MEMCAL .SCHOOL LEIEMAl&lf
IN MEMORIAH BERTRAM STONE, M.D.
A TEXT-BOOK
OF
PHYSIOLOGY
FOR
MEDICAL STUDENTS AND PHYSICIANS
BY
WILLIAM H. HOWELL, PH.D., M.D., LL.D.
PROFESSOR OF PHYSIOLOGY IN THE JOHNS HOPKINS UNIVERSITY, BALTIMORE
SeconD jemtion, Gborougblg
PHILADELPHIA AND LONDON
W. B. SAUNDERS COMPANY
1907
Set up, electrotyped, printed, and copyrighted. September, 1905. Reprinted,,
February, 1906, September, 1906, and January, 1907. Revised,
reprinted, and recopyrighted, August, 1907.
Copyright, 1907, by W. B. Saunders Company.
PRESS OF W. B. 8AUNDERS COMPANY. PHILADA.
PREFACE TO THE SECOND EDITION.
IN the preparation of the second edition of this book the author has made no fundamental change in its arrangement or scope. Additions and changes havp been made freely throughout the work, with the object of keeping the presentation of the subject abreast of the times, but as far as possible the additions have been counterbalanced by the elimination of such material as could be spared. The book remains, therefore, of practically the same size, an object which the author has purposely kept in view, since he is convinced that in text-books there is a natural tendency to overexpansion which should be guarded against with care. New figures have been introduced whenever it seemed that an actual improvement could be effected by this means.
The author has been gratified with the generous approval accorded to the first edition and hopes that the present edition may continue to find favor with teachers of physiology and medical students, as well as among physicians who may feel the need of keeping themselves in touch with the progress of physiology. There are, in fact, many indications that the physiological side of medi- cine is likely to receive a fuller recognition than has been given to it in the recent past. Medical schools are providing courses in experimental pathology and surgery, subjects in which physiological methods and training are all important, and in clinical medicine also it is becoming evident that the methods of physiological experimentation and the application of physiological discoveries are of practical value in diagnosis as well as in investigation. No one doubts that anatomy, physiology, and pathology, using these terms in a broad sense, constitute the basis upon which a rational system of medicine must be constructed, but it would seem that, in this country at least, the clinicians have failed to make full use of the material offered to them by the subject of physiology. Some explanation of this neglect is found in the fact -that the physiologists themselves, not being practitioners, have no good
l
2 PREFACE TO THE SECOND EDITION.
opportunity to enforce the practical applications of their subject. According to the division of labor existing in medicine to-day it is the main duty of the physiologist to till his own field, and to the clinician and practising physician belong the responsibility and the opportunity of utilizing the results thus obtained by giving them their practical application to diagnosis and treatment. It is gratifying to find that tlje attention of the clinicians is being directed more to this side of the subject. Without doubt this tendency will serve to emphasize to the student the importance of a sound training in the physiological sciences.
PREFACE.
In the preparation of this book the author has endeavored to keep in mind two guiding principles: first, the importance of simplicity and lucidity in the presentation of facts and theories; and, second, the need of a judicious limitation of the material selected. In regard to the second point every specialist is aware of the bewildering number of researches that have been and are being published in physiology and the closely related sciences, and the difficulty of justly estimating the value of conflicting results. He who seeks for the truth in any matter under discussion is often- times forced to be satisfied with a suspension of judgment, and the writer who attempts to formulate our present knowledge upon almost any part of the subject is in many instances obliged to present the literature as it exists and let the reader make his own deductions. This latter method is doubtless the most satis- factory and the most suitable for large treatises prepared for the use of the specialist or advanced student, but for beginners it is absolutely necessary to follow a different plan. The amount of material and the discussion of details of controversies must be brought within reasonable limits. The author must assume the responsibility of sifting the evidence and emphasizing those con- clusions that seem to be most justified by experiment and obser- vation. As far as material is concerned, it is evident that the selection of what to give and what to omit is a matter of judg- ment and experience upon the part of the writer, but the present author is convinced that the necessary reduction in material should be made by a process of elimination rather than by con- densation. The latter method is suitable for the specialist with his background of knowledge and experience, but it is entirely unfitted for the elementary student. For the purposes of the latter brief, comprehensive statements are oftentimes misleading, or fail at least to make a clear impression. Those subjects that are presented to him must be given with a certain degree of full- ness if he is expected to obtain a serviceable conception of the facts, and it follows that a treatment of the wide subject of physi- ology is possible, when undertaken with this intention, only by the adoption of a system of selection and elimination.
The fundamental facts of physiology, its principles and modes
3
4 PREFACE.
of reasoning are not difficult to understand. The obstacle that is most frequently encountered by the student lies in the com- plexity of the subject, — the large number of more or less dis- connected facts and theories which must be considered in a dis- cussion of the structure, physics, and chemistry of such an intri- cate organism as the human body. But once a selection has been made of those facts and principles which it is most desirable that the student should know, there is no intrinsic difficulty to prevent them from being stated so clearly that they may be comprehended by anyone who possesses an elementary knowledge of anatomy, physics, and chemistry. It is doubtless the art of presentation that makes a text-book successful or unsuccessful. It must be admitted, however, that certain parts of physiology, at this par- ticular period in its development, offer peculiar difficulties to the writers of text-books. During recent years chemical work in the fields of digestion and nutrition has been very full, and as a result theories hitherto generally accepted have been subjected to crit- icism and alteration, particularly as the important advances in theoretical chemistry and physics have greatly modified the attitude and point of view of the investigators in physiology. Some former views have been unsettled and much information has been collected which at present it is difficult to formulate and apply to the explanation of the normal processes of the animal body. It would seem that in some of the fundamental problems of metabolism physiological investigation has pushed its experi- mental results to a point at which, for further progress, a deeper knowledge of the chemistry of the body is especially needed. Cer- tainly the amount of work of a chemical character that bears di- rectly or indirectly on the problems of physiology has shown a re- markable increase within the last decade. Amid the conflicting results of this literature it is difficult or impossible to follow always the true trend of development. The best that the text-book can hope to accomplish in such cases is to give as clear a picture as possible of the tendencies of the time.
Some critics have contended that only those facts or conclu- sions about which there is no difference of opinion should be pre- sented to medical students. Those who are acquainted with the subject, however, understand that books written from this standpoint contain much that represents the uncertain compromises of past generations, and that the need of revision is felt as fre- quently for such books as for those constructed on more liberal principles. There does not seem to be any sound reason why a text-book for medical students should aim to present only those conclusions that have crystallized out of the controversies of other times, and ignore entirely the live issues of the day which are
PREFACE. 5
of so much interest and importance not only to physiology, but to all branches of medicine. With this idea in mind the author has endeavored to make the student realize that physiology is a growing subject, continually widening its knowledge and read- justing its theories. It is important that the student should grasp this conception, because, in the first place, it is true; and, in the second place, it may save him later from disappointment and distrust in science if he recognizes that many of our conclu- sions are not the final truth, but provisional only, representing the best that can be done 'with the knowledge at our command. To emphasize this fact as well as to add somewhat to the interest of the reader short historical resumes have been introduced from time to time, although the question of space alone, not to men- tion other considerations, has prevented any extensive use of such material. It is a feature, however, that a teacher might develop with profit. Some knowledge of the gradual evolution of our present beliefs is useful in demonstrating "Mie enduring value of experimental work as compared with mere theorizing, and also in engendering a certain appreciation and respect for knowledge that has been gained so slowly by the exertions of successive generations of able investigators.
A word may be said regarding the references to literature inserted in the book. It is perfectly obvious that a complete or approximately complete bibliography is neither appropriate nor useful, however agreeable it maybe to give every worker full recognition of the results of his labors. But for the sake of those who may for any reason wish to follow any particular subject more in detail some references have been given, and these have been selected usually with the idea of citing those works which themselves contain a more or less extensive discussion and litera- ture. Occasionally also references have been made to works of historical importance or to separate papers that contain the experi- mental evidence for some special view.
TABLE OF CONTENTS.
SECTION I. THE PHYSIOLOGY 'OF MUSCLE AND NERVE.
PAGE
CHAPTER I. — THE PHENOMENON OF CONTRACTION 17
The Histological Structure of the Muscle Fiber, 18. — Its Appearance by Polarized Light, 19. — The Extensibility and Elasticity of Muscular Tissue, 19. — The Independent Irritability of Muscle, 22. — Definition and Enumeration of Artificial Stimuli, 23. — The Duration of the Simple Muscle Contraction, 25. — The Curve of a Simple Muscle Contraction, 25. — The Latent Period, 26. — The Phases of Shortening and Relaxation, 26. — Isotonic and Isometric Contrac- tions, 27. — Maximal and Submaximal Contractions, 27. — Effect of Temperature upon the Simple Contraction, 28. — Effect of Veratrin on the Simple Contraction, 30. — Contracture, 33. — Fatigue, the Treppe, and Effect of Rapidly Repeated Stimulation, 33. — The Wave of Contraction and Means of Measuring, 34. — Idiomuscular Contractions, 34. — The Energy Liberated During a Muscular Contraction, 35. — The Proportional Amount of this Energy Utilized in Work, 36.— The Curve of Work and the Absolute Power of a Muscle, 38.— Definition of Tetanus or Compound Contraction, 39. — The Summation of Contractions, 41. — Discontinuity of the Processes of Contraction in Tetanus, 42. — The Muscle-tone, 41. — The Rate of Stimulation Necessary for Complete Tetanus, 42. — The Tetanic Nature of Voluntary Contractions, 43. — The Ergograph, 45. — Results of Ergographic Experiments, 47. — Sense of Fatigue, 48. — Muscle Tonus, 48. — Rigor Mortis and Rigor Caloris, 49. — The Occurrence and Struc- ture of Plain Muscle Tissue, 52.— Distinctive Properties of Plain Muscle, 53.— The General Properties of Cardiac Muscular Tissue, 54. — The Contractility of Cilia and Their General Properties, 54.
CHAPTER II. — THE CHEMICAL COMPOSITION OF MUSCLE AND THE CHEM- ICAL CHANGES OF CONTRACTION AND OF RIGOR MORTIS 57
The Composition of Muscle Plasma, 57.— The Proteins of Muscle, 58.— The Carbohydrates of Muscle, 59. — Phosphocarnic Acid, 60. — Lactic Acid in Muscle, 60. — The Nitrogenous Extractives of Muscle, 61. — Pigments of Muscle, 61. — Enzymes of Muscle, 61. — Inorganic Constituents of Muscle, 62. — The Chemi- cal Changes in Muscle during Contraction, 62. — The Chemical Changes during Rigor Mortis, 66. — The Relation of the Waste Products to Fatigue, the Chemical Theory of Fatigue, 66. — Theories of the Mechanism of the Contraction of Muscle, 68.
CHAPTER III. — THE PHENOMENON OF CONDUCTION. PROPERTIES OF
THE NERVE FIBER 72
General Statement Regarding Property of Conductivity, 72. — Structure of the Nerve Fiber, 73. — Function of the Myelin Sheath, 73.— The Nerve Trunk an Anatomical Unit Only, 74. — Definition of Afferent and Efferent Nerve Fibers, 75. -^-Classification of Nerve Fibers, 75. — The Bell-Magendie Law of the Composition of the Anterior and the Posterior Roots of the Spinal Nerves, 77. — Cells of Origin of the Anterior and Posterior Root Fibers, 78. — Origin of the Afferent and Efferent Fibers in the Cranial Nerves, 79. — Independent Irritability of Nerve Fibers, Artificial Nerve Stimuli, 80. — Du Bois-Reymond's Law of Stimulation by the Galvanic Current, 82. — Electrotonus, 83. — Pfluger's Law of Stimulation, 84.— The Opening and the Closing Tetanus, 86.— M9de of Stimulating Nerves in Man, 86. — Motor Points of Muscles, 88. — Physical and Physiological Poles, 89.
CHAPTER IV. — THE ELECTRICAL PHENOMENA SHOWN BY NERVE AND
MUSCLE 91
The Demarcation Current, 91. — Construction of the Galvanometer, 92. — Con- struction of the Capillary Electrometer, 94. — Non-polarizable Electrodes, 95. — Action Current or Negative Variation, 96. — Monophasic and Diphasic Action Currents, 98. — The Rheoscopic Frog Preparation, 99. — Relation of Action Current to the Contraction Wave and Nerve Impulse, 100. — The Electrotonic Currents, 101.— The Core-model, 102.
7
8 TABLE OF CONTENTS.
PAGE
CHAPTER V. — THE NATURE OF THE NERVE IMPULSE AND THE NUTRI- TIVE RELATIONS OF NERVE FIBER AND NERVE CELL 104
Historical, 104. — Velocity of the Nerve Impulse, 105. — Relation of the Nerve Impulse to the Wave of Negativity, 107. — Direction of Conduction in the Nerve, 107. — Effect of Various Influences on the Nerve Impulse, 109. — The Fatigue of Nerve Fibers, 110. — The Metabolism of the Nerve Fiber during Functional Activity, 112. — Theories of the Nerve Impulse, 113. — Qualitative Differences in Nerve Impulses, 115. — Doctrine of Specific Nerve Energies, 116. — Nutritive Relations of Nerve Fibers and Nerve Cells, 117. — Nerve Degen- eration and Regeneration, 118. — Degenerative Changes in the Central End of the Neuron, 121.
SECTION II.
THE PHYSIOLOGY OF THE CENTRAL NERVOUS SYSTEM.
CHAPTER VI. — STRUCTURE AND GENERAL PROPERTIES OF THE NERVE
CELL 123
The Neuron Doctrine, 123. — The Varieties of Neurons, 125. — Internal Structure of the Nerve Cell, 127. — General Physiology of the Nerve Cell, 129. — Sum- mation of Stimuli in Nerve Cells, 131. — Response of the Nerve Cell to Varying Rates of Stimulation, 132. — The Refractory Period of the Nerve Cell, 133.
CHAPTER VII.— REFLEX ACTIONS 134
Definition and Historical, 134.— The Reflex Arc, 134.— The Reflex Frog, 136.— Spinal Reflex Movements, 136. — Theory of Co-ordinated Reflexes, 138. — Spinal Reflexes in Mammals, 139. — Dependence of Co-ordinated Reflexes upon the Excitation of the Sensory Endings, 139. — Reflex Time, 140. — Inhibition of Reflexes, 140. — Influence of the Condition of the Cord on its Reflex Activities, 142.— Reflexes from Other Parts of the Nervous System, 143.— Reflexes Through Peripheral Ganglia, Axon Reflexes, 144. — The Tonic Activity of the Spinal Cord, 145. — Effects of the Removal of the Spinal Cord, 145. — Knee-jerk, 147. — Reinforcement of the Knee-jerk, 147. — Is the Knee-jerk a Reflex Act? 149. — Conditions Influencing the Extent of the Knee-jerk, 150. — The Knee- jerk and Spinal Reflexes as Diagnostic Signs, 151. — Location of the Centers for the Different Spinal Reflexes, 152.
CHAPTER VIII. — THE SPINAL CORD AS A PATH OF CONDUCTION 155
Arrangement and Classification of the Nerve Cells in the Cord, 155. — General Relations of the Gray and White Matter in the Cord, 157. — Ihe Methods of Determining the Tracts of the Cord, 157. — General Classification of the Tracts of the Cord, 158. — The Names and Locations of the Long Tracts, 160. — The Termination in the Cord of the Fibers of the Posterior Root, 161. — Ascend- ing or Afferent Paths in the Posterior Columns, 162. — Ascending or Afferent Paths in the Lateral Columns, 165. — The Spinal Paths for the Cutaneous Senses (Touch, Pain, Temperature), 167.— The Homolateral or Contralateral Conduction of the Cutaneous Impulses, 168. — The Descending or Efferent Paths in the Anterolateral Columns (Pyramidal System), 168. — Less Well- known Tracts in the Cord, 170.
CHAPTER IX. — THE GENERAL PHYSIOLOGY OF THE CEREBRUM AND ITS
MOTOR FUNCTIONS 173
The Histology of the Cortex, 174. — The Classification of the Systems of Fibers in the Cerebrum (Projection, Association, and Commissural), 175. — Physio- logical Deductions from the Histology of the Cortex, 177. — Extirpation of the Cerebrum, 179. — Localization of Functions in the Cerebrum, Historical, 181. — The Motor Areas of the Cortex, 184. — Differences in Paralysis from Injury to the Spinal Neuron and the Pyramidal Neuron, 186. — Voluntary Motor Paths Other than the Pyramidal Tract, 186.— The Crossed Control of the Muscles and Bilateral Motor Representation in the Cortex, 187. — Are the Motor Areas Exclusively Motor ? 188.
CHAPTER X. — THE SENSE AREAS AND THE ASSOCIATION AREAS IN THE
CORTEX 190
The Body-sense Area, 191. — The Course of the Fillet, 192. — The Center for Vision, 194. — Histological Evidence of the Course of the Optic Fibers, 195. — The Decussation in the Chiasma, 197. — The Projection of the Retina on the Occipital Cortex, 197. — The Function of the Lower Visual Centers, 199. — The Auditory Center, 200. — Course of the Cochlear Nerve, 202. — The Physio- logical Significance of the Lower Auditory Centers, 203. — Motor Responses from the Auditory Cortex, 203.— The Olfactory Center, 204.— The Olfactory Bulb and its Connections, 204. — The Cortical Center for Smell, 205. — The Cortical Center for Taste, 206.— Aphasia, 206.— Sensory Aphasia, 208.— The Association Areas, 209. — Subdivision of the Association Areas, 211. — The Development of the Cortical Areas, 212. — Histological Differentiation in Cor- tical Structure, 215. — Physiology of the Coipus Callosum, 216. — Physiology of the Corpora Striata and Optic Thalami, 216.
TABLK OK CONTENTS. 9
PAGE
CHAPTKR XL — THE FUNCTIONS OF THK CEREBELLUM, THE PONS, AND
THE MEDULLA 'J 1 s
Anatomical Structure and Relations of the Cerebellum, 218. — General State- ment of Theories Regarding the Cerebellum, 222. — Experiments upon Ablation of the Cerebellum, 223. — Interpretation of the Experimental and Clinical Results, 224. — Conclusions as to the General Functions of the Cerebellum, 226. — The Psychical Functions of the Cerebellum, 227. — Localization of Function in the Cerebellum, 227. — The Functions of the Medulla Oblongata, 228.— The Nuclei of Origin and the Functions of the Cranial Nerves, 229.
CHAPTER XII. — THE SYMPATHETIC OK AUTOXOMIC NERVOUS SYSTEM. . . . 'Jo 4
General Statements, 234. — Autonomic Nervous System, 235. — The Use of the Nicotin Method, 236.— General Course of the Autonomic Fibers Arising from the Cord, 236. — General Course of the Fibers Arising from the Brain, 237. — General Course of the Fibers Arising from the Sacral Cord, 239. — Normal Mode of Stimulation of Autonomic Nerve Fibers, 239.
CHAPTER XIII. — THE PHYSIOLOGY OF SLEEP -'A
General Statements, 241. — Physiological Relations during Sleep, 241. — The Intensity of Sleep, 242. — Changes in the Circulation during Sleep, 245. — Effect of Sensory Stimulation, 246. — Theories of Sleep, 247. — Hypnotic Sleep, 251.
SECTION III. THE SPECIAL SENSES. CHAPTER XIV. — CLASSIFICATION OF THE SENSES AND GENERAL STATE-
252
Classification of the Senses, 252. — The Doctrine of Specific Nerve Energies, 254.— The Weber-Feehner Psychophysical Law, 2.'.0.
CHAPTER XV. — CUTANEOUS AND INTERNAL SENSATIONS 2">9
General Statements, 259. — The Punctiform Distribution of the Cutaneous Senses, 260. — Specific Nerve Energies of the Cutaneous Nerves, 262. — The Temperature Senses, 263.— The Sense of Pressure, 263.— The Threshold Stimu- lus and the Localizing Power, 264. — The Pain Sense, 266. — Localization or Projection of Pain Sensations, 267. — Reflected or Misreferred Pains, 267. — The Muscle Sense, 268. — The Quality of the Muscle Sense, 269. — Sensations of Hunger and Thirst, 270. — The Sense of Thirst, 272.
CHAPTER XVI. — SENSATIONS OF TASTE AND SMELL 274
The Nerves of Taste, 274.— The End-organ of the Taste Fibers. 276.— Classi- fication of Taste Sensations, 276. — Distribution and Specific Energy of the Fundamental Taste Sensations. 277. — Method of Sapid Stimulation, 278. — The Threshold Stimulus for Taste, 279.— The Olfactory Organ, 279.— The Mechanism of Smelling, 280. — Nature of the Olfactory Stimulus, 281. — The Qualities of the Olfactory Sensations, 281. — Fatigue of the Olfactory Apparatus, 283. — Delicacy of the Olfactory Sense, 283. — Conflict of Olfactory Sensations, 285. — Olfactory Associations, 285.
CHAPTER XVII. — THE EYE AS AN OPTICAL INSTRUMENT. DIOPTRICS
OF THE EYE 280
Formation of an Image by a Biconvex Lens, 286. — Formation of an Image in the Eye, 289. — The Inversion of the Image on the Retina, 291 . — The Size of the Retinal Image, 292. — Accommodation of the Eye, 293. — Limit of the Power of Accommodation and Near Point of Distinct Vision, 296.— Far Point of Distinct Vision, 297. — The Refractive Power of the Surfaces in the Eye, 297.— Optical Defects of the Normal Eye, 298.— Spherical Aberration, 299.— Abnormalities in the Refraction of the Eye, Myopia, 299. — Hypermetropia, 300. — Presbyopia, 301. — Astigmatism, 302. — Innervation and Control of the Ciliary "Muscle and the Muscles of the Iris, 304. — The Accommodation Reflex and the Light Reflex, 306. — Action of Drugs upon the Iris, 308. — The Antagonism of the Sphincter and Dilator Muscles of the Iris, 309.— In- traocular Pressure, 310. — The Ophthalmoscope, 311. — Retinoscope, 313. — Ophtalmometer, 314.
CHAPTER XVIII. — THE PROPERTIES OF THE RETINA. VISUAL STIMULI
AND VISUAL SENSATIONS 316
The Portion of the Retina Stimulated by Light, 316. — The Action Current Caused by Stimulation of the Retina, 317. — The Visual Purple, Rhodopsin, 318. — Extent of the Visual Field, Perimetry, 320. — Central and Peripheral Fields of Vision, 321. — Visual Acuity, 323. — Relation Between Stimulus and Sensation, Threshold Stimulus, 325. — The Light Adapted and the Dark Adapted
10 TABLE OF CONTENTS.
PAGE
Eye, 326. — Luminosity or Brightness, 327. — Qualities of "Visual Sensations, 328. — The Achromatic Series, 329. — The Chromatic Series, 329. — Color Satura- tion and Color Fusion, 329. — The Fundamental Colors, 330. — The Comple- mentary Colors, 331. — After Images, Positive and Negative, 331. — Color Contrasts, 332. — Color Blindness, 333. — Dichromatic Vision, 334. — Tests for Color Blindness, 335. — Monochromatic Vision, 336. — Distribution of Color Sense in the Retina, 336. — Functions of the Rods and Cones, 337. — Theories of Color Vision, 340. — Entoptic Phenomena, 344. — Shadows of Corpuscles and Blood-vessels, 345. — Shadows from Lens and Vitreous Humor, 346.
