analysis of inhibition, 563

apex beat of, 524

auriculoventricular bundle, 520, 556

automaticity of, 543

capacity of ventricles of, 535

cardiac nerves of, course, 561

cardiogram, 525

cardio-inhibitory center of, 566

causation of beat, 543

change in form of ventricle in sys-
tole, 523

compensatory pause of, 554

contraction wave in, 521

coronary circulation in, 537

course of cardiac nerves, 561

depressor nerve of, 594

diastasis of, 529

diastole and systole of, 5 1 8
time relations of, 535

effect- of drugs on, 569
of calcium upon, 549
of occlusion of coronaries upon,

54 I
of potassium upon, 549

INDEX.

987

Heart, effect of sodium upon, 549
electrical changes in, 522
escape from inhibition, 566
events of a cardiac cycle, 534
fibrillary contractions, 541
historical account of beat of, 544
inhibition of auricle, 565

of ventricle, 565
intraventricular pressure during

systole, 526
intrinsic nerves of, 545
maximal contractions of, 552
musculature of, 519
myogenic theory of beat of, 546
negative pressure in, 539
neurogenic theory of beat of, 545
rate of beat as affected by age, 576
by blood-pressure, 577
by extrinsic nerves, 577
by muscular exercise, 578
by sex, 576
by size, 576
by temperature, 579
reflex acceleration of beat, 573
refractory period of, 552
sequence of beat of, 554
sounds of, 531
suction-pump action of, 539
systole and diastole of, 518

time relations of, 535
systolic plateau of beat, 527
theories of inhibition of, 569
third sound of, 533
tonic inhibition of, 567
tonicity of muscle of, 558
vasomotors of, 601
ventricle of, in systole, 523
ventricular output of, 528
volume curve of, 528
work done by, 535
Heart-block, 557
Heart-muscle, general properties of,

57, 552
Heat centers, 916

equivalent of foodstuffs, 896

loss of, physiological regulation of,

912
nerves, 916
production in hydrolysis, 895

physiological regulation of, 915
puncture, 917
regulation, chemical, 916
general statement of, 912
physical, 914
rigor of muscle, 53
sexual, in lower animals, 928
Helmholtz theory of color vision, 352
Helweg's bundle, spinal cord, 181
Hematin, 415, 424
Hematoidin, 425
Hematopoietic tissue, 427
Hematoporphyrin, 425

Hemeralopia (night-blindness), 351
Hemin, 424
Hemipeptone, 764
Hemiplegia, 195
Hemochromogen, 414, 425
Hemodromograph, 468
Hemoglobin, absorption spectra of,
419

compounds of, with carbon dioxid,
417

monoxid, 416
nitric oxid, 416
oxygen, 416

condition of, in corpuscles, 408

crystals of, 418

curve of dissociation of oxyhemo-
globin, 655

derivative compounds of, 423

iron in, 417

nature and amount of, 414
Hemolysins, natural and acquired,

411
Hemolysis, 409
Hemorrhage, effect of, 453
Hepatothrombin, 447
Heredity, definition and history, 953
Hering theory of color vision, 353
Heterotypical division of ovum, 935
Hexon bases, 950
Hippuric acid, 821
Histidin, 766, 965
Histohematins, 425
Histons, 950, 970

effect of, on coagulation of blood,
450
Hofacker-Sadler law, 958
Homoiothermous animals, 905
Homolateral conduction in cord, 176
Homotypical division of ovum, 935
Hormones, 749
Horopter, 365
Hunger, sense of, 283
Hydrocele liquid, 437
Hydrochloric acid, combined, in gas-
tric secretion, 745
function of, in peptic digestion,

751
in gastric juice, 744
Hydrolysis, 721

heat energy of, 895
Hydrostatic factor in circulation, 500
Hyperglycemia, 870
Hypermetropia, 312
Hyperpnea, 675
Hypertonic solutions, 976
Hypnotic sleep, 263
Hypoglossal nerve, nucleus of, 245
Hypotonic solutions, 976
Hypoxanthin, 64, S17

Identical points of retina, 362
Identity theory of nerve impulse, 124

98S

INDEX.

Immune body, 413
Incongruence of retinas, 364
Indican, 822

Indirect calorimetry, 911
field of vision, eye, 333
Indol group in protein molecule, 766
Indoxyl sulphuric acid, 779, 822
Induction coil, 24
Inert layer in circulation, 466
Inheritance, Mendelian, 956
Inhibition, escape from, in heart, 566
of heart, 561
of knee-jerk, 157
of reflexes, 149

of respiratory movements, 668
reflex of heart, 566
theories of, 569
Inotropic nerves to heart, 565
Inspiration (see also Respiration)
definition of, 623
increased heart-rate during, 643
means of producing, 624
muscles of, 626
Inspired air, composition of, 644
Intermediary products of muscle
metabolism, 67
metabolism of carbohydrates, 869
of fats, 875
of nucleoproteins, 862
of proteins, 856
Intermittent claudication, 34
Internal secretion, adrenals, 841

definition and historical account,

834
kidney, 851
liver, 835
ovary, 847
pancreas, 849
testis, 847
thyroid tissues, 835
sensations, 266
Intestinal movements, effect of
various conditions upon, 704
secretion, 770
Intestines, bacterial action in, 778
large, movements of, 705
nervous control of movements of,

703
reaction of contents of, 778
small, movements of, 700
Intracellular enzymes. (.r_'i
Intracranial pressure, 007
Intra-ocular pressure, 322
Intrapulmonic pressure, 635
Intrathoracic pressure, 636
origin of, 638

variations of, with forced breath-
ing, 637
Intraventricular pressure, 526
Introductory contractions of muscle,

34
In vert a se, 722, 771

Involuntary muscle, 54

Iodothyrin, 836

Iris, action of drugs upon, 320

antagonistic action of muscles
upon, 317

muscles and nerves of, 316
Iron, effect of removal of spleen on,
801

in hemoglobin, 417

salts, source and nutritive impor-
tance of, 882
Irritability, definition of, 22

of muscle, 22

of nerve fibers, 85
Isodynamic equivalent of foodstuffs,

899
Isoleucin, 965

Isometric muscular contractions, 27
Isotonic muscular contractions, 27

solutions, definition of, 976
Isotropous substance in muscle, 19

Jacobson, nerve of, 724
Judgments, visual, of distance and
size, 371
of perspective or solidity, 366

Kenotoxin, 70, 647

Kidney, action of diuretics on, 809

blood-flow through, 809

composition of secretion of (urine),
812

function of convoluted tubules, 807
of glomerulus, 805

internal secretion of, 851

secretion of urine in, 803

structure of, 802
Kinases, 722
Kjeldalil's method for determination

of nitrogen, 813, 853
Knee-jerk, conditions influencing, 159

definition of, 156

explanation of, 158

reinforcement of, 156

use of, as diagnostic sign, 160

Labor, physiology of, 942
Lactic acid in muscle, 63

increase of, during contraction,
67
Laked blood, 409
Langerhans, islands of, 850
Large intestine, digestion and absorp-
tion of food in, 777
movements of, 705
Larynx, reflex effects from, on respi-
rations, 669
I, a lent period of muscular contrac-
tion, 27

INDEX.

989

Law of constant energy consumption,
963
growth-quotient, 963

of surface area, 912
Lecithin, 79, 787

as complement, 413
Lecithoproteins, 971
Lemniscus, lateral, 212

median, 201
Leucin, 766, 965

Leucocytes, effect of hemorrhage
upon, 454

functions of, 429

structure and classification, 429

variations in number of, 431
Leuconuclein, effect upon blood coag-
ulation, 450
Leucothrombin, 447
Liebermann's reaction for proteins,

968
Liebig's classification of foodstuffs,

890
Light-reflex in eye, 318
Lipase, 720

activation of, 770

gastric, 755

in pancreatic secretion, 768

reversible reaction of, 718
Lipoids, 78
Listing's law, 361

schematic eye, 302
Liver, bile-pigments of, 784
acids of, 785

defensive action of, in coagulation,
448

formation of urea in, 798

glycogen of, 792

glycogenic action of, 796

internal secretion of, 835

pulse, 513

quantity of bile, 783

relation ofr to fat metabolism, 876

secretion of bile, 788
Localization of function in cerebellum,
239
in cerebrum, 190
Localizing power of skin, 276
Locke's solution, 550
Locomotor ataxia, 172
Ludwig theory of urinary secretion,

803
Luminosity of visual sensations, 339
Lungs, gaseous exchanges in, 658

total surface of, 623, 660

vasomotors of, 602
Lymph, action of lymphagogues, 459

circulation of, 616

formation of, 457

summary of factors concerned in
formation of, 462
Lymphocytes, 429
Lysin, 766, 965, 970