CHAPTER XIX.— BINOCULAR VISION 347
Movements of the Eyeballs, 347. — Co-ordination of the Eye Muscles, Muscular Insufficiency and Strabismus, 349. — The Binocular Field of Vision, 350. — Corresponding or Identical Points, 350. — Physiological Diplopia, 351. — The Horopter, 353. — Suppression of Visual Images, 353. — Struggle of the Visual Fields, 353. — Judgments of Solidity, 354. — Monocular Perspective, 354. — Binocular Perspective, 356. — Stereoscopic Vision, 356. — Explanation of Binoc- ular Perspective, 358. — Judgments of Distance and Size, 359. — Optical Decep- tions, 360.
CHAPTER XX. — THE EAR AS AN ORGAN FOR SOUND SENSATIONS 363
The Pinna or Auricle, 364.— The Tympanic Membrane, 364.— The Ear Bones, 365.— Mode of Action of the Ear Bones, 366.— Muscles of the Middle Ear, 368. — The Eustachian Tube, 369. — Projection of the Auditory Sensations, 370. — Sensory Epithelium of the Cochlea, 370.— Nature and Action of the Sound Waves, 371. — Classification and Properties of Musical Sounds, 372. — Upper Harmonics or Overtones, 374.— Sympathetic Vibrations and Resonance, 376. — Functions of the Cochlea, 376. — Sensations of Harmony and Discord, 379.— Limits of Hearing, 380.
CHAPTER XXI. — FUNCTIONS OF THE SEMICIRCULAR CANALS AND THE
VESTIBULE 382
Position and Structure of the Semicircular Canal s 382. — Flouren's Experi- ments upon the Semicircular Canals, 383. — Temporary and Permanent Effects of the Operations, 384. — Effect of Direct Stimulation of the Canals, 384.— Effect of Section of the Ampullary or the Acoustic Nerve, 385. — Is the Effect of Section of the Canals Due to Stimulation? 385. — Theories of the Functions of the Semicircular Canals, 385. — Summary of the Views upon the Function of the Semicircular Canals, 388. — Functions of the Utriculus and Sacculus, 389.
SECTION IV. BLOOD AND LYMPHi
CHAPTER XXII. — GENERAL PROPERTIES OF BLOOD. PHYSIOLOGY OF
THE CORPUSCLES 392
Histological Structure of Blood, 392. — Reaction of the Blood, 393. — Specific Gravity of the Blood, 394.— The Red Corpuscles, 395.— Condition of the Hemoglobin in the Corpuscles, 396. — Hemolysis, 397. — Hemolysis Due to Variations in Osmotic Pressure, 397. — Hemolysis Due to Action of Hemoly- sins, 398. — Nature and Amount of Hemoglobin, 401. — Compounds of Hemo- globin with Oxygen and Other Gases, 403. — The Iron in the Hemoglobin, 404. — Crystals of Hemoglobin, 405. — Absorption Spectra of Hemoglobin and Oxy- hemoglobin, 406. — Derivative Compounds of Hemoglobin,. 410. — Origin and Fate of the Red Corpuscles, 412. — Variations in the Number of Red Corpuscles, 414. — Physiology of the Blood Leucocytes, 416. — Variations in Number of the Leucocytes, 417. — Functions of the Leucocytes, 417. — Physiology of the Blood Plates, 418.
CHAPTER XXIII. — CHEMICAL COMPOSITION OF THE BLOOD PLASMA; COAGULATION; QUANTITY OF BLOOD; REGENERATION AFTER HEMORRHAGE 420
Composition of the Plasma and Corpuscles, 420. — Proteins of the Blood Plasma, 422. — Serum Albumin, 422. — Paraglpbulin (Serum Globulin), 423. — Fibrin- ogen, 424. — Less Well-known Proteins of the Blood, 426. — Coagulation of Blood, 426. — Theories of Clotting, 427. — Why Blood Does Not Clot Within the Vessels, 432. — Intravascular Clotting, 433. — Means of Hastening or of Retarding Coagulation, 434.— Total Quantity of Blood in the Body, 436.— Regeneration of the Blood after Hemorrhage, 437. — Blood Transfusion, 439.
CHAPTER XXIV. — COMPOSITION AND FORMATION OF LYMPH 440
General Statements, 440. — Formation of Lymph, 441. — Lymphagogues of the First Class, 443. — Lymphagogues of the Second Class, 444. — Summary of the Factors Controlling the Flow of Lymph, 445.
TABLE OF CONTEXTS. 11
SECTION V.
PHYSIOLOGY OF THE ORGANS OF CIRCULATION OF THE BLOOD AND LYMPH.
PAGE
CHAPTER XXV. — THE VELOCITY AND PRESSURE OF THE BLOOD FLOW. . . 447
The Circulation as Seen under the Microscope, 447. — The Velocity of the Blood Flow, 448. — Mean Velocity in the Arteries, Veins, and Capillaries, 451. — Cause of the Variations in Velocity, 452. — Variations of Velocity with the Heart Beat or Changes in the Blood-vessels, 453. — Time Necessary for a Com- plete Circulation of the Blood, 454. — The Pressure Relations in the Vascular System, 455. — Methods of Recording Blood-pressure, 455. — Systolic, Dias- tolic, and Mean Arterial Pressure, 459. — Method of Measuring Systolic and Diastolic Pressure in Animals, 461. — Data as to the Mean Pressure in Arteries, Veins, and Capillaries, 463. — Methods of Determining Blood-pressure in the Large Arteries of Man, 466. — Normal Pressure in Man and Its Variations, 471.
CHAPTER XXVI. — THE PHYSICAL FACTORS CONCERNED IN THE PRODUC- TION OF BLOOD-PRESSURE AND BLOOD-VELOCITY 473
Side Pressure and Velocity Pressure, 473. — The Factors Concerned in Pro- ducing Normal Pressure and Velocity, 476. — General Conditions Influencing Blood-pressure and Blood-velocity, 477. — The Hydrostatic Effect, 478. — Venous Pressures, 479. — Accessory Factors Aiding the Circulation, 480. — The Con- ditions of Pressure and Velocity in the Pulmonary Circulation, 480. — Variations of Pressure in the Pulmonary Circuit, 481.
CHAPTER XXVII.— THE PULSE 483
General Statement, 483.— Velocity of the Pulse Wave, 484.— Form of the Pulse Wave, Sphygmography, 486. — Explanation of the Catacrotic Waves, 488. — Anacrotic Waves, 489. — The Kinds of Pulse in Health and Disease, 490. — Venous Pulse, 491.
CHAPTER XXVIIL— THE HEART BEAT 494
General Statement, 494. — Musculature of the Auricles and Ventricles, 495. — Contraction Wave of the Heart, 496.— The Electrical Variation, 497.— Change of Form during Systole, 499. — The Apex Beat, 500. — Cardiogram, 500. — Intraventricular Pressure during Systole. 502. — The Heart Sounds, 503. — Events Occurring during a Cardiac Cycle, 506. — Time Relations of Systole and Diastole, 507. — Normal Capacity of Ventricle and Work Done by the Heart, 507. — Coronary Circulation during the Heart-beat, 509. — Suction-pump Action of the Heart, 510. — Occlusion of the Coronary Vessels, 512. — Fibrillar Con- tractions of Heart Muscle, 513.
CHAPTER XXIX. — THE CAUSE AND THE SEQUENCE OF THE HEART BEAT.
PROPERTIES OF THE HEART MUSCLE 514
General Statement, 514. — The Neurogenic Theory of the Heart Beat, 516. — Myogenic Theory, 517. — Automaticity of the Heart, 519. — Action of Calcium, Potassium, and Sodium Ions on the Heart, 520. — Connection of Inorganic Salts with the Causation of the Beat, 521. — Maximal Contractions of the Heart, 523. — Refractory Period of the Heart Beat, 523. — The Compensatory Pause, 525. — Normal Sequence of the Heart Beat, 525. — Tonicity of the Heart Muscle, 529.
CHAPTER XXX. — THE CARDIAC NERVES AND THEIR PHYSIOLOGICAL
ACTION 531
Course of the Cardiac Nerves, 531. — Action of the Inhibitory Fibers, 531. — Analysis of the Inhibitory Action, 533. — Effect of Vagus on the Auricle and the Ventricle, 535. — Escape from Inhibition, 536. — Reflex Inhibition of the Heart Beat, the Cardio-inhibitory Center, 536. — The Tonic Activity of the Cardio-inhibitory Center, 537. — The Action of Drugs on the Inhibitory Appara- tus, 539. — The Nature of Inhibition, 539. — Course of the Accelerator Fibers, 541. — Action of the Accelerator Fibers, 543. — Tonicity of the Accelerators and Reflex Acceleration, 543. — The Accelerator Center, 545.
CHAPTER XXXI. — THE RATE OF THE HEART BEAT AND ITS VARIATIONS
UNDER NORMAL CONDITIONS 546
Variations in Rate with Sex, Size, and Age, 546. — Variations through the Extrinsic Cardiac Nerves, 547. — Variations with Blood-pressure, 547. — With Muscular Exercise, 548. — With the Gases of the Blood, 549. — With Tempera- ture of the Blood, 549.
12 TABLE OP CONTENTS.
CHAPTER XXXII. — THE VASOMOTOR NERVES AND THEIR PHYSIOLOGICAL
ACTIVITY 551
Historical, 551. — Methods Used to Determine Vasomotor Action, 552. — The Plethysmograph, 553. — General Distribution and Course of the Vasoconstrictor Nerve Fibers, 555. — Tonic Activity of the Vasoconstrictors, 558. — The Vaso- constrictor Center, 558. — Vasoconstrictor Reflexes, Pressor and Depressor Fibers, 560. — Depressor Nerve of the Heart, 583. — Vasoconstrictor Centers in the Spinal Cord. 564. — Rhythmical Activity of the Vasoconstrictor Center, 564.— Course and Distribution of the Dilator Fibers, 565. — General Properties of Vasodilator Fibers, 565.— Vasodilator Center and Reflexes, 566.— Vasodila- tation Due to Antidromic Impulses, 568. — Regulation of the Blood-supply by Chemical and Mechanical Stimuli, 569.
CHAPTER XXXIII. — THE VASOMOTOR SUPPLY OF THE DIFFERENT
ORGANS 570
Vasomotors of the Heart, 570. — Vasomotors of the Pulmonary Arteries, 571. — Circulation in the Brain and Its Regulation, 572. — Arterial Supply, 572. — Venous Supply, 573. — The Meningeal Spaces, 574. — Intracranial Pressure, 576. — Effect of Changes in Arterial Pressure upon the Blood-flow through the Brain, 577. — The Regulation of the Brain Circulation, 579. — Vasomotor Nerves of the Head Region, 581. — Of the Trunk and the Limbs, 582. — Of the Abdominal Organs, 582. — Of the Genital Organs, 583. — Of the Skeletal Muscles, 583.— The Vasomotor Nerves to the Veins, 584.— The Circulation of the Lymph, 585.
SECTION VI.
PHYSIOLOGY OF RESPIRATION.
CHAPTER XXXIV. — HISTORICAL STATEMENT. THE ORGANS OF EXTER- NAL RESPIRATION AND THE RESPIRATORY MOVEMENTS 587
Historical, 587. — Anatomy of Organs of Respiration, 591. — Thorax as a Closed Cavity, 592. — Normal Position of the Thorax, 592. — Inspiration by Contraction of the Diaphragm, 593. — Inspiration by Elevation of the Ribs, 594. — The Muscles of Inspiration, 595. — Muscles of Expiration, 595. — Quiet and Forced Respiratory Movements, Eupnea and Dyspnea, 596. — Costal and Abdominal Types of Respiration, 597. — Accessory Respiratory Movements, 598. — Registra- tion of the Respiratory Movements, 598. — Volumes of Air Respired, Vital Capacity, Tidal Air, Complemental Air, Supplemental Air, Residual Air, Minimal Air, 600. — Size of the Bronchial Tree, 602. — Artificial Respiration, 602.
CHAPTER XXXV. — THE PRESSURE CONDITIONS IN THE LUNGS AND
THORAX AND THEIR INFLUENCE UPON THE CIRCULATION 604
The Intrapulmonic Pressure and Its Variations, 604. — Intrathoracic Pressure, 605. — Variations of, with Forced and Unusual Respirations, 606. — Origin of the Negative Pressure in the Thorax, 607. — Pneumothorax, 608. — Aspiratory Action of the Thorax, 608. — Respiratory Waves of Blood-pressure, 609.
CHAPTER XXXVI. — THE CHEMICAL AND PHYSICAL CHANGES IN THE AIR
AND THE BLOOD CAUSED BY RESPIRATION 613
The Inspired and Expired Air, 613. — Physical Changes in the Expired Air, 613. — Injurious Action of Expired Air, 614. — Ventilation, 616. — The Gases of the Blood, 617. — The Pressure of Gases, 620. — Absorption of Gases in Liquids, 620.— The Tension of Gases in Solution, 622.— The Condition of Nitrogen in the Blood, 623. — Condition of Oxygen in the Blood, 624. — Con- dition of Carbon Dioxid in the Blood, 625. — The Physical Theory of Respira- tion, 627.— Gaseous Exchanges in the Lungs, 627. — Exchange of Gases in the Tissues, 629.— Secretory Activity of Lungs, 630.
CHAPTER XXXVII. — INNERVATION OF THE RESPIRATORY MOVEMENTS . . 631
The Respiratory Center, 631. — Spinal Respiratory Centers, 632. — Automatic Activity of the Respiratory Center, 633. — Reflex Stimulation of the Center, 633. — Afferent Relations of the Vagus to the Center, 635. — The Inspiratory and Inhibitory Fibers of the Vagus, 637. — Respiratory Reflexes from the Larynx, Pharynx, and Nose, 638. — Voluntary Control of the Respiratory Movements, 639. — Nature of the Respiratory Center, 639. — Respiratory Cen- ters in the Midbrain, 640. — Automatic Stimulus to the Respiratory Center, 640. — Cause of the First Respiratory Movements, 643. — Dyspnea, Hyperpnea, and Apnea, 643. — Innervation of the Bronchial Musculature, 646.
TABLE OF CONTEXTS. 13
PAGE
CHAPTER XXXVIII. — THE INFLUENCE OF VARIOUS CONDITIONS UPON
THE RESPIRATION 648
Effect of Muscular Work on the Respiratory Movements, 048. — Effect of Variations in the Composition of the Air, 648. — High and Low Barometric Pressures, Mountain Sickness, Caisson Disease, 650. — The Respiratory Quotient and Its Variations, 652. — Modified Respiratory Movements, 653.
SECTION VII.
PHYSIOLOGY OF DIGESTION AND SECRETION. CHAPTER XXXIX. — MOVEMENTS O-F THE ALIMENTARY CANAL 655
Mastication, 655. — Deglutition, 655. — Nervous Control of Deglutition, 659. — Anatomy of the Stomach, 660. — Musculature of the Stomach, 661. — Move- ments of the Stomach, 661. — Effect of the Nerves on the Movements of the Stomach, 664. — Movements of the Intestines, 666. — Peristaltic and Pendular Movements of the Intestines, 666. — Nervous Control of the Intestinal Move- ments, 669. — Effect of Various Conditions on the Intestinal Movements, 669. — Movements of the Large Intestines, 670.— Defecation, 671. — Vomiting, 672. — Nervous Mechanism of Vomiting, 674.
CHAPTER XL. — GENERAL CONSIDERATION OF THE COMPOSITION OF THE
FOOD AND THE ACTION OF ENZYMES 675
Foods and Foodstuffs, 675. — Accessory Articles of Diet, 677. — Enzymes, Historical, 678. — Reversible Reactions, 680.— Specificity of Enzymes, 682. — Definition and Classification of Enzymes, 682. — General Properties of Enzymes, 684. — Partial List of Enzymes, 685. — Chemical Composition of the Enzymes, 685.
CHAPTER XLL— THE SALIVARY GLANDS AND THEIR DIGESTIVE ACTION . 687
Anatomy of the Salivary Glands, 687. — Histological Structure, 689,-^Com- position of the Secretion, 690. — The Secretory Nerves, 691. — Trophic and Secretory Nerve Fibers, 693. — Histological Changes during Activity, 694. — Action o*f Drugs upon the Secretory Nerves, 697. — Paralytic Secretion, 698. — Normal Mechanism of Salivary Secretion, 698. — Electrical Changes in Glands, 700. — Digestive Action of Saliva; Ptyalin, 700. — Conditions Influencing the Action of Ptyalin, 701. — Functions of the Saliva, 702.
CHAPTER XLII. — DIGESTION AND ABSORPTION IN THE STOMACH 703
Structure of the Gastric Glands, 703. — Histological Changes during Secretion, 704. — Method of Obtaining the Gastric Secretion and Its Normal Composition, 705.— The Acid of Gastric Juice, 707.— Origin cf the HC1, 707.— Secretory Nerves of the Gastric Glands, 708. — Normal Mechanism of the Secretion of the Gastric Juice, 709. — Nature and Properties ct Pepsin, 711. — Artificial Gastric Juice, 713.— Pepsin-hydrochloric Digestion, 713. — The Rennin En- zyme, 715. — Digestive Changes in the Stomach, 717. — Absorption in the Stomach, 718.
CHAPTER XLIII. — DIGESTION AND ABSORPTION IN THE INTESTINES 721
Structure of the Pancreas, 721. — Composition of the Secretion, 722. — Secre- tory Nerve Fibers to the Pancreas, 722. — The Curve of Secretion, 723. — Nor- mal Mechanism of Pancreatic Secretion, 724. — Secretin. 725.— Enterokinase, 725. — Digestive Action of Pancreatic Juice, 725. — Significanceof Tryptic Diges- tion, 728. — Action of the Diastatic Enzyme (Amylopsin), 729. — Action of the Lipolytic Enzyme (Lipase, Steapsin), 730. — The Intestinal Secretion (Succus Entericus), 731. — Absorption in the Small Intestine, 733. — Absorption of Carbohydrates, 734. — Absorption of Fats, 735. — Absorption of Proteins, 737. — Digestion and Absorption in the Large Intestine, 738. — Bacterial Action in the Small Intestine, 739.— Bacterial Action in the Large Intestine, 740. — Physiological Importance of Intestinal Putrefaction, 740. — Composition of the Feces, 741.
CHAPTER XLIV. — PHYSIOLOGY OF THE LIVER AND SPLEEN 743
Structure of the Liver, 743. — Composition of Bile, 744.— The Bile Pigments, 745.— The Bile Acids, 746.— Cholesterin, 747.— Lecithin, Fats, and Nucleo- albumins, 748. — Secretion of the Bile. 748. — Ejection of the Bile — Function of the Gall-bladder, 749. — Occlusion of the Bile-ducts, 751. — Physiological Im- portance of Bile, 751 . — Occurrence of Glycogen, 752. — Origin of Glycogen. 753. — Function of Glycogen. Glyrogenic Theory, 756. — Glycogen in the Muscles and Other Tissues, 757. — Conditions Affecting the Supply of Glycogen, 757. — For- mation of Urea in the Liver, 758. — Physiology of the Spleen, 759.
14 TABLE OF CONTENTS.
PAGE
CHAPTER XLV. — THE KIDNEY AND SKIN AS EXCRETORY ORGANS 762
Structure of the Kidney, 762. — The Secretion of Urine, 763. — Function of the Glomeralus, 765. — Function of the Convoluted Tubule, 767. — Action of Diuretics, 769. — The Blood-flow Through the Kidneys, 769. — The Composi- tion of Urine, 772. — The Nitrogenous Excreta in the Urine, 773. — Origin and Significance of Urea, 774. — Origin and Significance of the Purin Bodies (Uric Acid, Xanthin, Hypoxanthin), 777.— ^-Origin and Significance of the Creatinin, 780. — Hippuric Acid, 781. — The Conjugated Sulphates and the Sulphur Excre- tion, 781. — Secretion of the Water and Inorganic Salts, 782. — Micturition, 783. — Contractions of the Bladder, 784. — Nervous Mechanism of Micturition, 787. — Excretory Functions of the Skin, 788. — Composition of Sweat, 788. — Secretory Fibers of Sweat Glands, 789. — Sweat Centers, 791. — Sebaceous Secretion, 791. — Excretion of Carbon Dioxid through the Skin, 792.
CHAPTER XLVI. — SECRETION OF THE DUCTLESS GLANDS — INTERNAL
SECRETION 793
Internal Secretion of Liver, 794. — Internal Secretion of the Thyroid Tissues, 794. — Extirpation of Thyroids and Parathyroids, 795.— Function of the Para- thyroids, 795. — Theories of General Functions of Thyroid and Parathyroids, 797. — Cyon's View of Function of Thyroid, 797. — Function of Thymus, 798. — Structure and Properties of Adrenal Bodies, 798. — General Function of Adre- nals, 801.— Pituitary Body, 801.— Internal Secretion of Testis and Ovary, 802. — Internal Secretion of Pancreas, 804. — Internal Secretion of Kidney, 806.
SECTION VIII. NUTRITION AND HEAT PRODUCTION AND REGULATION.
CHAPTER XLVII. — GENERAL METHODS. HISTORY OF THE PROTEIN
FOOD 808
General Statement, 808. — Nitrogen Equilibrium, 808. — Carbon Equilibrium and Body Equilibrium, 810. — Balance Experiments, 810. — Respiration Cham- ber, 811. — Effect of Non-protein Food on Nitrogen Equilibrium, 811. — Nutri- tive History of the Protein Food, 811. — Tissue Protein and Circulating Protein, 812. — Amount of Protein Necessary in Normal Nutrition, Question of Luxus Consumption, 813. — Specific Character of Protein Metabolism, 815. — Specific Dynamic Action of Proteins, 818. — Nutritive Value of Albuminoids, 818.
CHAPTER XLVIII. — NUTRITIVE HISTORY OF CARBOHYDRATES AND FATS 821
The Carbohydrate Supply of the Body, 821. — Regulation of the Sugar Supply of the Body, 821. — Fate of the Carbohydrates in the Body, 824. — Functions of the Carbohydrate Food, 825. — Nutritive Value of Fats, 826. — Fate of Fats in the Tissues, 826.— Origin of Body Fat, 827.— Origin of Body Fat from Carbohy- drates, 829. — Origin of Body Fat from Food Fat, 828. — Source of Fat in Ordinary Diets, 829.— Cause of the Formation of Fat, Obesity, 829.— General Functions of Fat, 830.
CHAPTER XLIX. — NUTRITIVE VALUE OF THE INORGANIC SALTS AND THE
ACCESSORY ARTICLES OF DIET 832
The Inorganic Salts of the Body, 831. — Effect of Ash-free and Ash-poor Diets, 833. — Special Importance of Sodium Chlorid, Calcium, and Iron Salts, 833. — The Condiments, Flavors, and Stimulants, 835. — Physiological Effects of Alcohol, 836.
CHAPTER L. — EFFECT OF MUSCULAR WORK AND TEMPERATURE ON BODY
METABOLISM; HEAT ENERGY OF FOODS; DIETETICS 840
The Effect of Muscular Work, 840. — Effect of Sleep, 842. — Effect of Variations in Temperature, 842. — Effect of Starvation, 843. — The Potential Energy of Food, 845.— Dietetics, 848.
CHAPTER LI. — THE PRODUCTION OF HEAT IN THE BODY; ITS MEASURE- MENT AND REGULATION; BODY TEMPERATURE; CALORIMETRY; PHYSIOLOGICAL OXIDATIONS 852
Historical Account of Theories of Animal Heat, 852. — Body Temperature in Man, 853. — Calorimetry, 855. — Heat Regulation, 860. — Regulation of Heat Loss, 860. — Regulation of Heat Production, 863. — Existence of Heat Centers and Heat Nerves, 864. — Theories of Physiological Oxidations, 866.
TABLE OF CONTENTS. 15
SECTION IX. PHYSIOLOGY OF REPRODUCTION.
PAGE
CHAPTER LII. — PHYSIOLOGY OF THE FEMALE REPRODUCTIVE ORGANS . . 872
The Relation of the Ovaries to Menstruation, 876. — Physiological Significance of Menstruation, 878. — Effect of the Menstrual Cycle on Other Functions, 879. — Passage of the Ovum into the Uterus, 879. — Maturation of the Ovum, 880. — Fertilization of the Ovum, 883. — Implantation of the Ovum, 884. — Nutrition of the Ovum — Physiology of the Placenta, 885. — Changes in the Maternal Organism during Pregnancy, 887. — Parturition, 888. — The Mammary Glands, 889. — Connection between the Uterus and the Mammary Glands, 889.— Composition of Milk, 891.
CHAPTER LIII. — PHYSIOLOGY OF THE MALE REPRODUCTIVE ORGANS .... 893
Sexual Life of Male, 893. — Properties of the Spermatozoa, 893. — Chemistry of the Spermatozoa, 895. — The Act of Erection, 896. — Reflex Apparatus of Erection and Ejaculation, 897.
CHAPTER LIV. — HEREDITY; DETERMINATION OF SEX; GROWTH AND
SENESCENCE 899
Definition of Heredity, 899. — Evolution and Epigenesis, 899. — Determination of Sex, 901. — Growth and Senescence, 904.
APPENDIX. I. — PROTEINS AND THEIR CLASSIFICATION 907
Definition and General Structure of Proteins, 907. — Reactions of Proteins, 908. — Classification of Proteins, 910. — The Albumins, 911. — The Globulins, 911. — The Albuminates, 911. — Nucleo-albumins or Phosphoproteins, 911. — Pro- teoses and Peptones, 912. — Protamins and Histons, 912. — The Compound Proteins, 913.— The Albuminoids, 913.
II. — DIFFUSION AND OSMOSIS 914
Diffusion, Dialysis, and Osmosis, 914. — Osmotic Pressure, 914. — Electrolytes, 915.— Gram-molecular Solutions, 916. — Calculation of Osmotic Pressure in Solutions, 916. — Determination of Osmotic Pressure by the Freezing Point, 917.— Application to Physiological Processes, 917. — Osmotic Pressure of Proteins, 917. — Isotonic, Hypertonic, and Hypotonic Solutions, 918. — Diffu- sion or Dialysis of Soluble Constituents, 918. — Diffusion of Proteins, 919.
INDEX.. , 921
A TEXT-BOOK
OF
PHYSIOLOGY.
SECTION I. THE PHYSIOLOGY OF MUSCLE AND NERVE.
CHAPTER I. THE PHENOMENON OF CONTRACTION.
The tissues in the mammalian body in which the property of contractility has been developed to a notable extent are the mus- cular and the ciliated epithelial cells. The functional value of the muscles and the cilia to the body as an organism depends, in fact, upon the special development of this property. The muscular tissues of the body fall into three large groups, considered from either a histologicalor a functional standpoint, — namely, the striated skeletal muscle, the striated cardiac muscle, and the plain 'muscle. These tissues exhibit certain marked differences in properties which are described farther on. In each group, moreover, there are certain minor differences in structure which are associated with differences in properties; thus, skeletal muscle from different re- gions of the same animal may show variations in properties, — for instance, in the rapidity of contraction; and similar, perhaps more marked differences are observed in the plain muscular tissue of various organs. The muscular tissues from animals belonging to different classes exhibit naturally even wider variations in proper- ties, and these differences in some cases are not associated with visible variations in structure.
2 17
18
THE PHYSIOLOGY OF MUSCLE AND NERVE.
THE PHYSIOLOGY OF SKELETAL MUSCLE TISSUE.
This tissue makes up the essential part of the skeletal muscles by means of which our voluntary movements are effected. Each muscle fiber arises from a single cell and in its fully developed condition may be regarded as a multinuclear giant cell. It is inclosed entirely in a thin, structureless, elastic membrane, the sarcolemma. The material of the fiber is supposed to be semifluid or viscous when in the living condition; it is designated in general as the muscle
There is on record an interesting observation by Kiihne* which seems to demonstrate the fluid nature of the living muscle substance. He hap- pened, on one occasion, to find a frog's muscle fiber containing a nematode worm within the sarcolemma. The animal swam readily from one end of the fiber to the other, pushing aside the cross bands, which fell into place
Fig. 1. — A cross-section of muscle fiber of rabbit. The bundles of fibrils are dark; the intervening small amount of sarcoplasm is represented by the clear spaces. — (Kolliker.')
Fig. 2. — Cross-section of two muscle fibers of the fly: Ms, The columns of fibrils; Sp, the sarcoplasm. — (Schieffer- decker.)
again after the animal had passed. At one end, where the fiber had been injured, the worm was unable to force its way. The muscle substance at this point was dead and apparently had passed into a solid condition. The fact that the cross bands were displaced only temporarily by the movement and fell back into their normal position would indicate that they may have a more solid structure.
Disregarding the nuclei, the muscle plasma consists of two different structures: the fibrils, which are long and thread-like and run the length of the fiber, and the intervening sarcoplasm. The fibrils consist of alternating dim and light discs or segments, which, falling together in the different fibrils, give the cross-striation that is characteristic. In mammalian muscles the fibrils are grouped more or less distinctly into bundles or columns, between which lies the scanty sarcoplasm. The relative amount of sarcoplasm to fibrillar substance varies greatly in the striped muscles of different * Kiihne, 'Archiv fur pathologische Anatomic," 26, 222, 1863.
THE PHENOMENON OF CONTRACTION.
19
animals, as is indicated in the accompanying illustrations. The
evidence from comparative physiology indicates that the fibrils
are the contractile element of the fiber, while the sarcoplasm, it
may be assumed, possesses a general nutritive function. Com-
parative histology suggests that in the
fibrils we possess, so to speak, a mechanism
adapted to rapid contraction, and that the
perfection of the mechanism — -that is, the
rapidity of the contraction — ;3 proportional
to the clearness of the cross-striation. The
fibril, moreover, shows two kinds of sub-
stance, the alternating dim and light sub-
stance, and these two materials are obviously
different in physical structure as seen by
ordinary light. When examined by polarized
light this difference becomes more evident,
for the dim substance possesses the property
of double refraction. When the muscle fiber
is placed between crossed Nicol prisms
the dim bands appear bright, while the
light bands remain dark, as is shown in
Fig. 3. From this standpoint the material
of the light bands in the normal fibrils is
spoken of as isotropous, while the dim bands
are anisotropous. The anisotropic material
of the dim bands is composed Of doubly
refracting positive uniaxial particles, and
Engelmann has shown that such particles
may be discovered in all contractile tissues.
The inference made by him is that this
anisotropic substance is the contractile p
material in the protoplasm, the machinery, Fig. 3.— TO show the
so to speak, through which its shortening ?aTsot?SpCfc)ofandhe HgS
is accomplished. In the striated fiber this £3t£SSt£StonfaJL Sen
Conclusion is Supported by the fact, repre- by ordinary and by polar-
J . ized light. The figure rep-
sented in Fig. 3, that during contraction resents a muscle fiber
-.. . , ,, ,, /T i j_\ i i (beetle) in which the lower
liquid passes from the ISOtrOpOUS (light) band portion has been fixed in a
<
into the anisotropous (dim) band.*
The Extensibility and Elasticity of
Muscular Tissue. — The muscular tissue when acted upon by a weight extends quite readily, and when the weight is removed it regains its original form by virtue of its elasticity. In our bodies the muscles stretched from bone to bone are, in fact, in
* Biedermann, "Electro-physiology," vol. i, translated by Welby, and Engelmann, "Archiv fiir die gesammte Physiologic," 18, 1.
20 THE PHYSIOLOGY OF MUSCLE AND NERVE.
a state of elastic tension. If a muscle is severed by an incision across its belly the ends retract. The extensibility and elasticity of the muscles add to the effectiveness of the muscular-skeletal machinery. A muscle that is in a state of elastic tension con- tracts more promptly and more effectively for a given stimu- lus than one which is entirely relaxed. Moreover, in our joints the arrangement of antagonists — flexors and extensors — is such that the contraction of one moves the bone against the pull of the extensible and elastic antagonist. It would seem that the movements of the skeleton must gain much in smoothness and delicacy by this arrangement. The physical advantages of the extensibility and elasticity of muscular tissue are evident not
Ffc. 4.— a, Curve of extension of a rubber band, to show the equal extensions for equal increments of weight. The band had an initial load of 17 gms., and this was increased by increments of 3 gms. in each of the nine extensions, the final load being 44 gms. The line joining the ends of the ordinates is a straight line, b. Curve of extension of a frog s muscle (gastrocnemius). The initial load and the increment of weight were the same as with the rubber. The curve shows a decreasing extension for equal increments. The line join- ing the ends of the ordinates is curved.
only in the contractions of our voluntary muscles, but, as we shall see, in a striking way also in the circulation, in which the force of the heart beat is stored and economically distributed, as it were, by the elastic tension of the distended arteries. The extensibility of muscular tissue has been studied in comparison with the extensi- bility of dead elastic bodies. With regard to the latter it is known that the strain that the body undergoes is proportional, within the limits of elasticity, to the stress put upon it. If, for instance, weights are attached to a rubber band suspended at one end the amount of extension of the band will be directly proportional to the weights used. If the extensions are measured the relation- ship may be represented as shown in the accompanying figure, the equal increments in weight being indicated by laying off equal
THE PHENOMENON OF CONTRACTION.
21
distances on the abscissa, and the resulting extensions by the height of the ordinates dropped from each point. If the ends of the ordinates are joined the result is a straight line. When a similar experiment is made with a living muscle it is found that the extension is not proportional to the weight used. The amount of extension is greatest in the beginning and decreases propor- tionately with new increments of weight. If the results of such an experiment are plotted, as above, representing the equal incre- ments of weight by equal ^distances along the abscissa and the resulting extensions by ordinates dropped from these points, then upon joining the ends of the ordinates we obtain a curve concave to the abscissa. At first the muscle shows a relatively large exten- sion, but the effect becomes less and less with each new increment of weight, the curve at the end approaching slowly to a horizontal. If the weight is in- creased until it is sufficient to overcome the elasticity of the muscle the curve is altered — it becomes convex to the abscissa, or, in other words, the amount of extension increases with increasing increments of weight up to the point of rupture, as is shown in the accom- panying curve* (Fig. 5). Haycraftf calls attention to the fact that under normal conditions the physiological extension of the frog's muscles in the body is equal to that produced by a weight of 10 to 15 gms., and that when the excised muscle is extended by weights below this limit it follows the law of dead elastic bodies, giving equal extensions for equal increments of weight. It is only after passing this limit that the law stated above holds good. It should be added also that the amount of extension exhibited by a muscle or other living tissue placed under a stress varies with the time that the stress is allowed to act. The muscle is composed of viscous material, and yields slowly to the force acting upon it. In experiments of this kind, therefore, the weights should be allowed to act for equal intervals
* See Marey, "Du mouvement dans les fonctions de la vie," 1868, p. 284. t Haycraft, "Journal of Physiology," 31, 392, 1904.
JC
Fig. 5. — Curve given by Marey to show the effect upon the extension of muscle caused by increasing the load regularly to the point of rupture : From o to a the extension of the muscle decreases as the weight increases, giving a curve concave to the abscissa, ox; at a the limit of elasticity is passed and the muscle lengthens by in- creasing extensions for equal increments ; at x rupture (,750 gms. for frog's gastrocnemius).
22 THE PHYSIOLOGY OF MUSCLE AND NERVE.
of time. It has been shown that the extensibility of a muscle is greater in the contracted than in the resting state.
The curve of extension described above for skeletal muscle holds also for so-called plain muscle. This latter tissue forms a portion of the walls of the various viscera, the stomach, bladder, uterus, blood-vessels, etc., and the facts shown by the.above curve enter frequently into the explanation of the physical phenomena exhibited by the viscera. For instance, it follows from this curve that the force of the heart beat will cause less expansion in an artery already distended by a high blood-pressure than in one in which the blood-pressure is lower.
The Irritability and Contractility of Muscle. — Under normal conditions in the body a muscle is made to contract by a stimulus received from the central nervous system through its motor nerve. If the latter is severed the muscle is paralyzed. We owe to Haller, the great physiologist of the eighteenth century, the proof that a muscle thus isolated can still be made to contract by an artificial stimulus — e. g., an electrical shock — applied directly to it. This significant discovery removed from physiology the old and harmful idea of animal spirits, which were supposed to be generated in the central nervous system and to cause the swelling of a muscle during contraction by flowing to it along the connecting nerve. But to remove a muscle from the body and make it contract by an artificial stimulus does not prove that the muscle substance itself is capable of being acted upon by the stimulus, since in such an experiment the endings of the nerve in the muscle are still intact, and it may be that the stimulus acts only on them and thus affects the muscle indirectly. In a number of ways, however, physiologists have found that the muscle substance can be made to contract by a stimulus applied directly to it, and therefore exhibits what is known as independent irritability. The term irritability, according to modern usage, means that a tissue can be made to exhibit its peculiar form of functional activity when stimulated, — e. g., a muscle cell will contract, a gland cell will secrete, etc., — and inde- pendent irritability in the case under consideration means simply that the muscle gives its reaction of contraction when artificial stimuli are applied directly to its substance. This conception of irritability was first introduced by Francis Glisson (1597-1677), a celebrated English physician.* Subsequent writers frequently used the term as synonymous with contractility and as applicable only to the muscle. But it is now used for all living tissues in the sense here indicated. A simple proof of the independent irritability of a striated muscle is obtained by cutting the motor nerve going to it and stimulating the muscle after several days. *See Foster's " History of Physiology," p. 287.
THE PHENOMENON OF CONTRACTION. 23
We know now that in the course of several days the severed nerve fibers degenerate completely down to their terminations in the muscle fibers, and the muscle, thus freed from its nerve fibers by the process of degeneration, can still be made to contract by an artificial stimulus. The classical proof of the independent irri- tability of muscle fibers was given by Claude Bernard, the great French physiologist of the nineteenth century. He made use of the so-called arrow poison of the South American Indians. This substance or mixture o£. substances is known generally under the name curare; it is prepared from the juices of several plants (strychnos) (Thorpe). The poisonous part of the material is soluble in water, and Bernard showed that when such an extract is injected into the blood or hypodermically it paralyzes the motor nerves at their peripheral end, so that direct stimulation of these nerves
Fig. 6. — The induction coil as used for physiological purposes (du Bois-Reymond pattern): A, The primary coil; B, the secondary coil; P', binding posts to which are at- tached the wires from the battery, they connect with the ends of coil A : P", binding posts connecting with ends of coil B, through which the induction current is led off; S, the slide, with scale, in which coil B is moved to alter its distance from A.
is ineffective. Direct stimulation of the muscle substance, on the contrary, causes a contraction.*
Artificial Stimuli. — If we designate the stimulus that the muscle receives normally from its nerve as its normal stimulus, all other forms of energy which may be used to start its contraction may be grouped under the designation artificial stimuli. Experi- ments have shown that a contraction may be aroused by mechanical stimuli, — for instance, by a sharp blow applied to the muscle; by thermal stimuli, — that is, by a sudden change in temperature; by chemical stimuli, — for example, by the action of concentrated solu- tions of salts, and finally by electrical stimuli. In practice, however, only the last form of stimulus is found to be convenient. The mechanical and thermal stimuli cannot be well applied without at the same time injuring the muscle substance, and the same is prob- ably true of chemical stimuli, which possess the disadvantage, more- over, of not exciting simultaneously the different fibers of which the
* 'Lecons sur les effets des substances toxiques et medicamenteuses/' 1857, pp. 238 et seq.
24 THE PHYSIOLOGY OF MUSCLE AND NERVE.
muscle is composed. Electrical stimuli, on the contrary, are applied easily, are readily controlled as regards their intensity, and affect all the fibers simultaneously, thus giving a co-ordinated contraction of the entire bundle, as is the case with the normal stimulus. For electrical stimulation we may use the galvanic current taken directly from the battery, or the induced or so-called faradic current obtained from an induction coil. Under most conditions the latter is more convenient, since it gives brief shocks, the strength and number of which can be controlled readily. The form in which this instrument is used in experimental work in physiology we owe to du Bois-Reymond (1849-); hence it is frequently known as the du Bois-Revmond induction coil. Experi-
A B
Fig. 7.— Schema of induction apparatus. — (Lombard.) b represents the galvanic battery connected by wires to the primary coil, A. On the course of one of these wires is a key (k) to make and break the current. B shows the principle of the secondary coil, and the connection of its two ends with the nerve of a nerve-muscle preparation. When the battery current is closed or made in A, a brief current of high intensity is induced in B. This is known as the making or closing shock. When the battery current is broken in A, a second brief induction current is aroused in B. This is known as the breaking or opening shock.
mental physiology owes a great deal to this simple and serviceable instrument. A figure and brief description of the apparatus is appended (Figs. 6 and 7).
SIMPLE CONTRACTION OF MUSCLE.
Experiments may be made upon the muscles of various animals, but ordinarily in physiological laboratories one of the muscles (gastrocnemius) of the hind leg of the frog is employed. If such a muscle is isolated and connected with the terminals from an induction coil it may be stimulated by a single shock or by a series of rapidly repeated shocks. The contraction that results from a single stimulus is designated as a simple contraction. In the frog's muscle it is very brief, lasting for 0.1 second or less; but in this, as in other respects, cross-striated muscular tissue varies in different animals,* as is shown by the accompanying table, which gives an idea of the range of rapidity of contraction.
* Cash, "Archiv f. Anat. u. Physiol.," 1880, suppl. volume, p. 147.
THE PHENOMENON OF CONTRACTION. 25
DURATION OF A SIMPLE MUSCULAR CONTRACTION.
Insect 0.003 sec.
Rabbit (Marey) 0.070 "
Frog 0.100 "
Terrapin. 1.000 "
The series may be continued by the figures obtained from the plain muscle, thus:
The involuntary muscle (mammal) 10.00
Foot muscle of slug* (Ariolimax) 20.00
There is reason to believe that the rapidity of contraction is re- lated to the distinctness of the cross-striation. This is indicated by the properties of the so-called red and pale muscles that occur in some animals — the rabbit, for instance. The pale muscles con- tract much more rapidly than the red ones, and corresponding with
Fig. 8. — Curve of simple muscular contraction.
this fact it is found that the cross-striation is more distinct in the former. As was explained above, the active agent in contraction is contained in the dim bands of the fibers, and the more highly differentiated this structure becomes the more perfect apparently is its work as a mechanism for shortening. According to Cash, the duration of contraction of the soleus muscle (red) in rabbits is one second, while that of the gastrocnemius medialis (white) is only 0.25 second.
The Curve of Contraction. — When a contracting muscle is attached to a lever this lever may be made to write upon a smoked surface and thus record the movement, more or less magnified according to the leverage chosen. If the recording surface is sta- tionary the record obtained is a straight line and indicates only the extent of the shortening. If, however, the recording surface is in movement during the contraction the record will be in the form of a curve, which, making use of the system of right-angled co-ordinates, * Carlson, " American Journal of Physiology," 10, 418, 1904.
26 THE PHYSIOLOGY OF MUSCLE AND NERVE.
will indicate not only the full extent of the shortening, but also the amount of shortening or subsequent relaxation at any moment during the entire period. To obtain such records from the rapidly contracting frog's muscle it is evident that the recording surface must move with considerable rapidity and with a uniform velocity. A curve of this kind is represented in Fig. 8, on page 25. C rep- resents the axis of abscissas and gives the factor of time. A vertical ordinate erected at any point on C gives the extent of shortening at that moment. Below the jcurve of the muscle is the record of the vibrations of a tuning fork giving 100 double vibrations per second; that is, the distance from crest to crest represents an interval of T-J-7 of a second. Three principal facts are brought out by an analysis of the curve: I. The latent period. By this is meant that the muscle does not begin to shorten until a certain time after the stimulus is applied. On the curve the stimulus enters the muscle at S, and the distance between this point and the beginning of the rise of the curve, interpreted in time, is the latent period. II. The phase of shortening, which has a definite course and at its end immediately passes into III., the phase of relaxation.
The Latent Period. — In the contraction of the isolated frog's muscles as usually recorded the latent period amounts to 0.01 sec., but it is generally assumed that this period is exaggerated by the method of recording used, since the elasticity of the muscle itself prevents the immediate registration of the movement. By improve- ments in methods of technique the latent period for a fresh muscle may be reduced to as little as 0.005 or even 0.004 sec. Under the conditions in the body, however, the muscle contracts against a load, as when lifting a lever; hence, we may assume that normally there is a lost time of at least 0.01 sec. after the stimulus enters the ' muscle. In addition to the latent period due to the elasticity of the muscle it is certain that a brief amount of time actually elapses after the stimulus enters the muscle before the act of shortening begins ; some time is taken up in the chemical changes and the effect of these changes in putting the mechanism of con- traction into play (see below on the Theory of Muscle Contractions). The latent period varies greatly in muscles of different kinds, and in the same muscle varies with its conditions as regards temperature, fatigue, load to be raised, etc.
The Phases of Shortening and of Relaxation. — In the normal frog's muscle the phase of shortening for a simple contraction occu- pies about 0.04 second, while the relaxation may be a trifle longer, 0.05 sec. In muscles whose duration of contraction differs from that of the frog the time values for the shortening and the relaxation exhibit corresponding differences. As we have seen, the appearance of the muscle fiber when viewed by polarized light indicates that during the phase of shortening some of the material in the light
THE PHENOMENON OF CONTRACTION. 27
bands is imbibed into the substance composing the dim bands. The process is evidently a reversible one; during the phase of relaxation the absorbed or imbibed material passes back to the light band. Many conditions, some of which will be described below, alter the time necessary for these processes, that is, the duration of the simple contraction. It is noteworthy that it is the phase of relaxation which may be most easily prolonged or shortened by varying conditions.
?
Isotonic and Isometric Contractions. — In the method of recording the shortening of the muscle that is described above the muscle is supposed to con- tract against a constant load which it can lift. Such a contraction is spoken of as an isotonic contraction. If the muscle is allowed to contract against a tension too great for it to overcome — a stiff spring, for instance — it is prac- tically prevented from shortening, and a contraction of this kind, in which the length of the muscle remains unchanged, is spoken of as an isometric- contraction. A curve of such a contraction may be obtained by magnifying greatly, by means of levers, the slight change in the stiff spring against which the muscle is contracting. Such a curve gives a picture of the liberation of energy within the muscle during contraction.
The usual oval form of dynamometer employed to record the grip of the flexors of the fingers gives an isometric record of the energy of contraction of these muscles.
Fig. 9. — Effect of varying the strength of stimulus. The figure shows the effect upon the gastrocnemius muscle of a frog of gradually increasing the stimulus (breaking induction shock) until maximum contractions were obtained. The stimuli were then decreased in strength and the contractions fell off through a series of gradually decreasing submaximal •contractions. The series up and down is not absolutely regular owing to the difficulty of obtaining a regular increase or decrease in the stimulus. (The prolongations of the curves below the base line are due to the elastic extension of the muscle by the weight dur- ing relaxation.)
Effect of Strength of Stimulus upon the Simple Contraction.