Maltase, 722, 737, 768, 771
Maltose, 738, 768

Mammary glands, effect of uterus
upon, 943
structure and functions, 942
Manometer, Fick's spring, 479
Hurthle's, 480

maximum and minimum, 480
use of, for determining blood-pres-
sure, 473
Mast cells, 430
Mastication, 689
Mathematical perspective, 367
Mean blood-pressure, 478
Medulla oblongata, 240

respiratory center in, 662
Medullary striae, 212
Mendelian law of inheritance, 956
Meningeal spaces, 605
Menstruation, 927

effect of, on other functions, 932
physiological significance of, 931
Mercury manometer, use of, for blood-
pressures, 473
Metabolism, definition of, 852

intermediary, of carbohydrates, 869
of fats, 875
of nucleoproteins, 862
of proteins, 856
Metaproteins, 972
Methemoglobin, 423
Methylpurins, 818
Microphags, 431
Micturition, physiology of, 824
Milk, composition of, 945
Millon's reaction for proteins, 968
Minimal air, 632
Miosis, definition of, 320
Molisch reaction for proteins, 969
Monakow's bundle, 180
Motor aphasia, 216
areas of brain, 193
paths in spinal cord, 177
points in man, 93
Mountain sickness, 682
Movements of alimentary canal, defe-
cation, 706
deglutition, 689
large intestine, 705
mastication, 689
small intestine, 700
stomach, 696
vomiting, 709
Mucin in saliva, 727
Muscarin, action of, on heart, 569
on iris, 320
on sweat glands, 832
Muscle, absolute power of, 38
action current of, 103
artificial stimulation of, 24
calcium rigor of. 54
carbohydrates of, 62

990

INDEX.

Muscle, cardiac, properties of, 57, 552
chemical changes of, in contrac-
tion, 65

composition of, 60
compound contractions of, 40
contraction of, 25

wave of, 35
contracture of, 32
curve of work of, 39
death rigor, 51
demarcation current of, 96
direct irritability of, 22
disappearance of glycogen in, 66
effect of temperature upon, 29

of veratrin upon, 31
energy liberated in, 36
Engelmann's artificial, 73
enzymes of, 64
ergographic records from, 47
extensibility and elasticity of, 20
fatigue of, 35, 48, 69
glycogen of, 797
heat rigor of, 51
inorganic salts of, 65
introductory contractions of, 34
isotonic and isometric contractions

of, 27
lactic acid of, 63

latent period of contraction of, 27
maximal and submaximal contrac-
tions of, 28
myogenic tonus of, 56
neurogenic tonus of, 56
nitrogenous extractives of, 64
number of stimuli necessary for

tetanus. 44
pale fibers in, 19, 25
pigments of, 64
plain, 54
plasma, 18, 60
proteins of, 60
red fibers in, 19, 25
sarcoplasm, 18
simple contraction of, 25
smooth, 54
stroma, 62
structure of fiber, 18

by polarized light, 19
summation of contractions of, 42
theories of nature of contraction,

71
tone of, during contraction, 43
tonicity of, 50
vasomotor supply of, 614
voluntary contractions of, 44
water rigor of, 54
white and red fibers of, 19
Muscle-sense, cortical area for, 200
importance of, in visual judgments,

368
paths for, in spinal cord, 173, 175
quality of, 282

Muscular contraction, electrical varia-
tion in, 107
intermediary chemical products
in, 65
insufficiency in movements of eye-
balls, 361
or deep sensibility, 280
work, effect of, on heart rate, 578
on physiological oxidations, 890
on protein metabolism, 891
on respiratory movements, 680
Musical sounds, classification and

properties of, 384
Mutations, theories of, 955
Mydriasis, definition of, 320
Myelin sheath of nerve fibers, func-
tion of, 77
Myelinization method of Flechsigr

166, 222
Myogen, 61
fibrin, 61
Myogenic theory of heart beat, 546

tonus, 56
Myohematin, 425
Myopia, 312
Myosin, 61

fibrin, 61 .
Myxedema, 836

Narcosis, effect of, upon nerve-
impulse, 117

Near point of distinct vision, 308

Negative pressure in thorax, 636, 638
in ventricle, 539
variation in muscle and nerve, 103,
104

Nerve, abducens, nucleus of, 244
auditory, 210

chorda tympani, 286, 725, 728
facial, nucleus of, 244
fourth cranial, nucleus of, 243
glossopharyngeal, nucleus of, 245
hemorrhoidalis inferior, 707
hypoglossal, nucleus of, 245
motor and sensory roots of, 82
olfactory, 213
optic, 204
pudendus, 707
recurrent, sensibility of anterior

roots, 82
spinal accessory, nucleus of, 245
third cranial, nucleus of, 241
trigeminal, nucleus of, 244
twelfth cranial, nucleus of, 245
vagus, nucleus of, 245

Nerve-cell, chromatolysis of, 130
classification of, in spinal cord,

163
degenerative changes in, 129
general physiology of, 137
internal structure of, 136

INDEX.

991

Nerve-cell, metabolism in, 139
neuron doctrine, 131
reaction of, 138
refractory period of, 141
summation of stimuli in, 139
varieties of, 133
Nerve-fibers, action current of, 103
afferent and efferent, 80
anodal and cathodal stimulation

of, 88
antidromic impulses in, 83
artificial stimuli of, 85
autoregeneration of, 128
chemistry of, 78
classification of, 80
core model of, 109
degeneration and regeneration of,

127
demarcation current of, 96
direction of conduction, 115
du Bois- Raymond's law of stim-
ulation, 87
electrical stimulation of, in man,

94
electrotonic currents of, 108
electrotonus of, 88
impulse in, historical, 111
independent irritability of, 85
metabolism in, during activity,

120
myelin sheath of, 77
nutritive relations to nerve-cells,

125
opening and closing tetanus of, 91
Pfliiger's law of stimulation of, 89
stimulation of, in man, 91
structure of, 76

unipolar method of stimulating,
92
Nerve-impulse, historical, 111
metabolism during, 119
modification of, by various influ-
ences, 117
qualitative changes in, 81, 124
relation of, to action current, 107,

115
theories of, 121
velocity of, 112
Nervi erigentes, 251, 597, 614
Nervous secretion, gastric, 749

pancreatic, 763
Neurogenic theory of heart beat, 545

tonus, 56
Neuron doctrine, 131
Neurons, varieties of, 132
Nicotin, action of, on salivary secre-
tion, 734
on sweat secretion, 831
use of, in tracing autonomic fibers,
248
Night-blindness, hemeralopia, 351
Ninth cranial nerve, nucleus of, 245

Nissl's granules, 136
Nitric oxid hemoglobin, 417
Nitrogen, condition of, in blood, 654

determination of, 853

equilibrium, 852

effect of non-protein food on, 855

excretion in urine, 813
Nitrogenous extractives of muscle, 64
Nodal point of eye, 302
Non-polarizable electrodes, 101
Normoblasts, 427
Nuclease, 723, 819
Nucleo-albumin in bile, 788
Nucleon, 63
Nucleoproteins, 971

in blood, 440

intermediary metabolism of, 862

Obesity, physiological cause of, 879
Ohm's law of composition of sound

waves, 387
Olfaction, end-organ for, 291

mechanism of, 292
Olfactometer, 296
Olfactory associations, 297

bulb, histological structure of, 213

center in cortex, 213

nerve, course of fibers of, in brain,
214

organs, fatigue of, 295

sensations, classification of, 293
conflict of, 297
qualities of, 293
threshold stimulus, 295

sense cells, 292

stifnuli, nature of, 293
Oncometer, 810
Ophthalmometer, 326
Ophthalmoscope, 323
Opotherapy, 834
Opsonins, 431
Optic chiasma, decussation in, 206

nerve, course of fibers of, in brain,
204

radiation, 205

thalamus, functions of, in vision,
209

tracts, structure of, 206
Optical deceptions, 372
Optograms on retina, 331
Osmosis, definition of, 972
Osmotic pressure, definition of, 973
determination of, 974
of blood, 410
Oval field of Flechsig, 180
Ovaries, internal secretion of, 848

relation of, to menstruation, 930
Overtones, production of, 386
Ovulation, 926
Ovum, fertilization of, 936

implantation of, in uterus, 938

992

IXDEX.

Ovum, maturation of, 934

passage of, into uterus, 933
Oxalate solutions, effect of, on coagu-
lation, 451
Oxidases, 720. 918
Oxidations, theories of, 918
Oxygen, action of, on respiratory
center, 673, 68 1
compound of, with hemoglobin, 416
condition of, in blood, 655
effects of varying pressures of, on

respiration, 68*1
tension of, in alveolar air, 659
in tissues, 660
in venous blood, 659
Oxygenase, 921
Oxyhemoglobin, 416
Oxyprolin, 965
Oxyproteic acid, 814
Oxypurins, 818

Pacchionian bodies of brain, 606
Pain sense, distribution and char-
acteristics of, 279
localization of, 279
path for, in cord, 175
Pale fibers of muscle, 19, 25
Pancreas, action of lipase in, 768

anatomy of, 759

curve of secretion of, 761

digestive action of secretion, 764
on carbohydrates, 768

internal secretion of, 849

normal mechanism of secretion, 762

secretory nerves of, 760
Pancreatic secretion, nervous, 763

chemical, 763
Paraglobulin, 437
Paralysis (motor), 195
Paralytic secretion (saliva), 735
Parapeptone, 752
Parathyroid, structure and function

of, 835, 836
Parthenogenesis, 938, 959
Parturition, physiology of, 942
Pendular movements (intestine), 700

sound waves, 385
Pep in, 7 I'.i

discovery of, 715

proper! ies of, 710
Pepsiii-hvdrochloiic acid digestion.