—The strength of electrical stimuli can be varied conveniently and
28 THE PHYSIOLOGY OP MUSCLE AND NERVE.
with great accuracy. When the stimulus is of such a strength as to produce a just visible contraction it is spoken of as a minimal stimulus and the resulting contraction as a minimal contraction. Stimuli of less strength than the minimal are designated as sub- minimal. If one increases gradually the intensity of the electrical current used as a stimulus without altering its duration, beginning with a stimulus sufficient to cause a minimal contraction, the result- ing contractions increase proportionally up to a certain maximum beyond which further increase of stimulus, other conditions remain- ing the same, causes no greater extent of shortening. Contrac- tions between the minimal and the maximal are designated as- submaximal.* (See Fig. 9.)
Effect of Temperature upon the Simple Contraction. — Varia- tions in temperature affect both the extent and the duration of the contraction. The relationship is, however, not a simple one in the case of the frog's muscle upon which it has been studied most fre- quently. If we pay attention to the extent of the contraction alone it will be found that at a certain temperature, 0° C., or slightly below,
Fig. 10. — Curve showing the effect of temperature. The temperatures at which the contractions were obtained are indicated on the figure. In this experiment a large resis- tance was introduced into the secondary circuit so that changes in the resistance of the muscle itself due to heating could not affect the strength of the stimulus.
the muscle loses its irritability entirely. As its temperature is raised a given stimulus, chosen of such a strength as to be maximal for the muscle at room temperatures, causes greater and greater • contractions up to a certain maximum, which is reached at about 5° to 9° C. As the temperature rises beyond this point the con- tractions decrease somewhat to a minimum that is reached at about 15° to 18° C. Beyond this the contractions again increase in
* Fick, " Untersuchungen iiber elektrische Nervenreizung," Braun- schweig, 1864.
THE PHENOMENON OF CONTRACTION.
29
extent to a second maximum at about 26° to 30° C., this maxi- mum being in some cases greater, and in others less than the first maximum. Beyond the second maximum the contractions again decrease rather rapidly as the temperature rises until at a certain temperature, 37° C., irritability is entirely lost (Fig. 10). If the tem- perature is raised somewhat beyond this latter point heat rigor makes its appearance, and the muscle may be considered as dead. The re- lationship between temperature and extent of contraction, therefore,
38*
Fig. 11. — Curve to show the effect of a rise of temperature from 0° C. to 38° C. upon the height of contraction of frog's muscle. The first maximum at 9° C, the second at 28° C. Beyond 38° C. the muscle lost its irritability and went into rigor mortis.
Fig. 12. — Curve to show the effect of a rise of temperature from 5° C. to 39° C. upon the duration of contraction of frog's muscle. The relative dura- tions at the different temperatures are represented by the height of the cor- responding ordinates.
may be expressed by a curve such as is represented in Fig. 11, in which there are two maxima and two points at which irritability is lost . The second maximum indicates a fact of general physiological in- terest,— namely, that in all of the tissues of the body there is a certain high temperature at which optimum activity is exhibited, and if the temperature is raised beyond this point functional activity becomes more and more depressed. The point of optimum effect is not identi- cal for the different tissues of the same animal, much less so for those of different animals, but the fact may be emphasized that in no case do protoplasmic tissues withstand a very high temperature.
30 THE PHYSIOLOGY OF MUSCLE AND NERVE.
Functional activity is lost usually at 45° C. or below. The duration of the contraction shows usually in frogs' muscles a simple relation- ship to the changes of temperature. At low temperatures, 4 or 5° C., the contractions are enormously prolonged, particularly in the phase of relaxation ; but as the temperature is raised the duration of the contractions diminishes, at first rapidly, then more slowly, to a certain point — about 18° to 20° C., beyond which it remains more or less constant in spite of the changes in extent of shortening. The relationship between duration of contraction and temperature may therefore be expressed by such a curve as is shown in Fig. 12, in which the heights of the ordinates represent the relative durations of the contractions. Muscles from different frogs show considerable minor variations in their reactions to changes in temperature, and we may suppose that these variations depend upon differences in nutritive condition. In this, as in many other respects, the reactions obtained from so-called winter frogs after they have prepared for hibernation are more regular and typical than those obtained in the spring or summer.
Effect of Veratrin. — The alkaloid veratrin exhibits a peculiar and interesting effect upon the contraction of muscle. A muscle taken from an animal that has been veratrinized and stimulated in the usual way by a single stimulus gives a contraction such as is exhibited in the accompanying curve (Fig. 13). Two peculiarities are shown by the curve : (1) The phase of shortening is not altered, but the phase of relaxation is greatly prolonged. (2) The curve
Fig. 13. — Curve showing the effect of veratrin.
shows two summits, — that is, after the first shortening there is a brief relaxation followed by a second, slower contraction. The cause of this second shortening is not known. Biedemann has suggested that it is due to the presence in the muscle of the two kinds of fibers — red and pale — which were spoken of on p. 25, and that the veratrin dissociates their action, but this expla- nation, according to Carvallo and Weiss,* is disproved by the fact that muscles composed entirely of white or red fibers show * "Journal de la physiol. et de la path, generate," 1899.
THE PHENOMENON OF CONTRACTION.
31
a similar result from the action of veratrin. Although the explana- tion is not forthcoming, the fact that a single stimulus gives under
these conditions two processes of contractions is interesting as an exception to the general rule. It may be added that a curarized frog's muscle, when heated to the point of optimum activity (28° C.)
32 THE PHYSIOLOGY OF MUSCLE AND NERVE.
sometimes shows also a double contraction for a single stimulus. The very prolonged relaxation is, however, the most peculiar effect
Fig. 15. — Effect of repeated stimulation; complete curve, showing late contracture. The muscle was stimulated by induction shocks at the rate of 50 per minute. The separate contractions are so close together that they can not be distinguished.
of the veratrin. A somewhat similar effect is produced by the action of glycerin. We have in such substances reagents that affect one phase of the contraction process without materially influencing the other. As regards the veratrin effect, it becomes less and less
Fig. 16. — Effect of repeated stimulation, curve showing no contracture or very little. "The muscle was stimulated by induction shocks at the rate of 50 per minute. A very slight contracture is shown in the beginning, but subsequently the contractions show only a diminished extent, the rate of relaxation remaining apparently unchanged.
marked if the muscle is made to give repeated contractions, but reappears after a suitable period of rest. The peculiar action of the veratrin is therefore antagonized seemingly by the chemical products formed during contraction.
THE PHENOMENON OF CONTRACTION. 33
Contracture. — The prolonged relaxation that is so character- istic of the veratrinized muscles may be observed in frog's muscle under other circumstances, and is described usually as a condition of contracture. By contracture, therefore, we mean a state of con- tinuous contraction, or, looking at it from the other point of view, a state of retarded relaxation. This condition is apparent in muscles that have been cooled to a low temperature, and is shown also as a result of repeated stimulations. In Fig. 14 the phe- nomenon is exhibited very clearly in the form in which it was first described by Kronecker and Tiegel,* while in the following figure (Fig. 15) the phenomenon is shown as it usually appears, that is, after many contractions, and at a time when fatigue is beginning to make itself felt.
The Effect of Rapidly Repeated Contractions. — When a muscle is stimulated repeatedly by stimuli of equal strength that fall into the muscle at equal intervals the contractions show certain features that, in a general way, are constant, although the precise degree in which they are exhibited varies curiously in different animals. Such curves are exhibited in Figs. 14, 15, and 16, and the features worthy of note may be specified briefly as follows :
1. The Introductory Contractions. — The first three or four con- tractions decrease slightly in extent, showing that the muscle at first loses a little in irritability on account of previous contractions. This phenomenon is frequently absent.
2. The Staircase or " Treppe."— After the first slight fall in height has passed off the contractions increase in extent with great regularity and often for a surprisingly large number of contractions. This gradual increase in extent of shortening, with a constant stimulus, was first noticed by Bowditch upon the heart muscle, and was by him named the phenomenon of "treppe/' the German word for staircase. It indicates that the effect of activity is in the beginning beneficial to the muscle in that its irritability steadily increases, and the fact that the same result has been ob- tained from heart muscle, plain muscle, and nerve fibers indicates that it may be a general physiological law that functional activity leads at first to a heightened irritability.
3. Contracture. — This phenomenon of retarded relaxation has been described above. In frog's muscles stimulated repeatedly it makes its appearance, as a rule, sooner or later in the series of contractions; but there is a curious amount of variation in the muscles of different individuals in this respect.
4. Fatigue. — After the period of the " treppe " has passed the contractions diminish steadily in height until at last the muscle
* Tiegel, "Pfliiger's Archiv fur die gesammte Physiologic/' etc., 13, 71, 1876.
3
34 THE PHYSIOLOGY OF MUSCLE AND NERVE.
fails entirely to respond to the stimulus. This progressive loss of irritability in the muscle caused by repeated activity is designated as fatigue. It will be considered more in detail under the head of Compound Muscular Contractions and in Chapter II.
Lee has discovered the interesting fact that while in frog's muscle, as a rule, fatigue is accompanied by a prolongation, especially of the phase of relaxation, this does not hold for mammalian muscle. In the latter muscle the successive contractions become smaller as fatigue sets in, but their duration is not increased.
The Contraction Wave. — Under ordinary conditions the fibers of a muscle when stimulated contract simultaneously or nearly so, and the whole extent of the muscle is practically in the same phase of contraction at a given instant. It is comparatively easy to show, however, that the process of contraction spreads over the fibers, from the point stimulated, in the form of a wave which moves with a definite velocity. In a long muscle with parallel fibers one may prove, by proper recording apparatus, that if the muscle is stimulated at one end a point near this end enters into contraction before a point farther off. Knowing the difference in time between the appearance of the contraction at the two points and their distance apart, we have the data for determining the velocity of its propagation. In frog's muscles this velocity is found to be equal to 3 to 4 meters per second, while in human muscle, at the body temperature, it is estimated at 10 to 13 meters per second. Know- ing the time it takes this wave to pass a given point (d) and its velocity (v), its entire length is given by the formula 1= vd. In the frog's muscle, therefore, with a velocity of 3000 mm. per second, and a duration of, say, 0.1 second, the product 3000 X 0.1 = 300 mms. gives the length of the wave or the length of muscle which is in some phase of contraction at any given instant. Under normal conditions the muscle fibers are stimulated through their motor plates, which are situated toward the middle of the fiber, or perhaps one muscle fiber may have two or more motor plates, giving two or more points of stimulation. It follows, therefore, from this anatomical arrangement and the great velocity of the wave, that all parts of the fibers are in contraction at the same instant and, indeed, in nearly the same phase of contraction. Under abnormal conditions muscles may exhibit fibrillar contractions ; that is, separate fibrils or bundles of fibrils contract and relax at different times, giving a flickering, trembling movement to the muscle.
Idipmuscular Contractions. — In a fatigued or moribund muscle mechan- ical stimulation may give a localized contraction which does not spread or spreads very slowly, showing that the abnormal changes in the muscle prevent the excitation from traveling at its normal velocity. A localized contraction of this kind was designated by Schiff as an idiomuscular contraction. It may
THE PHENOMENON OF CONTRACTION. 35
be produced in the muscle of a dying or recently dead animal by localized mechanical stimulation, as by drawing a blunt instrument — e. g., the handle of a scalpel — across the belly of the muscle. The point thus stimulated stands out as a wheal, owing to the idiomuscular contraction.
The Energy Liberated in the Contraction. — When a muscle contracts, energy is, as we say, liberated in several forms, and can be measured quantitatively. First there is a production of heat, which is indicated by a rise in temperature of the muscle. According to Heiclenhain, the temperature of the frog's muscle is increased in a single contraction by 0.001° C. to 0.005° C. Larger muscles, such as those of the thigh of the dog, when repeatedly stimulated may cause a rise of temperature of from 1° to 2° C. The thermometer does not, of course, measure the amount of heat produced, but only the temperature of the muscle. Heat is esti- mated quantitatively in terms of calories. By a calorie is meant the quantity of heat necessary to raise 1 gm. of water 1° C. Knowing the specific heat and weight of muscle, we can readily calculate the number of calories produced. Thus, if a frog's muscle weighing 2 gms. shows a rise of temperature of 0.005° C. from a single contraction the production of heat in calories is given by multiplying the weight of the muscle by its specific heat, 0.83, to reduce it to an equivalent weight of water, and this product by the rise in temperature: 2 X 0.83 X 0.005 = 0.0083 calorie. The fact that muscular exercise increases the produc- tion of heat in the body is a matter of general observation. Second. Some electrical energy is developed during the contraction. The means of detecting and measuring this energy will be described in a subsequent chapter. Considered quantitatively, the amount is small. Third. Work is done if the muscle is allowed to shorten during the contraction. By work is meant external or useful work — that is, the muscle lifts a weight or overcomes an opposing resistance. If a muscle contracts against a weight too heavy to be lifted or a resistance too strong to be overcome it does no external work, although, of course, much energy is liberated as heat or, as it is sometimes called, internal work. The work done by a muscle during contraction is measured in the usual mechanical units, by the product of the load into the lift. That is, if a muscle lifts a weight of 40 grams to a height of 10 millimeters, the work done is 40 X 10 = 400 gram-millimeters, or 0.4 grammeter. We can in calculations convert external work into heat or internal work by making use of the ascertained mechanical equivalent of heat, according to which 1 calorie -= 425 grammeters of work. The work, 0.4 grammeter, supposed to be done in the above experi- ment would be equivalent, therefore, to 0.4 ~ 425, or about 0.001 of a calorie.
36 THE PHYSIOLOGY OF MUSCLE AND NERVE.
The Proportion of the Total Energy Liberated that may be Utilized in Work. — All of the energy liberated in the muscle has its origin in the chemical changes that follow upon stimulation. We assume that these changes are such that complex molecules are broken down, with the formation of simpler ones, and that some of the so-called chemical or internal energy that holds together the atoms in the complex molecule is liberated and takes the three forms described above. The chemical changes occurring in the muscle during contraction are complex and not entirely understood, but the significant ones from our present standpoint are oxidations which destroy some of ^ the material in the muscle, with the forma- tion of carbon dioxid and water and the liberation of heat. It is a matter of interest to inquire as to the proportion of the total heat energy which may be converted into useful work and the conditions under which the optimum amount of work may be realized. Regarded from this standpoint, the muscle may be considered as a piece of machinery comparable, let us say, to a gas engine. In the latter the heat generated by the explosive chemical change is converted partially into external work by a properly adapted mechanism— and in a well-constructed engine as much as 15 to 25 per cent, of the total energy may be obtained as work. In the muscle there is also a mechanism of some kind, not as yet understood, by means of which a part of the energy liberated may be converted into work. Experiments made by Fick with frogs' muscles indicate that the proportion of the total energy which under optimum conditions may be utilized as work is, in round numbers, from 25 to 30 per cent. Chauveau,* in experiments made upon the elevator of the upper lip in the horse, found a pro- portion of only 12 to 15 per cent. The last observer points out that this proportion must vary greatly for different muscles and for muscles in different animals, while for the same muscle it will vary with the extent and duration of the contractions and other conditions. From experiments made upon dogs in which a meas- ured amount of work was done and in which the energy changes were estimated from the oxygen absorbed and carbon dioxid eliminated, Zuntz f calculates that somewhat more than ^ of the total chemical energy liberated in the muscles may be applied to external work, the other § taking the form of heat. Similar ex- periments made by the same observer J upon men have indicated that the muscles work most economically in lifting the weight of the body, as in mountain-climbing. In this form of muscular work he estimates that from 35 to 40 per cent, of the heat energy
* Chauveau, "Le travail musculaire, etc.," Paris, 1891.
t Zuntz, "Archiv f. d. gesammte Physiologic," 68, 191, 1897.
J Zuntz and Schumberg, "Physiologic des Marsches," Berlin, 1901.
THE PHENOMENON OF CONTRACTION. 37
yielded by the material oxidized in the body may take the form
Fig. 17. — To show the decrease in extent of contraction of the gastrocnemius muscle of a frog with increase in load. In the first contraction, to the right, the load was 14.2 gms. At each successive contraction the load was increased by 5.3 gms. With a load of 182 gms. the lever gave only the slightest indication of a shortening, and this may have been due to some lateral movement.
Fig. 18. — The curve of work obtained by plotting the results shown in Fig. 17. The initial contraction was made with a load of 14.2 gms., and the work done in gram-milli- meters is represented by the ordinate erected at this point. The maximum work was done with a load of 88.6 gms., and the absolute power of this particular muscle was found to be equal to 182 gms.
of external work. When the muscular work performed was effected by the muscles of the arms and upper part of the body, as in turning
38 THE PHYSIOLOGY OF MUSCLE AND NERVE.
a wheel, a smaller yield (25 per cent.) was obtained. It appears from these figures that the muscular machine is an especially efficient one as regards the amount of external work that can be obtained from the oxidation of a given amount of material. Steam engines are said to be capable of yielding only 10 to 15 per cent, of the heat energy of the fuel in the form of mechanical or useful work.
The Curve of Work and the Absolute Power of a Muscle.— The statements in the preceding paragraph prove that the muscle, judged from the standpoint of a machine to do work, compares most favorably in its efficiency with machinery of human construction. But it should be borne in mind that in this as in other respects the properties of cross-striated muscular tissues vary greatly. In some animals or individuals it is a much more efficient machine than in others. This fact is indicated by our general experience regarding variations in muscular strength in different individuals, and is proved more precisely by direct experiments on single muscles. A frog's muscle may be isolated and the extent of its contractions and the work done may be estimated directly. Under such conditions it will be found that, while the height of the successive contractions diminishes as the load increases (see Fig. 17), the work done — that is, the product of the load into the lift — first increases and then decreases. For example :
Work Done in Gram-millimeters. Load in Grams. Lift in Millimeters. Load X Lift.
5 27.6 138.0
15 25.1 376.5
25 11.45 286.25
35 6.3 220.5
A series of experiments of this kind furnishes data for construct- ing a curve of work by plotting off along the abscissa at equal inter- vals the equal increments in load and erecting over each load an ordinate showing the proportional amount of work done. The curve has the general form indicated in Fig. 18. Three facts are expressed by this curve: First, that if the muscle lifts no weight no work will be done; this follows theoretically from the formula W = L H, in which W represents the work done, L the load, and H the lift. If either L or H is equal to zero the product, of course, is zero; that is, no external work is done; the chemical energy liberated in the contraction takes the form of heat. Under such circumstances the amount of heat given off from the muscle should be greater than when a load is lifted. In accordance with this fact it is found that a muscle lifting a light load gives off more heat during the contraction than when lifting a heavier load. Second, There is an optimum load for each muscle with which the greatest
THE PHENOMENON OF CONTRACTION. 39
proportion of work can be obtained. Third. When the load is just sufficient to counteract the contraction of the muscle no work i? done, H in the above formula being zero. This amount of load measures what Weber called the absolute power of the muscle. As will be seen from the above curve, it is measured by the weight which the muscle cannot lift and which, on the other hand, cannot cause any extension of the muscle while contracting. Or, in more general terms (Hermann), the absolute power of a muscle is the maximum of tension which it can reach without alteration of its natural length. This absolute power can be measured for the muscles of different animals and for convenience of comparison can then be expressed in terms of the cross-area of the muscle given in square centimeters. Weber has shown that the absolute power of a muscle varies with the cross-area, since this depends upon the number of constituent fibers whose united contraction makes the contraction of the muscle. Expressed in this way, it is found that the absolute power of human muscle is, size for size, much greater than that of frog's muscle. For in- stance, the absolute power of a frog's muscle of 1 square centimeter cross-area is estimated at from 0.7 kilogram to 3 kilograms, while that of a human muscle of the same size is estimated by Hermann at 6.24 kilograms. Taken as a whole, the human muscle is a better machine for work, but it seems possible, although exact figures are lacking, that the absolute power of the muscles of some insects reckoned for the same unit of cross-area would be much greater than in human muscle.
COMPOUND OR TETANIC CONTRACTIONS.
Definition of Tetanus — When a muscle receives a series of rapidly repeated stimuli it remains in a condition of contraction as long as the stimuli are sent in or until it loses its irritability from the effect of fatigue. A contraction of this character is described as a compound contraction or tetanus. If the stimuli follow each other with sufficient rapidity the muscle shows no external sign of relaxation in the intervals between stimuli, and if its contractions are recorded upon a kymographion by means of an attached lever a curve is obtained such as is shown at 5 in Fig. 19. A con- traction of this character is described as a complete tetanus. If, however, the rate of stimulation is not sufficiently rapid the mus- cle will relax more or less after each stimulus and its recorded curve, therefore, will present the appearance shown in 1,2, 3, and 4 of Fig. 19. A tetanus of this character is described as an incom- plete tetanus. It is obvious that according to the rate of stimu- lation there may be numerous degrees of incomplete tetanus, as shown in Fig. 19, extending from a series of separate single con-
40
THE PHYSIOLOGY OF MUSCLE AND NERVE.
Fig. 19. — Analysis of tetanus. Experiment made upon the gastrocnemius muscle of a frog to show that by increasing the rate of stimulation the contractions, at first separate ( 1), fuse more and more through a series of incomplete tetani (2, 3, 4) into a complete tetanus (5) in which there is no indication, so far as the record goes, of a separate effect for each stimulus.
THE PHENOMENON OF CONTRACTION. 41
tractions, on the one hand, to a perfect fusion of the contractions, a complete tetanus, on the other. Tetanic contractions present two peculiarities in addition to the mere matter of duration, which is governed, of course, by the duration of the stimu- lation: First, the more or less complete fusion of the contrac- tions due to the separate stimuli. This, as stated above, is the distinctive sign of a tetanus. Second, the phenomenon of sum- mation in consequence of which the total shortening of the muscle in tetanus may be considerably greater than that caused by a maxi- mal simple contraction.
Summation. — The facts of summation may be shown most read- ily by employing a device to send into the muscle two successive stimuli at varying intervals. If the second stimulus falls into the muscle at the apex of the contraction caused by the first stimulus, then, even if the first contraction is maximal, the muscle will shorten still farther; the first and second contractions are summated, giv- ing a total shortening greater than can be obtained by a single stim- ulus (see Fig. 20). The extent of the summation in such cases varies with a number of conditions, such as the intervals between the
Fig. 20. — Summation of two successive contractions. Curve 1 shows a simple con- traction due to a single stimulus, the latent period being indicated at the beginning of the contraction. Curve 2 shows the summation due to two succeeding stimuli.
stimuli, the relative strengths of the stimuli, the load carried by the muscle, etc. Taking the simplest conditions of a moderately loaded muscle and two maximal stimuli, it is found that the greatest sum- mation occurs when the stimuli are so spaced that the second contrac- tion begins at the apex of the first. If the stimuli are closer together, so that, for instance, the second contraction follows shortly after the first has begun, the total shortening is less, and the same is true
42 THE PHYSIOLOGY OF MUSCLE AND NERVE.
to an increasing^ extent as the second contraction falls later and later in the period of relaxation after the first contraction.* If instead of two we use three successive stimuli, falling into the muscle at proper intervals, a still further summation occurs. In this way the total extent of shortening in a muscle completely tetanized may be several times as great as that of a single maximal contraction.
The Discontinuous Character of the Tetanic Contraction —The Muscle-tone. — In complete tetanus the muscle seems to be in a condition of continuous uniform contraction; the re- corded curve shows no sign of relaxation between stimuli and no external indication, in fact, that the separate stimuli do more than maintain a state of uniform contraction. It can be shown, how- ever, that in reality each stimulus has its own effect, and that the chemical changes underlying the phenomenon of contraction are probably not continuous, but form an interrupted series correspond- ing, within limits, to the series of stimuli sent in. The clearest proof for this belief is found in the electrical changes that result from each stimulus, and the facts relating to this side of the question will be stated subsequently in the chapter on The Electrical Phenomena of Muscle and Nerve. Another proof is found in the phenomenon of the muscle-tone. When a muscle is stimulated directly or through its motor nerve a musical note may be heard by applying the ear or a stethoscope to the muscle. -The note that is heard corresponds in pitch, up to a certain point, with the num- ber of stimuli sent in, — that is, the muscle vibrates, as it were, in unison with the number of stimuli, and, although the vibrations are not sufficient to affect the recording lever, they can be heard as a musical note. This fact, therefore, may be taken as a proof that during complete tetanus there is a discontinuous series of changes in the muscle the rate of which corresponds with that of the stimulation. The series of electrical changes corresponding with the series of stimuli sent in may be made audible by applying a telephone to the muscle. Making use of this method, Wedenskif has shown that the ability of the muscle to respond isorhythmically to the rate of stimulation is limited. In frog's muscle the pitch of the musical tone may correspond with the rate of stimulation up to about 200 stimuli per second. In the muscle of the warm-blooded animal the correspondence may extend to about 1000 stimuli per second. If the rate of stimulation is increased beyond these limits the musical note heard does not correspond, but falls to a lower pitch, indicating that some of the stimuli under these conditions become ineffective. It should be added that the high
* Von Kries, "Archiv fur Physiologic," 1888, p. 537.
fWedenski, "Du rhythme musculaire dans la contraction normale," "Archives de physiologic," 1891, p. 58.
THE PHENOMENON OF CONTRACTION.
43
figures given above for the correspondence between the stimuli and the muscle-tone hold good only for entirely fresh preparations. The lability of the muscle quickly becomes less as it is fatigued ; so that in the frog, for instance, the correspondence in long-continued contractions is accurate only when the rate of stimulation does not exceed 30 per second.
The Number of Stimuli Necessary for Complete Tetanus. — The number of stimuli necessary to produce complete tetanus varies, as we should expect, wath the kind of muscle used and in accordance with the rapidity of the process of relaxation shown by these muscles in simple contractions. The series that may be arranged to demonstrate this variation is quite large, extending from a supposed rate of 300 per second for insect muscle to a low limit of one stimulus in 5 to 7 seconds for plain muscle. The frog's muscle goes into complete tetanus with a rate of stimulation of from 20 to 30 per second. Inasmuch as the rapidity of relaxation of the muscle is much retarded by certain influences, such as a low temperature or fatigue, it follows that these same influences affect in a corresponding way the rate of stimulation necessary to give complete tetanus. A frog's muscle stimulated at the rate of 10 stimuli per second may record an incomplete tetanus, but if the stimulus is maintained for some time the tetanus finally becomes complete in consequence of the slowing of the phase of relaxation.
Voluntary Contractions. — After ascertaining that muscles may give either simple or tetanic contractions one asks naturally whether in our voluntary movements we can also obtain both sorts of contractions. In the first place, it is obvious that most of our voluntary movements are too long continued to be simple contractions. The time element alone would place them in the group of tetanic contractions, and this is the usual conclusion regarding them. In voluntary move- ments a neuromuscular me- chanism comes into play. This mechanism consists, on the motor side, of at least two nerve units or neurons and the muscle, as indicated in the accompanying diagram (Fig. 21) . If in ordinary voluntary movements the muscular con- tractions are tetanic, we must suppose that the motor nerve cells discharge a series of nerve impulses through the motor
ing. 21. — Schema to show the mnerva- tion of the skeletal (voluntary) muscles: 1, the inter-central (pyramidal) neuron; 2, the spinal neuron; 3, the muscle.
44 THE PHYSIOLOGY OF MUSCLE AND NERVE.
nerve into the muscle. The contraction of voluntary muscle has been investigated, therefore, in various ways to ascertain whether there is any objective indication of the number of separate con- tractions that are fused together to make this normal tetanus. In the first place, the normal movements of the muscles have been re- corded graphically by levers or tambours. The records thus obtained show that our usual contractions are not entirely complete tetani, — that is, there is an indication in some part of the curve of the single contractions that are being fused. According to most observers,* these records show that our normal contractions are compounded of single contractions following at the rate of 10 per second, or, in other words, the motor neurons discharge about 10 impulses per second into the muscle. The so-called natural muscle-tone has been used for the same purpose. When one places a stethoscope or lays his ear upon a contracting muscle a low tone is heard the pitch of which corresponds with 40 vibrations per second. It is assumed, however, that this note does not represent the actual rate of stimulation of the muscle, since the number is higher than that obtained by other methods. The ear cannot perceive a musical note much lower than 40 vibrations per second, and if the muscle were really vibrating 10 or 20 times per second we could not perceive this fact directly by the ear. Vibrating bodies, however, give out overtones of a higher pitch, and it is supposed, therefore, that the normal muscle tone (40) represents either the first octave of the muscle vibrations, 20 per second, or the second octave, 10 per second. Helmholtz made use of a simple and direct method to determine this point. He utilized the prin- ciple of sympathetic vibrations, according to which a vibrating body will be set into movement most easily by vibrations that correspond in number to its own period. Helmholtz attached to the muscle watch springs that had different periods of vibration and found that when the muscle was contracted the spring that vibrated 20 times per second was set into most active movement. He concluded, therefore, that the muscle receives 20 stimuli per second in ordinary contractions and that the tone that is heard, 40 vibrations per second, represents the first overtone. The agree- ment among the results of those who have made graphic records of voluntary contractions would lead us, however, to suppose that 10 stimuli per second is more probably the true rate of stimulation and that the muscle-tone heard represents the overtone correspond- ing to the second octave of this vibration. It is to be borne in mind, however, that the motor nerve cells do not necessarily discharge their impulses into the muscle at a perfectly uniform rate. The rate is, in fact, liable to vary in different individuals or in the same *Horsley and Schafer, "Journal of Physiology," 7, 96, 1886.
THE PHENOMENON OF CONTRACTION. 45
individual under different circumstances. Von Kries,* for instance, states that the rate of stimulation in voluntary movements may vary according to the character of the movement. In slow, sus- tained movements the rate is from 8 to 12 per second, while in short, sharp, rhythmical movements of the fingers the rate may be as rapid as 40 per second. The fact that movements of this latter character — the trilling movements of the fingers of the pianist, for instance — may last for only T^ of a second or less, is considered by some authors as a proof that they are not tetanic contractions, .and that therefore we can voluntarily make either long-continued tetanic contractions or quick, simple contractions. Von Kries has shown, however, that when these quick, rhythmical movements of the fingers are recorded the curves, even of such brief contractions, show that they are short-lasting tetani. It is the usual belief, therefore, that all voluntary movements are tetanic in character and that it is not possible for us, by a so-called act of the will, to cause a simple contraction, — that is, to cause the motor nerve cells to discharge a single motor impulse. This general conclusion is sup- ported by the results of artificial stimulation of the motor regions of the brain. In experiments of this kind made by Horsley and Schafer it was shown that, at whatever rate the stimulus might be applied to the motor cells, they responded by motor discharges of about 10 per second, so far as this could be determined from the contractions of the muscle. The interesting conclusion from the whole discussion, therefore, is that our motor centers, under the stimulus of the will, discharge motor impulses at a certain low rate, which, while somewhat variable, averages in ordinary move- ments about 10 per second.
The Ergograph. — Voluntary contractions in man may be re- corded in a great many ways, but Mosso has devised a special in- strument for this purpose, known as the ergograph. It has been much used in quantitative investigations upon muscular work and the conditions influencing it. The apparatus is shown and described in Fig. 22. The person experimented upon makes a series of short contractions of the flexor muscle of the middle finger, thereby lifting a known weight to a definite height which is recorded upon a drum. In a set of experiments the rate of the series of contractions — that is, the interval of rest between the contractions — is kept constant, as also is the load lifted. Under these conditions the contractions become less and less ex- tensive as fatigue comes on, and finally, with the strongest voluntary effort, the contraction of the muscles is insufficient to lift the weight. In this way a record is obtained such as is shown in Fig. 23 In such a record we can easily calculate the total work done by * Von Kries, " Archiv fur Physiologic/' suppl. volume, 1886, p. 1.
46 THE PHYSIOLOGY OF MUSCLE AND NERVE.
obtaining the product of the load into the lift for each contrac-
Fig. 22. — Mosso's ergograph: c is the carriage moving to and fro on runners by means of the cord d, which passes Trom the carriage to a holder attached to the last two phalanges of the middle finger (the adjoining fingers are held in place by clamps) ; p, the writing point of the carriage, c, which makes the record of its movements on the kymographion ; w, the weight to be lifted.
tion and adding these products together. By this means the- capacity for work of the muscle used can be studied objectively
Fig. 23. — Normal fatigue curve of the flexors of the middle finger of right hand. 3 kilograms, contractions at intervals of two seconds. — (Maggiora.)
Weight?,
under varying conditions, and many suggestive results have beeni
THE PHENOMENON OF CONTRACTION. 47
obtained, some of which will be referred to specifically.* It should be borne in mind, however, that the ergograph in this form does not enable us to compute the total work that the muscle is capable of performing. It is obvious that when the point of complete fatigue is reached, as illustrated in the record, Fig. 23, the muscle is still capable of doing work, that is external work, if we replace the heavy load by a lighter one. For this reason some investigators have substituted a spring in place of the load,f giving thus a spring ergograph instead of a weight ergograph. Although with the spring ergograph every muscular contraction is recorded and the entire work done may be calculated, it also possesses certain theo- retical and practical disadvantages, for a discussion of which refer- ence must be made to the authors quoted.
The weight ergograph has, so far at least, given us the most sug- gestive results. Among these the following may be mentioned: (1) If a sufficient interval is allowed between contractions no fatigue is apparent. With a load of 6 kilograms, for instance, the flexor sublimis showed no fatigue when a rest of 10 seconds was given between contractions. (2) After complete fatigue with a given load a very long interval (two hours) is necessary for the muscle to make a complete recovery and give a second record as extensive as the first. (3) After complete fatigue efforts to still further contract the muscle greatly prolong this period of complete recovery, — a fact that demonstrates the injurious effect of straining a fatigued muscle. (4) The power of a muscle to do work is diminished by conditions that depress the general nutritive state of the body or the local nutrition of the muscle used; for instance, by loss of sleep, hunger, mental activity, anemia of the muscle, etc. (5) On the contrary, improved circulation fh the muscle — produced by massage, for example — increases the power to do work. Food also has the same effect, and some particularly interesting experi- ments show that sugar, as a soluble and easily absorbed foodstuff, quickly increases the amount of muscular work that can be per- formed. (6) Marked activity in one set of muscles — the use of the leg muscles in long walks, for example — will diminish the amount of work obtainable from other muscles, such as those of the arm. It is very evident that the instrument may be used to advantage in the investigation of many problems connected with gymnastics, dietetics, stimulants, { medicines, etc.
A point of general physiological interest that has been brought out in connection with the use of the ergograph calls for a few words of special mention. Mosso found that if a muscle — e. g., the flexor sublimis — is stimu-
*Mosso, "Archives italiennes de biologic," 13, 187, 1890; also "Archiv f. Physiologic," 1899, p. 191, 342. Lombard, a Journal of Physiology," 13, 1, 1892.
t Franz, " American Journal of Physiology," 4, 348, 1900; also Hough, ibid., 5, 240, 1901.
JSchumberg, "Archiv f. Physiol.," 1899, suppl. volume, p. 289.
48 THE PHYSIOLOGY OF MUSCLE AND NERVE.
lated directly by the electrical current and its contractions are recorded by the ergograph, it will give a curve similar to that figured above for the volun- tary contractions, except that the contractions are not so extensive. Under these conditions the muscle', when completely fatigued to electrical stimula- tion, will respond to voluntary stimulation from the nerve centers. It seems likely, as suggested by Hough, that this result is due mainly to the fact that the electrical current cannot be applied to a muscle in its normal position so as to excite uniformly all the constituent muscle fibers, although it is also possible that what we call the normal or voluntary stimulus is more effective or, to use a physiological term, more adequate to the muscle fibers than the electrical shock. On the other hand, after fatigue from a series of voluntary contractions it has been observed that the muscle will still give contractions if stimulated directly by electricity. This fact has been interpreted to mean that, in the neuromuscular complex involved in a mus- cular contraction — namely, motor nerve cell, motor nerve fiber, and muscle fiber — the first named fatigues most easily, and that the ordinary fatigue curve obtained from the ergograph does not represent pure 'muscle fatigue, but fatigue of the neuromuscular apparatus as a whole, the point of complete fatigue being reached in the neural component of the mechanism before the muscle itself loses its power of contraction. This interpretation, however, is not entirely certain. Wedenski has called attention to the fact that in the neuromuscular apparatus the motor end-plate is a sensitive link in the chain, and that, when the nerve is stimulated strongly with artificial stimuli, at least, this structure falls into a condition in which it fails to conduct the nerve impulse to the muscle. It may be, therefore, that in sustained volun- tary contractions the end-plate fails first, and thus is directly responsible for the failure of the apparatus to perform further work. That the fatigue in ordinary voluntary contractions affects the muscles before the motor nerve centers is indicated by the experiments of Storey.* Making use of a weight ergograph and experimenting upon the abductor indicis he found that after fatiguing this muscle to voluntary contractions with a certain weight, re- moval of the weight enabled the individual to make contractions as high and as rapid as before the fatigue. On the other hand, if after removing the weight the muscle was stimulated electrically the contractions were lower and slower than before the fatigue. So far as our knowledge goes, therefore, fatigue as it appears in sustained voluntary contractions is due probably primarily to a loss of irritability in the muscle and in the motor end-plates. The motor nerve fibers do not fatigue, and as regards the motor nerve centers it is not possible as yet to say what may be their relative susceptibility to fatigue.
Sense of Fatigue. — It should be noted in passing that in con- tinued voluntary contractions we are conscious of a sense of fatigue, which eventually leads us, if possible, to discontinue our efforts. This sensation must arise from a stimulus of sensory nerve fibers within the muscle or its tendons, and it may be regarded as an important regulation whereby we are prevented from pushing our muscular exertions to the point of " straining."
Muscle Tonus, — In addition to the conditions of contraction and of relaxation the living muscle exhibits the phenomenon of "tone." By muscle tone we mean a state of continuous shortening or contraction which under normal conditions is slight in extent and varies from time to time. This condition is dependent upon the connection of the muscle with the nerve centers, and we may assume that under normal circumstances the motor centers are continually discharging subminimal nerve impulses into the muscles * Story, 'American Journal of Physiology," 1903, viii., 355.
THE PHENOMENON OF CONTRACTION. • 49
which cause chemical changes similar in kind to those set up by an ordinary voluntary effort, but less in degree; the result being that the muscles enter into a state of contraction which, while slight in extent, is more or less continuous. According to this view, the whole neuromuscular apparatus is in a condition of tonic ac- tivity, and this state may be referred in the long run to the con- tinual inflow of sensory impulses into the central nervous system. The tone of any particular muscle or group of muscles may be destroyed, therefore, by cutting its motor nerve, or less completely by severing the sensory paths from the same region. If, for in- stance, one severs in a dog the posterior roots of the spinal nerves innervating the leg there will be a distinct loss of muscular tone, although the motor nerves remain intact. While we speak of this muscle tone as a state of continuous contraction, it may be that the apparently uniform condition is only superficial; that, in fact, this phenomenon is substantially only a minimal tetanus, due to a series of feeble but discontinuous stimuli received through the motor nerve, each of which stimuli sets up its own chemical change in the muscle. However this may be, the fact of muscle tone is important in a number of ways. It is of value, without doubt, for the normal nutrition of the muscle, and, as is explained in the chapter on animal heat, it plays a very important part in controlling the production of heat in the body. The extent of mus- cle tone varies with many conditions, the most important of which, perhaps, are external temperature and mental activity. With regard to the first, it is known that, as the external temperature falls and the skin becomes chilled, the sensory stimulation thus produced acts upon the nerve centers and leads to an increased discharge along the motor paths to the muscle. The tone of the muscles increases and may pass into the visible movements of shivering. By this means the production of heat within the body is increased automatically. Similarly, an increase in mental activity, so-called mental concentration, whether of an emotional or an intellectual kind, leads, by its effect on the spinal motor centers, to a state of greater muscle tonus, the increased muscular tension being, indeed, visible to our eyes.
The Condition of Rigor. — When the muscle substance dies it becomes rigid, or goes into a condition of rigor: it passes from a viscous to a solid state. The rigor that appears in the muscles after somatic death is designated usually as rigor mortis, since its oc- currence explains the death stiffening in the cadaver. It is charac- terized by several features: the muscles become rigid, they shorten, they develop an acid reaction, and they lose their irritability to stimuli. Whether all of these features are necessary parts of the •condition of rigor mortis it is difficult to say; the matter will be
4
50 . THE PHYSIOLOGY OF MUSCLE AND NERVE.
discussed briefly below. Some of the facts which have been ob- served regarding rigor mortis are as follows: After the death of an individual the muscles enter into rigor mortis at different times. Usually there is a certain sequence, the order given being the jaws, neck, trunk, upper limbs, lower limbs, the rigor taking, therefore, a descending course. The actual time of the appearance of the rigidity varies greatly, however; it may come on within a few minutes or a number of hours may elapse before it can be detected, the chief de- termining factor in this respect being the condition of the muscle itself. Death after great muscular exertion, as in the case of hunted animals or soldiers killed in battle, is usually followed quickly by muscle rigor; indeed, in extreme cases it may develop almost imme- diately. Death after wasting diseases is also followed by an early
Fig. 24. — Curve of normal rigor mortis, gastrocnemius muscle of frog. The curve was obtained upon a kymographion making one revolution in eight days. The marks on the line below the curve indicate intervals of six hours. It will be seen that the shortening required eighteen hours, the relaxation about seventy-two hours.
rigor, which in this case is of a more feeble character and shorter duration. The development of rigor is very much hastened by many drugs that bring about the rapid death of the muscle substance, such as veratrin, hydrocyanic acid, caffein, and chloroform. A frog's mus- cle exposed to chloroform vapor goes into rigor at once and shortens to a remarkable extent. Rigor is said also to occur more rapidly in a muscle still connected with the central nervous system than in one whose motor nerve has been severed. After a certain interval, which also varies greatly, — from one to six days in human beings, — the rigidity passes off, the muscles again become soft and flexible; this phenomenon is known as the release from rigor. In the cold-blooded animals the development of rigor is very much slower than in warm-blooded animals. Upon an isolated frog's muscle the most striking fact regarding rigor mortis is the shortening that the muscle undergoes. This shortening or contraction comes on slowly, as is shown in the accompanying figure, but in extent
THE PHENOMENON OF CONTRACTION. 51
it exceeds the simple contraction obtainable from the living muscle by means of a maximal stimulus. This part of the phenomenon is, however, much less marked apparently in mammalian muscle, and Folin* states that, if rigor be caused in frog's muscle by lowering its temperature to — 15° C., the muscle becomes rigid merely without undergoing any shortening or change in translu- cency. The usual explanation that is given of rigor is that it is due to a coagulation of the fluid substance, the muscle plasma, of which the fibers are constituted. During life the proteins exist in a liquid or viscous condition;' after death they coagulate into a solid form. This view is referred to again in the chapter dealing with the chemistry of muscle and nerve; it has received much support from the investigations of Kiihne,f who proved that the muscle plasma is really coagulable. After first freezing and mincing the muscles he succeeded in squeezing out the plasma from the living fibers and showed that it subsequently clotted. While the coagulation theory of rigor explains the greater rigidity of the muscle, it does not furnish in itself a satisfactory explanation of the shortening, and the fact, as stated above, that the rigidity may occur without the shortening indicates that this latter process may possibly be due to changes that precede the appearance of rigidity. In addition to the rigor mortis that occurs after death at ordinary temperatures, a condition of rigor may be induced rapidly by raising the temperature of the muscle to a certain point. Rigor induced in this way is designated as heat rigor or rigor caloris. Much uncertainty has prevailed as to whether heat rigor is different essentially from death rigor. According to some physiologists, the processes may be regarded as the same, the heat rigor being simply a death rigor that is rapidly developed by the high temperature, this latter condition accelerating the chemical changes leading to rigor, as is the case, for instance, in the action of chloroform. This view is supported by a study of the chemical changes that take place under the two conditions, as will be described later, and by the fact that some of the conditions that influence one phenomenon have a parallel effect upon the other. For instance, death rigor is accel- erated by previous use of the muscle, and the same is true for heat rigor. While a resting frog's muscle begins to go into heat rigor, as judged by the shortening, at 37° to 40° C.; a muscle that has been greatly fatigued shows the same phenomenon at 25° to 27° C4 According to other observers, heat rigor is due to an ordinary heat coagulation of the proteins present in the muscle
* " American Journal of Physiology," 9, 374, 1903.
fKiihne, " Archiv f. Physiologie," 1859, p. 788.
j JLatimer, " American Journal of Physiology/' 2, 29, 1899.
52 THE PHYSIOLOGY OF MUSCLE AND NERVE.
fiber. It has been pointed out,* for instance, that in frogs' muscles three different proteins are known to be present, with three dif- ferent temperatures of heat coagulation, — namely, myogen fibrin, 35° to 40° C. ; myosin, 47° to 50° C. ; and myogen, 58° to 65° Cv and that when the living muscle is heated what is ordinarily designated as the contraction of heat rigor comes on at the first temperature, 35° to 40° C., while small additional contractions occur at the temperatures of coagulation of the other two proteins. This view, however, does not make clear why the first of these coagulations, that of myogen fibrin at 40°, should produce such a large contrac- tion, 80 to 90 per cent, of the total shortening, although this protein is present in smaller quantities than the other two. As long, how- ever, as it remains uncertain whether or not the shortening and the coagulation are necessary features of death stiffening, it seems premature to speculate upon the identity or difference between the coagulation and shortening caused by death and the similar phenomenon caused by high temperatures.
PLAIN OR LONG STRIATED MUSCULAR TISSUE.
Occurrence and Innervation. — Plain or long striated muscular tissue occurs in the walls of all the so-called hollow viscera of the body, such as the arteries and veins, the alimentary canal, the genital and urinary organs, the bronchi, etc., and in other special localities, such as the intrinsic muscles of the eyeball, the muscles attached to the hair follicles, etc. In structure it differs fundamentally from cross-striated muscle, in that it occurs in the form of relatively minute cells, each with a single nucleus, which are united to form, in most cases, muscular membranes constituting a part of the walls of the hollow viscera. These muscle cells, in most cases at least, are supplied with nerve fibers which originate directly from the so-called sympathetic nerve cells, and only in- directly, therefore, from the central nervous system.
Speaking generally, the contractions of this tissue are removed from the direct control of the will, being regulated by reflex and usually unconscious stimulations from the central nervous system. All the important movements of the internal organs, or, as they are sometimes called, the organs of vegetative life, are effected through the activity of this contractile tissue. From this stand- point their function may be regarded as more important than that of the mass of the voluntary musculature, since so far as the mere maintenance of the life of the organism is concerned, the proper action and co-ordination of the movements of the visceral organs is at all times essential.
* Brodie and Richardson, 'Philosophical Trans., Roy. Spc.," London, 1899, 191, p. 127; also Inagaki, 'Zeitschrift f. Biol.," 1906, xlviii., 313.