751
Peptids, 767, 966
Peptone, 75]

absorption of, in stomach, 758

effect on clotting of blood, 151

hemi- and Miit i - , 7<i I
Peptozym, 152
Pericardial li<imd. \M
Perimeter, 333

Pei ipheral field of vision, 333
tance in circulal ion, 199

Peristalsis, 700
Peroxidases, 921
Perspiration (see Sweat)
Pettenkofer's reaction, 785
Pfltiger law of stimulation, 89

tetanus, 91
Phagocytes, 431
Phenolsulphuric acid, 822
Phenylalanin, 766, 965
Phloridzin diabetes, 872
Phosphocarnic acid, 63
Phosphoproteins, 971
Phrenology, 190
Phrenosin, 80

Physical heat, regulation, 914
Physiological diplopia, 364
oxidations, theories of, 918

Lavoisier's work, 619, 904
point (vision), 335
saline, 41 1
Physostigmin, action of, on iris, 320
Pilocarpin, action of, on heart, 569

on iris, 320

on salivary glands, 734

on sweat glands, 832
Piqure, 870

Pituitary body, structure and func-
tions of, 844
Placenta,, functions of, 939
Plain muscle, 54

Plasma of blood, composition of, 434
Plethysmography, 584
Pneumogastric nerve (see Vagus)
Pneumograph, 629
Pneumothorax, 639
Poikilothermous animals, 905
Polar bodies of ovum, 935
Polypcptid, 767, 966
Positive electrical variation in heart,

570
Posterior funiculi, descending tracts
of, 177, 180

tracts of, 1 70
root, termination in cord, 169

cells of, origin of, 83

ganglia, type of cells in, 134
Postganglionic nerve-fibers, 247
Potassium salts, action of, on heart,

549
Potential energy of food, 895
Precipil ins, '.167
Predicrotic pulse wave, 510
Preganglionic nerve-fibers, 247
Pregnancy, changes in, 941
Prepyramidal tracts, 180
Presbyopia, 308, 313
Pressor nerve-fibers, 591

Pressure of gases in solution, 653

sense, disl ribul ion of, 270
deep, 272

localizing power, etc., 276
Primary proteoses, 752

INDEX.

993

Principal axis of lens, 299

focal distance, 299
Projection system of fibers (brain),

184
Prolamines, 970
Prolin, 766, 965
Propeptone, 752
Prostate gland, 948, 952
Protalbumoses, 752
Protamins, 949, 970
Protanopia, 346

Proteins, absorption of, in intestine,
775

as glycogen-formers, 794

classification of, 969

definition and structure of, 965

diffusion of, 977

excretion of nitrogen of, 813

general reactions of, 967

in blood-plasma, 436

necessary amount of, in diet, 858,
898

normal metabolism in body, 856

of muscle, 60

osmotic pressure of, 976

putrefaction of, in large intestine,
779

specific dynamic action of, 864

synthesis of, in body, 776
Proteolytic enzymes, 720
Proteoses, 972

general properties of, 752
Prothrombin, 443
Protopathic sensations, 272

sensibility, 271
Proximate principles of food, 712
Psychophysical law, 268
Ptyalin, 727

action of, in stomach, 698

digestive action of, 737

effect of various conditions upon,
738
Puberty, 927, 947

Pulmonary arteries, vasomotors of,
602

circulation, peculiarities of, 503
variations of pressure in, 503
Pulse, anacrotic waves of, 511

catacrotic waves of, 510

form of wave, 509

general statement, 505

varieties of, in health and disease,
512

velocity of propagation of, 506

venous, 513
Pulse-pressure, 477
Purin bases, 64, 817
Purkinje, images of, 306

phenomenon, 340
Putrefaction in intestines, 779
Pyloric glands of stomach, 740
secretion of, 750

63

Pyramidal tract in brain, 194

in spinal cord, 178
Pyrrol compounds in protein mole-
cule, 766
Pyrrolidin-carboxylic acid, 766, 965

Reaction of degeneration, 94

time, 113
Reactions, biological, 412
for proteins, 967
Gmelin's, 784
of blood, 405

of contents of small intestine, 778
of urine, 812
Pettenkofer's, 785
Recesswe characteristics in inherit-
ance, 956
Reciprocal innervation, 150
Recurrent sensibility of anterior roots,

82
Red blood-corpuscles, chemical com-
position of, 435
condition of hemoglobin in, 408
effect of hemorrhage upon, 427
hemolysis of, 409
influence of spleen upon, 426
number and size of, 408
origin and fate of, 425
variations in number of, 427
fibers in muscles, 19, 25
Reduced hemoglobin, 416

schematic eye, 302
Reflex actions, axon reflexes, 153
classification of, 145
definition and historical, 142
from parts of brain, 151
influence of condition of cord on,
151
of sensory endings upon, 147
inhibition of, 149

of heart, 568
knee-jerk, 156

of erection and ejaculation, 951
of respiratory center, 664, 669
of vasomotor nerves, 591
preparation of reflex frog, 144
reflex arc, 142
respiratory, from nose, larynx,

and pharynx, 669
special and deep reflexes of cord,

161
spinal reflexes, 144
theory of, 146
through peripheral ganglia, 152

vasodilator nerves, 597
time of, 148

Tiirck's method of studying, 151
Reflexes, deep, 161
extensor thrust, 159
special spinal, 161
spinal, 144

994

IXDEX.

Refractive power of eye, 309
Refractory period of heart beat, 552

of nerve-cell, 141
Regeneration in nerve-fibers, 127
Reinforcement of knee-kick, 156
Rennin, 753

of kidney, 851
Reproduction, changes during preg-
nancy, 941
in uterus in menstruation, 928
chemistry of spermatozoa, 949
determination of sex, 957
erection, 950

fertilization of ovum, 936
functions of placenta, 939
general statements, 1(24
growth and senescence, 960
heredity, 953

implantation of ovum, 938
mammary glands, 942
menstruation, 927
nutrition of embryo, 939
ovulation, 925
parturition, 942
properties of spermatozoa, 947
relation of ovaries to menstrua-
tion, 929
structure and functions of corpus
luteum, 925
of Graafian follicles, 925
Residual air, 632

Resonance, importance of, in func-
tions of ear, 388
Respiration, abdominal type, 628
acapnia, 678, 683
accessory centers of, in brain, 672

respiratory movements, 629
anatomy of thorax, 622
apnea, 675
artificial, 633, 643
aspiratory action of, on blood-flow,

639
asphyxia, 676
automatic action of respiratory

center, 664
bronchoconstrictor and broncho-
dilator fibers, 679
calorimeter, 911
capacity of the bronchi, 633
chamber, 85 1
chemical composition of inspired

and expired air, 644
Cheyne-Stokes type of, 686
complement al air, 632
condition of carbon dioxid in blood,

656
costal, 628

definition of inspiration and expira-
tion, 623

dissocial ion of oxyhemoglobin, 655

dyspnea, 027, 675

effect of anemia upon, 687

Respiration, effect of changes in baro-
metric pressure upon, 682
in composition of air, 680

of muscular work upon, 680
exchange of gases in, 644
forced, 627

gaseous exchange in lungs, 658
gases of blood, 648
history of, 618
hyperpnea, 675

increased heart rate during inspira-
tion, 643
injurious effect of expired air, 645
intrapulmonic pressure, 635
intrathoracic pressure, 636
mechanism of inspiration, 624
methods of recording, 629
minimal air, 632
modified, respiratory movements,

686
mountain sickness,- 682
muscles of expiration, 626

of inspiration, 626
negative pressure in thorax, 637
normal stimulus of, 672

ventilation of alveoli, 633
of swallowing, 691
origin of negative pressure in

thorax, 638
physical theory of, 658
physiological anatomy of organs

of, 622
pneumothorax, 639
reflex stimulation of respiratory

center, 664
relation of vagus nerve to, 666
residual air, 632
respiratory center, 662

quotient, 684

waves of blood-pressure, 640
secretion of gases in lungs, 661
spinal respiratory centers, 663
supplemental air, 632
tension of gases in alveolar air, 659
in arterial blood, 660
in tissues, 660
in venous blood, 659
tidal air, 632
value of nitrogen in, 654
ventilation, principles of, 645
vital capacity, 631
volumes of air respired, 631
voluntary control of, 670
Respiratory center, 662, 670

automatic activity of, 664

normal stimulus of, (172

reflex stimulation of, 664
movements, electrical changes in,

668
quotient, 684

waves of blood-pressure, 640
Restiform body, 2,31

INDEX.