THE PHENOMENON OF CONTRACTION. 53
Distinctive Properties. — The phenomena of contraction shown by plain muscles are, in general, closely similar to those already studied for striated muscle, the one great difference being the much greater sluggishness of the changes. Plain muscles differ among themselves, of course, as do the striated muscles, but, speak- ing generally, the simple contractions of plain muscle have a very long latent period that may be a hundred or five hundred times as long as that of cross-striated muscle, and the phases of shortening and of relaxation are also similarly prolonged; so that the whole movement of contraction is relatively slow and gentle (see Fig. 25). Plain muscle responds to artificial stimuli, but the electrical current is obviously a less adequate — that is, a less normal — stimulus for this tissue than for the striped muscle. The amount of current
Fig. 25. — Curve of simple contraction of plain muscle. The middle line is the time record, marking intervals of a second. The lowermost line indicates at the break the mo- ment of stimulation (short-lasting, tetanizing current). It will be seen that the latent period between beginning of stimulation and beginning of' contraction is equal to about three seconds.
necessary to make it contract is far greater. The amount of con- traction varies with the strength of stimulus, — that is, the tissue gives submaximal and maximal contractions. Two successive stimuli properly spaced will cause a larger or summated contraction, and a series of stimuli will give a fused or tetanic contraction. The rate of stimulation necessary to produce tetanus is, of course, much slower than for cross-striped muscle. The stomach muscle of the frog, for instance, requires only one stimulus at each five sec- onds to cause tetanus.* A distinguishing and important charac- teristic of the plain muscle is its power to remain in tone, — that is, to remain for long periods in a condition of greater or less con- traction. Doubtless this tonic contraction under normal relations is usually dependent upon stimulation received through the ner- vous system, but the muscle when completely isolated from the
* Schultz, "Zur Physiologie der langsgestreiften (glatten) Muskeln," " Archiv f. Physiologie," suppl. volume, 1903, p. 1. See also Stewart, "Amer- ican Journal of Physiology," 4, 185, 1900.
54 THE PHYSIOLOGY OF MUSCLE AND NERVE.
central nervous system, whether in or out of the body, continues to exhibit the phenomenon of tone to a remarkable degree. In most of the organs in which plain muscle occurs there are present also numerous nerve cells, and it is therefore still a question as to whether the tonic changes shown by this tissue depend upon a property of the muscle itself or upon their intrinsic nerve cells. Most observers adopt the former view. The importance of this property of tone in the plain muscle tissues will be made fully apparent in the descriptions of the physiology of the organs of cir- culation and digestion. Plain muscle may exhibit also the phenome- non of rhythmical activity, — that is, under proper conditions it may contract and relax rhythmically like heart tissue.* Such movements have been observed and studied upon the plain muscle of the ureter, the bladder, the esophagus, stomach, and other portions of the alimentary canal, the spleen, the blood-vessels, etc. This property seems to be very unequally distributed among the different kinds of plain muscle found in the same or different animals, but this fact serves only to illustrate the point already sufficiently empha- sized, that grouping one kind of tissue — e. g., plain muscle — into a common class does not signify that the properties of all the mem- bers of the group are identical. The question as to how far the phe- nomenon of rhythmical contraction is entirely muscular and how far it depends upon intrinsic nerve cells is a complex one; the answer will probably vary for different organs, and the subject will therefore be considered in the organs as they are treated.
Cardiac Muscular Tissue. — As the muscle cells of cardiac tissue are somewhat intermediate in structure between the striated fibers of voluntary muscle and the cells of plain muscles, so their physiological properties to some extent stand between these two extremes. The rate of contraction, for instance, while slower than that of the fibers of skeletal muscles, is more rapid than that of plain muscle. The most striking peculiarity of heart muscle is, however, its power of rhythmical contractility, and this, as well as its other properties, is so directly concerned with its functions as an organ of circulation that it may be discussed more profitably in that connection.
Ciliated Cells. — In the mammalian body the phenomenon of contractility is exhibited not only by the well-defined muscular tissue, but also by the leucocytes and especially by the cilia of the ciliated epithelium. Epithelium with motile cilia is found lining the mucous membrane of the air-passages in the trachea, larynx, bronchi, and nose, in the lacrimal duct and sac, in the genital pas- sages, uterus and Fallopian tubes and the tubules of the epididymis,
*Engelmann, "Archiv f. d. ges. Physiologie," 2, 243, 1869. Stiles, "Amer. Jour, of Physiology," 5, 338, 1901.
THE PHENOMENON OF CONTRACTION. 55
and in the Eustachian tube and part of the middle ear. Similar cells are found lining the ventricles of the brain and the central canal of the cord. The cilia in this latter position have been demon- strated to be motile in the frog, but whether this is true for the mam- mal has not been shown. So also in the neck of the uriniferous tubule ciliated cells are said to occur, but whether they are motile or not has not been demonstrated. In the internal ear and the olfactory mucous membrane the so-called sense cells are also ciliated, but here at least the cilia are probably not motile. Ordinarily each ciliated epithelial cell carries a bunch of cilia, all of which contract together, but motile protoplasmic prolongations of the cell may occur singly, as is illustrated in the spermatozoa, for instance, and in many of the protozoa and plant cells. In the lower forms of life cilia play obviously a very important role in locomotion, the capture of food, and respiration, and their form and manner of movement vary greatly. The form of movement or manner of contraction was formerly described under four heads, — the hook form, the pendular, the undulatory or wave-like, and the funnel form or infundibulary. With the exception of the spermatozoa, the cilia found in mam- mals show the first form of contraction. The little processes are contracted quickly in one direction, so as to take a hook shape, and then relax more slowly, the relaxation taking several times as long as the contraction. The whole movement is rhythmical and very rapid. The cilia of the epithelium of the frog's pharynx and esophagus, which have been the most frequently studied in the higher animals, contract, according to Engelmann, at the rate of 12 times per second. When a field of epithelium is observed under the microscope the contractions pass over it in a definite direction, but so rapidly that the eye is not able to analyze them; one obtains the impression simply of a swiftly flowing current. As the cilia begin to die, their movements become less rapid, and the nature of the contractions and their progress from cell to cell can be satisfactorily determined. In the mammalia the function of the ciliated epithelium is supposed to be entirely mechanical, — that is, they move along substances lying upon them. In the oviducts they move or help to move the ovum toward the uterus, and in this latter organ their motion is supposed to guide the spermatozoa from the uterus toward the oviducts, — that is, the resistance offered to the motile spermatozoa guides their move- ments. So in the respiratory passages foreign particles of various sorts, together with the secretion of the mucous glands, are moved toward the mouth, the effect being to free the air-passages from obstruction. The contraction and relaxation of the cilia are assumed to be phenomena of essentially the same order as those exhibited by the muscle tissue. A theory that will adequatelv
56 THE PHYSIOLOGY OF MUSCLE AND NERVE.
explain one will doubtless be applicable to the other. Many interesting facts have been established regarding ciliary move- ments. The contractions of the cilia in any given field — the trachea, for instance — follow in a definite sequence and are co- ordinated. The waves of contraction progress in a definite direction. This fact increases greatly the effectiveness of the cilia in per- forming work. Thus, in spite of their extremely minute size, it is estimated that an area of a square centimeter is capable of moving a load of 336 gms. The contractions are automatic,— that is, the stimulus causing them is not dependent upon a con- nection with the nervous system, but upon processes arising within the cell itself; the cilia of a single completely isolated cell may continue to contract vigorously. The movement may continue for several days after the death of the individual, thus again showing the physiological independence of the structure. The ciliated cells may conduct a stimulus or impulse to other cells even after its own cilia have lost their contractility. This fact is particularly significant in general physiology, as it aids in showing that the property of conductivity which is exhibited in such high degree by nerve fibers is possessed to a lower degree by other tissues. The ciliary movement is affected by variations in temperature, and if the temperature passes beyond an optimum point the cilia fall into a condition resembling heat rigor in the muscle. Their move- ments are affected also by the reaction of the medium, being at first accelerated and then slowed or destroyed by a slight degree of acidity and favored by a very slight degree of alkalinity.*
* References for physiology of ciliary movement: Verworn, "General Physiology," English translation by Lee; Putter, "Ergebnisse der Physiol- ogic," 1902, vol. ii, part n; Engelmann, article, "Gils vibratils," in Richet's " Dictionnaire de Physiologic," vol. iii, 1898.
CHAPTER II.
THE CHEMICAL COMPOSITION OF MUSCLE AND THE
CHEMICAL CHANGES OF CONTRACTION AND
OF RIGOR MORTIS,
Muscle Plasma. — The beginning of our present knowledge of the chemical composition of muscle is found in some interesting ex- periments made by Kiihne upon frog's muscle. Kiihne froze the living muscle to a hard mass, cut it into fine shavings with cold knives, and ground the pieces thoroughly in a cold mortar. The fine muscle snow thus obtained was put under high pressure and a liquid expressed which was assumed to represent the fluid living substance in the normal fiber. This muscle plasma clotted on stand- ing, much as blood does, the muscle clot shrinking and squeezing out a muscle serum. Similar experiments have since been per- formed by Halliburton* on mammalian muscle. This spontaneous clotting of the living plasma has been held to be important in showing the probable cause of death rigor.
Composition of the Muscle Plasma. — Using the term muscle plasma to designate the entire contents of the muscle fiber within the sarcolemma, it is obvious that it should contain all the con- stituents that properly belong to the muscle, in contradistinction to the substances found in the connective tissue binding the muscle fibers together.
The constituents in addition to water that are known to occur in muscle are very numerous indeed, and difficult to classify. They may be grouped under the following heads: (1) Proteins. (2) Car- bohydrates and fats. (3) Nitrogenous waste products. (4) Special substances, such as lactic acid, inosite, inosinic acid, phosphocarnic acid. (5) Pigments. (6) Ferments. (7) Inorganic salts. Very little that is positive can be stated regarding the physiological role of most of these constituents, the interest that attaches to them at present being largely on the chemical side.
The Muscle Proteins.t — The proteins of the muscle have been investigated by a number of observers, but unfortunately the
* Halliburton, "Journal of Physiology," 8, 133, 1888.
f Von Fiirth, "Archiv f. exper. Path. u. Pharmakol.," 36, 231, 1895. See also Halliburton, "Journal of Physiology," 8, 133, 1888; and Stewart and Sollman, ibid., 24, 427, 1899.
57
58 THE PHYSIOLOGY OF MUSCLE AND NERVE.
terminology employed has not been uniform, and the facts so far as they are known to us seem to be obviously incomplete. Ac- cording to von Fiirt h, two proteins may be obtained from mam- malian muscle by extracting it with dilute saline solutions, — namely, myosin and myogen, the latter existing to three or four times the amount of the former. Myosin belongs to the globulin group of proteins (see appendix); it is coagulated by heat at 44° to 50° C., it is precipitated by dialysis or by weak acids, it is easily precipi- tated from its solutions by adding an excess of neutral salts, such as sodium chlorid, magnesium or ammonium sulphate. With the last salt it is completely precipitated when the salt is added to one-half saturation or less. Its most interesting property, how- ever, is that on standing at ordinary temperatures it passes over into an insoluble modification which separates out as a sort of clot. Following the terminology used for the blood, this insoluble modification is called myosin fibrin. Myogen, the other protein, seems to fall into the group of albumins rather than globulins. It is not precipitated by dialysis and requires more than half saturation with ammonium sulphate for its complete precipitation. It is coagulated by heat at a temperature of 55° to 65° C. Solutions of myogen on standing also undergo a species of clotting, the in- soluble protein that is formed in this case being called myogen fibrin. It appears, however, that in changing to myogen fibrin the myogen passes through an intermediate stage, designated as soluble myogen fibrin, in which its temperature of heat coagulation is as low as 30° to 40° C., — the lowest temperature recorded for any protein. As was stated in the paragraph on muscle rigor, it is known that frog's muscle goes into heat rigor at about 37° to 40° C., and in accordance with this fact it is stated that this protein, soluble myogen fibrin, which is not present in mammalian muscle, occurs normally in the muscle of the frog and also of the fishes. On the basis of these facts the rigidity of death rigor is explained by as- suming that both of these proteins exist in the living muscle, and that after death they undergo a partial or complete coagulation according to the following schema:
Myosin. Myogen.
I I
Myosin fibrin. Soluble myogen fibrin.
T Myogen fibrin.
In the dead muscle we should find, therefore, the insoluble myosin fibrin and myogen fibrin, together with more or less of the original myosin and myogen. Myogen is said not to occur in the
THE CHEMISTRY OF MUSCLE. 59
muscles of the invertebrates. It should be added that after the most complete extraction with saline solutions the muscle fiber still retains much protein material, and its structural appearance, so far as cross-striation is concerned, remains unaltered. The portion of protein material thus left in the muscle fiber as a sort of skeleton framework is designated as the muscle stroma; it is not soluble in solutions of neutral salts, but dissolves readily in solutions of dilute alkalies. In striped muscle this so-called stroma forms about 9 per cent, of the weight of the muscle; while in the heart muscle it makes about 56 per cent., and in the smooth muscle, 72 per cent. It is at present uncertain whether the myosin and myogen represent the protein constituents of the contractile ele- ments of the muscle fibers or of the undifferentiated portion, the sarcoplasm. The protein of plain muscle tissue and of cardiac muscle have not received so much attention as those of voluntary muscle. It is stated, however, that the proteins extracted from these tissues by salt solutions are coagulable on standing, as in the case of the extracts of voluntary muscle. In plain muscle two proteins, in addition to some nucleoprotein, are described, one belonging to the albumin and one to the globulin class, but the identity or relationship of these proteins to those above de- scribed has not been established. In heart muscle, myosin and myogen occur in practically the same proportions as in voluntary muscle, but the amount of stroma left undissolved after treatment with saline solutions is, as stated above, much greater than in skeletal muscle.*
The Carbohydrates of Muscle. — Muscle contains a certain amount of sugar, dextrose or dextrose and isomaltose, and also under normal conditions a considerable quantity of glycogen, or so-called animal starch. The formation and the consumption of glycogen in the body constitute one of the most interesting chapters in the physiology of nutrition, and the relations of glycogen will be treated more fully under that head. It may be stated here, however, that the muscular tissue has the power of converting the sugar brought to it by the blood into glycogen. This glycogenetic action of the muscle is represented in principle by the reaction
C6H1208 — H20 = C?H1005.
Dextrose. Glycogen.
The glycogen thus formed is stored in the muscle and forms a constant constituent of well-nourished muscle in the resting condition, the amount varying between 0.5 and 0.9 per cent, of the weight of the muscle. The glycogen thus stored in the muscle
* Vincent and Lewis, " Journal of Physiology," 26, 445, 1901 ; also " Zeit- schrift f. physiolog. Chemie," 34, 417, 1901-2 ; Stewart and Sollman, loc. rit.; Saxl, " Hofmeister's Beitriige," 1906, ix., 1.
60 THE PHYSIOLOGY OF MUSCLE AND NERVE.
is consumed by the tissue during its activity, and it is assumed that before it is thus consumed it is converted back into sugar by the action of an amylolytic enzyme contained in the muscle. The glycogen, therefore, itself represents a local deposit of carbohydrate nutritive material, resembling in this respect the fat. The sugar and the glycogen must be considered as one from the standpoint of the nutrition of the muscle. During muscular activity the store of glycogen is used up, and if the activity is sufficiently pro- longed it may be made to disappear entirely. Among the many uncertain and contradictory statements regarding the chemical changes in active muscle, this fact stands out in pleasant contrast as one that is satisfactorily demonstrated.
Phosphocarnic Acid (Nucleon). — A peculiar substance containing phos- phorus was discovered by Siegfried in the muscle extracts.* This substance seems to resemble the proteins, but has a complex and peculiar structure, as is shown by its split products when hydrolyzed by boiling with baryta water. Under these conditions there are formed carbon dioxid, phosphoric acid,, a carbohydrate body, succinic and lactic acids, and a crystallizable nitrogen- ous acid body which is designated as carnic acid (C10H15N5O3). Siegfried assumes that this latter substance is identical with one of the peptones (antipeptone) formed during digestion, and conceives, therefore, that his phosphocarnic acid is a complex substance built up from a peptone and a phosphorus-containing compound. Compounds of simple proteins with phosphorus-containing bodies (nucleic acids) are designated usually as nucleins ; for this compound of a peptone with a phosphorus-containing com- plex Siegfried suggests the name of nucleon. By the addition of ferric chlorid the nucleon is precipitated readily from muscle extracts as an iron compound, carniferrin, and under this name has come into the market as a presumably efficient therapeutic preparation of iron. The discoverer of nucleon has attributed to it a very great physiological importance, as a source of energy to t>he muscle, and as an efficient means of transportation of iron, calcium, potassium, and magnesium into the muscle substance, particularly in such articles of diet as soups, bouillons, meat extracts, etc. It must be stated, however, that there still remains doubt as to the chemical individuality of the nucleon or the nucleons, their existence in normal muscle, and their physiological role. The substance, whether a well-defined chemical individual or not, is most interesting. Its properties are such as would aid in explaining the occurrence of some of the known products of the chemical changes during contraction; but obviously further investigation is still needed before such an application can be made with confidence.
Lactic Acid (CHH6O3). — Lactic acid is found in varying amounts in the extracts of muscle. The acid that is obtained is the so-called ethidene lactic acid or «-hydroxypropionic acid (CH3CHOHOOOH), and differs from the lactic acid found in sour milk in that it ro- tates the plane of polarized light to the right. The lactic acid in sour milk is produced by bacterial fermentation, and is inactive to- polarized light, because it exists in racemic form ; that is, it con- sists of equal amounts of the right-handed form which turns the plane of polarization to the right and of the left-handed form which turns it to the left. In the muscle the right-handed form
* Siegfried, " Zeitschrift f. physiol. Chemie," 21, 360, 1896 ; also 28, 524, 1899.
THE CHEMISTRY OF MUSCLE. 61
is found mainly or only, and this form therefore is frequently designated as sarcolactic (or paralactic) acid.
The Nitrogenous Extractives (Nitrogenous Wastes).—- Muscle extracts contain numerous crystallizable nitrogenous sub- stances which are regarded as the end-products of the disassimila- tion or catabolism of the living protein material of the muscle. The number of these substances that have been found in traces or weighable quantities is rather large. They have aroused great interest because their structure throws some light on the nature of protein catabolism. The one that occurs in largest amount is creatin, C4H9N302, or methyl-guanidin-acetic acid, NHCNH2NCH3- CH2COOH. Creatin may be present in amounts equal to 0.3 per cent, of the weight of the muscle. It is supposed to be given off to the blood and eventually excreted in the urine as creatinin (C4H-N30), which is formed from creatin by the loss of a molecule of water (seep. 780). The creatinin itself may occur in the muscle in small quantities. In addition there is a group of bodies supposed to represent the end-products of the breaking up of the nucleins of the muscle, all of which belong to the so-called purin bases. These are : Uric acid (C5H4N4O3), xanthin (C5H4N4O2), hypoxanthin (C5H4N4O), guanin (C5H5N5O), adenin (C5H5N5), and carnin (C7H8- N4O3). They will be referred to more fully in the section on Nutri- tion. Still other bodies of similar physiological significance have been described from time to time. These nitrogenous products are found in the various meat extracts and meat juices used in dietetics. While they possess no direct nutritive value, it seems probable (see chapter on Gastric Digestion) that they may be very effective indirectly by stimulating the secretion of the gastric glands.
Pigments. — The red color of many muscles is believed to be due to the presence of a special pigment which resembles in its structure and its properties the hemoglobin of the red blood corpuscles, and perhaps is identical with it. This pigment is known as myohematin or myochrome. It belongs presumably to the group of so-called respiratory pigments, which have the property of holding oxygen in loose combination, and by virtue of this property it takes part in the absorption of oxygen by the muscular tissue.
Enzymes. — A number of unorganized ferments or enzymes have been described by one observer or another. In this tissue as in others the processes of nutrition seem to be connected with the development of special enzymes. A proteolytic enzyme capable of digesting proteins has been described by Brucke and others; an amylolytic enzyme capable of converting the glycogen to sugar by Nasse ; a glycolytic enzyme capable of destroying the sugars by Brunto'n, Cohnheim, and others ; a lipase capable of splitting
62 THE PHYSIOLOGY OF MUSCLE AND NERVE.
the fats by Kastle and Loevenhart; and, finally, a coagulating enzyme responsible for the coagulation of the muscle plasma after death by Halliburton.
The Inorganic Constituents. — Muscle tissue contains a number of salts, chiefly in the form of the chlorids, sulphates, and phos- phates of sodium, potassium, calcium, magnesium, and iron. As in other tissues, the potassium salts predominate in the tissue itself. These inorganic constituents are most important to the normal activity of the muscle, and, indeed, in two ways: first, in that they maintain a normal osmotic pressure within the substance of the fibers and thus control the exchange of water with the sur- rounding lymph and blood; second, in that they are necessary to the normal structure and irritability of the living muscular tissue. Serious variations in the relative amounts of these salts cause marked changes in the properties of the tissues, as is ex- plained in the section on nutrition, in which the general nutritive importance of the salts is discussed, and also in connection with the cause of the rhythmical activity of the heart.
Chemical Changes in the Muscle during Contraction and Rigor. — Perhaps the most significant change in the muscle during contraction is the production of carbon dicxid. After increased muscular activity it may be shown that an animal gives off a larger amount of carbon dioxid in its expired air. In such cases the carbon dioxid produced in the muscles is given off to the blood, carried to the lungs, and then exhaled in the expired air. Pettenkofer and Voit, for instance, found that during a day in which much muscular work was done a man expired nearly twice as much CO2 as during a resting day. The same fact can be shown directly upon an isolated muscle of a frog made to con- tract by electrical stimulation. The carbon dioxid in this case diffuses out of the muscle in part to the surrounding air, and in part remains in solution, or in chemical combination as car- bonates, in the liquids of the tissue. It has been shown by Hermann* and others that a muscle that has been tetanized gives off more carbon dioxid than a resting muscle when their contained gases are extracted by a gas pump. This CO2 arises from the oxidation of the carbon of some of the constituents of the muscle, and its existence is an indication that in their final products the changes in the muscle are equivalent in those of ordinary combus- tion at high temperatures, the burning of wood or fats, for instance. Moreover, the formation of the CO2 in the muscle is accompanied by the production of heat, as in combustion; and for the same amount of CO2 produced in the two cases the same amount of heat
* Hermann, " Untersuchungen iiber den Stoffwechsel der Muskeln, etc.," Berlin, 1867.
THE CHEMISTRY OF MUSCLE. 63
is liberated. It has been shown, however, in the frog's muscle freshly removed from the body, that the CO2 is produced whether or not any oxygen is supplied to the muscle, — that is, when the muscle is made to contract in an atmosphere containing no oxygen, or in a vacuum. In this respect the parallel between physiological oxidation and ordinary combustion fails. Wood, oil, and other combustible material cannot be burnt at high temperatures in the absence of oxygen. We must believe, therefore, that in the muscle there is a supply of stored oxygen, and that the muscle will give off CO2 as long as 'this supply lasts. The oxidation, instead of being direct, as in the case of combustions, is indirect. The views regarding the nature of the oxidations in the body are treated in the section on Nutrition.
The oxygen is absolutely necessary to the normal activity of the muscular tissue, but the tissue, by storing the oxygen, can function for some time when the supply is suspended. As Pfliiger has expressed it, in a most interesting paper,* the oxygen is like the spring to a clock : once wound up, the clock will go for a cer- tain time without further winding. It must be borne in mind, however, that different tissues show considerable variation in the time during which they will function normally after suspension of their oxygen supply. The cortex of the brain, for instance, loses its activity, — that is, unconsciousness ensues almost imme- diately upon cessation or serious diminution in the supply of blood, and the same may be said of the functional activity of the kidney. In the cold-blooded animals, with their slower chemical changes, the supply of stored oxygen maintains irritability for a longer time than in the warm-blooded animals.
Disappearance of the Gli/cogen. — An equally positive chemical change in the muscle during contraction is the disappearance of its contained glycogen. Satisfactory proof has been furnished that the amount of glycogen in a muscle disappears more or less in proportion to the extent and duration of the contractions, and that after pro- longed muscular activity, especially in the starving animal, the supply may be exhausted entirely. In what way the glycogen is consumed is not completely known; the matter is discussed in the section on Nutrition. The most probable view is that the glycogen is first converted to sugar (dextrose) by the action of an amylolytic enzyme, and the sugar in turn is destroyed by the serial action of several enzymes. The first step, probably, is a conversion to lactic acid (C6H12O. == 2C3H6O3), and the lactic acid then undergoes oxidation, with the production of CO2 and H2O, under the influence of an oxidizing enzyme, either directly or after conversion to still lower members of the fatty acid series (acetic or formic acid). *Pfliiger, "Archiv f. die gesammte Physiologic," 10, 251, 1875.
64 THE PHYSIOLOGY OF MUSCLE AND NERVE.
It is in the last step, that of oxidation, that the heat energy is given off. The fact that the glycogen disappears as a result of the con- tractions does not mean necessarily that this substance or the sugar into which it is converted is absolutely necessary for the chemical changes of contraction. It is stated that the muscle will continue to contract after all its glycogen is used up * ; still it must be borne in mind that the using up of the local store of glycogen does not mean that all the sugar supply of the body is consumed. After the most prolonged starvation the blood contains its normal ;supply of sugar, and we can only suppose that this sugar comes from the material of the body itself, probably from its proteins, and it remains quite possible that a constant supply of sugar from some source is necessary to the chemical changes that occur in normal contractions.
The Formation of Lactic Acid. — The lactic acid that is present in the muscle is believed to be increased in quantity by muscular activity. Attention was first called to this point by du Bois- Reymond, who showed that the reaction of the tetanized muscle is distinctly, acid, while that of the resting muscle is neutral or islightly alkaline. This fact can be demonstrated by the use of litmus paper, but perhaps more strikingly by the use of acid fuchsin.| If a solution of acid fuchsin is injected under the skin of a frog it is gradually absorbed and distributed to the body without injuring the tissues. In the normal media of the body this solution remains colorless or nearly so. If now one of the legs is tetanized the muscles take on a red color, showing that an acid is produced locally. The supposition generally made is that the acidity during activity is due to an increased production of sarcolactic acid. Experiments have been made by a number of observers to determine quantita- tively the amount of lactic acid in the resting and the worked muscle respectively. Several have stated that the amount is act- ually less in the worked muscle; others have found an increase. J The balance of evidence seems to show that there is an increased production, but that this increase may be obscured in the living animal by the fact that the acid is removed by the circulating blood. In accordance with this view we find that the so-called titration-alkalinity of the blood may be decreased after muscular activity, and some observers have shown that the lactates in the blood are correspondingly increased. That lactic acid is produced in the living muscle is shown by experiments § in which blood was transfused for several hours through the legs of a freshly killed ;animal. In such cases the amount of lactic acid in the blood was
* Jensen, " Zeitschrift f. physiol. Chemie," 35, 525.
fDreser, " Centralblatt fur Physiologic," 1, 195, 1887.
JWerther, " Pfluger's Archiv," 46, 63, 1890.
% Berlinerblau, "Archiv. f. exp. Path. u. Pharm.," 23, 333, 1887.
THE CHEMISTRY OF MUSCLE. 65
distinctly increased. We must believe, therefore, that lactic acid is a constant product of the chemical changes of nutrition going on in the muscle, and that its production is increased by the greater chemical activity which occurs during visible contraction. Normally we must suppose that this lactic acid, as stated above, undergoes oxidation with the production of heat, and this oxidation takes place in the muscle itself. When the production is rapid or ex- cessive some may be carried off by the blood and be oxidized else- where or even be excreted in the urine as a lactate. The increased acidity of the muscl^ during activity, especially when the circulation is interrupted, is referable, in the long run, to this greater production of lactic acid; but as the acid after its formation probably reacts with the alkaline salts present it is frequently stated that the actual acidity shown to litmus or other indicator is due to acid salts produced by reaction with lactic acid, presumably the acid phosphate of potassium (KH2PO4).
Much interest has been shown in the question of the origin of the lactic acid. According to some observers, it arises from the carbohydrates in the muscle, the glycogen or the sugar. In support of this view it has been claimed that in contraction and especially in rigor mortis the glycogen disappears as the lactic acid increases. This relationship, however, is denied, as far as rigor mortis is con- cerned, by competent observers*. Chemical studies, however, upon the action of the enzymes contained in muscle tend strongly to support the view that normally the glycogen after conversion to sugar is split first into lactic acid before undergoing oxidation (consult section on Nutrition, p. 824). Another suggestion is that the lactic acid arises from the phosphocarnic acid described above. This compound, when split by hydrolysis, yields lactic acid; so that if we could obtain convincing proof that such a compound exists in living muscle it would serve very well to explain the production of lactic acid. From experiments made upon general nutrition it has been shown that in birds the uric acid in the urine is replaced largely by lactic acid (ammomium lactate) when the liver is excised. Under these conditions the quantity of lactic acid secreted varies with the albumin destroyed in the body, and some physiologists are of the opinion that the lactic acid produced in the muscle or in other tissues is derived from the breaking down of the living protein material. A decisive answer to this problem is not possible at present, but it may be said perhaps that the trend of modern work tends to support the view that lactic acid constitutes what is called an intermediary product in the metabolism of the sugar (glycogen) of the muscle.
*B6hm, "Pfliiger's Archiv f. d. gesammte Physiologic," 23, 44, 1880. 5
66 THE PHYSIOLOGY OF MUSCLE AND NERVE.
The Formation of Creatin. — Great in constitutes the chief nitrog- enous waste product in the muscle, and we should expect that the greater metabolism during activity would result in an increase in the creatin. Some observers state positively that the creatin is increased during contraction.
Chemical Changes during Rigor Mortis. — The chemical changes during rigor have been referred to above, but may be summarized here in brief form :
1. There is a coagulation of the protein material of the muscle plasma, which at present may be explained by supposing that the contained myosin and myogen, spontaneously, or under the action of an enzyme, pass into their insoluble forms, — namely, myosin fibrin and myogen fibrin.
2. There is an increased acidity, due doubtless to a production of lactic acid.
3. There is a production of CO2. Hermann, in his original ex- periments, asserts that in rigor there is, so to speak, a maximal production of CO2, — that is, all of the material in the muscle capable of yielding CO2 is broken down during rigor. The amount of CO2 given off, therefore, by a resting muscle when it goes into rigor is greater than in the case of a worked muscle, since in the latter some of the material capable of yielding CO2 has been used up during contraction.
4. The consumption of glycogen. According to some observers, glycogen disappears during rigor as it does during contraction; but others find that the amount is not changed during this process, As the glycogen after death is converted to sugar with some rapidity it is possible that the disappearance noted by the former observers! was not due to the rigor process, but to post-mortem fermentation-.*
The Relation of the Chemical Changes during Contraction to Fatigue; Chemical Theory of Fatigue. — As we have seen, a muscle kept in continuous contraction soon shows fatigue ; it relaxes more and more until, in spite of constant stimulation, it becomes completely unirritable. We may define fatigue, there- fore, as a more or less complete loss of irritability and contractility brought on by functional activity. But even when the fatigue is complete and the muscle fails to respond at all to maximal stimulation, a very short interval of rest is sufficient to bring about some return of irritability. For a complete restoration to its normal condition a long interval of time may be necessary. If the muscle is isolated from the body and thus deprived of its cir- culation, the recovery from fatigue is less rapid and less complete than under normal conditions. In such an isolated muscle, more-
* Kisch, Hofmeister's "Beitrage zur chem. Physiol. u. Pathol./' viii., 210, 1906.
THE CHEMISTRY OF MUSCLE. 67
over, if provision is made to irrigate its blood-vessels with a solution of physiological saline (NaCl, 0.7 per cent.) the recovery from fatigue is hastened. These facts seem to indicate clearly that fatigue is not due to a complete consumption of the material in the muscle that supplies the energy for the contractions. In other words, fatigue as it usually presents itself to us in life or under experi- mental conditions is a phenomenon different from exhaustion. Ranke,* who made the first complete study of this subject, was convinced that a muscle when ,tetanized to the point of complete fatigue consumes only a fraction of the oxidizable or energy-yielding material contained in its substance. He believed that there exists in the fatigued muscle a something brought into existence by the contraction itself, which retards or prevents further physiological oxidation. In support of this view he found that if an extract was made from the fatigued muscles of one frog and injected into the circulation of a second frog, the muscles of this latter animal gave evidence of fatigue, — that is, they showed diminished power of contraction upon stimulation. A similar experiment made with an extract from resting muscle gave no such effect. Investigation of the separate products formed in a muscle during contraction demonstrate that the sarcolactic acid, acid potassium phosphate, and carbon dioxid are apparently responsible for this effect. | According to these experiments, the accumulation of these products is responsible for the appearance of fatigue; the muscle's own metabolic products, therefore, serve to limit its responsiveness to stimulation, and thus form a protective mechanism that saves it from complete exhaustion. Under normal conditions these prod- ucts are quickly removed by the blood or, in the case of the lactic acid, destroyed by oxidation. It should be added that Lee has published experiments which indicate that the first effect of these so-called fatigue substances is to increase the irritability of the muscle, while the later effect is to diminish the irritability or to suppress it altogether. In this initial favoring influence Lee finds an explanation of the phenomenon of Treppe (see p. 33). This chemical theory of fatigue does not, however, explain all the phenomena, particularly the after-results. As was stated in describ- ing the experiments made with the ergograph, a very short rest suffices to make the muscle again capable of lifting its load, but a very long interval of rest, two hours, may be required before the muscle is restored entirely to its normal condition. Such a long interval is evidently not necessary for the removal of the metabolic products, and we must recognize that a part of the fatigue is due to a
*Ranke, "Tetanus," Leipzig, 1865.
f For discussion and experiments, see Lee ; Harvey Lectures, 1905-06, Philadelphia, 1906; also Journal of the American Medical Association, May 19, 1906, and American Journal of Physiology, xviii., 267, 1907.
68 THE PHYSIOLOGY OF MUSCLE AND NERVE.
using up of the material from which the energy is obtained. That is, during contraction the processes of disassimilation or catabolism are in excess of those of assimilation or anabolism, so that at the end of prolonged muscular activity the muscle contains a diminished supply of oxidizable or energy-yielding material. To supply this deficiency new food material, including under this term also the necessary oxygen,* must be assimilated by the muscle. We must suppose, therefore, that two factors, accumulation of the products of metabolism and exhaustion of energy-yielding material, co- operate to produce the conditions actually observed; but the former of these, the formation of metabolic products, seems to be the protective mechanism that is especially adapted to save the muscle from complete exhaustion. In what way these products depress the irritability and contractility of the muscles is not known; their presence may, as Ranke supposed, prevent the underlying chemical changes, the so-called physiological oxidations, or their action may be exerted on the contractile machinery alone, — that is, the mechanism by means of which the shortening is effected.
Theories of Muscle Contraction. — It is universally admitted that the ultimate cause of the muscle contraction is the chemical change caused by the stimulus. While the nature of this chemical reaction is not known, it is admitted also that it consists in a process of splitting and oxidation whereby large and relatively unstable molecules are reduced to smaller and more stable ones, such as H2O and the CO2 and lactic acid which we recognize among the products. This reaction is exothermic,— that is, some of the chemical or internal energy of the complex compound is liberated as heat. Both of these results are so frequently observed in other chemical reactions that they call for no special comment in this case. The particular problem regarding the muscle is how this chemical reaction leads to the shortening of the muscle and thereby makes it do mechanical work. We must assume that there is some mechanism in the muscle by means of which the energy liberated during the chemical change is utilized in causing movement, some- what in the same way as the heat energy developed in a gas-engine is converted by a mechanism into mechanical movement, or the electrical energy in the coils of a motor is utilized by a device to develop movement. Regarding the means used in the muscle to transform the original chemical or internal energy to mechanical movement we have no or very little positive knowledge. Numer- ous theories of a more or less speculative character have been pro- posed. It has been suggested (Weber) that the muscular force is essentially due to the elasticity of the muscle. It is known that the elasticity of substances may change with conditions, and it is * Verworn, "Archiv f. Physiologie, " 1900, suppl. volume, p. 152.
THE CHEMISTRY OF MUSCLE.
69
assumed that after stimulation the physical condition of the muscle is changed and that the increased elastic attraction between the particles gives it the form of the contracted muscle. According to others (Fick), the mechanical contraction is a direct result of an increased chemical affinity, while others (Miiller) find an ex- planation in supposed electrical charges upon the doubly refractive particles of the muscle in consequence of which there are developed electrical attractions and repulsions at the different poles. The most specific and comprehensible hypothesis advanced is that formulated by Engelmann.* This author has shown that all con- tractile tissues contain doubly refractive particles, that in the striped muscle fiber these par- ticles are arranged in discs, — the dim bands, — with the singly refracting material form- ing the light bands on either side. During contraction it has been shown that the material of this latter structure is ab- sorbed by the doubly refractive substance. Engelmann has shown, moreover, that dead substances, which contain doubly refractive particles, such as catgut, when soaked with water will shorten upon heating and relax again upon cooling. His explanation of
f
I
Fig. 26. — Engelmann's artificial muscle. The artificial muscle is represented by the catgut string, m. This is surrounded by a coil of platinum wire, w, through which an electrical current may be sent. The catgut is attached to a lever, h, whose fulcrum is at c. The catgut is immersed in a beaker of water at 50° to 55° C., and "stimulated" by the sudden increase in temperature caused by the passage of a current through the coil. — (After Engelmann.)
the mechanics of contraction in brief is that the chemical change brought about in the muscle liberates heat, and that the effect of this heat upon the adjacent doubly refractive par- ticles is to make them imbibe the surrounding water. If we
further suppose that these particles in the resting muscle are linear or prismatic in shape, then upon imbibing water they will tend to become spherical, causing thus a shortening in the long diameter and an increase in the cross diameter. The muscle, in other words, is an apparatus comparable, let us say, to a gas engine : each stimulus, like a spark, causes the physiological oxidation of a portion
* Ens;elmann, "Ueber den Ursprung der Muskelkraft," Leipzig, 1893; see also " Pfluger's Archiv," 7, 155, 1873.
70 THE PHYSIOLOGY OF MUSCLE AND NERVE.
of the usable material in the muscle, and the heat thus produced acts upon the doubly refractive material as upon a piece of machin- ery and causes it to shorten by imbibition. Contraction, in a word, is a phenomenon of thermic imbibition. Engelmann has given an appearance of verisimilitude to this hypothesis by constructing an artificial muscle from a piece of violin string. The apparatus used is illustrated in Fig. 26. A catgut string (ra) is surrounded by a coil of platinum wire (w) through which an electrical current may be sent. The object of this arrangement is to heat the catgut suddenly. The platinum coil should not actually touch the catgut. The catgut is attached to a lever, as shown in the figure. The
Fig. 27. — Curve of simple contraction obtained from an artificial muscle. The dura- tion of the stimulus (heating effect caused by the current) is shown by the break in the line beneath the curve.
catgut is thoroughly soaked by immersing it in a beaker of water and the temperature is then raised to 50° to 55° C. If then a current is turned into the coil the slight but somewhat rapid heating of the catgut will cause it to shorten, owing to the imbibition of more water. When the current is broken the catgut cools and relaxes slowly. Records may be obtained in this way which are altogether similar or identical with those given by a strip of plain muscle when stimulated (see Figs. 27 and 28). The model may be used to show the effect of temperature upon the extent and dur^ tion of the contractions, the effect of variations in strength of
THE CHEMISTRY OF MUSCLE. 71
stimulus as expressed in the amount of current used, the summation
Fig. 28. — Imitation of incomplete tetanus by the artificial muscle. The time and duration of the successive heatings are indicated by the breaks in the lower line. Each such heating causes a separate contraction, and these contractions are summated as in the tetanic contraction of muscle.
of successive stimuli, etc. Under all of these conditions it imitates closely the behavior of plain muscular tissue.
CHAPTER III.
THE PHENOMENON OF CONDUCTION— PROPERTIES OF THE NERVE FIBER.
Conduction. — When living matter is excited or stimulated in any way the excitation is not localized to the point acted upon, but is or may be propagated throughout its substance. This prop- erty of conducting a change that has been initiated by a stimulus applied locally is a general property of protoplasm, and is exhib- ited in a striking way by many of the simplest forms of life. A light touch, for instance, applied to a vorticella will cause a retrac- tion of its vibrating cilia and a shortening of its stalk. In the most specialized animals, such as the mammalia, this property of con- duction finds its greatest development in the nervous tissue, and indeed, especially in the axis cylinder processes of the nerve cells, the so-called nerve fibers. But the property is exhibited also to- a greater or less extent by other tissues. When a muscular mass is stimulated at one point the excitation set up may be propagated not only through the substance of the cells or fibers directly affected, but from cell to cell for a considerable distance. In the heart tissue and in plain muscle it has been shown that a change of this sort may be conducted independently of the phenomenon of visible contraction. A stimulus applied to the venous end of a frog's heart, for instance, may, under certain conditions, be conducted through the auricular tissue without causing in it 'a visible change, and yet arouse a contraction in the ventricular muscle (Engelmann). The change thus conducted may be spoken of as a muscle impulse. Under normal conditions a muscle fiber is stimulated through its motor nerve fiber at some point near the middle of its course, but the stimulus thus applied must be con- ceived as arousing a muscle impulse that travels over the length of the muscle fiber and precedes the change of contraction. Similarly it can be shown that ciliary cells can convey an impulse from cell to cell. A stimulus applied to one point of a field of ciliary epi- thelium may set up a change that is conveyed as a ciliary impulse to distant cells. The universality of this property of conduction in the simpler, less differentiated forms of life, and its presence in some form in many of the tissues of the higher forms would justify the assumption that the underlying change is essentially the same in all cases. But in nerve fibers this property has become special-
72
THE PHENOMENON OF CONDUCTION. 73
ized to the highest degree, and in this tissue it may be studied therefore with the greatest success and profit.
Structure of the Nerve Fiber. — The peripheral nerve fiber, as we find it in the nerve trunks and nerve plexuses of the body, may be either medulla ted or non-medullated. All the nerve fibers that arise histologically from the nerve cells of the central nervous system proper — that is, the brain and cord and the outlying sensory ganglia of the cranial nerves and the posterior spinal roots— are medullated. These fibers contain a central core, the axis cylinder, which is usually regarded as an enormously elongated process of the nerve cell with which it is connected. The axis cylinder shows a differentiation into fibrils (neurofibrils) and interfibrillar sub- stance (neuroplasm). All of our evidence goes to show that the axis cylinder is the essential part of the nerve fiber so far as its property of conduction is concerned. It is further assumed that the neurofibrils in the axis cylinder form the conducting mech- anism rather than the interfibrillar substance. Surrounding the axis cylinder we have the medullary or myelin sheath, varying much in thickness in different fibers. This sheath is composed of peculiar material and is interrupted or divided into segments at cer- tain intervals, the so-called nodes of Ranvier. Outside the myelin there is a delicate elastic sheath comparable to the sarcolemma of the muscle fiber and designated as the neurilemma. Lying under the neurilemma are found nuclei, one for each internodal segment of the myelin, surrounded by a small amount of granular proto- plasm. The non-medullated fibers have no myelin sheath. They are to be considered as an axis cylinder process from a nerve cell, surrounded by or inclosed in a neurilemmal sheath. These fibers arise histologically from the nerve cells found in the outlying ganglia of the body, the ganglia of the sympathetic system and its appendages.
The Function of the Myelin Sheath. — The myelin sheath of the cerebrospinal nerve fibers is a structure that is interesting and peculiar, both as regards its origin and its composition. Much speculation has been indulged in with regard to its function, but practically nothing that is certain can be said upon this point. It has been supposed by some to act as a sort of insulator, preventing contact between neighboring axis cylinders and thus insuring better conduction. But against this view it may be urged that we have no proof that the non-medullated fibers do not conduct equally as well. The view has some probability to it, however, for we must remember that the non-medullated fibers do not run in large nerve trunks that supply a number of different organs, and therefore in them a provision for isolated conduction is not so necessary. Moreover, in the medullated fibers the myelin sheath
74 THE PHYSIOLOGY OF MUSCLE AND NERVE.
is lost toward its peripheral end after the nerve has entered the tissue to which it is to be distributed, indicating that its function is then no longer necessary. According to the older conceptions of the process of conduction in nerve fibers, not only anatomical but also physiological continuity is necessary. Mere contact of living axis cylinders would not enable the nerve impulse to pass from one to the other. The newer views, included in the so-called neuron theory, assume that mere contact of living, entirely normal nerve substance does permit an excitatory change to pass from one to the other. So that it is not impossible that the myelin sheath may serve to prevent one axis cylinder from influencing the neighboring axis cylinders in a nerve trunk. Others have supposed that the myelin sheath serves as a source of nutrition to the inclosed axis cylinder, or as a regulator in some way of its metabolism. No fact is reported that would make this suggestion seem probable. In general, it is found that the myelin sheath is larger in those fibers that have the longest course; the size of the sheath, in fact, in- creases with that of the axis cylinder. It is known also that the medullated fibers in general are more irritable to artificial stimuli than the non-medullated ones, and that when induction shocks are employed the non-medullated fibers lose their irritability more rapidly at the point stimulated. None of these facts are sufficient, however, to indicate the probable function of the myelin. The embryological development of the sheath also fails to throw light on its physiological significance. For, while it is usually supposed that the axis cylinder itself is simply an outgrowth from the nerve cell, and the myelin sheath arises from separate mesoblastic cells which surround the axis cylinder, this view, so far as the myelin is con- cerned, is not beyond question, and the study of the process of regeneration of nerve fibers indicates that the actual production of myelin is controlled in some way by the functional axis cylinder. The axis cylinder outgrowths from the sympathetic nerve cells found in the ganglia of the sympathetic chain and in the peripheral ganglia generally of the body are usually non-medullated, although apparently this is not an invariable rule. In the birds all such fibers, on the contrary, are medullated. (Langley.*) Nothing is known as to the conditions that determine whether a nerve fiber process shall or shall not be surrounded by a myelin sheath.
Union of Nerve Fibers into Nerves or Nerve Trunks. — The assembling of nerve fibers into larger or smaller nerve trunks resem- bles histoiogically the combination of muscle fibers to form a muscle. Physiologically, however, there is no similarity. The various fibers in a muscle act together in a co-ordinated way as a physio- logical unit. On the other hand, the hundreds or thousands of * Langley, "Journal of Physiology," 30, 221, 1903; 20, 55, 1890.