995

Retina, action current of, 329

acuity of vision in, 335

after-images from, 343

color blindness of, 345
contrasts in, 344
vision in, 340

corresponding points of, 362

distribution of color sense in, 348

entopic phenomena, 357

function of rods and cones of, 349

fundamental and complementary
colors, 342

light adapted and dark adapted,
338

portion of, stimulated by light, 328

projection of, on occipital lobes, 206

qualities of visual sensations from,
340

size of fovea in, 335

theories of color vision in, 352

threshold stimulus of, 337

visual purple of, 330
Retinoscope, 325

Reversible chemical reactions, 717
Rheoscopic frog preparation, 106
Rhodopsin, 330

Ribs, action of, in inspiration, 625
Rigor, calcium, 54

of muscle, 51, 69

water, 54
Ringer's solution, 549
Ritter's tetanus, 91
Rivinus, ducts of, 724
Rods and cones of eye, functions of,

349
Romberg's symptom, 235
Rubner's laws of growth, 963

surface area law, 912
Rubrospinal tract, 180, 196

Sacculus, functions of, 402
Saliva, chorda, 729
composition of, 727
digestive action of, 737
general functions of, 739
secretory nerves for, 728
sympathetic, 729
Salivary glands, action of drugs upon,
734
anatomical relations, 724
histological changes during ac-
tivity, 732
structure of, 724
normal stimulation of, 736
secretory centers for, 736

nerve-fibers of, 728
theory of secretory nerves, 730
Salts, absorption of, in stomach, 757
excretion of, 823, 882
general nutritive importance of, 882
Sarcolactic acid, 63

Sarcomeres, 75

Sarcostyles, 18

Sebaceous glands, secretion of, 832

Secondary axes of a lens, 300

degeneration, nerve-fibers, 125, 166

proteoses, 752
Secretin, gastric, 748

pancreatic, 763
Secretion, 724

internal, 834

paralytic (saliva), 735

of bile, 788

of gastric juice, 746

of intestinal juice, 770

of pancreatic juice, 760

of saliva, 728

of sebaceous glands, 832

of sweat, 829

of urine, 812
Secretogogues of gastric glands, 747
Secretory nerves of salivary glands,

'728
Semicircular canals, direct stimula-
tion of, 397
Flourens's experiments upon, 395
structure of, 394
temporary and permanent effects

of operations on, 396
theories of functions of, 398
Seminal vesicles, function of, 948
Senescence, 960
Senses, classification of, 264

cutaneous and internal, 271
Sensibility, muscular, 280

of glans penis, 272

protopathic and epicritic, 271
Sensory aphasia, 218

areas of cortex, 199

paths in spinal cord, 170, 173
Sequence of heart beat, 554
Serin, 965

Serum, action of foreign, 411
Serum-albumin, 436
Serum-globulin, 437
Seventh cranial nerve, nucleus of, 244
Sex, determination of, 957
Side-pressure in blood-vessels, 495
Sixth cranial nerve, nucleus of, 244
Skatoxylsulphuric acid, 822
Skeletal muscular tissue, structure

of, 18
Skiascope, 325
Skin, excretory functions of, 828

sweat glands of, 829
Sleep, changes in circulation during,
256

curves of intensity of, 255

effect of sensory stimulation dur-
ing, 259

hypnotic, 263

metabolism during, S92

physiological phenomena of, 253

996

INDEX.

Sleep, theories of, 260

Small intestine, absorption in, 771

Smegma praeputii, 833

Smell, center for, in brain, 213

end-organ of, 291
Smelling, mechanism of, 292
Sodium chlorid, nutritive value of,
882
salts, effect of, on heart beat, 549
Somatoplasm, definition of, 962
Sound, sensations of (see Ear)
waves, nature and action of, 384
overtones of, 386
simple and compound, 385
Specific energy of taste sensations,
289
gravity of blood, 407
nerve energies, doctrine of, 124, 266
of cutaneous nerves, 274
Spectra, absorption, blood, 419
Spectroscope, 420
Spermatozoa, chemistry of, 949
maturation of, 948
properties of, 948
Spermin, 847

Spherical aberration in eye, 311
Sphincter, cardiac, 693
external, of anus, 707
ileocecal, 705
internal, of anus, 707
of bile-duct, 790
of bladder, 825
Sphygmography, 508
Sphygmomanometers for determining

blood-pressure in man, 485
Spinal cord as path of conduction, 163
classification of tracts in, 166
effect of removing, 155
general relations of gray and

white matter in, 165
groups of cells in, 163
Helweg's bundle in, 181
homolateral and contralateral

conduction in, 176
less well-known tracts of, 179
Monakow's bundle in, 180
put lis in, for cutaneous impulses,

175
pyramidal tracts of, 177
reflex activities of, 142
tonic activity of, 154
tracts of, in lateral funiculi, L73
in posterior funiculi, 170
in white ma1 ter, 166
vestibulospinal tract, 180, 231
reflex movements, I 11

reflexes, 144

in mammals, 147
respiratory cent er, 663
Spirometer, 63 1
Spleen, physiology of, 799
Stannius, (ii-t ligature of, 557

Stapedius muscle, function of, 380
Starvation, effect of, on body-metab-
olism, 893
Steapsin (see Lipase)
Stenson's duct, 724
Stereognostic sense, 200
Stereoscopic vision, 369
Stethoscope, 531
Stimulants, 714

nutritive importance of, 885
Stimuli, artificial, of muscle, 24

of nerve, 85
Stokes-Adams syndrome, 557
Stokes' reducing agent, 422
Stomach, absorption in, 756

anatomy of, 694

automaticity of, 699

digestion in, 755

glands of, 740

histological changes in, during
activity, 741

means of obtaining secretion of, 742

mechanism of gastric secretion, 747

movements of, 696

musculature of, 695

properties of pepsin of, 749

secretory nerves of, 746
Strabismus, 361
String galvanometer, 100
Stromuhr, 467
Subliminal stimulus, 337
Submaxillary ganglion, 724
Substrata, 719
Succus entericus, 770
Sugar puncture, 870

regulation of supply of, in body, 870
Sugars (see Carbohydrates)
Sulphur, forms in which excreted, 822
Summation of muscular contractions,
42

of stimuli in nerve-centers, 139
Superior olivary body, relation of, to

auditory paths, 212
Supplemental air, 632
Surface area law, 912
Swallowing, 689

respiration, 691
Sweat, amount and composition of,
829

nerve-centers for, 832

nerves, action of, in heat regu-
lation, 913

secretory fibers of, 830
Sympathetic nervous system, general

relnl ions, 246

resonance, 388
Syntonin, 752
Systole, duration of, in heart, 535

Systolic arterial pressure, 477

determination of, in animals,

•179
in man, 485

INDEX.

997

Systolic plateau of ventricular con-
traction, 527

Tabes dorsalis, 172

Tactile discrimination, 176, 279

localization, 176, 279
paths of, in cord, 176
Taste buds, 288

center for, in brain, 215

nerves of, 286

sensations, classification of, 288
specific energy of, 289
threshold stimulus, 291

sense of, 286

stimuli, mode of action, 290
Taurin, 786
Taurocholic acid, 786
Tectorial membrane, 390
Temperature (see Heat)

coefficient, 116

effect of, on body metabolism, 893
on gases in solution, 652
on heart rate, 580
on muscular contraction, 29

of human body, 906

sense, distribution and character-
istics, 272, 275
path for, in spinal cord, 175
punctiform distribution of, 272
Tension of gases in solution, 653
Tensor tympani muscle, function of,

380
Tenth cranial nerve, nucleus of, 245
Testis, internal secretion of, 847
Tetanus, number of stimuli necessary
for, 43

of artificial muscle, 74

of muscle, 40

opening and closing, 91
Theobromin, 818, 886
Third cranial nerve, nucleus of, 241

heart sound, 533
Thirst, sense of, 285
Thorax as closed cavity, 622

aspiratory action of, 639

normal position of, 623

origin of negative pressure in, 638
Thrombin, 443
Thrombogen, 444
Thrombokinase, 444
Thyroid, extirpation of, 836

function of, 838

internal secretion of, 835

theory of (Cyon), 840
Tidal air, 632

Tigroid substance in nerve-cells, 136
Tissue protein, 856
Tissues, exchanges of gases in, 660
Tone (musical) of muscular contrac-
tion, 43 •
Tonicity of heart muscle, 558

Tonicity of muscle, 50

of nerve-centers, 154
Tonus, myogenic, 56

neurogenic, 56
Touch sense, path of, in cord, 175
Tracts in cerebellum, 231

in spinal cord, 166

of Flechsig, 168

of Gowers, 168

of Helweg (olivo-spinal), 181

of Monakow (rubro-spinal), 180, 196
Traube-Hering waves, 596
Treppe on muscular contractions, 34
Trigeminal nerve, area of distribu-
tion of, 243
nucleus of, 244
Tritanopia, 346
Trophic nerve fibers, salivary glands,

730
Trypsin, 720, 764
Tryptophan, 766

Tiirck's method for reflex time, 151
Twelfth cranial nerve, nucleus of,

245
Tympanic membrane, 376
Tyrosin, 766, 965

Unipolar method of stimulation, 92
Urea, formation of, in liver, 798

origin and significance of, 814, 861
Ureters, contractions of, 824
Urethra, sphincter of, 825
Uric acid, 64, 817
in spleen, 801
significance of, 817, 863
Uricolytic enzyme, 819
Urinary bladder, movements of, 825
nerves of, 827
pigments, 812
Urination, physiological mechanism

of, 824
Urine, composition of, 812
nitrogenous excreta of, 813
origin of acidity of, 808, 812
reaction of, 812
secretion of, 803
pressure of, 807
Uterus, changes of, during menstrua-
tion, 928
effect of, on mammary glands, 943
Utriculus, function of, 402

Vagus nerve, action of, on gastric
secretion, 746
on heart, 561 (see also Inhibi-
tion)
on pancreas, 760
as motor nerve to stomach, 699
nucleus of, 245

relations of, to respiratory cen-
ter, 666

99S

INDEX.

Valin, 765, 965

Vasomotor fibers, centers for, in cord,
595

in brain, 612

to pulmonary arteries, 602
nerves, action of, in heat regula-
tion, 914

antidromic impulses in, 599

course and distribution, 586, 596

general properties of dilators, 597

history of discovery of, 582

methods used to demonstrate,
583

of heart, 601

position of constrictor center, 589

reflex actions of, 591

rhythmical action of constrictor
center, 595

to abdominal organs, 613

to dilator center and reflexes, 597

to genital organs, 614

to head, 612

to kidneys, 810

to skeletal muscles, 614

to trunk and limbs, 613

to veins, 615

tonic activity of, 589
Vasothrombin, 447
Veins, vasomotor supply of, 615
Velocity of blood-flow (see Circu-
lation )
pressure in blood-vessels, 496
Venous blood-pressures, 491
pulse, 513

in brain sinuses, 609
Ventilation, principles of, 645
Ventricle (see Heart)
Veratrin, effect of, on muscle, 31

Vernix caseosa, 833
Vestibular nerve, 210
Vestibulospinal tract of spinal cord,

180, 231
Vision (see Eye and Retina)
Visual acuity, 335

center in cortex, 203

field, binocular, 362
monocular, 334

fields, conflict of, in binocular
A'ision, 366

purple, 330
Vital capacity, 631
Volume curve of heart, 528
Voluntary muscular contractions, 44
Vomiting, 709

Wallerian degeneration, 125, 166

Warm spots of skin, 272

"Water, absorption of, in stomach, 757

excretion of, 823

rigor, 54
Weber-Fechner law, 268
Wharton's duct, 724
Wirsung, duct of, 759
Work done by contracting muscle, 39

Xanthin, 64, 817

oxidase, 819, 863
Xanthoproteic reaction for proteins,

968

Zymogen, 722

granules, 733
Zymoids, 720
Zymoplastic substance, 444

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Orville Horwitz, M.D.
Allen B. Kanavel, M.D.
Albert Kocher, M.D.
Karl Gustav Lennander, M.D,
Bransford Lewis, M.D.
R. W. Lovett, M.D.
Edward Martin, M.D.
Rudolph Matas, M.D.
Chas. A. Mayo, M.D.
Wm. J. Mayo, M.D.
Maj. Walter D. McCaw, M.D.

E. E. Montgomery, M.D.
B. G. A. Moynihan, F.R.C.S.
J. G. Mumford, M.D.
John C. Munro, M.D.
John B. Murphy, M.D.

E. H. Nichols, M.D.
A. J. Ochsner, M.D.
Surg.-Gen.R.M.O' Reilly.U.S.A.
Edmund Owen, F.R.C.S.

Jos. Ransohoff, M.D., F.R.C.S.
Surg.-Gen. P. M. Rixey,U.S.N.
John B. Roberts, M.D.
A. W. Mayo Robson, F.R.C.S.
W. L. Rodman, M.D.
Eugene A. Smith, M.D.
Harmon Smith, M.D.
Wm. G. Spiller, M.D.
Weller Van Hook, M.D.
J. P. Warbasse, M.D.

F. C. Wood, M.D.
George Woolsey, M.D.
Hugh H. Young, M.D.
Fredrik Zachrisson, M.D.

SURGERY AND ANATOMY

Crandon's
Surgical After-treatment

Surgical After=treatment. A Manual of the Conduct of Surgical
Convalescence. By L. R. G. Crandon, M. D., Assistant in Surgery
at Harvard Medical School; Assistant Visiting Surgeon to the Boston
City Hospital. Octavo of 750 pages, with 300 original illustrations.

READY IN FEBRUARY

This work tells how best to manage all problems and emergencies of surgical
convalescence from recovery-room to discharge. It gives all the details com-
pletely, definitely, yet concisely, and does not refer the reader to some other
work perhaps not then available. The post-operative conduct of all operations
is given, arranged alphabetically by regions. A special feature is the elaborate
chapter on Vaccine Therapy, Immunization by Inoculation and Specific Sera,
written by Dr. George P. Sanborn, a leading disciple of Sir Almroth E. Wright.
This is undoubtedly the best and most complete exposition of these subjects
yet published. The text is illustrated, fixing by the aid of the eye those points
in technic less easily grasped by description alone.

Moynihan's Duodenal Ulcers

Duodenal Ulcers. By B. G. A. Moynihan, M. S. (London),
F. R. C. S., Senior Assistant Surgeon to Leeds General Infirmary,
England. Octavo of 450 pages, illustrated.

READY IN MARCH

Every surgeon and every practitioner meets with cases of duodenal ulcer, so
that each must have a good work on the subject by some recognized authority.
It must not only give the etiology, pathology, and symptoms, but — most important
of all — the diagnosis, differential diagnosis, and treatment. Mr. Moynihan's ex-
tensive experience in this field gives his book the stamp of authority. And he
has presented his subject in a style at once forceful, definite, yet concise. For
the practitioner he fixes the diagnosis with precision, so that the case, if desired,
may be referred to the surgeon. For the surgeon, he describes the best technic
in a way that admits of no hesitation. The illustrations are a feature worthy of
the text.

SAUNDERS' BOOKS ON

Cotton's

Dislocations and Joint Fractures

Dislocations and Joint Fractures. By Frederic Jay Cotton, M. D-,
Associate Professor of Clinical Surgery at Tuft's Medical School, Boston.
Octavo volume of 600 pages, with 1200 original illustrations.

READY IN MARCH— ORIGINAL ILLUSTRATIONS

Dr. Cotton's clinical and teaching experience in this field has especially fitted
him to write a practical work on this subject. He has written a book clear and
definite in style, systematic in presentation, and accurate in statement. The
illustrations possess the feature of showing just those points the author wishes to
emphasize. This is made possible because the author is himself the artist, by
far the greater majority of the illustrations being the work of his own hand.
They are strikingly artistic as well as unusually practical.

Kemp on
Stomach and Intestines

Diseases of the Stomach and Intestines. By Robert Coleman
Kemp, M. D., Professor of Gastro-intestinal Diseases at the New
York School of Clinical Medicine. Octavo of 750 pages, with 300
illustrations.

JUST READY— MEDICAL AND SURGICAL

Of the many works on gastro-intestinal diseases, this is perhaps the only one
in which the needs of the general practitioner are given pre-eminent emphasis.
It is t!ie practitioner who first meets with these cases, and it is he upon whom the
burden of diagnosis rests. After the diagnosis is established, the practitioner, if
properly equipped, could frequently treat the case himself instead of transferring
it to a specialist. This work is intended to equip the practitioner with this end in
view. As visceral displacements have assumed such an important position, their
symptoms, diagnosis, and treatment, notably by mechanical methods, are specially
desf ribed. Auto-intoxication has been given unusual attention. Typhoid fever
is also included because of its local manifestations.

SURGER Y AND ANA TO MY

Kelly and Noble's
Gynecology
and Abdominal Surgery

Gynecology and Abdominal Surgery. Edited by Howard A.
Kelly, M. D., Professor of Gynecology in Johns Hopkins University ;
and Charles P. Noble, M. D., Clinical Professor of Gynecology in the
Woman's Medical College, Philadelphia. Two imperial octavo volumes
of 950 pages each, containing 880 original illustrations, some in colors.
Per volume: Cloth, $8.oo net; Half Morocco, $9.50 net.