THE PHENOMENON OF CONDUCTION. 75
nerve fibers found in a nerve may form groups which are entirely independent in their physiological activity. In the vagus nerve, for instance, we have nerve fibers running side by side, some of which supply the heart, some the muscles of the larynx, some the muscles of the stomach or intestines, some the glands of the stom- ach or pancreas, and so on. Nerves are, therefore, anatomical units simply, containing groups of fibers which have very different activities and which may function entirely independently of one another. 9
Afferent and Efferent Nerve Fibers. — The older physiologists believed that one and the same nerve or nerve fiber might conduct sensory impulses toward the central nervous system or motor im- pulses from the central nervous system to the periphery. Bell and Magendie succeeded in establishing the great truth that a nerve fiber cannot be both motor and sensory. Since their time it has been recognized that we must divide the nerve fibers connected with the central nervous system into two great groups : the efferent fibers, which carry impulses outwardly from the nervous system to the peripheral tissues, and the afferent fibers, which carry their impulses inwardly, — that is, from the peripheral tissues to the nerve centers. Under normal conditions the afferent fibers are stimulated only at their endings in the peripheral tissues, in the skin, the mucous membranes, the sense organs, etc., while the efferent fibers are stimulated only at their central origin, — that is, through the nerve cells from which they spring. The difference in the direction of conduction depends, therefore, on the anatomical fact that the efferent fibers have a stimulating mechanism at their central ends only, while the afferent fibers are adapted only for stimulation at their peripheral ends.
Classification of Nerve Fibers. — In addition to this funda- mental separation we may subdivide peripheral nerve fibers into smaller groups, making use of either anatomical or physiological differences upon which to base a classification. For the purpose here in view a classification that is physiological as far as possible seems preferable. In the first place, experimental physiology has shown that the effect of the impulse conveyed by nerve fibers may be either exciting or inhibiting. That is, the tissue or the cell to which the impulse is carried may be thereby stimulated to ac- tivity, in which case the effect is excitatory, or, on the contrary, it may, if already in activity, be reduced to a condition of rest or lessened activity; the effect in this case is inhibitory. Many physiologists believe that one and the same nerve fiber may carry excitatory or inhibitory impulses, but in some cases at least we have positive proof that these functions are discharged by separate fibers. We may subdivide both the afferent and the efferent sys- tems into excitatory and inhibitory fibers. Each of these sub-
76
THE PHYSIOLOGY OF MUSCLE AND NERVE.
groups again falls into smaller divisions according to the kind of activity it excites or inhibits. In the efferent system, for instance, the excitatory fibers may cause contraction or motion if they ter- minate in muscular tissue, or secretion if they terminate in glandu- lar tissue. For convenience of description each of the groups in turn may be further classified according to the kind of muscle in which it ends or the kind of glandular tissue. In the motor group we speak of vasomotor fibers in reference to those that end in the plain muscle of the walls of the blood-vessels; visceromotor fibers, those ending in the muscular tissue of the abdominal and thoracic viscera; pilomotor fibers, those ending in the muscles attached to the hair follicles. The classification that is suggested in tabular form below depends, therefore, on three principles: first, the direc- tion in which the impulse travels normally; second, whether this impulse excites or inhibits; third, the kind of action excited or inhibited, which in turn depends upon the kind of tissue in which the fibers end.
Efferent
Afferent
Excitatory
Inhibitory
Excitatory
Inhibitory j
Motor
Secretory
Inhibito-mo- tor
In hibi to-se- cretory
Sensory
Reflex
Inhibito-re- flex
(Motor. Vasomotor. Cardioinotor. Visceromotor. Pilomotor. ( Salivary. J Gastric. ) Pancreatic. <• Sweat.
f Subdivisions corresponding to the varieties of mo- ( tor fibers above.
\ Subdivisions corresponding to the varieties of se- 1 cretory fibers above. V Visual. Auditory. Olfactory. Gustatory. Pressu re. Temperature. Pain. Hunger. Thirst, etc.
According to the efferent fibers affected. Inhibitory effects upon the conscious sensations are
not demonstrated.
The reflex fibers that cause unconscious reflexes are known to be inhibited in some cases at least.
That the final action of a peripheral nerve fiber is determined by the tissue in which it ends rather than by the nature of the nerve fiber itself or the nature of the impulse that it carries is indi- cated strongly by the regeneration experiments made by Langley.* For instance, the chorda tympani nerve contains fibers which cause a dilatation in the blood-vessels of the submaxillary gland, while the cervical sympathetic contains fibers which cause a constriction of the vessels in the same gland. If the lingual nerve (containing the chorda tympani fibers) is divided and the central end sutured
* Langley, "Journal of Physiology," 23, 240, 1898; ibid., 30, 439, 1904; "Proceedings Royal Society," 73, 1904.
THE PHENOMENON OF CONDUCTION. 77
to the peripheral end of the severed cervical sympathetic, the chorda fibers will grow along the paths of the old constrictor fibers of the sympathetic. If time is given for regeneration to take place, stimulation of the chorda now causes a constriction in the vessels. The experiment can also be reversed. That is, by suturing the central end of the cervical sympathetic to the peripheral end of the divided lingual the fibers of the former grow along the paths of the old dilator fibers, and after regeneration has taken place stimulation of the sympathetic causes dilatation of the blood- vessels in the gland. These results are particularly instructive, as vasoconstriction is an example of the excitatory effect of the nerve impulse, being the result of a contraction of the circular muscles in the vessels, while vasodilatation is an example of inhibitory action, being due to an inhibition of the contraction of the same muscles. Yet obviously these two opposite effects are determined not by the nature of the nerve fibers, but by their place or mode of ending in the gland.
Separation of the Afferent and Efferent Fibers in the Roots of the Spinal Nerves. — According to the Bell-Magendie discovery, the motor fibers to the voluntary muscles emerge from the spinal cord in the anterior roots, while the fibers that give rise to sensa- tions enter the cord through the posterior roots. These facts have been demonstrated beyond all doubt. Magendie discovered an apparent exception in the phenomenon of recurrent sensibility. When the anterior root is severed and its peripheral end is stimu- lated only motor effects should be obtained. Magendie observed, however, upon dogs that in certain cases the animals showed signs of pain. This apparent exception to the general rule was after- ward explained satisfactorily. It was shown that the fibers in question do not really belong to the anterior root, — that is, they do not emerge from the cord with the root fibers; they are, in fact, sensory fibers for the meningeal membranes of the cord which are on their way to the posterior roots and which enter the cord with the fibers of the latter. Since the work of Bell and Magendie it has been a question whether their law applies to all afferent and efferent fibers and not simply to the motor and sensory fibers proper. The experimental evidence upon this point, as far as the mammals are concerned, has accumulated slowly. Various authors have shown that stimulation of the anterior roots of certain spinal nerves may cause a constriction of the blood-vessels, an erection of the hairs (stimulation of the pilomotor fibers), a secretion of sweat, and so on, while stimulation of the posterior roots in the same regions is without effect upon these peripheral tissues. One apparent excep- tion, however, has been noted. A number of observers have found that stimulation of the peripheral end of the divided posterior
78 THE PHYSIOLOGY OF MUSCLE AND NERVE.
roots (fifth lumbar to first sacral) causes a vascular dilatation in the hind limb. The matter has been particularly investigated by Bayliss,* who gives undoubted proof of the general fact. At the same time he shows that the fibers in question are not efferent fibers from the cord passing out by the posterior instead of the an- terior roots. This is shown by the fact that they do not degenerate when the root is cut between the ganglion and the cord, as they should do if they originated from cells in the cord. Bayliss's own explanation of this curious fact is that the fibers in question are ordinary afferent fibers, but that they are capable of a double ac- tion: they can convey sensory impulses from the blood-vessels to the cord according to the usual type of sensory fibers, but they can also convey efferent impulses, antidromic impulses as he desig- nates them, to the muscles of the blood-vessels. In other words, for this special set of fibers he attempts to re-establish the view held by physiologists before the time of Bell, — namely, that one and the same fiber transmits normally both afferent and efferent impulses. An exception so peculiar as this to an otherwise general rule cannot be accepted without hesitation. It is possible that future work may give an explanation less opposed to current views than that offered by Bayliss.
Cells of Origin of the Anterior and Posterior Root Fibers.— The efferent fibers of the anterior root arise as axons or axis cylinder processes from nerve cells in the gray matter of the cord at or near the exit of the root. The motor fibers to the voluntary muscles arise from the large cells of the anterior horn of gray matter; the fibers to the plain muscle and glands, autonomic fibers according to Langley's nomenclature, take their origin from spindle-shaped nerve cells lying in the so-called lateral horn of the gray matter.f According to the accepted belief regarding the nutrition of nerve fibers, any section or lesion involving these portions of the gray mat- ter or the anterior root will be followed by a complete degeneration of the efferent fibers. In the case of the fibers to the voluntary muscles this degeneration will extend to the muscles and include the end-plates. In the case of the autonomic fibers the degenera- tion will extend to the peripheral ganglia in which they terminate, involving, therefore, the whole extent of what is called the pre- ganglionic fiber (see the chapter on the autonomic nerves and the sympathetic system). The posterior root fibers have their origin in the nerve cells contained in the posterior root ganglia. These cells are unipolar, the single process given off being an axis cylinder process or axon. It divides into two branches, one passing into the cord by way of the posterior root, the other toward the periph-
* Bayliss, "Journal of Physiology," 26, 173, 1901, and 28, 276, 1902. t Herring, "Journal of Physiology," 29, 282, 1903.
THE PHENOMENON OF CONDUCTION. 791
eral tissues in the corresponding spinal nerve in which they form the peripheral sensory nerve fibers. It follows that a section or lesion of the posterior root will result in a degeneration of the branch entering the cord, this branch having been cut off from its nutri- tive relationship with its cells of origin. The degeneration will in- volve the entire length of the branch and its collaterals to their terminations among the dendrites of other spinal or bulbar- neurons (see the chapter on the spinal cord). After a lesion of this sort the stump of the posterior root that remains in connection with the posterior root ganglion mairftains its normal structure. On the other hand, a section or lesion involving the spinal nerve will be followed by a degeneration of all the" fibers, efferent and afferent, lying to the peripheral side of the lesion, since these fibers are cut off from connection with their cells of origin, while the fibers in the central stump of the divided nerve will retain their normal structure. Afferent and Efferent Fibers in the Cranial Nerves.- — The first and second cranial nerves, the olfactory and the optic, contain only afferent fibers, which arise in the former nerve from the olfac- tory epithelium in the nasal cavity, in the latter from the nerve cells in the retina. The third, fourth, and sixth nerves contain only efferent fibers which arise from the nerve cells constituting their nuclei of origin in the midbrain and pons. The fifth nerve resembles the spinal nerves in that it has two roots, one containing afferent and the other efferent fibers. The efferent fibers, consti- tuting the small root, arise from nerve cells in the pons and mid- brain, the afferent fibers arise from the nerve cells in the Gasserian ganglion. This ganglion, being a sensory ganglion, is constituted like the posterior root ganglia. Its nerve cells give off a single process which divides in T, one branch passing into the brain by way of the large root, while the other passes to the peripheral tissues as a sensory fiber of the fifth nerve. The seventh nerve may also be homologized with a spinal nerve. The facial nerve proper consists of only efferent fibers, which arise from nerve cells constituting its nucleus of origin in the pons. £The geniculate ganglion, attached to this nerve shortly after its emergence, is similar in structure to the Gasserian or a posterior root ganglion. Its nerve cells send off processes which divide in T and constitute afferent fibers in the so-called nervus intermedius or nerve of Wrisberg. The eighth nerve consists only of afferent fibers which arise from the nerve cells in the spinal ganglion of the cochlea, cochlear branch, and from there constituting the vestibular or Scarpa's ganglion, the vestibu- lar branch. Both of these ganglia are sensory, resembling the posterior root ganglia in structure. The ninth nerve is also mixed, the efferent fibers arising from the motor nucleus in the medulla, while the sensory fibers arise in the superior and petrosal ganglia
80 THE PHYSIOLOGY OF MUSCLE AND NERVE.
found on the nerve at its emergence from the skull. The tenth is a mixed nerve, its efferent fibers arising in motor nuclei in the me- dulla, the afferent fibers in the nerve cells of the ganglia lying upon the trunk of the nerve at its exit from the skull (ganglion jugulare and nodosum). The eleventh and twelfth cranial nerves contain only efferent fibers that arise from motor nuclei in the medulla.
It will be seen from these brief statements that in all the nerve trunks of the central nervous system — that is, the spinal and the cranial nerves — the cells of origin of the efferent fibers lie within the gray matter of the brain or cord, while the cells of origin of the afferent fibers lie in sensory ganglia outside the central nervous system, — namely, in the posterior root ganglia for the spinai nerves, in the ganglion semilunare (Gasseri), the g. geniculi, the g. spirale, the g. vestibulare, the g. superius, and g. petrosum of the glossopharyngeal, and the g. jugulare and g. nodosum of the vagus. These various sensory ganglia attached to the cranial nerves corre- spond essentially in their structure and physiology with the posterior root ganglia of the spinal nerves.
Independent Irritability of Nerve Fibers. — Although the nerve fibers under normal conditions are stimulated only at their ends, the efferent fibers at the central end, the afferent at the peripheral end, yet any nerve fiber may be stimulated by artificial means at any point in its course. Artificial stimuli capable of affecting the nerve fiber — that is, capable of generating in it a nerve impulse which then propagates itself along the fiber — may be divided into the following groups :
1. Chemical stimuli. Various chemical reagents, when applied directly to a nerve trunk, excite the nerve fibers. Such reagents are concentrated solutions of the neutral salts of the alkalies, acids, alkalies, glycerin, etc. This method of stimulation is not, however, of much practical value in experimental work, since it is difficult or impossible to control the reaction.
2. Mechanical stimuli. A blow or pressure or a mechanical in- jury of any kind applied to a nerve trunk also excites the fibers. This method of stimulating the fibers is also difficult to control and has had, therefore, a limited application in experimental work. The mechanical stimulus is essentially a pressure stimulus, and the difficulty lies in controlling this pressure so that it shall not actually destroy the nerve fiber by rupturing the delicate axis cylinder. Various instruments have been devised by means of which light blows may be given to the nerve, sufficient to arouse an impulse, but insufficient to permanently injure the fibers. The results ob- tained by this method have been very valuable in physiology as con- trols for the experiments made by the usual method of electrical stimulation. It may be mentioned also that under certain condi-
THE PHENOMENON OF CONDUCTION. 81
tions — for instance, at one stage in the regeneration of nerve fibers mechanical stimuli may be more effective than electrical, that is, may stimulate the nerve fiber when electrical stimuli totally fail to do so.
3. Thermal stimuli. A sudden change in temperature may stimulate the nerve fibers. This method of stimulation is very ineffective for motor fibers, only very extreme and sudden changes, such as may be obtained by applying a heated wire directly to the nerve trunk, are capable of so stimulating them as to produce a muscular contraction. On the other hand, the sensory nerve fibers are quite sensitive to changes of temperature. If a nerve trunk in a man or animal is suddenly cooled, or especially if it is suddenly heated to 60° to 70° C., violent pain results from the stimulation of the sensory fibers in the trunk, while the motor fibers are apparently not acted upon. We have in this fact one of several differences in reaction between motor and sensory fibers which have been noted from time to time, and which seem to
Fig. 29. — Stimulating (catheter) electrodes for nerves: 6, Binding posts for attachment of wires from the secondary coil; 8, insulating sheath of hard rubber; p, platinum points laid upon the nerve.
indicate that there is some important difference in structure or composition between them.
4. Electrical stimuli. Some form of the electrical current is be- yond question the most effective and convenient means of stimulat- ing nerve fibers. We may employ either the galvanic current — that is, the current taken directly from a battery — or the induced current from the secondary coil of an induction apparatus or the so-called static electricity from a Ley den jar or other source. In most experi- mental work the induced current is used. The terminal wires from the secondary coil are connected usually with platinum wires im- bedded in hard rubber, forming what is known as a stimulating elec- trode. (See Fig. 29). By this means the platinum ends which now form the electrodes, anode and cathode, can be placed close together upon the nerve trunk, and the induced current passing from one to the other through a short stretch of the nerve sets up at that point nerve impulses which then propagate themselves along the nerve fibers. The induction current is convenient because of its intensity, which overcomes the great resistance offered by the moist tissue ; be- cause of its very brief duration, in consequence of which it acts as a sharp, quick, single stimulus or shock, and because of the great ease 6
82
THE PHYSIOLOGY OF MUSCLE AND NERVE.
with which it may be varied as to rate and as to intensity. Each time that the battery current in the primary coil is made or broken there is an induction current established in the secondary coil, and if the nerve is on the electrode the current passes through it and stimulates it. This induced current is, however, extremely short, and alternates in direction, passing in one direction when the primary current is made and in the opposite direction when it is broken. The induced current set up by the making of the battery current in the primary coil we designate as the making shock, that set up by the breaking of the current in the primary as the breaking shock. On account of the very brief duration of the induced cur- rent it is difficult to distinguish between the effects of its opening and closing.
The Stimulation of the Nerve by the Galvanic Current. — When
however, we employ the galvanic current, taken directly from a bat- tery, as a stimulus, we can, of course, allow the current to pass through the nerve as long as we please and can thus study the effect of the closing of the current as distinguished from that of the open- ing, or the effect of duration or direction of the current, etc.
Du Bois-Reymond's Law of Stim- ulation.— When a galvanic current is led into a motor nerve it is found, as a rule, that with all moderate strengths of currents there is a stimulus to the nerve at the moment it is closed, the making or closing stimulus, and another when the current is broken, the breaking or opening stimulus, while during the passage of the current through the nerve no stimulation takes, place: the muscle remains relaxed. We may express this fact by saying that the motor nerve fibers are stimulated by the mak- ing and the breaking of the current or by any sudden change in its intensity, but remain unstimulated during the passage of cur- rents whose intensity does not vary.
The Anodal and Cathodal Stimuli. — It has been shown quite con- clusively that the nerve impulse started by the making of the current arises at the cathode, while that at the breaking of the current begins at the anode, or, in other words, the making shock or stimulus is cathodal, while the breaking stimulus is anodal. This
Fig. 30. — Schema of the arrange- ment of apparatus for stimulating the nerve by a galvanic current: b, The battery; k, the key for opening and closing the circuit ; c, the commutator for reversing the direction of the cur- rent; + the anode or positive pole; — the cathode or negative pole.
THE PHENOMENON OF CONDUCTION. 83
fact is true for muscle as well as nerve, and possibly for all irritable tissues capable of stimulation by the galvanic current. This important generalization may be demonstrated for motor nerves by separating the anode and cathode as far as possible and re- cording the latent period for the contractions caused respect- ively by the making and the breaking of the current in the nerve. If the cathode is nearer to the muscle the latent period of the mak- ing contraction of the muscle will be shorter than that of the break- . ing contraction by a time equal to that necessary for a nerve impulse to travel the distance between anode and cathode. If the position of the electrodes is reversed the latent period of the making con- traction will be correspondingly longer than that of the breaking contraction. It is very evident from these facts that when a current is passed into a nerve or muscle the changes at the two poles are different, as shown by the differences in reactions and properties of the nerve at these points. Bethe has shown that a difference may be demonstrated even by histological means. After the passage of a current through a nerve for some time the axis cylinders stain more deeply than normal at the cathode with certain dyes (toluidin blue), while at the anode they stain less deeply.
Electrotonus. — The altered physiological condition of the nerve at the poles during the passage of the galvanic current is designated as electrotonus, the condition round the anode being known as anelectrotonus, that round the cathode as catelectrotonus. Elec- trotonus expresses itself as a change in the electrical condition of the nerve which gives rise to currents known as the electrotonic currents, — a brief description of these currents will be given in the next chapter, — and also by a change in irritability and con- ductivity. The latter changes were first carefully investigated by Pfliiger, who showed that when the galvanic current, or, as it is usually called in this connection, the polarizing current, is not too strong there is an increase in irritability and conductivity in the neighborhood of the cathode, the so-called catelectrotonic increase of irritability, while in the region of the anode there is an anelec- trotonic decrease in irritability and conductivity. These opposite variations in the state of the nerve are represented in the accom- panying diagram. Between the two poles — that is. in the intrapolar region — there is, of course, an indifferent point, on one side of which the irritability of the nerve is above normal and on the other side below normal. The position of this indifferent point shifts toward the cathode as the strength of the polarizing current is increased. In other words, as the current increases the anelectrotonus spreads more rapidly and becomes more intense, and the conductivity in this region soon becomes so depressed as to block entirely the
84 THE PHYSIOLOGY OF MUSCLE AND NERVE.
passage of a nerve impulse through it. The changes on the cathodal side are not so constant nor so distinct. Later observers * have shown, in fact, that if the polarizing current is continued for some time the heightened irritability at the cathode soon diminishes and sinks below normal, so that in fact at the cathode as well as at the anode the irritability may be lost entirely. If the polarizing current is very strong this depressed irritability at the cathode comes on practically at once. Moreover, when a strong current that has been passing through a nerve is broken the condition of depressed irritability at the cathode persists for some time after the opening of the current.
Pfliiger's Law of Stimulation. — It was said above that when a galvanic current is passed into a nerve there is a stimulus (catho- dal) at the making of the current and another stimulus (anodal)
Fig. 31. — Electrotonic alterations of irritability caused by weak, medium, and strong battery currents: A and B indicate the points of application of the electrodes to the nerve, A being the anode, B the cathode. The horizontal line represents the nerve at normal irri- tability; the curved lines illustrate how the irritability is altered at different parts of the nerve with currents of different strengths. Curve yl shows the effect of a weak current, the part below the line indicating decreased, and that above the line increased irritability; at xl the curve crosses the line, this being the indifferent point at which the catelectrotonic effects are compensated for by anelectrotonic effects; y- gives the effect of a stronger current, and y3, of a still stronger current. As the strength of the current is increased the effect becomes greater and extends farther into the extrapolar regions. In the intrapolar region the in- different point is seen to advance, with increasing strengths of current, from the anode toward the cathode. — (Lombard.)
at the breaking of the current. This statement is true, however, only for a certain range of currents. Of the two stimuli, the making or cathodal stimulus is the stronger, and it follows, therefore, that when the strength of the current is diminished there will come a certain point at which the anodal stimulus will drop out. With weak currents there is then a stimulus only at the make. On the other hand, when very strong currents are used the stimuli that act at the two poles set up nerve impulses whose passage to the muscle may be blocked by the depressed conductivity caused by the electro- tonic changes. Whether or not the stimulus will be effective in
*Werigo, "Pfliiger's Archiv," 84, 547, 1901. See Biedermann, " Elec- trophysiology," translated by Welby, vol. ii, p. 140.
THE PHENOMENON OF CONDUCTION. 85
causing a contraction in the attached muscle will depend naturally on the relative positions of the electrodes, — that is, on the direction of the current in the nerve. In describing the effect of these strong currents we must distinguish between what are called ascending and descending currents. Ascending currents are those in which the direction of the current in the nerve is away from the muscle, a position of the poles, therefore, in which the anode is closer to the muscle. In descending currents the positions are reversed. Pfluger's law of contraction or of stimulation takes account of the effect of extreme variations in the -strength of the current and is usually expressed in tabular form as follows : The letter C indicates that the nerve is stimulated and causes a contraction in the attached muscle, and O indicates a failure in the stimulation (weak currents) or a failure in the nerve impulse to reach the muscle owing to blocking (strong currents) .
Fig. 32. — Schema to show the arrangement of apparatus for an ascending and a descending current: A, ascending; £>, descending.
ASCENDING CURRENT. DESCENDING CURRENT. Making. Breaking. Making. Breaking.
Very weak currents . . C O C O
Moderate " C C C C
Very strong " O C C O
The effects obtained with the strong currents are readily under- stood if we bear in mind the facts stated above regarding electro- tonus. When the current is ascending the stimulus on making starts from the cathode, but cannot reach the muscle because it is blocked by a region of anelectrotonus in which the conduc- tivity is depressed. The stimulus on breaking takes place