BOTH VOLUMES NOW READY
WITH 880 ILLUSTRATIONS BY HERMANN BECKER AND MAX BRODEL

In view of the intimate association of gynecology with abdominal surgery the
editors have combined these two important subjects in one work. For this reason
the work will be doubly valuable, for not only the gynecologist and general prac-
titioner will find it an exhaustive treatise, but the surgeon also will find here the
latest technic of the various abdominal operations. It possesses a number of
valuable features not to be found in any other publication covering the same fields.
It contains a chapter upon the bacteriology and one upon the pathology of gyne-
cology, dealing fully with the scientific basis of gynecology. In no other work
can this information, prepared by specialists, be found as separate chapters.
There is a large chapter devoted entirely to medical gynecology , written especially
for the physician engaged in general practice. Heretofore the general practi-
tioner was compelled to search through an entire work in order to obtain the in-
formation desired. Abdominal surgery proper, as distinct from gynecology, is
fully treated, embracing operations upon the stomach, upon the intestines, upon
the liver and bile-ducts, upon the pancreas and spleen, upon the kidneys, ureter,
bladder, and the peritoneum. The illustrations are truly magnificent, being the
work of Mr. Hermann Becker and Mr. Max Brodel.

American Journal of the Medical Sciences

" It is needless to say that the work has been thoroughly done; the names of the authors
and editors would guarantee this, but much may be said in praise of the method of presentation,
and attention may be called to the inclusion of matter not to be found elsewhere."

SAUNDERS' BOOKS ON

Sisson's
Veterinary Anatomy

Text=Book of Veterinary Anatomy. By Septimus Sisson, S. B.,

V. S., Professor of Comparative Anatomy in Ohio State University.
Octavo volume of 900 pages, with over 500 illustrations, mostly original
and many in colors.

READY IN JULY— WITH SUPERB ILLUSTRATIONS

This is the first original systematic work on this subject in English within the
last quarter of a century, and represents the accumulated practical results of twenty
years' actual experience. It is a clear and concise statement of the essential facts
regarding the structure of the principal domesticated animals, containing many
hitherto unpublished data resulting from the detailed study of formalin-hardened
subjects and frozen sections. The author has devoted much time and care to
the illustrations in order to have each one represent just that particular feature
which he desired to illustrate. Nearly all of them are original, the majority being
reproduced from photographs, and colors are used wherever desirable to render
the pictures more readily understood. The terminology used has been carefully
revised with reference to the B. N. A. and the nomenclature adopted by European
comparative anatomists. The work supplies a long-felt need.

Gant on Constipation and
Intestinal Obstruction

Constipation and Intestinal Obstruction. By Samuel G. Gant,
M. D., Professor of Diseases of the Rectum and Anus, New York
Post-Graduate Medical School and Hospital. Octavo of 559 pages,
with 250 original illustrations. Cloth, $6.00 net ; Half Morocco, $7.50 net.

INCLUDING RECTUM AND ANUS

In this work the consideration given to the medical treatment of constipation
is unusually extensive. The practitioner will find of great assistance the chapter
devoted to formulas. The descriptions of the operative procedures are concise,
yet fully explicit.

The Proctologist

• ' Were the profession better posted on the contents of this book there would
be less suffering from the ill effects of constipation. We congratulate the author
on this most complete book."

SURGER Y AND ANA TOMY

Scrudders
Treatment of Fractures

WITH NOTES ON DISLOCATIONS

The Treatment of Fractures : with Notes on a few Common
Dislocations. By Charles L. Scudder, M.D., Surgeon to the Massa-
chusetts General Hospital, Boston. Octavo of 628 pages, with 854
original illustrations. Polished Buckram, $5.50 net; Half Morocco,
$7.00 net.

THE NEW (6th) EDITION, REVISED AND ENLARGED
OVER 28.500 COPIES

The fact that this work has attained a sixth edition indicates its practical
value. In this edition Dr. Scudder has made numerous additions throughout
the text, and has added many new illustrations, greatly enhancing the value of
the work. The articles on Dislocations, illustrated in that practical manner
which has made Dr. Scudder' s work so useful, will be found extremely val-
uable.

Joseph D. Bryant, M.D., Professor of the Principles and Practice of Surgery, University
a?id Bellevue Hospital Medical College.

"As a practical demonstration of the topic it is excellent, and as an example of bookmaking
it is highly commendable."

Bickham's Operative Surgery

A Text=Book of Operative Surgery. By Warren Stone Bickham,
M. D., Phar. M., of New Orleans. Octavo of 1200 pages, with 854
original illustrations. Cloth, $6.50 net ; Half Morocco, $8.00 net.

THE NEW (3d) EDITION

This absolutely new work completely covers the surgical anatomy and opera-
tive technic involved in the operations of general surgery. The practicability of
the work is particularly emphasized in the 854 magnificent illustrations which form
a useful and striking feature.

Boston Medical and Surgical Journal

" The book is a valuable contribution to the literature of operative surgery. It represents
a vast amount of careful work and technical knowledge on the part of the author. For the sur-
geon in active practice or the instructor of surgery, it is an unusually good review of the subject."

SAUNDERS' BOOKS ON

Bier's
Hyperemic Treatment

By WILLY MEYER, M. D.. and Prof. V. SCHMIEDEN

Bier's Hyperemic Treatment in Surgery, Medicine, and the Special-
ties : A Manual of its Practical Application. By Willy Meyer, M. D.,
Professor of Surgery at the New York Post-Graduate Medical School
and Hospital ; and Prof. Dr. Victor Schmieden, Assistant to Prof.
Bier, University of Berlin, Germany. Octavo of 280 pages, with
original illustrations. Cloth, $3.00 net

RECENTLY ISSUED— NEW (2d) EDITION— FOR THE PRACTITIONER

For the practitioner this work has a particular value, because it gives special
attention to the hyperemic treatment of those conditions with which he comes in
daily contact. Yet the needs of the surgeon and the specialist have not, by any
means, been neglected. The work is not a translation, but an entirely original
book, by Dr. Willy Meyer, who has practised the treatment for the past fifteen
years, and Prof. Schmieden, Professor Bier's assistant at Berlin University. In
the first part the three methods of inducing hyperemia are described; in the second,
are taken up the details of application.

New York State Journal of Medicine

" We commend this work to all those who are interested in the treatment of infections,
either acute or chronic, for it is the only authoritative treatise we have in the English language."

Campbell's Surgical Anatomy

A Text=Book of Surgical Anatomy. By William Francis Camp-
bell, M. D., Professor of Anatomy, Long Island College Hospital.
Octavo of 675 pages, with 319 original illustrations. Cloth, $5.00 net;
Half Morocco, $6.50 net.

WITH 319 PRACTICAL ILLUSTRATIONS

The first aim in the preparation of this original work was to emphasize the
practical. It is in the fullest sense an applied anatomy — an anatomy that will be
of inestimable value to the surgeon because only those facts are discussed and
only those structures and regions emphasized that have a peculiar interest to him.
I Jr. Campbell has treated his subject in a very systematic way. The magnificent
original illustrations will be found extremely practical.

Boston Medical and Surgical Journal

"The author has an excellent command of his subject, and treats it with the freedom and
the conviction ol the experienced anatomist. He is also an admirable clinician."

SURGER Y AND ANA TOM\

Schultze arid Stewart's
Topographic Anatomy

Atlas and Text=Book of Topographic and Applied Anatomy. By

Prof. Dr. O. Schultze, of Wurzburg. Edited, with additions, by
George D. Stewart, M.D., Professor of Anatomy and Clinical Sur-
gery, University and Bellevue Hospital Medical College, N. Y. Large
quarto of 189 pages, with 25 colored figures on 22 colored lithographic
plates, and 89 text-cuts, 60 in colors. Cloth, $5.50 net.

WITH BEAUTIFUL COLORED PLATES

It was Professor Schultze's special aim, in preparing this work, to produce a
Text-Book and Atlas, not for the anatomist alone, but more particularly for the
general practitioner. The value of the knowledge of topographic anatomy in bed-
side diagnosis is emphasized throughout the book. The many colored lithographic
plates are exceptionally excellent.

Arthur Dean Bevan. M. D., Professor of Surgery in Rush Medical College, Chicago.

" I regard Schultze and Stewart's Topographic and Applied Anatomy as a very admirable
work, for students especially, and I find the plates and the text excellent."

Sobotta arid McMurrich's
Human Anatomy

Atlas and Text=Book of Human Anatomy. In Three Volumes. By
J. Sobotta, M.D., of Wurzburg. Edited, with additions, by J. Playfair
McMurrich, A. M., Ph. D., Professor of Anatomy, University of
Toronto, Canada. Three large quartos, each containing about 250
pages of text and over 300 illustrations, mostly in colors. Per volume :
Cloth, $6.00 net ; Half Morocco, $7.50 net.

VOLUME III NOW READY— COMPLETING THE WORK

The great advantage of this over other similar works lies in the large number
of magnificent lithographic plates which it contains, without question the best that
have ever been produced in this field. They are accurate and beautiful reproduc-
tions of the various anatomic parts represented.
Edward Martin, M.D., Professor of Clinical Surgery, University of Pennsylvania.

"This is a piece of bookmaking which is truly admirable, with plates and text so W«ll
chosen and so clear that the work is most useful to the practising surgeon."

io SAUNDERS1 BOOKS ON

Eisendrath's
Surgical Diagnosis

A Text=Book of Surgical Diagnosis. By Daniel N. Eisendrath,
M.D., Professor of Surgery in the College of Physicians and Surgeons,
Chicago. Octavo of 885 pages, with 574 entirely new and original
text-illustrations and some colored plates. Cloth, $6.50 net; Half
Morocco, 58.00 net.

JUST ISSUED— THE NEW (2d) EDITION

Of first importance in every surgical condition is a correct diagnosis, for upon
this depends the treatment to be pursued ; and the two — diagnosis and treatment —
constitute the most practical part of practical surgery. Dr. Eisendrath takes up
each disease and injury amenable to surgical treatment, and sets forth the means
of correct diagnosis in a systematic and comprehensive way. Definite directions
as to methods of examination are presented clearly and concisely, providing for
all contingencies that might arise in any given case. Each illustration indi-
cates precisely how to diagnose the condition considered.

Surgery, Gynecology, and Obstetrics

"The book is one which is well adapted to the uses of the practising surgeon who desires
information concisely and accurately given. . . . Nothing of diagnostic importance is omitted,
yet the author does not run into endless detail."

Eisendrath's Clinical Anatomy

A Text=Book of Clinical Anatomy. By Daniel N. Eisendrath,
A.B., M.D., Professor of Surgery in the College of Physicians and
Surgeons, Chicago. Octavo of 535 pages, illustrated. Cloth, $5.00
net; Half Morocco, $6.50 net.

THE NEW (2d) EDITION

This new anatomy discusses the subject from the clinical standpoint. A por-
tion of each chapter is devoted to the examination of the living through palpation
and marking of surface outlines of landmarks, vessels, nerves, thoracic and
abdominal viscera. The illustrations are from new and original drawings and
photographs. This edition has been carefully revised.

Medical Record, New York

"A special recommendation for the figures is that they are mostly original and were
made for tin purpose in view. The sections of joints and trunks are those of formalin i zed
cadavers ami arc unimpeachable in accuracy."

SURGERY AND ANATOMY

Moynihan's
Abdominal Operations

Abdominal Operations. By B. G. A. Moynihan, M. S. (Lond.),
F.R.C.S., Senior Assistant Surgeon, Leeds General Infirmary, England.
Octavo, beautifully illustrated. Cloth, $7.00 net ; Half Morocco, $8.50 net

THE NEW (2d) EDITION
TWO LARGE EDITIONS IN ONE YEAR

It has been said of Mr. Moynihan that in describing details of operations he
is at his best. The appearance of this, his latest work, therefore, will be widely
welcomed by the medical profession, giving, as it does, in most clear and exact
language, not only the actual modus operandi of the various abdominal operations,
but also the preliminary technic of preparation and sterilization. Complications
and sequelae and after-treatment are presented in the same clear, clean-cut manner
as the operations themselves. The beautiful illustrations have been especially drawn.

Edward Martin, M. D.

Professor of Clinical Surgery, University of Pennsylvania

" It is a wonderfully good book. He has achieved complete success in illustrating, both
by words and pictures, the best technic of the abdominal operations now commonly performed. "

Moynihan on Gall-stones

Qall=stones and Their Surgical Treatment. By B. G. A. Moyni-
han, M. S. (Lond.), F.R.C.S., Senior Assistant Surgeon, Leeds General
Infirmary, England. Octavo of 458 pages, fully illustrated. Cloth,
$ 5.00 net ; Half Morocco, $6.50 net.

THE NEW (2d) EDITION

Mr. Moynihan, in revising his book, has made many additions to the text, so
as to include the most recent advances. Especial attention has been given to a
detailed description of the early symptoms in cholelithiasis, enabling a diagnosis
to be made in the stage in which surgical treatment can be most safely adopted.
Every phrase of gall-stone disease is dealt with, and is illustrated by a large
number of clinical records. The account of the operative treatment of all the
forms and complications of gall-stone disease is full and accurate. A number of
the illustrations are in color.

British Medical Journal

" He expresses his views with admirable clearness, and he supports them by a large num-
ber of clinical examples, which will be much prized by those who know the difficult problems
and tasks which gall-stone surgery not infrequently presents."

SAUNDERS' BOOKS ON

Gould's Operations on the
Intestines and Stomach

The Technic of Operations upon the Intestines and Stomach. By

Alfred H. Gould, M. D., of Boston. Large octavo, with ioo original
illustrations, some in colors. Cloth, $5.00 net ; Half Morocco |6.5Qiiet.

WITH 190 ORIGINAL ILLUSTRATIONS

Dr. Gould' s new work is the result of exhaustive experimentation, the technic
of the operations described being simplified as far as possible by experiments on
animals, thus leading to the development of many new features. The text is pur-
posely concise, the technic being presented very clearly by the numerous practical
illustrations, all made from actual operations done either upon the animal or the
human being. As the success of gastro-intestinal surgery depends upon an accur-
ate knowledge of the elementary steps, a thorough account of repair is included.

New York State Journal of Medicine

" The illustrations are so good that one scarcely needs the text to elucidate the steps of
the operations described. The work represents the best surgical knowledge and skill."

DaCosta*s Modern Surgery

Modern Surgery — General and Operative. By John Chalmers
DaCosta, M. D., Professor of Surgery and of Clinical Surgery in the
Jefferson Medical College, Philadelphia. Octavo of 1283 pages, with
872 illustrations. Cloth, $5.50 net; Half Morocco, $7.00 net.

THE NEW (5th) EDITION

For this new fifth edition the work has been entirely rewritten and reset. One
hundred and fifty new illustrations have been added ; and the work has been en-
larged by the addition of two hundred pages. To keep the book of a size to handle
conveniently, a thinner but high-grade paper has been used. DaCosta' s Surgery
in this edition will more than maintain the reputation already won.

Boston Medical and Surgical Journal

" We commend the hook, as we have previously commended it, to surgeons and to students
as the most satisfactory one-volume contemporaneous treastise on surgery published in this
country."

SURCER Y AND ANA TOMY

Preiswerk and Warren's Dentistry

Atlas and Epitome of Dentistry. By Prof. G. Preiswerk, of Basil. Ed-
ited, with additions, by George W. Warren, D.D.S., Professor of Operative
Dentistry, Pennsylvania College of Dental Surgery, Philadelphia. With 44
lithographic plates, 152 text-cuts, and 343 pages of text. Cloth, $3.50 net
In Saunders Atlas Series.

" Nowhere in dental literature have we ever seen illustrations which can begin to compare
with the exquisite colored plates produced in this volume." — Dental Review.

Griffith's Hand-Book of Surgery

A Manual of Surgery. By Frederic R. Griffith, M. D., Surgeon to the
Bellevue Dispensary, New York City. i2mo of 579 pages, with 417 illus-
trations. Flexible leather, $2.00 net.

" Well adapted to the needs of the student and to the husy practitioner for a hasty review of important
points in surgery." — American Medicine.

Keen's Addresses and Other Papers

Addresses and Other Papers. Delivered by William W. Keen, M. L>.,
LL.D., F. R. C. S. (Hon.), Professor of the Principles of Surgery and of Clin-
ical Surgery, Jefferson Medical College, Philadelphia. Octavo volume of
441 pages, illustrated. Cloth, $3.75 net,

Keen on the Surgery of Typhoid

The Surgical Complications and Sequels of Typhoid Fever. By Wi. W.

Keen, M.D., LL.D., F.R.C.S. (Hon.), Professor of the Principles of Surgery
and of Clinical Surgery, Jefferson Medical College, Philadelphia, etc
Octavo volume of 386 pages, illustrated. Cloth, $3.00 net.

** Every surgical incident which can occur during or after typhoid fever is amply discussed and fully
illustrated by cases. . . . The book will be useful both to the surgeon and physician." — 'J he
Practitioner, London.

Lewis' Anatomy and Physiology for Nurses

Just Ready— New (2d) Edition
Anatomy and Physiology for Nurses. By LeRoy Lewis, M. D., Surgeon
to and Lecturer on Anatomy and Physiology for Nurses at the Lewis Hospital,
Bay City, Michigan. i2mo, 375 pages, with 150 illustrations. Cloth, $1.75 net.

A demand for such a work as this, treating the subjects from the nurse's point of view, has
long existed. Dr. Lewis has based the plan and scope of this work on the methods em-
ployed by him in teaching these branches, making the text unusually simple and clear.
" It is not in any sense rudimentary, but comprehensive in its treatment of the subjects in hand." —
Nurses, Journal of the Pacific Coast.

McClellan's Art Anatomy

Anatomy in Its Relation to Art. By George McClellan, M. D. , Professor
of Anatomy, Pennsylvania Academy of the Fine Arts. Quarto volume, 9 by
\iyi inches, with 338 original drawings and photographs, and 260 pages of
text. Dark blue vellum, $10.00 net ; Half Russia, $12.50 net.

14 SAUNDERS* BOOKS ON

Haynes' Anatomy

A Manual of Anatomy. By Irving S. Haynes, M.D., Professor of Prac-
tical Anatomy, Cornell University Medical College. Octavo, 680 pages,
with 42 diagrams and 134 full-page half-tones. Cloth, $2.50 net.

American Pocket Dictionary ^SSiSSL

The American Pocket Medical Dictionary. Edited by W. A. Newman

Dorland, A.M..M.D., Assistant Obstetrician, Hospital of the University of
Pennsylvania, etc. 598 pages. Full leather, limp, with gold edges, $1.00
net; with patent thumb index, $1.25 net.

Grant on Face, Mouth, and Jaws

A Text*- Book of the Surgical Principles and Surgical Diseases of the
Face, Mouth, and Jaws. For Dental Students. By H. Horace Grant,
A.M., M.D., Professor of Surgery and of Clinical Surgery, Hospital College
of Medicine. Octavo of 231 pages, with 68 illustrations. Cloth, $2.50 net.

Fowler's Surgery In Two Volumes

A Treatise on Surgery. By George R. Fowler, M. D., Emeritus Pro-
fessor of Surgery, New York Polyclinic. Two imperial octavos of 725 pages
each, with 888 original text-illustrations and 4 colored plates. Per set :
Cloth, $15.00 net ; Half Morocco, $18.00 net.

International Text- Book of Surgery second Edition

The International Text=Book of Surgery. In two volumes. By Ameri-
can and British authors. Edited by J. Collins Warren, M. D., LL. D.,
F. R. C. S. (Hon.), Professor of Surgery, Harvard Medical School ; and A.
Pearce Gould, M. S., F. R. C. S. , of London, England. Vol. I. : General
and Operative Surgery. Royal octavo, 975 pages, 461 illustrations, 9 full-
page colored plates. Vol. II. : Special or Regional Surgery. Royal octavo,
1 1 22 pages, 499 illustrations, and 8 full-page colored plates. Per volume :
Cloth, $5.00 net ; Half Morocco, $6.50 net.

American Text-Book of Surgery Fourth Edition

American Text-Book of Surgery. Edited by W. W. Keen, M. D.,
LL. D., Hon. F. R. C. S., Eng. and Edin., and J. William White,
\1. D., Ph. D. Octavo, 1363 pages, 551 text-cuts and 39 colored and
half-tone plates. Cloth, #7.00 net ; Half Morocco, #8.50 net.

Robson and Cammidge on the Pancreas

The Pancreas : Its Surgery and Pathology. By A. W. Mayo Robson,
I •'. R. C. S., of London, England; and P. J. Cammidge, F. R. C. S., of
London, England. Octavo of 546 pages, illustrated. Cloth, $5.00 net;
Half Morocco, #6.50 net.

SURGERY AND ANATOMY. 15

American Illustrated Dictionary ^ New ,,£'£

The American Illustrated Medical Dictionary. With tables
of Arteries, Muscles, Nerves, Veins, etc. ; of Bacilli, Bacteria, etc. ;
Eponymic Tables of Diseases, Operations, Stains, Tests, etc. By W. A.
Newman Dorland, M.D. Large octavo, 876 pages. Flexible leather,
$4.50 net; with thumb index, $5.00 net.

Howard A. Kelly, M.D., Professor of Gynecology \ Johns Hopkins University , Baltimore.

"Dr. Dorland's dictionary is admirable. It is so well gotten up and of such con-
venient size. No errors have been found in my use of it."

Golebiewski and Bailey's Accident Diseases

Atlas and Epitome of Diseases Caused by Accidents. By Dr.

Ed. Golebiewski, of Berlin. Edited, with additions, by Pearce Bailey,
M.D. Consulting Neurologist to St. Luke's Hospital, New York City.
With 71 colored figures on 40 plates, 143 text-cuts, and 549 pages of
text. Cloth, $4.00 net. In Saunders'' Hand- Atlas Series.

Helferich and Bloodgood on Fractures

Atlas and Epitome of Traumatic Fractures and Dislocations

By Prof. Dr. H. Helferich, of Greifswald, Prussia. Edited, with ad-
ditions, by Joseph C. Bloodgood, M. D., Associate in Surgery, Johns
Hopkins University, Baltimore. 216 colored figures on 64 lithographic
plates, 190 text-cuts, and 353 pages of text. Cloth, $3.00 net. In Saun-
ders' Atlas Series.

Sultan and Coley on Abdominal Hernias

Atlas and Epitome of Abdominal Hernias. By Pr. Dr. G. Sul-
tan, ofGottingen. Edited, with additions, by Wm. B. Coley, M. D.,
Clinical Lecturer and Instructor in Surgery, Columbia University, New
York. 119 illustrations, 36 in colors, and 277 pages of text. Cloth,
$3.00 net. In Saunders' Hand- Atlas Series.

Warren's Surgical Pathology |ed^

Surgical Pathology and Therapeutics. By J. Collins Warren,
M.D., LL.D., F.R.C.S. (Hon.), Professor of Surgery, Harvard Medical
School. Octavo, 873 pages; 136 illustrations, t,^ in colors. Cloth,
$5.00 net; Half Morocco, $6.50 net.

Zuckerkandl and DaCosta's Surgery f3g£j|

Atlas and Epitome of Operative Surgery. By Dr. O. Zucker-
kandl, of Vienna. Edited, with additions, by J. Chalmers DaCosta,
M. D., Professor of Surgery and Clinical Surgery, Jefferson Medical Col-
lege, Phila. 40 colored plates, 278 text-cuts, and 410 pages of text.
Cloth, $3.50 net. In Saunders' Atlas Series.

16 SURGER Y AND ANA TOMY

Moore's Orthopedic Surgery

A Manual of Orthopedic Surgery. By James E. Moore, M.D., Professor
of Clinical Surgery, University of Minnesota, College of Medicine and Surgery.
Octavo of 356 pages, handsomely illustrated. Cloth, $2.50 net.

"The book is eminently practical. It is a safe guide in the understanding- and treatment of
orthopedic cases. Should be owned by every surgeon and practitioner." — Annals of Surgery.

Fowler's Operating Room New (2d) Edition

The Operating Room and the Patient, By Russell S. Fowler, M. D.,

Surgeon to the German Hospital, Brooklyn, New York. Octavo of 284

pages, illustrated. Cloth, $2.00 net.

Dr. Fowler has written his book for surgeons, nurses assisting at an operation, internes,
and all others whose duties bring them into the operating room. It contains explicit
directions for the preparation of material, instruments needed, position of patient, etc.,
all beautifully illustrated.

Nancrede's Principles of Surgery New (2d) Edition

Lectures on the Principles of Surgery. By Chas. B. Naxcrede, M.D.,
LL. D., Professor of Surgery and of Clinical Surgery, University of Michigan,
Ann Arbor. Octavo, 407 pages, illustrated. Cloth, #2.50 net.

" We can strongly recommend this book to all students and those who would see something
of the scientific foundation upon which the art of surgery is built." — Quarterly Medical Journal,
Sheffield, England.

Nancrede's Essentials of Anatomy. Seventh Edition

Essentials of Anatomy,' including the Anatomy of the Viscera. By Chas.
B. Nancrede, M.D., Professor of Surgery and of Clinical Surgery, University
of Michigan, Ann Arbor. Crown octavo, 388 pages ; 180 cuts. With an
Appendix containing over 60 illustrations of the osteology of the body. Based
on Gray 's Anatomy. Cloth, $1.00 net. In Saunders1 Question Compends.

" The questions have been wisely selected, and the answers accurately and concisely given."—
University Medical Magazine.

Martin's Essentials of Surgery. Seve£evi?edtion

Essentials of Surgery. Containing also Venereal Diseases, Surgical Land-
marks, Minor and Operative Surgery, and a complete description, with illus-
trations, of the Handkerchief and Roller Bandages. By Edward Martin,
A.M., M.D., Professor of Clinical Surgery, University of Pennsylvania, etc.
Crown octavo, 338 pages, illustrated, With an Appendix on Antiseptic Sur-
gery, etc. Cloth, jUi.on net. In Saunders1 Question Compends.

" Written to assist the student, it will be A undoubted value to the practitioner, containing as it
doi the essence of surgical work." — Boston Medical and Surgical Journal.

Martin's Essentials of Minor Surgery, Band-
aging, and Venereal Diseases. Seco£di^onVised

Essentials of Minor Surgery, Bandaging, and Venereal Diseases. By

EDWARD MARTIN, A.M., M.D., Professor of Clinical Surgery, University of

Pennsylvania, etc. Crown octavo, 166 pages, with 78 illustrations.

Cloth, $1.00 net. In Saunders1 Question Compends.

"Tli* besl condensation of the subjects of which it treats yet placed before the profession,"—
The Medical News, Philadelphia,

COLUMBIA UNIVERSITY LIBRARIES

This book is due on the date indicated below, or at the
expiration of a definite period after the date of borrowing, as
provided by the rules of the Library or by special arrange-
ment with the Librarian in charge.

DATE BORROWED

DATE BORROWED DATE DUE

C28(ll4l)M100

COLUMBIA UNIVERSITY LIBRARIES (hsl.stx)

QP 34 H831 1909 C.1

A text-book of phvsioloqyfonriedica^t

aF34- *****

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